The use of plants in the traditional management of diabetes in Nigeria: Pharmacological and toxicological considerations

Udoamaka F. Ezuruike; Jose M. Prieto

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r^ Journal of Ethnopharmacology

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Review

The use of plants in the traditional management of diabetes in Nigeria: Pharmacological and toxicological considerations

Udoamaka F. Ezuruike * Jose M. Prieto1

Center for Pharmacognosy and Phytotherapy, Department of Pharmaceutical and Biological Chemistry, School of Pharmacy, University College London, 29-39 Brunswick Square, WC1N 1AX London, United Kingdom

ABSTRACT

Ethnopharmacological relevance: The prevalence of diabetes is on a steady increase worldwide and it is now identified as one of the main threats to human health in the 21st century. In Nigeria, the use of herbal medicine alone or alongside prescription drugs for its management is quite common. We hereby carry out a review of medicinal plants traditionally used for diabetes management in Nigeria. Based on the available evidence on the species' pharmacology and safety, we highlight ways in which their therapeutic potential can be properly harnessed for possible integration into the country's healthcare system.

Materials and methods: Ethnobotanical information was obtained from a literature search of electronic databases such as Google Scholar, Pubmed and Scopus up to 2013 for publications on medicinal plants used in diabetes management, in which the place of use and/or sample collection was identified as Nigeria. 'Diabetes' and 'Nigeria' were used as keywords for the primary searches; and then 'Plant name -accepted or synonyms', 'Constituents', 'Drug interaction' and/or 'Toxicity' for the secondary searches. Results: The hypoglycemic effect of over a hundred out of the 115 plants reviewed in this paper is backed by preclinical experimental evidence, either in vivo or in vitro. One-third of the plants have been studied for their mechanism of action, while isolation of the bioactive constituent(s) has been accomplished for twenty three plants.

Some plants showed specific organ toxicity, mostly nephrotoxic or hepatotoxic, with direct effects on the levels of some liver function enzymes. Twenty eight plants have been identified as in vitro modulators of P-glycoprotein and/or one or more of the cytochrome P450 enzymes, while eleven plants altered the levels of phase 2 metabolic enzymes, chiefly glutathione, with the potential to alter the pharmacokinetics of co-administered drugs.

Conclusion: This review, therefore, provides a useful resource to enable a thorough assessment of the profile of plants used in diabetes management so as to ensure a more rational use. By anticipating potential toxicities or possible herb-drug interactions, significant risks which would otherwise represent a burden on the country's healthcare system can be avoided.

(http://creativecommons.org/licenses/by/3.0/).

Contents

1. Introduction........................................................................................................858

1.1. Diabetes ..................................................................................................... 858

1.2. Traditional herbal medicines in diabetes management................................................................858

2. Ethno-pharmacological data collection................................................................................... 859

2.1. Method...................................................................................................... 859

Abbreviations: AAN, aristolochic acid nephropathy; ADME, absorption, distribution, metabolism and excretion; CYT P450, cytochrome P450; DPP-IV, dipeptidyl peptidase IV; GLP1, glucagon like peptide 1; GLUT4, glucose transporter 4; GSH, glutathione; GST, glutathione-S-transferase; IDDM, insulin dependent diabetes mellitus; NIDDM, noninsulin dependent diabetes mellitus; P-GP, P-glycoprotein; PPARy, peroxisome proliferator activated receptor gamma; STZ, streptozotocin; WHO, World Health Organization * Corresponding author. Tel.: + 44 2077535871. E-mail addresses: amaka.ezuruike@gmail.com (U.F. Ezuruike), j.prieto@ucl.ac.uk (J.M. Prieto). 1 Tel.: +44 2077535841.

http://dx.doi.org/10.1016/jjep.2014.05.055

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ARTICLE INFO

Article history:

Received 15 November 2013 Received in revised form 26 May 2014 Accepted 26 May 2014 Available online 12 June 2014

Keywords:

Diabetes

Nigeria

Ethnopharmacology

Herb-drug interactions

WHO Traditional Medicine Strategy

2.2. Results......................................................................................................859

3. Pharmacological evidence and its clinical implications......................................................................859

3.1. In vivo hypoglycemic activity....................................................................................859

3.2. In vitro pharmacological evidence................................................................................903

3.3. Bioactive compounds...........................................................................................904

3.3.1. Nitrogen containing compounds...........................................................................904

3.3.2. Terpenes..............................................................................................907

3.3.3. Phenolic compounds....................................................................................907

3.3.4. Hydroxylated compounds including sugars .................................................................. 908

3.4. Clinical studies................................................................................................ 908

4. Toxicological evidence and considerations ................................................................................ 908

5. Conclusions ........................................................................................................ 910

Acknowledgments ....................................................................................................... 910

Appendix A. Supplementary information..................................................................................910

References.............................................................................................................910

1. Introduction

1.1. Diabetes

Diabetes is a chronic metabolic disorder characterized by high blood glucose levels. This is either as a result of insufficient endogenous insulin production by the pancreatic beta cells (otherwise known as type-1 diabetes); or impaired insulin secretion and/or action (type-2 diabetes). type-1 diabetes is an autoimmune disease characterized by T-cell mediated destruction of the pancreatic beta cells. In type-2 diabetes, there is a gradual development of insulin resistance and beta cell dysfunction, strongly associated with obesity and a sedentary lifestyle (Zimmet et al., 2001). Due to a higher incidence of the risk factors, the prevalence of diabetes is increasing worldwide, but more evidently in developing countries. Current estimates indicate a 69% increase in the number of adults that would be affected by the disease between 2010 and 2030, compared to 20% for developed countries (Shaw et al., 2010).

Administration of exogenous insulin is the treatment for all type-1 diabetic patients and for some type-2 patients who do not achieve adequate blood glucose control with oral hypoglycemic drugs. Current drugs used in diabetes management can be categorized into three groups. Drugs in the first group increase endogenous insulin availability. These include the sulphonylureas such as glibenclamide, the glinides, insulin analogs, glucagon-like peptide 1 (GLP-1) agonists and dipeptidyl peptidase-IV (DPP-IV) inhibitors. The first two members of this group act on the sulfonylurea receptor in the pancreas to promote insulin secretion. GLP-1 agonists and DPP-IV inhibitors on the other hand act on the ileal cells of the small intestine. The second group of drugs enhance the sensitivity of insulin. This includes the thiazolidine-diones, which are agonists of the peroxisome proliferator-activated receptor gamma (PPARy) and the biguanide metformin. The third group comprises the a-glucosidase inhibitors such as acarbose, which reduce the digestion of polysaccharides and their bioavailability (Chehade and Mooradian, 2000; Sheehan, 2003). All the existing therapies however have limited efficacy, limited tolerability and/or significant mechanism based side effects (Moller 2001; Rotenstein et al., 2012).

Despite the existing pharmacotherapy, it is still difficult to attain adequate glycemic control amongst many diabetic patients due to the progressive decline in P-cell function (Wallace and Matthews, 2000). In Nigeria, polytherapy with two or more hypoglycemic agents to achieve better glucose control is common practice (Yusuff et al., 2008). There is also a high incidence of diabetic complications and hyperglycemic emergencies (Gill et al.,

2009; Ogbera et al., 2007, 2009). In the presence of these, the number of prescribed drugs increases to an average of four per day for each patient (Enwere et al., 2006). This need for the chronic intake of a large number of drugs with their attendant side effects in addition to their high costs which is often borne by the patients themselves is the identified reason for non-adherence to therapy amongst diabetic patients. As a result, patients often have recourse to alternative forms of therapy such as herbal medicines (Yusuff et al., 2008).

1.2. Traditional herbal medicines in diabetes management

A number of reviews on medicinal plants used in the management of diabetes in different parts of the world (Bailey and Day, 1989; Marles and Farnsworth, 1995), as well as those used specifically in certain regions, such as in West Africa (Bever, 1980), Central America (Andrade-Cetto and Heinrich, 2005) and Asia (Grover et al., 2002) exist. These reviews have highlighted the dependence of a large percentage of the world population on traditional medicine for diabetes management. This is also corroborated by the WHO fact sheet (No. 134), which estimates that about 80% of the population in African and Asian countries rely on traditional medicine for their primary healthcare (WHO, 2008). It also recognizes traditional medicine as 'an accessible, affordable and culturally acceptable form of healthcare trusted by large numbers of people, which stands out as a way of coping with the relentless rise of chronic non-communicable diseases in the midst of soaring health-care costs and nearly universal austerity' (WHO, 2013).

Ethnobotanical surveys of plants traditionally used in diabetes management in different parts of Nigeria have been carried out (Abo et al., 2008; Etuk and Mohammed, 2009; Gbolade, 2009; Soladoye et al., 2012). These medicinal plants are used either alone as a primary therapeutic choice, or in conjunction with conventional medicines. On an average, approximately 50% of diabetic patients visiting hospitals in urban cities like Lagos and Benin have used some forms of traditional medicine during the course of their disease management (unpublished results of field work conducted by first author). Unfortunately, clinicians are either unaware of their patients' herb use or the identity of the herbal product being taken. To complicate matters further, herbal practitioners are usually unwilling to divulge the identity of the constituents of their preparations to patients. Most patients are also not interested in finding this out as they consider herbal preparations to be 'safe'; thereby making it difficult to ascertain if the herb may have a significant contributory role to the efficacy or failure of the treatment.

In a systematic review of herbs and supplements clinically used for glycemic control, Allium sativum, Aloe vera and Momordica charantia were the only identified plants used in Nigeria. This inclusion was however based on clinical studies carried out outside Nigeria (Yeh et al., 2003). This indicates the lack of information about the clinical use (or monitoring thereof) of plants in diabetes management in Nigeria, despite widespread traditional use.

In line with the increasing importance of traditional medicine in various healthcare systems around the world, the WHO Traditional Medicine Strategy has recently been updated. 'The goals of the strategy for the next decade (2014-2023) are to support Member States in (a) harnessing the potential contribution of traditional medicine to health, wellness and people-centered health-care; and (b) promoting the safe and effective use of traditional medicine by regulating, researching and integrating traditional medicine products, practitioners and practice into health systems where appropriate' (WHO, 2013).

Given that diabetes is now considered as one of the main threats to human health in the 21st century (Zimmet et al., 2001), there might be an even greater reliance by diabetic patients in Nigeria on herbal medicines used in its management. Unfortunately, pharmacological and toxicological evidences validating the safety and efficacy of these medicinal plants are not readily available. The objective of this paper is to collate as much as possible, available information about medicinal plants traditionally used in diabetes management in Nigeria. In doing so, we aim to promote the rational use of these plants based on pharmacological evidence for their therapeutic use and their toxic/interaction profile.

2. Ethno-pharmacological data collection

2.1. Method

Information about medicinal plants traditionally used in the management of diabetes in Nigeria was obtained from published papers and texts on ethnobotanical studies, as well as those investigating the effect of plant(s) used in diabetes management, in which the place of use and/or sample collection was identified as Nigeria. A literature search of electronic databases such as Google Scholar, Pubmed and Scopus up to 2013 was carried out using 'Diabetes' and 'Nigeria' as keywords for the primary searches; and then 'Plant name - accepted or synonyms', 'Constituents', 'Drug interaction' and/or 'Toxicity' for the secondary searches.

In order to highlight medicinal plants traditionally used in diabetes management with the potential for integration into the healthcare system, not all identified plants were included in this paper. Only those with (1) more than one reference to its use in diabetes management in Nigeria based on ethnobotanical studies were retained; and/or (2) experimental evidence in one or more diabetes experimental models validating its activity. This review is therefore not exhaustive for all the plants used traditionally for diabetes management in Nigeria.

2.2. Results

Data for one hundred and fifteen plants traditionally used in diabetes management in Nigeria were obtained, either from previously conducted ethnobotanical studies (Abo et al., 2008; Aiyeloja and Bello, 2006; Ajibesin et al., 2008; Etuk and Mohammed, 2009; Gbolade, 2009; Igoli et al., 2005; Lawal et al., 2010; Ogbonnia and Anyakora, 2009; Okoli et al., 2007; Olowokudejo et al., 2008); or

from primary research papers (as indicated in Table 1). These are tabulated according to their accepted Latin Name (based on http://www.plantlist.org). Synonyms are included for plants which were not identified with their accepted names in the primary research paper. For each of the identified plants, the family name, common name(s), identified region of use in diabetes management, experimental evidence of activity (where available), other medicinal uses, plant part(s) used, traditional method(s) of preparation, identified active constituent(s), other relevant phyto-chemical constituents, as well as data on interaction and toxicity studies are included [Table 1].

Out of the 115 plants reviewed in this paper, only twelve of them have no experimental evaluation of their blood sugar reducing effects, either in vivo or in vitro. In selecting studies to be included, priority was given to investigations carried out with samples collected in Nigeria. Certain publications were not included if the study design of the experimental evidence was not appropriate enough for validating the effect of the plant, such as the absence of a suitable control or the use of improper doses. Two-thirds of the identified plants with experimental evidence for their biological activity involved samples collected from Nigeria. For the remaining one-third, although the studies were not carried out with plant samples sourced from within Nigeria, these were still included, as the experimental evidence could provide some information validating their use in diabetes management, since they are widely used in Nigeria. The ethnobotanical research carried out on Moringa oleifera provides a rationale for including information from studies carried out in different countries, as some of these locally available plants could have been initially sourced from elsewhere (Popoola and Obembe, 2013).

In-vitro experimental studies as well as phytochemical studies carried out on the plant species regardless of the source of the plant samples were also included. These together could provide more insight into the biological activity(s) of the plant, which would in turn help to promote a more rational use of the plant in diabetes management, either in the presence or absence of other co-morbidities. For completeness, reports on the antioxidant properties of many of the identified plants have been included as this has become a popular parameter in assessing the beneficial effects of a plant in diabetes management.

3. Pharmacological evidence and its clinical implications

3.1. In vivo hypoglycemic activity

Reducing blood sugar level is the classical clinical target in all forms of diabetes. Thus, the in vivo sugar lowering effect of putative hypoglycemic plants is therefore a premise to infer their potential clinical efficacy. In vivo validation also provides an indication of the relative toxicity of the plant. Although most herbal medicines have a long history of traditional use, only their experimental validation at known doses may give a clearer idea about its safety and efficacy, in line with the objectives of the WHO Traditional Medicine Strategy (WHO, 2013).

Ninety six out of the one hundred and fifteen plants here reviewed have been evaluated in various in vivo animal models of diabetes, mostly using alloxan and/or streptozotocin (STZ)-induced diabetic animals, which are the most frequently used animal diabetes models worldwide (Frode and Medeiros, 2008). These chemical agents are cytotoxic to the P-cells of the pancreatic islets, generating a state of insulin deficiency (akin to type-1 diabetes) with subsequent hyperglycemia (Szkudelski, 2001). The

Table 1

Medicinal plants used in the management of diabetes in Nigeria.

S/ Plant name Family Common Local Region of Experimental evidence for Other medicinal uses

no. name Nigerian use for its use in diabetes

name(s) diabetes* management

1 Abelmoschus Malvaceae Okro/Okra; Ha (Y); SW, SS 100 and 200 mg/kg of the Infections, Immune-

esculentus (L) Lady's fingers Okweje (I); seed and peel powder modulatory. Fevers,

Moench Kubewa (H) decreased blood glucose in Spasms, Gonorrhoea,

STZ induced diabetic rats Dysentry

(Sabitha et al., 2011 )§;

Antioxidant effects of the

aqueous extract of the leaves

(Tsumbu et al., 2011)

2 Abrus precatorius Leguminosae Cat's eye. Ojuologbo sw Inhibited a-amylase and a- Anti-infective,

(L.) Jequirity beans (Y), Oto- glucosidase enzymes and Convulsion,

berebere (I), antioxidant effects (Vadivel Rheumatism,

Idonzakara et al., 2011); 100 and 200 mg/ Abortifacient, Cold /

(H), kg aqueous extract of the Cough, Conjuctivitis,

Nneminua seeds produced a dose Contraceptive,

(Ib) dependent decrease in STZ- Aphrodisiac, Ulcers,

induced diabetic rats Anemia

(Nwanjo, 2008)

3 Acacia nilotica Leguminosae Gum arabic. Bagaruwa (H) NC 50 mg/kg of the ethyl acetate Anti-parasitic, Male

(L.) Delile Egyptian thorn fraction of the methanol sterility. Inflammation,

extract of the leaves Anti-microbial,

produced greater blood Hypertension, Anti-

glucose reducing effect spasms, Insomnia

( > 50%) in alloxan-induced

diabetic rats than the

n-butanol fraction (Tanko et

al., 2013)

4 Adansonia Malvaceae African baobab Ose (Y), Kuka NE, SW 100 mg/kg of the methanol Anti-sickling,

digitata L tree (H), Bokki extract of the stem bark Galactagogue,

(Fulani) decreased blood glucose Inflammation, Anti-

levels by 51% in STZ-induced pyretic, Analgesic, Anti-

diabetic rats (Tanko et al.. parasitic, Constipation,

2008) Skin lubricant. Asthma,

Nutritive value

5 Aframomum Zingiberaceae Alligator Atare (Y), SW Inhibitory effects on oc- Stimulant,

melegueta K. pepper. Grains Ose-orji (I), amylase and a-glucosidase Inflammation,

Schum. of paradise Citta (H) enzymes. Antioxidant Diarrhoea, Antifungal,

activity (Adefegha and Oboh, Insect repellent. Skin

2012) conditions. Malaria,

200 & 400mg/kg aqueous Analgesic

seed extract decreased blood

glucose in alloxan-induced

Plant part Traditional (s) used preparation method

Identified active constituent(s)

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

Fruit, Seed

Decoction, Maceration food

vegetable

Leaves, Seeds, Root

Decoction, Maceration

Trigonelline extracted from the seeds decreased blood glucose levels in alloxan induced diabetic rats (Monago and Nwodo, 2010)

Leaves, Pods, Maceration, Root, Bark, Infusion, Seeds Decoction

Stem bark. Leaves, Fruit pulp. Seeds

Seed, Fruits, Maceration, Leaves Tincture

p-l,3-d-glucans (Sheu and Lai, 2012); Hydroxy cinnamic derivatives, Oligomeric catechins, Isorhamnetin glycosides, Quercetin, Myricetin and Kaempferol and their glycosides (Arapitsas, 2008); Abelesculin (Kondo and Yoshikawa, 2007); Rhamnogalacturonans (Deters et al., 2005), Oleic, Stearic, Palmitic, Capric, Caprylic, Laurie, Myristic, Arachidic and Linoleic acids, Gossypol (Al-Wandawi, 1983) Epicatechin, Syringic acid, Caffeic acid (Vadivel et al., 2011); Abruquinones (Kuo et al., 1995); Abrusosides (Choi et al., 1989); Trigonelline, Hypaphorine, Precatorine, Abrine (Ghosal and Dutta, 1971)

Catechin and gallic acid derivatives (Malan, 1991); Androstene steroid (Chaubal et al., 2003); d-Pinitol (Chaubal et al., 2005); Kaempferol (Singh et al., 2008); Polygalloyltannin (Jigam et al., 2010); Lupenone, Acanilol A and B (Ahmadu et al., 2010)

Oleic, Linoleic and Myristic acids (Eteshola and Oraedu, 1996); Epicatechin, Epicatechin procyanidins, Dihydroxy and Trihydroxy flavan-4-one glycosides, Quercetin glycosides, oc-amyrin, p-amyrin palmitate. Ursolic acid, Adansonin, p-sitosterol, Stigmasterol (Refaat et al., 2013) 6-Gingerol, 6-shogaol, 6-paradol (Ilic et al., 2010); Linalool, 1,8-cineole, Citral, 2-heptyl acetate, 2-heptanol (Ukeh and Umoetok, 2011)

Water soluble fraction of the fruits decreased oral metformin absorption in-vivo (Khatun et al., 2011)

Abrin-Toxic component (Kirsten et al., 2003)

Co-incubation of 0.01% of the extract in Caco-2 cell monolayers decreased the integrity of the monolayer and the secretory transport of CsA indicating possible inhibition of P-gp (Deferme et al., 2003)

Inhibition of Cyp 3A4, 3A5 and 3A7 enzyme activity (Agbonon et al., 2010); Elevated levels of liver function enzymes with chronic dosing (Ilic et al., 2010)

S/ Plant name Family Common Local Region of Experimental evidence for

no. name Nigerian use for its use in diabetes

name(s)* diabetes# management

Other medicinal uses

Plant part (s) used

Traditional preparation method

Identified active constituent(s)

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

6 Ageratum Compositae

conyzoides (L.) L.

Goat weed

Imi esu (Y), Urata njele (I), Ebegho-edore (Bi)

diabetic rats (Adesokan et al., 2010)

100, 200 and 300 mg/kg of the aqueous extract of the leaves decreased blood

Wound ulcers, Antimicrobial, Skin infections, Analgesic,

Whole plant, Leaves

Fresh Juice

extract,

Infusion

glucose levels in both normal Anti-spasm, Insecticidal,

7 Alchornea cordifolia (Schumach and Thonn.) Mull.Arg.

Euphorbiaceae

Christmas bush

Ipa (Y), Mbom (Ib), Upia (Ige), Uwanwe (Es), Osokpo (I)

rats, STZ-induced diabetic rats and glucose-loaded rats (Nyunai et al., 2009)§; 100, 200 and 400 mg/kg of the ethanol extract of the shoot decreased blood glucose levels in normal and alloxan induced diabetic rats (Egunyomi et al., 2011)

SE, SW, SS Antioxidant activity and

8 Allium cepa L. Amaryllidaceae Onion

Alubosa (Y) SE

9 Allium sativum L. Amaryllidaceae Garlic

Aayu (Y), Ayo-ishi (I), Tafarunua (H)

Diarrhoea, Gonorrhoea, Emetic

hepatoprotective effects (Olaleye and Rocha, 2007, 2008); Significant decrease in blood glucose levels in STZ-induced diabetic rats administered 200, 400 and 800 mg/kg of the n-butanol fraction of the aqueous extract of the leaves (Mohammed et al., 2012a, 2012b)

100 and 300 mg/kg aqueous extract of the bulb administered for 30 days decreased blood glucose levels in alloxan-induced diabetic rabbits and restored decreased levels of antioxidant enzymes (Ogunmodede et al., 2012)

200-300 mg/kg aqueous extract of the cloves decreased blood glucose levels in alloxan-induced diabetis rats after one week (Eyo et al., 2011); 250 and 500 mg/kg ethanol extract of the cloves administered for 14 days produced a dose-dependent decrease in serum glucose, lipid levels and liver

Wound, Ulcers, Infections, Anti-parasitic, Liver disorders, Rheumatism, Fevers, Diuretic, Purgative, Analgesic, Gonorrhea, Cough

Stem bark, Decoction

Leaves,

Seeds, Root

Convulsion, Rheumatism, Vermifuge, Hypertension

Hypertension, High cholesterol, Stomach ache, General debility, Hemorrhoids, Tumours, Asthma, Anti-microbial

Cloves

Anti-diabetic effects of S-methylcysteine sulfoxide isolated from onion in alloxan-induced diabetic rats (Sheela et al., 1995)

Anti-diabetic effects of S-allylcysteine sulfoxide isolated from garlic in alloxan-induced diabetic rats (Sheela et al., 1995)

Eugenol, a-pinene, 1,8-cineole, ß-caryophyllene, Ocimene, Limonene, Precocene I and II, Encecalin derivatives, Coumarin, Quercetin and its glycosides, Kaempferol and its glycosides, ß-sitosterol, Friedelin, Stigmasterol, Echinatine, Lycopsamine, Polymethoxylated and Polyhydroxy flavones (Okunade, 2002) Alchornoic acid (Kleiman et al., 1977); Quercetin and its glycosides, Gallic acid, Triisopentenyl guanidine, Protocatechuic acid (Lamikanra et al., 1990); Ellagic acid (Banzouzi et al., 2002); Daucosterol, ß-sitosterol, Acetyl aleuritolic acid, Di(2-ethylhexyl) phthalate (Mavar-Manga et al., 2008); Caryophyllene, Eugenol, Nanocosaine, Cadinol, Linalool, a-bergamonene (Okoye et al., 2011) Quercetin and its glycosides, Kaempferol, Cepaenes, S-methylcysteine sulfoxide (SMCS), ß-chlorogenin (Corzo-Martínez et al., 2007); Tropeosides,

Ascalonicoside, Sitosterol, Amyrin, Oleanolic acid, Taxifolin, Diosgenin, Gitogenin, Apigenin, Luteolin, Myricetin (Lanzotti, 2006) S-allylcysteine sulfoxide (SACS), Allyl sulfides, Allicin and its breakdown products, Allixin, Eruboside B, Vitamin B6 and B12 (Corzo-Martínez et al., 2007); Sativosides, Proto-desgalactotigonin, Apigenin, Quercetin, Myricetin, N-feruloyl

Components of aged garlic extract did not produce significant inhibition of Cytochrome P450 enzymes in vitro (Greenblatt et al., 2006); and in humans (Markowitz et al., 2003)

SW, NC

SS, SE

S/ Plant name Family Common Local Region of Experimental evidence for Other medicinal uses

no. name Nigerian use for its use in diabetes

name(s)* diabetes* management

Plant part Traditional Identified active (s) used preparation constituent(s) method

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

10 Aloe vera (L.) Burm.f.

Asparagaceae

Barbados aloe Ahon erin (Y) SE

11 Alstonia boonei De Wild.

Apocynaceae

Stoolwood, Devil tree, Australian fever bush

Ahun (Y), Egbu (I)

12 Alstonia

congensis Engl.

Apocynaceae

Pattern wood Egbu ora (I), SW Alstonia Awogbo ahun

13 Anacardium occidentale L.

Anacardiaceae

Cashew

Kasu (Y), Sashu (I), Kanju (H)

function enzyme levels and increased serum insulin levels in STZ-induced diabetic rats (Eidi et al., 2006)§

150 mg/kg of the dried pulp extract/exudate administered to STZ-induced diabetic rats decreased fasting blood glucose levels and improved the levels of the antioxidant enzyme (Nwanjo, 2006); 1 mg/ml aloe vera whole gel extract prevented the onset of hyperglycaemia in alloxan-induced diabetic rabbits (Akinmoladun and Akinloye, 2007); 350 mg/kg of a polyphenol-rich gel extract administered to insulin resistant mice for 4 weeks improved insulin tolerance and fasting blood glucose levels (Pérez et al., 2007)§

In vitro antioxidant effects (Akinmoladun et al., 2010)

Skin diseases, Laxative, Immune booster, Wound ulcers, Tumours, Guinea worm, Amenorrhoea

Juice extract

Malaria, Infertility, Arthritis, Anti-infective

Stem bark

Decoction,

Tincture,

Maceration

Malaria, Diuretic, Analgesic, Astringent, Hypertension

Administration of 1 g/kg of a 1:1 mixture of a hydroethanolic extract of Alstonia congensis bark and Xylopia aethiopica fruits decreased blood glucose levels in normal mice (Ogbonnia et al., 2008a); In vitro antioxidant effects (Awah et al., 2012)

Stimulated glucose uptake in Cough, Malaria, Skin C2C12 myoblasts and rat liver infections, Anti-mitochondria (Tedong et al., 2010)§; 200 mg/kg methanol

Stem bark, Root, Leaves

Decoction, Maceration

parasitic, Fevers, Anti-helminthic

Stem bark, Leaves, Seed, Nuts

Decoction, Maceration

tyrosine, N-feruloyl tyramine (Lanzotti, 2006)

Mannose-6-phosphate, Barbaloin, Emodin, Aloin, Aloe emodin, Aloesin, p-sitosterol, Diethylhexyl phthalate (Choi and Chung, 2003); Aloetic acid, Veracylglucan A, B and C, Acemannan, Anthranol, Isobarbaloin,

Arabinogalactan, Cinnamic acid ester, Aloeride, Malic acid, Isorabaichromone, Neoaloesin A, Isoaloeresin D, 8-C-glucosyl derivatives of aloediol, aloesol, noreugenin, Ascorbic acid, p-carotene, a-tocopherol (Hamman, 2008); Myricetin, Kaempferol, Quercetin (Sultana and Anwar, 2008) B-amyrenone, p-amyrin acetate, Lupeol, Sitosterol (Faparusi and Bassir, 1972); Echitamine, Echitamidine (Kucera et al., 1972); Na-formyl echitamidine (Oguakwa, 1984); a-amyrin and its esters, Lupeol and its esters (Rajic et al., 2000); Na-formyl-12-methoxy echitamidine, Voacangine, Akuammidine, Ursolic acid, Loganin, Boonein (Adotey et al., 2012) Echitamine, Echitamidine, Nor-echitamine, 17-O-acetyl nor-echitamine, Akuammicine and its 12-Methoxy derivative, Tubotaiwine, 12-methoxy tubotaiwine and its 12-methoxy derivative, Akuammidine, Angustilobine A and B, Seco angustilobine A and B, Anugustilobine-B-N-oxide (Caron et al., 1989) 6-Alkyl salicylic acids (Anacardic acids), 5-alkyl resorcinols (Cardols), 3-alkyl phenols

Causes an opening of the tight junction between adjascent epithelial cells thereby increasing paracellular transport, with the potential to increase oral drug absorption (Hamman, 2008)

Possible nephrotoxic effects; Decreased creatinine levels in normal mice (Ogbonnia et al., 2008a).

SW, NC

SI Plant name no.

Family

Common Local Region of Experimental evidence for Other medicinal uses

name Nigerian use for its use in diabetes

name(s) diabetes* management

14 Ananas comosus Bromeliaceae (L.) Merr.

Pineapple

Ogede oyinbo SW (I)

extract of the stem bark administered to rats alongside a high-fructose diet prevented the onset of hyperglycaemia (Olatunji et al., 2005); 100-800 mg/kg aqueous and methanol extract of the stem bark decreased blood glucose levels in both fasted normal and STZ-induced diabetic rats dose dependently (Ojewole, 2003); Inhibits a-glucosidase and aldose reductase enzymes (Toyomizu et al., 1993f

The ethanolic extract at a dose of 400 mg/kg improved insulin sensitivity in diabetic dyslipidaemic rats; as well as improved glucose uptake in insulin resistant HepG2 cells (Xie et al., 2006)§

Inflammation, Antiparasitic

15 Anisopus mannii Apocynaceae N.E.Br.

Sakayau (H), Kashe zaki (H)

16 Annona muricata L.

Annonaceae

Soursop, Custard apple

Sapi sapi (Y) SW, SE

100, 200 and 400 mg/kg aqueous leaf extract decreased blood glucose levels in alloxan-induced diabetic mice (Manosroi et al., 2011); Antioxidant effect (Aliyu et al., 2010); 100-400 mg/kg of the aqueous stem extract decreased blood glucose in normal rats (Sani et al., 2009)

100 mg/kg aqueous leaf extract decreased blood glucose, increased serum insulin, decreased p-cell damage and possessed antioxidant effects in STZ induced diabetic rats (Adewole and Caxton-Martins, 2006); Methanol extract of the leaves inhibits oc-amylase and a-glucosidase enzymes, but less potent than acarbose (Kumar et al., 2011 )§

Analgesic, Antiparasitic, Inflammation, Hypertension, Antimicrobial, Infertility

Hypertension, Sedative, Cancer, Emetic, Lactagogue, Antimicrobial, Anticonvulsant, Antiparasitic, Rheumatism, Analgesic, Insecticide

Plant part Traditional Identified active Other relevant Interaction/toxicity

(s) used preparation constituent(s) phytoconstituents studies

method identified in the plant

(Cardanols), 2-methyl-5-alkyl resorcinol (Toyomizu et al., 1993); Stigmast-4-en-3-ol and Stigmast-4-en-3-one (Alexander-Undo et al., 2004); Lutein, p-carotene, Zeaxanthin, a-tocopherol, y-tocopherol, Thiamin, Stearic acid. Oleic acid and Linoleic acid (Trox et al., 2010)

Leaves, Fruits

Stem, Leaves, Whole plant

Bromelain, Chlorogenic, Caffeic, Coumaroylquinic, P-coumaric and Caffeic acids, Caffeoylglycerols, Coumaroylglycerols, Ferulic acid glucuronide, Hydroferuloylglucose, Ananaflavoside B and C, Ananasate, Dicaffeoyl glycerides, Tricin, Feruloyl glycerols (Ma et al., 2007) Anisopusine, Gingerdione, Lupen-3p-yl eicosanoate. Dehydro gingerdione, Ferulic acid (Tsopmo et al., 2009)

Leaves, Fruit, Infusion, Seeds, Bark, Decoction, Root Fruit juice

Reticuline, Coclaurine, Anomurine, Anomuricine, Coreximine (Lannuzel et al., 2002); Scyllitol, Oleic, Linoleic and P-coumaric acid, Procyanidins, Stigmasterol (Leboeuf et al., 1980); Annonaine, Asimilobine, Nornuciferine (Hasrat et al., 1997); Acetogenins (Carmen Zafra-Polo et al., 1998); Alkyl esters, Linalool, p-caryophyllene, Cadinene, Humulene, Caryophyllene oxide, Phellandrene, Cadinol (Fournier et al., 1999); Gallic acid, Epicatechin, Quercetin and its

Chronic intake of the fruit and infusions of the plant is thought to bring about neurodegeneration in the CNS; attributed to coreximine and reticuline alkaloids present in the plant (Lannuzel et al., 2002), as well as the acetogenin annonacin (Champy et al., 2005)

S/ Plant name Family Common Local Region of Experimental evidence for Other medicinal uses

no. name Nigerian use for its use in diabetes

name(s)* diabetes* management

Plant part Traditional Identified active (s) used preparation constituent(s) method

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

17 Annona Annonaceae

senegalensis Pers.

Wild custard apple

Anogeissus leiocarpus (DC.) Guill. and Perr.

Combretaceae

Axle wood, Giant fern

Anthocleista

djalonensis A. Chev.

Uburu ocha (I), Abo (Y), Gwander-daji (H), Ogoganto

Ndaweewu

SS, NC, NW, SW

Gentianaceae Cabbage tree

Orin-odan or

Ayin (Y), Atara (I), Marke (H)

Sapo (Y), Akpakoro or Uvuru (I), Putaa (H)

NC, NW, SW

SSc, SEb, SW

20 Anthocleista vogelii Planch.

Gentianaceae

Cabbage tree Kwari (H), NC, SW Opa oro (Y)

21 Aristolochia albida Duch.

Aristolochiaceae

Dutchmans pipe, Hill gourd

Duuman SW, NE, duutse (H), NW Paran funfun

100 mg/kg of the aqueous extract of a herbal preparation ADD-199 containing the roots of Annona senegalesis and three other plants decreased plasma glucose and increased plasma insulin in STZ-induced diabetic mice; as well as increased glucose uptake by isolated diaphragm (Okine et al., 2005)§; Antioxidant effects (Potchoo et al., 2008)§

Anti-parasitic, Antibacterial, Tumours, Erectile dysfunction, Wound-healing, Snake bites, Convulsions, Hemorrhage

Stem-bark, Root, Leaves

Antioxidant and hepatoprotective effects (Atawodi et al., 2011); 200 mg/kg aqueous extract decreased blood glucose levels after 2 h in alloxan-induced diabetic rats (Etuk and Mohammed, 2009)

< 111 mg/kg ethanolic root extract decreased blood glucose levels in alloxan-induced diabetic rats (Okokon et al., 2012); Alpha amylase inhibitory effects of the hydro-alcoholic extract of the leaves and stem bark as well as hypoglycaemic effect of 1 g/kg of the stem bark in alloxan-induced diabetic rats (Olubomehin et al., 2013) Hypoglycaemic effect of 100800 mg/kg aqueous extract in normal and alloxan-induced rodents (Abuh et al., 1990); Hydro-alcoholic extract of the leaves and stem bark produced < 50% alpha amylase inhibitory effects (Olubomehin et al., 2013)

Anti-parasitic, Hemorrhoids, Asthma, Anti-microbial, Anti-sickling

Anti-microbial, Inflammation, Wound-healing, Anti-parasitic, Fevers, Sexual disordes

Stem-bark Decoction

Stem-bark, Roots, Leaves

Purgative, Diuretic, Skin Root, Leaves, infections, Emmenagog, Stem-bark Anti-ulcer, Malaria

Anti-parasitic, Anti-venom, Analgesic, Inflammation, Skin infections, Anti-

Leaves, Stem,

Roots,

Rhizome

Infusion, Decoction

glycosides, Catechin, Chlorogenic acid, Argentinine, kaempferol and its glycosides (Nawwar et al., 2012) Acetogenins (Carmen Zafra-Polo et al., 1998); Roemerine, Isocorydine, 8,8-Bisdihydrosiringenin, Syringaresinol (You et al., 1995); Kaurane diterpenes, Quercetin, Sitosterol, Oleic acid, Linoleic acid, Sitosterol (Leboeuf et al., 1980); Rutin, Epicatechin, Catechin, Isoquercetin (Potchoo et al., 2008); Cadinol, a-phellandrene, Z-ocimene, Limonene, a and p-pinene, Linalool, Myrcene, Caryophyllenol, 1,8-cineole (Fournier et al., 1999)

Castalagin, Ellagic acid, Flavogallonic acid (Shuaibu et al., 2008); Leiocarpan A and B (Aspinall et al., 1969); Gallic acid, Chlorogenic acid, Protocatechuic acid P-comaric acid (Kone et al., 2012)

Djalonenol, Djalonensone, Sweroside, Ursolic acid, Sitosterone, Sitosterol, Stigmasterol, Bornesitol, Lichexanthone (Onocha et al., 1995)

Sweroside, Vogeloside, Fagaramide (Abuh et al., 1990); Tetraoxygenated xanthones (Chapelle, 1974)

Columbin (Nok et al., 2005); Aristolic acid, Aristolochic acid A, Aristolactam, 6-hydroxy

Stem bark extract inhibited P-gp mediated Rh-123 efflux (Ezuruike et al., 2012); Roemerine interacts with P-gp and enhances vinblastine cytotoxicity (You et al., 1995); ADD-199 did not interact with Cyt P-450 isozymes nor produce ay organ toxicity (Nyarko et al., 2005)

Dose-dependent toxicity of the aqueous leaf extract in rat lungs characterised by inflammation and lesions (Agaie et al., 2007)

Gastrointestinal upsets (Tchacondo et al., 2011)

Risk of AAN (Aristolochic acid nephropathy) (Heinrich et al., 2009)

Decoction

S/ Plant name Family Common Local Region of Experimental evidence for

no. name Nigerian use for its use in diabetes

name(s)* diabetes# management

Other medicinal uses

Plant part (s) used

Traditional preparation method

Identified active constituent(s)

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

22 Aristolochia Aristolochiaceae Snake wort, Gadau kuka

bracteolata Lam. Birth wort (H)

23 Aristolochia repens Mill.

24 Azadirachta indica A.Juss.

Aristolochiaceae

Meliaceae

Neem, Indian lilac

Akoigun (Y) SW, SS

Dogonyaro (Y), Ogwu akom (I)

25 Bauhinia

monandra Kurz

Leguminosae

Pink orchid,

Napoleon's

Abafe (Y)

26 Bauhinia thonningii Schum. Syn:

Leguminosae

Camel's foot

Kalgo (H), Abafe (Y)

NC, NW, SE, SW

spasmodic, Aphrodisiac, STDs

Skin infections, Anti- Leaves Roots, helminthic, Anti-venom, Seeds Analgesic Stimulant, Insecticide

Hemorrhoids, Rheumatism, Aphrodisiac

25 mg/ml ethanolic leaf extract increased insulin release from the pancreas (Chattopadhyay, 1999)§; 400 mg/kg hydro-ethanolic extract of the leaves decreased blood glucose in alloxan-induced diabetic rats, and produced a synergistic effect with Vernonia amygdalina (Ebong et al., 2008); 500 mg/kg ethanol extract of the leaves decreased blood glucose levels and improved pancreatic lesions in STZ-induced diabetic rats (Akinola et al., 2010) Antioxidant effects (Argolo et al., 2004); 1 g/kg stem bark extract decreased blood glucose levels in alloxan-induced and glucose loaded diabetic rats (Abo and Jimoh, 2004)

Antioxidant effects (Taofeek, 2011); 500 mg/kg aqueous extract of the leaves decreased blood glucose as

Anti-parasitic, Antipyretic, Anti-microbial, Anti-ulcer, Jaundice, Ringworm, Liver problems, Hemorrhoids, Inflammation, Wound-healing

Stem bark

Leaves, Seed, Bark, Root, Fruit, Gum

Infusion Decoction

Post-natal hemorrhage, Leaves, Anti-microbial, Laxative, Stem-bark, Inflammation, Pesticidal Pods, Root

Anti-parasitic, Antimicrobial, Malaria, Inflammation, Snake bites, Purgative

Leaves, Roots, Stem-bark

aristolochic acid A, Aristolone (Lajide et al., 1993); Aristolochic acids I, II, IV, C and C-beta-D-glucoside, Aristolactam I-beta-D-glucoside Campesterol, Stigmasterol, Sitosterol (Choudhury and Haruna, 1994) Aristolochic acid I and II, Aristolactam A (Kumar et al., 2003); Magnoflorine (El Tahir, 1991); N-acetyl nornuciferine, Aristo red, p-sitosterol (Chakravarty et al., 1988)

Aristolochic acids I, II, IV, C and D, Aristolochic acid d-beta-d-glucoside, Aristolactam I-beta-d-glucoside (Michl et al., 2011)

Quercetin, Myricetin and Kaempferol glycosides (Chattopadhyay, 1999); Nimbidin, Azadirachtin, Nimbin, Nimbolide, Sodium nimbidinate, Gedunin, Mahmoodin, Gallic acid, Epicatechin, Catechin, Gallocatechin, Epigallocatechin, Cyclic trisulphide and tetrasulphide, Margolone, Margolonone, Isomargolonone, GIa, GIIa, GIIIa, GIb (Biswas et al., 2002)

Rutin and Quercetin identified as the bioactive

constituents for the anti-

hyperglycaemic effect in alloxan-induced diabetic rats and insulin stimulatory effect in INS-1 cells (Alade et al., 2011, 2012)

D-3-O-methyl chiroinositol isolated from the methanol extract of

Risk of AAN (Heinrich et al., 2009); Chronic dosing of goats with the aqueous leaf extract resulted in toxic effects culminating in death (Barakati et al., 1983) Risk ofAAN (Heinrich et al., 2009)

Various pharmaco-toxic effects were seen with Neem oil with an LD50 of 14 and 24 ml/kg in rats and rabbits respectively; and more toxic than edible mustard seed oil suggesting a narrow margin of safety when used therapeutically. (Gandhi et al., 1988)

Quercetin, Quercetin-3-O-rutinoside (Aderogba et al., 2006); 3,7-Di-O-a-rhamno pyranosyl quercetin (Menezes et al., 2007); BmoRoL and BmoLL lectins (Souza et al., 2011)

Epicatechin, ( + )-pinitol, Esters of p-hydroxyphenyl ethanol and p-coumaryl alcohol, Kaur-16-en-19-oic

Co-incubation of 0.01% of the extract in Caco-2 cell monolayers decreased the integrity

Decoction

SS, SW

NW, SW

Decoction

S/ Plant name Family Common Local Region of Experimental evidence for

no. name Nigerian use for its use in diabetes

name(s)* diabetes* management

Other medicinal uses

Plant part (s) used

Traditional preparation method

Identified active constituent(s)

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

Piliostigma thonningii

Bauhinia tomentosa L.

Leguminosae

Yellowbell orchid, Camel foot tree

28 aauhinia

rufescens Lam.

Leguminosae

Jinga (H), Abafe-pupa

Jirga (F), Matsatsagi

29 aidens pilosa L. Compositae

Spanish needle, Needle grass, Black jack

Abere-oloko

well as improved serum lipid profile in alloxan-induced diabetic rats (Ojezele and Abatan, 2011)

Antioxidant effects (Aderogba et al., 2008); 500 mg/kg ethanol root extract decreased blood glucose in both normal glucose-loaded rats and alloxan induced diabetic rats (Kaur et al., 2011)§

Antioxidant effects (Aliyu et al., 2009; Compaoré et al., 2011); Dose dependent (200400 mg/kg) decrease in blood glucose levels by methanol extract of the leaves in alloxan-induced diabetic rats (Aguh et al., 2013) Acetylenic glucosides decreased blood gucose in C57BL/Ks-db/db mice, a type 2 diabetes model (Ubillas et al., 2000)§

30 Bixa orellana L. Bixaceae

Lipstick tree, Osun-buke

Bixa plant, (Y), Aje (Y),

Annatto, Uhie (I) Achiote

NE, SW, SE 80 mg/kg of the seed coat extract decreased blood glucose levels and increased plasma insulin levels and insulin binding to blood corpuscles in normoglycaemic dogs

Anti-microbial, Diuretic, Roots, Vermifuge, Aphrodisiac, Leaves, Anti-tumours Flower

Anti-infective, Anti-parasitic, Wound healing, Fibrosis, Inflammation

Anti-cancer, Antipyretic, Anti-microbial, Inflammation, Diuretic, Anti-parasitic, Colic, Wound ulcers, Hemorrhoids, Malaria

Stem-bark, Root, Fruit

Seeds, Decoction,

Leaves, Infusion

Roots, Aerial parts

Anti-microbial, Anti-parasitic, Skin infections, Anti-tumour, Analgesic, Anti-pyretic, Jaundice, Gonorrhea, Purgative, Snake bites

Leaves, Seeds Decoction

the stem bark decreased blood glucose levels in alloxan-induced diabetic rats dose-dependently (Asuzu and Nwaehujor, 2013)

Acetylenic

glucosides: 3-ß-D-

glucopyranosyl-1-

hydroxy-6(E)-

tetradecene-

8,10,12-triyne and

2-ß-D-

glucopyranosyl-1-hydroxy-6(E)-tetradecene-7,9,11-triyne (Ubillas et al., 2000)

Aldose reductase inhibitory effects of isoscutellarein isolated from the leaf extract (Terashima et al., 1991)

acid, Labd-13-en-8-0l-19-oic acid (Baratta et al., 1999); Quercetin, Quercitrin, C-methyl quercetin ethers, C-methyl kaempferol ethers, Piliostigmin (Ibewuike et al., 1997); Kaurane diterpenes (Martin et al., 1997); Griffonilide, Rhamnetin, Carotenoids (Okwute et al., 1986) Quercetin-3-O-glucoside, Quercetin-3-O-rutinoside, Kaempferol-7-O-rhamonoside, Kaempferol-3-O-glucoside (Aderogba et al., 2008); Quercetin, Isoquercetin, Lectins, Protocatechuic acid (Anju et al., 2011)

Hyperoside, Isoquercitrin, Quercetin, Quercitrin, P-coumaric acid, Ferulic acid, Rutin, Kaempferol (Compaore et al., 2011); Benzopyrandiol and triol derivatives (Maillard et al., 1991)

Polyacetylenic compounds, Pyrocatechin, Vanillin,

P-hydroxybenzoic acid, Gallic acid, Salicylic acid, Protocatechuic acid, P-coumaric acid, Ferulic acid, Caffeic acid, Caffeoyl quinic acids, Eugenol, Esculetin, Chlorogenic acid, Sulfuretin, Chalcones, Apigenin and its glycosides, Luteolin and its glycosides, Quercetin and its glycosides, Kaempferol glycoside, Caryophyllene, Humulene, Lupeol, p-sitosterol, Campestrol, p-amyrin, Friedelin, a-tocopherol, Centaureidin, Centaurein (Lima Silva et al., 2011)

Apocarotenoids, Norbixin, Bixin, Geranylgeranyl and its acetate, octadecanoate, and formiate, Farnesyl acetone (Gutierrez et al., 2011); p-tocopherol, Vitamin E (Ponnusamy et

of the monolayer and the secretory transport of Cyclosporin A (CsA) indicating possible inhibition of P-gp (Deferme et al., 2003)

The carotenoid Bixin, isolated from the seed coat extract has been shown to induce Cyt P450 enzymes in the liver, kidney and lungs (Jewell and O'Brien,

NW, NE

S/ Plant name no.

Family

Common name

Nigerian

name(s)*

Region of use for diabetes*

Experimental evidence for its use in diabetes management

Other medicinal uses

Plant part (s) used

Traditional preparation method

Identified active constituent(s)

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

31 Blighia sapida K. Sapindaceae D.Koenig

Ackee apple, Breadfruit tree

Okpu ulla (I), Ishin (Y), Gwanja-kusa (H), Ila (Nu)

SW, NC

Bridelia

ferruginea Benth.

Phyllanthaceae

Ira or

Iralodan (Y), Kirni or Kizni (H), Ola (I)

Bridelia micrantha (Hochst.) Baill.

Phyllanthaceae

Sweet berry, Coastal golden leaf

Iranje, Ogaofia (I), Ugoagu (i)

(Russell et al., 2005)§; Methanol extract of the leaves (49 ^g/ml) produced inhibitory effects against human pancreatic amylase enzyme (Ponnusamy et al., 2011)§

Aqueous root bark extract (100 and 200 mg/kg) decreased blood glucose in normoglycaemic rats (Saidu et al., 2012)

Wound ulcers, Malaria, Anti-parasitic, Migraine, Laxative, Diuretic, Epilepsy, Liver diseases, Anti-emetic, Snake bites

Root, Bark, Fruits, Leaves

100 and 200 mg/kg aqueous and methanol extracts of the leaves decreased blood glucose levels in normal rats and alloxan-induced rats when pre-treated; Also daily intake of 15 mg of the extract as an infusion lowered blood glucose levels of type-2 diabetic patients in a clinical study (Iwu, 1983); Radical scavenging effects (Cimanga et al., 2001); Administration of 250 mg/kg ethanol extract of the root for 4 weeks improved glucose tolerance in high-fructose fed Wistar rats (Bakoma et al., 2011) 250 mg/kg of the methanol extract of the leaves decreased blood glucose in alloxan-induced diabetic rats and produced good antioxidant effects (Adika et al., 2011)

Inflammation, Oral thrush, Anti-parasitic, Anti-microbial, Hemorrhoids, Anti-tumour

Leaves, Stem bark, Root

Infusion, Decoction

Oral gargle, Antimicrobial, Jaundice, Dysentry

Leaves, Stem bark

al., 2011); Stigmasterol, Polyprenol, Sitosterol, Ishwarane, Phytol (Raga et al., 2011); Capric, Palmitic, Stearic, Oleic and Linoleic acids (Silva et al., 2008); Gallic acid, Pyrogarrol, Isoscutellarein (Terashima et al., 1991); ß-carotene, Cryptoxanthin, Lutein, Zeazanthin, Methyl bixin (Tirimanna, 1981)

Hypoglycaemic effect of hypoglycin A and B from the fruit was observed in rabbits, monkeys, rats and mice but not cats, dogs and pigeons with lethality at doses > 50 mg and 150 mg/kg for hypoglycin A and B respectively in mice (Chen et al., 1957) Hypoglycaemic effect of a mixture of quercetin-3-neohesperidoside, Quercitrin, Quercetin-3-glucoside and Myricetin-3-rhamnoside isolated from the hydro-alcoholic extract of the leaves in fasted rabbits (Addae-Mensah and Munenge, 1989)

Hypoglycin A, Hypoglycin B (Hassall et al., 1954); Glycyl-l-alanine, y-l-glutamyl-trans-a- l-(carboxy cyclopropyl) glycine, Glyclyglycine, Diglycylglycine (Fowden and Smith, 1969); Blighinone, Stigmasterol and its fructoside, Oleanolic acid, Hederagenin and its glucosides (Garg and Mitra, 1967)

Myricetin-3-rhamnoside, Quercetin-3-glucoside, Quercitrin, Quercetin-3-neohesperidoside (Addae-Mensah and Achenbach, 1985); Kaempferol, Vitexin, Apigenin (Iwu, 1983); ß-peltatin-5-O-ß-d-glucopyranoside and its 5-demethoxy derivative (Rashid et al., 2000); 3-O-methyl quercetin, Rutisin, Myricetin, Ferrugin, Tetra-

0-methyl myricetin, Gallocatechin-(4-O-7)-epigallocatechin (Cimanga et al., 2001)

Delphinidin, Gallic acid, Caffeic acid, Ellagic acid, Friedelin, Epifriedelinol Taraxerol, Taraxerone (Pegel and Rogers, 1968); Camphene, a-pinene, 1,8-cineole, Camphor, Linalool,

1-a-terpineol, a-caryophyllene oxide, 5-ß-pregnene, Quinoline (Green et al., 2011)

1999); Bixin as well as other constituents of annato dye from the seed extract play an important role in the induction of Cyp 1A and 2B enzymes in rats (De-Oliveira et al., 2003); Seed constituents have also been found to possess opposing hyperglycaemic effects (Fernandes et al., 2002; Gutierrez et al., 2011) Hypoglycin A and B in the unripe fruit, although responsible for the hypoglycemic effect can lead to death due to severe fatty acid degeneration and glycogenolysis (Hassall et al., 1954; Sherratt, 1986)

Inhibited P-gp mediated Rh-123 efflux in Caco-2 cells (Ezuruike et al., 2012); No observed acute or chronic toxicity in rats after 6 months intake or high doses up to 5 g/kg. However aqueous extract of the leaves prolonged pentobarbitone induced sleeping time, which might indicate possible interaction with Cyp enzymes (Owiredu et al., 2011)

SW, SE

Decoction

S/ Plant name Family no.

Common Local Region of Experimental evidence for Other medicinal uses

name Nigerian use for its use in diabetes

name(s) diabetes* management

34 Bryophyllum Crassulaceae pinnatum (Lam.) Oleen

Africa never Ewe abamoda SW die. Life plant, (Y) Resurrection plant

400 mg/kg of the aqueous extract of the fresh leaves produced hypoglycaemia in both normal and STZ-induced diabetic rats (Ojewole, 2005); Hypoglycemic effect of 500 mg/kg aqueous extract of the leaves in normal fasted glucose-loaded and STZ-induced diabetic rats (Ogbonnia et al., 2008c); In vitro antioxidant effects (Gupta and Banerjee, 2011 )§

Hypertension, Analgesic,

Inflammation, Wound ulcers. Anti-parasitic, Insect bites. Anti-cancer, Cough, Diarrhoea, Sedative, Diuretic, Antimicrobial, Convulsions

35 Calotropis

procera (Aitón) Dryand.

Apocynaceae Sodom apple, Bomu-bomu Giant (Y), Tumfafiya

milkweed, (H) Swallow wort. Mudar

400 mg/kg dried latex decreased blood glucose in alloxan-induced diabetic rats, increased hepatic glycogen content and produced antioxidant effects (Roy et al., 2005)§; 250 mg/kg of different solvent extracts of the root decreased blood glucose levels in STZ-induced diabetic rats (Bhaskar and Ajay, 2009)§; Antioxidant effects (Olaleye and Rocha, 2007)

Inflammation, Hypertension, Antimicrobial, Antiparasitic, Purgative, Convulsions, Abortifacient, Anticancer, Skin infections. Hemorrhoids, Antipyretic, Asthma, Leprosy

Plant part (s) used

Traditional preparation method

Identified active constituent(s)

Leaves, Flower

Juice extract

Leaves, Latex, Root, Stem bark. Flower

Maceration, Poultice

Syringic acid, Caffeic acid, 4-hydroxy-3-methoxy cinnamic acid, 4-hydroxy benzoic acid. Hydroxy cinnamic acid, P-coumaric acid, Protocatechuic acid, Phosphoenolpyruvate, Ferulic acid, Astragalin, Friedelin, Luteolin, Quercetin glycosides, Epigallocatechin-3-O-syringate, Kaempferol glycosides, Isorhamnetin glycosides, Myricetin glycosides, a- and p-amyrin and their acetates, Glutinol, Bryophollone, Bryophynol, Bryophyllol, Bryophyllin A and B, Bryotoxin A, B and C; Bryophollenone, Patuletin and glycosides Taraxasterol, Stigmasterol, p-sitosterol, Stigmasta-dienol (Afzal et al., 2012) Calotroposide, Calotropin, Calotoxin, Calotoxoside, Calactin, Calotropain, Calotropa H genin, Proceroside, Uscharin, Uscharidin, Voruscharin, Amyrin (Oliver-Bever, 1986); Calotropterpenyl, Calotropursenyl acetate, Calotropfriedelenyl acetate, 2-propenyl-2'-hydroxy ethyl carbonate, Calotropin FI, FII, DI and DII, Uzarigenin, Ascleposide,

Coroglaucigenin, Procerain (Juncker et al., 2009); Flavone-4'-0-p-glycoside, Epoxy dihydroxy methoxy cardenolide, p-anhydroepidigitoxigenin and its glycoside (Shaker et al., 2010); Calotropoceryl acetate A and B, Calotroprocerone, Calotroprocerol A, Pseudo-taraxasterol acetate, Taraxasterol, Stigmasterol, (E)-octadec-7-enoic acid (Ibrahim et al., 2012); CP-P (Apolipoprotein A-l) (Samy et al., 2012)

Risk of cardiac glycoside poisoning due to the bufadienolides Bryotoxin A, B, C (McKenzie et al., 1987); Significant decrease in serum ALT levels in rats after daily oral dosing of 2 g/kg aqueous extract of the leaves (Ozolua et al., 2010)

Cardenolides present in the plant are capable of causing death in mammals at high concentration thus caution should be exerted when extracts of the plant are being ingested (Juncker et al., 2009)

S/ Plant name Family Common Local Region of Experimental evidence for Other medicinal uses

no. name Nigerian use for its use in diabetes

name(s) diabetes* management

36 Capsicum annum Solanaceae Chilli, Bird Ata or Ata SW, SE Alpha glucosidase and a- Analgesic,

L, Syn: Capsicum pepper wewe (Y), amylase inhibitory activities Antimicrobial,

frutescens L. Ose (I), and antioxidant effects (Oboh Inflammation,

Barkono (H), et al., 2011 ; Kwon et al.. Hemorrhoids, Fevers,

Asin (Es) 2007); Incorporation of 2% of Dysentry, Malaria,

the fruit powder in a high fat Carminative, Stimulant

diet given to STZ-induced

diabetic rats increased serum insulin levels (Islam and Choi, 2008)§; 100 mg/1 fruit extracts possessed PPAR alpha and gamma agonistic activity (Rau et al., 2006)§

37 Carica papaya L. Caricaceae

Pawpaw Ibepe (Y), NW, SS, 100-400 mg/kg of the

Okworo SW aqueous seed extract

bekee or decreased blood glucose and

Okwere (I), improved serum lipid levels

Gwanda (H) in normal rats (Adeneye and

Olagunju, 2009); 400 mg/kg aqueous extract of the leaves decreased blood glucose in alloxan-induced diabetic rats (Maniyar and Bhixavatimath,

2012)§; Administration of 602 g of the fruit (equivalent to 50 g carbohydrate) to type 2 diabetic patients produced an increase in serum insulin levels in the patients (Fatema et al., 2003)§; Antioxidant effects of different parts of the unripe fruit (Oboh et al.,

Anti-microbial, Antiparasitic, Dyspepsia, Hemorrhoids, Hypertension, STDs, Purgative, Wound healing. Antivenin, Sickle cell anemia, Abortifacient, Anti-fertility, Cancer, Mental disorder. Malaria, Convulsion

38 Cassia fistula L. Leguminosae

Indian laburnum. Golden shower

Aidantoro (Y) SW

In vitro antioxidant effects (Luximon-Ramma et al., 2002; Manonmani et al., 2005); Hexane extract of the stem bark produced a dose dependent decrease in alloxan-induced diabetic rats (Nirmala et al., 2008); Ethanol and ethyl acetate extract of the bark decreased blood glucose levels in alloxan-induced diabetic rats

Liver disorders. Antimicrobial, Purgative, Astringent, Hemorrhoids, Rheumatism, Ulcers, Jaundice

Plant part Traditional Identified active Other relevant Interaction/toxicity

(s) used preparation constituent(s) phytoconstituents studies

method identified in the plant

Decoction

Leaves, Fruit Infusion pulp. Seed, Decoction, Latex Vegetable,

Juice extract

Seeds,

Leaves, Pods, Stem-bark

Catechin isolated from the stem bark decreased plasma gucose levels and increased the activity of glucose metabolizing enzymes in STZ-induced diabetic raats (Daisy et al., 2010)

Capsaicinoids (Schweiggert et al., 2006); Myricetin, Kaempferol, Apigenin, Luteolin, Quercetin (Miean and Mohamed, 2001); CAY-1 (Stergiopoulou et al., 2008); Alpha tocopherol (Ching and Mohamed, 2001); Ortho hydroxyl N-benzyl 16-Methyl 11,14-diene octadecamide, 9,12-diene-octadecanoic acid (Dastagir et al., 2012); Capsianocide VIII, IX, L, III, V, I and its methyl ester, Oxylipin, Capsidiol, Phosphatidylcholine, Loliolide, Blumenol C glucoside, 3-0-(9,12,15-octadecatrienoyl) glyceryl-p-D-galactopyranoside (De Marino et al., 2006) Caffeoyl and Protocatechuic acid hexoside, Gallic acid deoxyhexoside, Caffeoyl hexose-deoxyhexose, Ferulic and Caffeic acids, Myricetin, Isoharmnetin, Quercetin, Kaempferol, Rutin, Lycophene, p-cryptoxanthin, p-carotene, (Rivera-Pastrana et al., 2010); Chlorogenic and P-coumaric acids, 5,7-dimethoxy coumarin (Canini et al., 2007); Papain, Chymopapain A, B and C, Peptidase A and B, Lysozyme, Carpasamine, Dehydrocarpaine I and II, Carpaine, Aryl glucosides, Carposide, Caricin, Choline, Tropaeaoline (Krishna et al., 2008) Fistucacidin, Kaempferol, Rhein, Leucoperlagonidin derivatives. Sennoside A and B, Epiafzelechin and its 3-O-p-D-glucopyranoside, Epicatechin, Catechin, Procyanidin B2, Rhamnetin -3-0-gentibioside, Physcion, Chrysophanol, Fistulin, Fistulic acid, 3-formyl-l-

Aqueous extract of the leaves in alloxan-induced diabetic rats delayed the hypoglycaemic activity of glimepiride but hastened that of metformin (Fakeye et al., 2007); Contraindicated in patients taking warfarin as it increased the INR of a patient (Shaw et al., 1997); Aqueous extract of the leaves inhibited P-gp efflux activity in Caco-2 cells (Oga et al., 2012)

S/ Plant name Family Common Local Region of Experimental evidence for Other medicinal uses

no. name Nigerian use for its use in diabetes

name(s)* diabetes# management

Plant part Traditional Identified active (s) used preparation constituent(s) method

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

(Malpani and Manjunath, 2012)

39 Cassia sieberiana Leguminosae DC.

African

Ukosei (Es), NC, NW, In vitro antioxidant effects Veterinary,

laburnum, Margaa (H), Drumstick tree Margaje (F), Aridan-tooro

NE, SS,

(Awah et al., 2012)

Antimicrobial, Antiparasitic, Impotence, Convulsion, Inflammation, Analgesic, Malaria, Dys-menorrhea

Root, Leaves, Decoction Stem-bark

40 Cassytha Lauraceae

filiformis L., Syn: Cassytha

Love vine, Woevine

americana

Rumfar-gada SE, NC (H),

Sulunwahi

Otetebilete

Administration of 600 mg/kg Anti-parasitic,

methanol extract of the stem Uterotonic,

bark to alloxan-induced Hypertension, Diuretic,

diabetic mice decreased Aphrodisiac,

blood glucose levels by 46.8% Hemorrhoids, Anti-

(Ezeigbo and Asuzu, 2010) cancer, Anticoagulant,

In vitro antioxidant effects Hemorrhage (Mythili et al., 2011)§

Whole plant Decoction, Dried parts are chewed before meals

hydroxy-8-methoxy anthraquinone, 3ß-hydroxy 17-norpimar -8 (9)-en-15-one (Bahorun et al., 2005); 1,8-dihydroxy-6-methoxy-3-methyl anthraquinone, Tetrahydroxy dimethoxy flavone-3-O-a-arabino pyranoside, Trihydroxy trimethoxy flavone-3-O-a-l-rhamnosyl (1 — 2)-O-ß-d-glucopyranoside, ß-Sitosterol, Hexacosanol, Lupeol (Kanth et al., 2012); Aurantiamide acetate, Betulinic acid, Xanthone glycoside, Cyclopropenoid fatty acids, Biochanin A, Phytol, Lectins CSL-1. 2 and 3, Furfural derivatives, Fatty acids, Citreorosein, Scopoletin, Chromones and Benzyl derivatives (Danish et al., 2011)

Epiafzelechin (Kpegba et al., 2011); Myricetin and Quercetin 3-O-rhamnoside (Asase et al., 2008); Leucopelargonicol, Epicatechol, ß-sitosterol, Stigmasterol (Tamboura et al., 2005)

Cassythidine, Cassyfiline (Cassythine) and O-methyl cassyfiline, Cassamedine, Neolitsine, Cassameridine, Actinodaphnine and N-methyl actinodaphnine, Cassythicine, Cassythidine, Dicentrine, Bulbocapnine, Nornuciferine, Launobine (Cava et al., 1968); Cathafiline, Cathaformine, Lysicamine, Cassyformine, Predicentrine, Filiformine, Isoboldine, Thalicminine, Stepharine, Pronuciferine, Ocoteine, Syringaresinol, Diasyringaresinol, Yangambin, O-methyl flavinatine, Isovanillin, Vanillin, ß-sitosterol and Stigmasterol and their d-glucosides (Chang et al., 1998); Isorhamnetin,

Traditional use of the plant is associated with GIT side effects (Maiga et al., 2005); Liver and kidney toxicities of aqueous extracts of various parts of the plant (Toma et al., 2009; Obidah et al., 2009) 250 mg/kg aqueous extract of the whole plant increased cholesterol levels in mice and decreased plasma ALP levels (Babayi et al., 2007) Non-selective cytotoxicity to both cancer and non-cancer cell lines (Stévigny et al., 2002)

S/ Plant name no.

Family

Common Local Region of Experimental evidence for Other medicinal uses

name Nigerian use for its use in diabetes

name(s)* diabetes* management

Plant part Traditional Identified active (s) used preparation constituent(s) method

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

41 Catharanthus Apocynaceae roseus (L.) G.Don

Madagascar periwinkle

42 Chrysophyllum albidum G.Don

43 Citrus

aurantiifolia

(Christm.)

Swingle

Sapotaceae

African star Agbalumo apple, Cherry (Y), Udala (I)

Osan wewe (Y), Oroma nkilishi (I), Igbopin-nigue (Es),

SE, SW

250 mg/kg methanol extract of the leaves decreased blood glucose levels in alloxan-induced diabetic rats and increased the hypoglycaemic effect of metformin but not glibenclamide (Ohadoma and Michael 2011); Juice extract of the fresh leaves of the plant gave a dose dependent (0.5-1 ml/kg) decrease in blood glucose levels in normal and alloxan-induced diabetic rats (Nammi et al., 2003)§; 500 mg/kg dichloro-methane methanol (1:1) extract of the aerial parts showed a prophylactic action against STZ-induced hyperglycaemia in rats and increased the activity of some glucose metabolizing enzymes (Singh et al., 2001)§

Cancer, Malaria, Insect stings, Sore throat, Antibiotic, Diuretic, Expectorant, Wound healing, Hemorrhage, Hypertension

Whole plant, Leaves, Flower, Roots

100 and 200 mg/kg hydro- Cancer, Miscarriage,

ethanol extract of the seed cotyledon given to alloxan-induced diabetic mice for 7 days decreased serum glucose levels (Olorunnisola et al., 2008)

in vitro antioxidant effects (Guimarâes et al., 2010)§

Hemorrhoids, Asthma, Analgesic, Inflammation, Antimicrobial, Anti-parasitic

Seeds, Stem- Decoction bark, Leaves, Fruit, Root

Worm expeller, Weight loss, Anti-microbial, Anti-cancer, Antiparasitic, Colds, Arthritis

Juice extract

Quercetin and Kaempferol glycosides; Isorhamnetin, Cassythic acid, O-methyl cassythine, Isofiliformine, Phenylalcohol glycoside, Salutaridine, Nicotinic acid (Tsai et al., 2008) Hexamethyl-15-hydroxy methylene-n-octacostriene-10,18-diol-10-ß-d-gluco pyranoside, 3-Epibetulinic acid, n-pentadecanyl octa-dec-19-enoate, ß-Sitosterol (Chung et al., 2007); 3-O-glucosides and 3-O-(6-O-p-coumaroyl) glucosides of Hirsutin, Malvidin and Petunidin (Piovan and Filippini, 2007); Benzoic acid derivatives, Vanillic, Gallic, Cinnamic, o- and p-Coumaric, Caffeic and Ferulic acids; Hydroxy tyrosol, kaempferol, Quercetin, Syringetin glycosides (Mustafa and Verpoorte, 2007); Ursolic and Oleanolic acids (Usia et al., 2005); Ajmalicine, Serpentine, Lochnerine, Tetrahydroalstonine, Reserpine, Akuammine, Vinblastine, Vindoline, Perivine, Leurosine, Leurosidine, Virosine, Catharanthine, Vindolinine, Lochnericine, Pleurosine, Vincarodine, Catharicine, Leurocristine (Vincristine), Sitsirikine, Carosine (Svoboda et al., 1962)

Eleagnine, Anacardic acid, Ascorbic acid (Idowu et al., 2006); Myricetin-3-rhamnoside (Adebayo et al., 2011)

a- and ß-pinene, P-cymene, Limonene and its oxide, Linalool and its oxide, Citral, а- and ß-terpineol, Myrtenol (Asnaashari et al., 2010); Isoswertisin, 6-O-a-

Potent inhibitory effects on Cyp 2D6 of human liver microsomes of ajmalicine and serpentine isolated from the aerial parts (Usia et al., 2005); The vinca alkaloids are metabolized by Cyp3A4 and 3A5 enzymes; while vincristine and vinblastine have been identified as P-gp substrates in canine renal cells (Levêque and Jehl, 2007)

Bergamottin and other furanocoumarins found in citrus fruits have been identified as inducers and inhibitors of Cyt P450 enzymes (Baumgart et al., 2005)

Decoction

Rutaceae

S/ Plant name Family Common Local Region of Experimental evidence for Other medicinal uses Plant part Traditional Identified active Other relevant Interaction/toxicity

no. name Nigerian use for its use in diabetes (s) used preparation constituent(s) phytoconstituents studies

name(s)* diabetes* management method identified in the plant

44 Citrus aurantium Rutaceae L.

Sour orange, Seville orange

45 Citrus sinensis (L.) Rutaceae Osbeck

Orange

ganinganin or, Ijaganyin (Y), Oloma oyibo (I), Babban lemu (H), Ntom (Ibibio)

Citrullus colocynthis (L.) Schrad.

Cucurbitaceae

Egusi melon, Desert gourd, Bitter apple, Bitter cucumber

Osan mimu (Y), Oroma (I), Lemun misra (F), Alimo (Es)

Baala, Egusi NW, SW

875 mg of a mix of extracts of Weight loss, GIT

the fruit and Rauvolfia vomitoria foliage (RC tea) decreased serum glucose levels in diabetes type 2 model db/db mice and also decreased tissue lipid accumulation (Campbell et al., 2006); RC tea given daily for 4 months to type-2 diabetic patients decreased fasting and post prandial plasma glucose levels especially in patients with HbAlc levels <7.3% (Campbell-Tofte et al., 2011)

Antioxidant effects (Guimaraes et al., 2010)§; Free and bound phenolics extracted from the dried fruit peel exhibited potent dose-dependent a-amylase and a-glucosidase inhibitory effects (Oboh and Ademosun, 2011)

Saponin fractions of aqueous extract of the rind decreased plasma glucose at doses < 50 mg/kg in fasted normoglycaemic and

probems, Malaria, Fibroids, Cancer, Cough

Fruit, Leaves, Juice extract, Root, Stem- Decoction bark, Stem-twigs

Fruit, Seed

Juice extract Infusion

Constipation, Purgative, Anti-tumour, Abortafacient, Oedema, Infections, Rheumatism

Leaves Fruit, Rind, Seed, Pulp

Infusion, Decoction

arabinopyranosides of vitexin and isovitexin (Veitch and Grayer, 2011); Bergamottin, Limettin, Bergapten, 5-geranyloxy-7-methoxycoumarin, Isopimpinellin, 3-methyl-1,2-cyclopentadione,

1-methoxy-cyclohexene, Corylone, Umbelliferone, 5,8-dimethoxypsoralen, Hexenone, Caryophyllene oxide, Palmitic, Linoleic, Oleic acids, Bergamotene (Sandoval-Montemayor et al., 2012); Imperatorin, Kaempferol, Myricetin, ß-sitosterol, Rutin, 4,5,7-trihydroxy-3,6-dimethoxy flavones (Shalaby et al., 2011)

Synephrine, Octopamine, Limonene, Hesperidin, Neohesperidin, Naringin, Tangaretin, Bergapten, 6,7-dihydroxybergamottin (Fugh-Berman and Myers, 2004); Linalool, Nerol, Limonin, Methyl antranilate, Rutoside, Hesperidoside, Neohesperidoside, Naringoside,

Sinensetoside, Meranzin, Nobiletin, Narirutin, Rhoifolin, Citric, Ascorbic and Malic acids (Arias and Ramón-Laca, 2005); Didymin, Eriocitrin, Neoeriocitrin, Poncirin (Peterson et al., 2006) Psoralene, Xanthotoxin, Bergapten, Imperatorin, Mamesin, Umbelliferone, Quercetin and its glycoside, 4,5,7-trihydroxy-3,6-dimethoxy flavone, Rutin, Hyperin, Hesperidin, ß-sitosterol, Stigmasterol (Shalaby et al., 2011)

Cucurbitacin E, I, J, K and L

2-O-ß-d-glucopyranosides, 3,4' -dihydroxy-3' -methoxy propiophenone, 3,4'-

Bergapten and 6,7-dihydroxybergamottin inhibit Cyt P450 enzymes (Malhotra et al., 2001); Risk of cardio-toxicity due to synephrine (Calapai et al., 1999)

Bergapten has been shown to induce Cyp 3A4 (Malhotra et al., 2001)

Extracts of the plant have been shown to cause severe diarrhoea in animals with mortality at doses

S/ Plant name no.

Family

Common Local Region of Experimental evidence for Other medicinal uses Plant part Traditional Identified active

name Nigerian use for its use in diabetes (s) used preparation constituent(s)

name(s)* diabetes* management method

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

Citrullus lanatus (Thunb.) Mats. and Nakai

Cucurbitaceae

Water melon,

Kalahari

Egusi bara (Y), Guna (H)

alloxan-induced diabetic rabbits (Abdel-Hassan et al., 2000)§; Plasma glucose levels and pancreatic p-cell mass were restored to normal in STZ-induced diabetic rats fed an 8% colocynth oil diet (Sebbagh et al., 2009)§; Antioxidant effects (Kumar et al., 2008)

50 mg/kg globulin proteins extracted from the seeds decreased blood glucose levels when pre-administered to normal high glucose fed rats (Teugwa et al., 2013a)§; Antioxidant effects (Tlili et al., 2011)

Laxative, Wound ulcers, Anti-bacterial, Tumours

Leaves, Seeds, Fruit pulp

dihydroxypropiophenone, Colocynthosides A and B, Khekadengoside E, Hexano cucurbitacin I 2-O- p-d-glucopyranoside, Helicid, Isovitexin, Isosaponarin, Isoorientin-30-O-methyl ether, Benzyl and 4-hydroxybenzyl p-d-glucopyranoside, 4-(p-d-glucopyranosyloxy) benzyl alcohol (Yoshikawa et al., 2007); Isoorientin, 8-O and 6-O-p-

hydroxybenzoyl isovitexin and its glucosdie (Maatooq et al., 1997); Oleic, Linoleic, Linolenic, Arachidonic, Palmitate, Stearic and Myristic acids (Sebbagh et al., 2009); 2-(nonan-8-one)-(1H)-4-quinolone, 2-(nonan-8-one) 4-methoxy-quinoline, (2S)-3,4-methylenedioxy-5,7-dimethoxyflavan, Hispidulin 7-(6-E-p-coumaroyl-p-d glucopyranoside (Salama, 2012)

Cucurbitacin E (Abdelwahab et al., 2011); Lycophene, Phytofluene, Neurosporene, z- and p-carotene, Lutein, Phytoene (Perkins-Veazie et al., 2006); Protocatechuic acid glucosides, Phloroglucinol glucuronide, Ferulic acid hexosides, Isorhamnetin, Citrulline, Salicylic acid-O-hexoside, p-coumaric acid glucoside, Vanillin hexosides, Rutin, Salicin-2-benzoate, Sinapic acid glucoside, Feruloyl sugars, Caffeoylshikimic acids, Caffeoylhexose, Luteolin, Calodendroside; Naringenin, Chrysoeriol Apigenin, Kaempferol, Taxifolin, Saligenin and Isolariciresinol glucosides; Hydroquinone, Isovitexin, Aviprins, Shikonine, Icariside, Leachianol G, Glehlinoside C, Ajugol,

Z 200 mg/kg (Shafaei et al., 2012; Khoshvaghti and Hamidi, 2012); Possible inhibition of Cyp P450 enzymes when ethanolic extracts of the fruit were co-incubated with rat liver microsomes (Barth et al., 2002)

Decoction

S/ Plant name Family Common Local Region of Experimental evidence for Other medicinal uses

no. name Nigerian use for its use in diabetes

name(s)* diabetes* management

Plant part Traditional Identified active (s) used preparation constituent(s) method

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

Cola acuminata (P.Beauv.) Schott and Endl.

Malvaceae

Kolanut

49 Corchorus olitorius L.

Malvaceae

Long fruited jute, Jew's mallow

Obi agada (Y), SW Orji (I)

Ewedu (Y), Ulogburu (I)

Antioxidant effects (Atawodi Stimulant, Appetite et al., 2007) 500 mg/kg of the suppressants, methanol extract of the stem Aphrodisiac, Respiratory bark decreased blood glucose infections, levels in alloxan induced Hypertension, Antidiabetic rats after 21 days parasitic (Adediwura et al., 2011)

Nuts, Stem-bark, Leaves

Decoction, Juice extract

Methanol extract of the leaves inhibited both a-amylase and a-glucosidase enzymes (Oboh et al., 2012a) Antioxidant effects (Azuma et al., 1999)

Purgative, Diuretic, Tumours, Analgesic, Cystitis, Measles

Leaves, Seeds Decoction

50 Croton lobatus L. Euphorbiaceae

Lobed croton, Cascarilla

Eru Alamo (Y) SW

Wound ulcers, Purgative, Malaria, Dysentry

Fruit, Stems, Leaves, Seed

Dihydrophilonotisflavone, Catalposide, Obtusoside, Picrosides, Quercitrin, Coumarin, Cimifugin, (Abu-Reidah et al., 2013) Procyanidin B1 and B2, Catechin, Epicatechin, Caffeine (Atawodi et al., 2007); Theobromine (Niemenak et al., 2008); Chlorogenic, Quinnic and Tannic acids (Odebode, 1996)

3,5-Dicaffeoylquinic acid, Quercetin-3-galactoside, Quercetin-3-glucoside, Quercetin-3-(6-malonyl glucoside), Quercetin-3-(6-malonyl galactoside), Ascorbic acid, a-tocopherol (Azuma et al., 1999); Kaempferol glycosides, Rutin, Isoquercitrin (Sakakibara et al., 2003); Dicaffeoyl quininc acids, Caffeoyl and Dicaffeoyl quinic derivatives, Hyperoside, Chlorogenic acid, Isoquercitrin, Quercetin derivative (Ola et al., 2009); Corchorusides A and B, Capsugenin-25,30-O-ß-diglucopyranoside (Phuwapraisirisan et al., 2009); Caffeic acid and Isorhamnetin (Oboh et al., 2012a)

4,5-O-dicaffeoylquinic, acid Tiliroside, Isovitexin, Vitexin, Chlorogenic acid (Lagnika et al., 2009); Geranylgeraniol, Betulinic acid, Cholestan-3-one, 9,12,15-octadecatrienoic acid methyl ester, 3-(4-methoxy phenyl)-2-phenyl acrylic acid, Tetramethyl

tetraentetracosanoic acid, Octadecadienoic acid, Tetramethyl-hexadeca tetraenyl ester, Lobaceride, Cholestan-5,7-dien-3-ol, Ergosterol, 3-hydroxy-choles-5-en-7-one, N-(2-hydroxy-1-phenyl-propyl)

Ethanol extract of the aerial parts of the plant inhibited Cyt P450 3A4 and 3A7 (Agbonon et al., 2010)

S/ Plant name Family Common Local Region of Experimental evidence for

no. name Nigerian use for its use in diabetes

name(s)* diabetes* management

Other medicinal uses

Plant part (s) used

Traditional preparation method

Identified active constituent(s)

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

51 Cucumeropsis mannii Naudin

Cucurbitaceae

White melon, African melon

Egusi-itoo (Y), Ogiri (I)

Curculigo pilosa (Schumach. and Thonn.) Engl.

Hypoxidaceae

Golden eye grass,

Donkey's ear

Epakun

53 Curcuma longa L. Zingiberaceae Turmeric

Atale pupa SW, NC

54 Cymbopogon citratus (DC.) Stapf

Lemon grass

Koriko-oba (Y), Nche awula (I), Ihumibo (Es)

50 mg/kg of globulin proteins extracted from the seed when pre-administered to high glucose fed rats did not cause a significant decrease in blood glucose levels (Teugwa et al., 2013a)§; Antioxidant effects (Agbor et al., 2005)

Antioxidant effects (Sofidiya et al., 2011)

Ethanol extract of the rhizome incorporated in the diet of type 2 diabetic KK-Ay/ Ta mice as 0.2-1 g/100g produced a hypoglycaemic effect compared to control and showed PPARy binding activity (Kuroda et al., 2005)§; Antioxidant effects (Selvam et al., 1995)§; Plasma insulin levels of healthy subjects were significantly increased 2 h after ingestion of 6g turmeric powder (Wickenberg et al., 2010)§

Anti-microbial, Indigestion, Infant colic

Seed, Fruit

Juice extract,

Powdered

Anti-microbial, Epilepsy, Infertility, Sickle cell, Purgative, STDs

Peptic ulcer, Inflammation, Antimicrobial, Cancer, Malaria, Pesticide, Hypertension, Jaundice, Depression

Rhizome, Fruit

Rhizome, Leaves, Flower, Roots

Aqueous extract of the leaves produced a dose dependent (125-500 mg/kg) decrease in fasting plasma gucose levels after oral administration to normal rats for 42days (Adeneye and Agbaje, 2007); Antioxidant effects (Cheel et al., 2005)

Oral thrush, Inflammation, Athlete's foot, Fever, Cough, Malaria, Jaundice, Cancer, Infections, Diuretic, Hypertension, Obesity, Sedative, Insecticidal, Aromatherapy

Decoction, Infusion, Juice extract

Geraniol, myrcene and citral were identified as aldose reductase

inhibitors based on an in-silico approach (Vyshali et al., 2011)

benzamide (Chabert et al., 2006)

Linoleic acid, Oleic acid, Linolenic acid, Myristic acid, Palmitoleic acid, Palmitic acid, Aracchidic acid, Stearic acid (Kapseu et al., 1993)

Piloside A and B, Curculigoside, Curculigine, Nyasicoside, Pilosidine (Palazzino et al., 2000); B-amylase (Dicko et al., 1999); Nyasicoside, Pilosidine, Curculigine (Cometa et al., 2001) Curcumin, Bisdemethoxy curcumin, Demethoxy curcumin and Ar-turmerone (Kuroda et al., 2005; Roth et al., 1998); Tetrahydrocurcumin (Pari and Murugan, 2007); a and ß-Pinene, Myrcene, a, ß and sesqui-Phelandrene, p-Cymene, 1,8-Cineole, a and y-Terpinene, Ocimene, p-Methylacetophenone, a-Terpinoline, Terpineol, Thymol, Linalool, ar- and Y-Curcumene, Carvacrol, a-Zingiberene, ar-Tumerone, Dehydrocurcumene, Bisaboline (Leela et al., 2002); Vanillin, Vanillic acid, Ferulic acid and Ferulic aldehyde (Appiah-Opong et al., 2007) Isoorientin, Isoscoparin, Swertiajaponin, Isoorientin H-O-rhamnoside, Orientin, Chlorogenic acid, Caffeic acid (Cheel et al., 2005); p-Coumaric acid, Myrcene, Limonene, a-Ocimene, a-Pinene, a-Caryophyllene, Phellandrene, Methyl heptenone, Cimbopogonol, Oxobisabolene, Geraniol, Citral, Anisaldehyde, Cinammonaldehyde, Citronelal, Valeric, Salicyaldehyde, Luteolin

Methanol extracts of the rhizome inhibits CYP 3A4 activity in Caco-2 cells (Hou et al., 2007); Cuurcumin and its decomposition products inhibited CYP 1A2, 3A4, 2D6, 2C9 and 2B6 enzymes in Escherichia coli transfected with human plasmid cDNA (Appiah-Opong et al., 2007); Methanol extract of the rhizome enhances P-gp efflux activity but curcumin inhibits it (Hou et al., 2008)

Aqueous extract did not inhibit P-gp efflux activity in Caco-2 cells (Oga et al., 2012)

Decoction

Poaceae

SW, SE

S/ Plant name Family Common Local Region of Experimental evidence for Other medicinal uses Plant part Traditional Identified active Other relevant Interaction/toxicity

no. name Nigerian use for its use in diabetes (s) used preparation constituent(s) phytoconstituents studies

name(s)* diabetes* management method identified in the plant

Daniellia oliveri (Rolfe) Hutch. and Dalziel

Leguminosae

African balsam

Iya (Y), Maje

(H), Ozabwa

100, 200 and 400 mg/kg aqueous leaf extract decreased blood glucose levels in normal and alloxan-induced diabetic mice (Manosroi et al., 2011); 250 mg/kg aqueous extract of Sickle cell a mixture of the root with that of Sacrocephalus latifolius for 21days decreased blood glucose levels and increased the activity of various glucose metabolizing enzymes in alloxan-induced diabetic rats (Iwueke et al., 2010); Antioxidant effects (Muanda et al., 2011)

Analgesic, Inflammation, Anti-infective, Aphrodisiac, Hemorrhoids, Spasms, Fevers, Diarrhea, Wound ulcers, Tumours,

Root, Leaves, Stem bark

56 Detarium microcarpum Guill. and Perr.

Leguminosae

Taura (H), Ogbogbo (Y), Ofo (I)

NE, SE, NC 200 and 400 mg/kg aqueous bark extract decreased blood glucose levels in normal and alloxan-induced diabetic mice after 3hrs (Manosroi et al., 2011); 100 mg/kg of the gum administered alone or incorporated in a tablet containing 400 mg/kg metformin showed good blood glucose reducing effects in STZ-induced diabetic rats (Adikwu et al., 2004)

Anti-microbial, Anti-parasitic, Molluscicidal, Hemorrhoids, Malaria, Impotence, Sickle cell, Diarrhea

Bark, Seeds, Fruit, Gum, Roots

Decoction, Seed powder

57 Ficus exasperata Moraceae Vahl

Fig tree, Forest sandpaper

Eepin or Opoto (Y), Ogbu (I)

SWa 100 mg/kg aqueous extract of Analgesic, Arthritis,

the leaves given for 30 days Hemorrhoids, decreased blood glucose Hypertension, levels in obese zucker rats Arrythmias,

Leaves, Root, Fruits, Latex

and its 6-C and 7-O-glycosides, Quercetin, Kaempferol, Apigenin, Hydroquinone, Catechol, Citronelol, 1,8-Cineole, Myrcene, Tria and Dotriacontanol, Octa and Hexacosanol, Menthol, Elemicin, Linalool, Fuco-and sitosterol (Negrelle and Gomes, 2007)

Daniellic acid, Oliveric acid (Haeuser et al., 1970); Gallic acid, Protocatechuic acid, Chlorogenic acid, Caffeic acid, p-Coumaric acid, Homo-orientin, Orientin, Catechin, Rutin, Quercitrin, Quercitrin glucosyl, Quercitrin dehydrate, Coumarin, Delphinidin, Ascorbic acid (Muanda et al., 2011 ); Caryophyllene oxide, a-and ß-Hunulene, Humulene oxide, Humulenol, ß-Selinene, Cadinene, Germacrene (Schwob et al., 2008); Narcissin, Quercimeritrin, Quercitrin (Ahmadu et al., 2004)

3,4-Epoxyclerodan-13E-en-15-oic acid, 5a,8a(2-oxokovalenic acid), 3,4-dihydroxyclerodan-13E-en-15-oic acid, 3,4-dihydroxy clerodan-13Z-en-15-oic acid, 2-oxokolavenic acid, Copalic acid (Cavin et al., 2006); Sitosterol, Lupeol, Stigmasterol, Campestrol, y-quinide, Bornesitol, Pinitol, Myoinisitol (Akah et al., 2012); Myristoleic, Myristic and Linolenic acids (Igwenyi and Akubugwo, 2010); 1-naphthalene acetic-5-carboxy 6octahydro trimethyl acid, 1-naphthalene acetic-7-oxo-octahydro tetramethyl acid (Aquino et al., 1992) Glycerol-1,3-dilinolein, 3-O-glycerol acetate, Pheophorbides-a, -b and their derivatives,

Incorporation of 100 mg/kg of the gum extract into metformin tablets enhanced drug release from the formulation (Adikwu et al., 2004)

High doses of the ethanol leaf extract can lead to toxic injury in

SE, NE

Decoction

S/ Plant name Family Common Local Region of Experimental evidence for

no. name Nigerian use for its use in diabetes

name(s)* diabetes* management

Other medicinal uses

Plant part (s) used

Traditional preparation method

Identified active constituent(s)

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

58 Ficus thonningii Moraceae Blume

Loin cloth or Wild fig, Chinese banyan

Cediya (H) SW

59 Garcinia kola Heckel-

Clusiaceae

Bitter kola

Orogbo (Y), Agbi-ilu (I), Namiji-goro

SW, SE

and spontaneously hypertensive STZ-treated rats (Adewole et al., 2011); and reversed nephrotoxic effects of STZ (Adewole et al., 2012); 250 mg/kg aqueous extract of the leaves in fructose-fed rats improved glycaemic control (Taiwo et al., 2010); a-glucosidase & a-amylase inhibitory effects (Kazeem et al., 2013) Antioxidant effects (Abotsi et al., 2010) 0.5 mg/ml of the acetone extract of the leaves produced about 30% inhibitory effects against a-amylase and a-glucosidase enzymes (Olaokun et al., 2013); Dose dependent blood glucose lowering effects of the ethanol stembark extract in STZ-induced and normal diabetic rats (Musabayane et al., 2007)§

100 mg/kg kolaviron decreased blood sugar levels in normal and alloxan induced diabetic mice; as well as inhibited aldose reductase enzyme activity (Iwu et al., 1990a); Hypoglycaemic effect of kolaviron is due to GB1 and GB2 in normal and STZ-induced diabetic rats (Adaramoye and Adeyemi, 2006); Alpha glucosidase inhibitory effect of GB1 (Antia et al., 2010)

60 Gongronema Apocynaceae latifolium Benth.

Bush buck

Utazi (I), SE, SW, SS Ethanol extract of the leaves

Madumaro or decreased blood glucose

Arokeke (Y), levels in STZ-induced

Utasi (Ef) diabetic rats and increased

Abortafacient, Child birth, Insomnia, Infections, Eczema, Cancer, Fevers, Diarrhea, Ulcer, STDs

Malaria, Pain, Diarrhoea, Leaves, Purgative, Anti- Stem-bark

microbial

Cold symptoms, Antimicrobial, Diarrhea, Dysentry, Liver disorders, Aphrodisiac, Poison antidote, Sickle cell

Fruit Root, Stem-bark, Seed

Kolaviron-Mix of GB1, GB2 and kolaflavanone (Iwu et al., 1990a)

Anti-microbial, Anti-parasitic, Hypertension, Inflammation, Hepato-protective, GIT

Leaves, Stem, Root

Infusion

Maceration,

vegetable

The anti-hyperglycaemic effects of fractions of the methanol

Pyropheophorbide, N-methyl pyrimidine (Bafor et al., 2013); a-Terpineol, a and ß-Pinene, Sabinene, ß-Patchoulene, 1,8-cineole, a-thujopsene, ß-ocimene, Limonene, Linalool, ß-caryophyllene, Isocaryophyllene, ß-bisabolene, a-copaene, Globulol (Oladosu et al., 2009)

Benzaldehyde, a- and ß-pinene, ß-caryophyllene, Zingiberene, a- and ß-eudesmol, o- and a-xylene, Phytol, Caryophyllene and Isocaryophyllene oxide (Ogunwande et al., 2008)

Garcinia biflavanone (GB) 1, GB2, kolaflavanone (Cotterill et al., 1978); Apigenin-5,7,40-trimethyl ether, Apigenin 40 -methyl ether, Amentoflavone, Fisetin (Iwu and Igboko, 1982); Conrauanalactone, Kolanone, Cycloartenol, 24-methylene cycloartenol, Manniflavanone, Garcini-flavanone (Iwu et al., 1990b); Lavender lactone, Linalol and its oxides, Methyl heptenone, Benzaldehyde, Phenylacetaldehyde, ß-Myrcene, a-Terpineol, p-Cymen-9-ol, Geraniol, Geranial, ß-Caryophyllene, Methyl phenylacetate, ß-Farnesene, Manoyl oxide (Onayade et al., 1998); Garcinoic acid (Mazzini et al., 2009) ß-Caryophyllene, a- and ß-Pinene, Camphene, 1,8-Cineole, Linalol, a-Terpineol, Benzaldehyde,

liver and kidneys (Ahmed et al., 2012)

Possible testicular, lung and hepatic toxicities at doses > 500 mg/kg (Aniagu et al., 2008)

Pre-ingestion of the seeds by ten healthy volunteers 30 min prior to the administration of ofloxacin altered the serum

pharmacokinetics of the antibiotic (Esimone et al., 2007);

Pharmacokinetics of ciprofloxacin in rabbits was altered when co-administered with the seed extract (Esimone et al., 2002)

Decoction

S/ Plant name Family Common Local Region of Experimental evidence for Other medicinal uses

no. name Nigerian use for its use in diabetes

name(s) diabetes* management

activity of glucose problems. Chewing

metabolizing enzymes stick. Laxative, Ulcer,

(Ugochukwu and Babady, Analgesic, Fevers 2003)

Hypoglycaemic effect of 100 mg/kg of the methanol extract in alloxan-induced diabetic mice (Ogundipe et al., 2003)

Antioxidant effects (Fasakin et al., 2011 ; Ugochukwu and Babady, 2002)

150 ml of a (1:1:1) decoction mix of the leaves of Vernonia amygdalina, Ocimum gratissimum and Gongronema latifolium decreased baseline blood glucose levels when preadministered to normal subjects 45 min before an OGTT (Ejike et al., 2013)

61 Gossypium hirsutum L

Malvaceae

Auduga (H); Ela-owu (Y); Eto-ofo (Ibibio); Owu (Ige); Ebe-oru (Bi)

Aqueous extract of the leaves produced a non-significant blood glucose lowering effect of only 17% in alloxan-induced diabetic rats (Etuk and Mohammed, 2009)

Gonorrhea, Dysnetry, Sore throat. Malaria, Uterine fibroids

Gymnema sylvestre (Retz.) R. Br. Ex Sm.

Apocynaceae

Cow plant

SE GS4, a low MW component

of the aqueous extract of the leaves decreased blood glucose levels and increased insulin release in rats. Type 1 and 2 diabetic patients (Shanmugasundaram et al., 1990a, 1990b; Baskaran et al., 1990)§; The action of GS4 on insulin release is by increased membrane permeability (Persaud et al., 1999)§; A high MW extract of the leaves OSA® increased plasma insulin levels in-vitro and in humans through a direct stimulatory effect (Al~ Romaiyan et al., 2010)§;

Obesity, Anti-sweetner, Ulcer, Diuretics, Laxatives, Skin infectionsAsthma, Hepato-protective, Inflammation, Snake bites, Anti-microbial, Anti-plasmodial

Plant part Traditional (s) used preparation method

Identified active constituent(s)

extract of the stem and leaves in glucose loaded rats as well as the In vitro glucose stimulating effects in INS-1 cells led to the isolation of oc-and p-amyrin cinnamate, lupenyl cinnamate and lupenyl acetate as bioactive constituents (Adebajo et al., 2013)

Leaves, Root

Decoction, Maceration

Leaves, Roots Infusion

Aromadendrene and its hydrate, oc-Humulene, 8-Cadinene, Germacrene, a- and y-Eudesmol, (E)-Phytol, Methyl palmitate (Edet et al., 2005); 3-0-[6-deoxy-3-O-methyl-p-d-allopyranosyl-(l ->4)-p-d-canaropyranosyl-17p-mardenin and 3-0-[6-deoxy-3-O-methyl-p-d-allopyranosyl-(l ^4)-p-d-oleoandropyranosyl-17p-mardenin, 11-O-acetyl-and 12-0-acetyl-3-0-[6-deoxy-3-O-methyl-p-d-allopyranosyl-(l -+4)-p-canaropyranosyl ]-l 7p-marsdenin (Schneider et al., 1993)

Lupenyl acetate, Lupenyl cinnamate, p-Sitosterol, Lupeol (Ekundayo, 1980) a- and p-amyrin cinnamate (Adebajo et al., 2013)

Gossypol, Condensed tannin (Chan et al., 1978); Quercetin glucosides, Gossypetin glucosides, Cyanidin-3-p-glucoside (Chrysanthemin) (Hanny, 1980); Myrcene, a- and p-pinene, Limonene, p-caryophyllene and its oxide, y-bisabolene, Spathulenol, Gossonorol p-bisabolol (Elzen et al., 1985)

Gymnemic acids I-XVIII, Gymnemagenin or Genin L and its acetate (p-amyrin derivative), Genins G and J, Genin K acetate, Gymnemasaponins I-V, Gymnemasins A-D, Gymnemanol, Gypenosides XXVIII, XXXVII, LV, LXII and LXIII, Gymnemasides I-VII, Oleanane-type saponins, Gurmarin, Gymnamine, Gymnemosides A-E (Porchezhian and Dobriyal, 2003); Gymnemic acids A-D (Sinsheimer et al., 1970); Choline, Betaine, Adenine,

S/ Plant name Family Common Local Region of Experimental evidence for Other medicinal uses

no. name Nigerian use for its use in diabetes

name(s) diabetes* management

Antioxidant effects (Kang et al., 2012 )§

63 Hunteria umbellata (K. Schum.) Hallier f.

Apocynaceae

Mkpokiri (I), Erin or Abeere (Y), Osu (Bi)

Aqueous extract of the seed produced a dose-dependent (50-200 mg/kg) hypoglycaemic effect in 3 diabetic models (alloxan, fructose and dexamethasone-induced) (Adeneye and Adeyemi, 2009); Antioxidant effects (Adejuwon et al.,

2011); An alkaloidal fraction of the butanol extract decreased the post-absorptive glucose concentration in alloxan-induced rats (Adeneye et al.,

Labour induction. Antipyretic, Analgesic, Obesity, Gastric ulcer, Dys-menorrhea, Antimicrobial, Antiparasitic, Immune booster. Antihelminthic, STDs, Hypertension

Hymenocardia acida Tul. (in vivo)

Ipomoea batatas (L.) Poir.

Phyllanthaceae Heart fruit

Convolvulaceae Sweet potato

Janyaro (H), SE, NC, Methanol extract of the Enache (Id) NW leaves decreased blood

glucose levels in alloxan-induced diabetic rats at doses between 250 and 1000 mg/ kg (Ezeigbo and Asuzu, 2010); Antioxidant effects (Sofidiya et al., 2009)

Ji-oyibo or SW Aqueous extract of fresh

Ekimako (I), whole plants produced a

Odunkun (Y), dose-dependent (100-

Dankali (H) 400 mg/kg) decrease in blood

glucose in normal and STZ-induced diabetic rats (Olowu et al., 2011); Daily ingestion of 4 g by type 2 diabetic patients for 3 mths resulted in improved FBG and HbAlc levels (Ludvik et al., 2004)§; Improved glucose tolerance and decreased hyperinsulinemia in obese zucker fatty rats administered 100 mg/kg/day aqueous extract of the cortex (Shuichi and Abe, 2000)§

Anti-microbial, Antiparasitic, Sickle cell. Ulcers, Diarrhea, Dysentry, Analgesic, Malaria, Tumours, Arthritis, Anti-fertility, Insecticidal

Anti-proliferative, Antimicrobial, Purgative, Wound ulcers. Analgesic, Hemorrhoids

Plant part Traditional Identified active Other relevant Interaction/toxicity

(s) used preparation constituent(s) phytoconstituents studies

method identified in the plant

Seeds, Fruit Maceration, Pulp, Bark, Decoction, Roots Infusion

Bark, Fruit, Leaves

Decoction,

Maceration,

Infusion

Whole plant. Juice extract, Leaves, Bark Infusion

Aldose reductase inhibitory effects of ellagic acid and 3,5-dicaffeoyl quinic acid isolated from extract of the leaves (Terashima et al., 1991); Alpha glucosidase inhibitory effect of an isolated anthocyanin Peonidin-3-0-[2-0-(6-0-£-feruloyl-p-D-glucopyranosyl)-6-0-£-caffeoyl-p-D-glucopyranoside from the root (Matsui et al., 2002)

Leucine, Valine, Amino butyric acid, Trimethylamine oxide, Isoleucine (Sinsheimer and Mcllhenny, 1967); Nonacosane, Condruitol A, Hentriacontane, Tritricontane (Manni and Sinsheimer, 1965) Ikirydinium A, Ursolic acid. Serpentine, Pseudo-akuammigine, Huntrabrine methochloride, Strictosidinic acid (Ajala et al., 2011); Corymine, Isocorymine,

Acetylcorymine, Dehydro-isocorymine, Umbellamine, Eripine, Erinin, Erinincin, Abereamines 1-4 (delactonized 14-isopropyl hydroxy isocorymines) (Adejuwon et al., 2012); Segunoside (Ajala and Coker, 2012) Di-(2-ethylhexyl) phthalate, Homoorientin (Sofidiya et al., 2010); Friedelan-3-one, Betulinic acid, Lupeol, p-Sitosterol, Stigmasterol, Oleic acid (Igoli and Alexander, 2008); Hymenocardine (Pais et al., 1968) Non-, Mono- and Diacylated structures of 3-0-(2-0-/?-D-glucopyranosyl-/?-D-glucopyranoside)-5-0-/?-D-glucosides of Cyanidin and Penoidin (Montilla et al., 2011); Gallic, Gentisic, Caffeic, Chlorogenic, p-Coumaric, Sinapic, Benzoic, Anisic and Cinnamic acids; Catechin, Epicatechin, Kaempferol, Myricetin, Quercetin (Carvalho et al., 2010); 4,5-di-O-caffeoyldaucic acid, 3-O-caffeoylquinic acid (Chlorogenic acid), 3,5-di-O-caffeoylquinic acid, 3,4-di- O-caffeoylquinic acid, 3,4,5-tri-O-caffeoylquinic acid, Caffeic acid (Islam et

4-Ipomeanol produces an irreversible imhibition of Cyt 3A4 (Alvarez-Diez and Zheng, 2004)

S/ Plant name Family Common Local Region of Experimental evidence for Other medicinal uses

no. name Nigerian use for its use in diabetes

name(s)* diabetes* management

Plant part Traditional Identified active (s) used preparation constituent(s) method

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

66 Irvingia gabonensis (Aubry-Lecomte ex O'Rorke) Baill.

Irvingiaceae

Dikanut, African mango, Bush mango

Ogbono (I) SE, SS, SW

67 Jatropha curcas L. Euphorbiaceae

Pignut plant, Physic nut, Purging nut, Barbados nut

Botuje or Lapalapa (Y), Binida zugu (H), Owulo idu

Daily intake of a dikanut supplemented diet (4g/day) by type 2 diabetic patients for 1 month resulted in improved lipid profile and decreased blood glucose levels (Adamson et al., 1990) 2 g/kg administered 2 ce daily to STZ-induced diabetic rats decreased blood glucose, and lactate dehydrogenase and pyruvate kinase enzymes (Ozolua et al., 2006)

Overweight volunteers given the seed extract in a randomized double-blinded study had decreased blood glucose, adiponectin, leptin and C-reactive protein levels and improved plasma lipid profile compared to placebo (Ngondi et al., 2009)§ Antioxidant effects (Donfack et al., 2010; Awah et al., 2012) Antioxidant effects (Igbinosa et al., 2011 ) 250 and 500 mg/ kg of the hydro-ethanolic extract of the leaves decreased blood glucose levels in alloxan-induced diabetic rats (Mishra et al., 2010)§ 100 mg/l ethanol extract of the stipe showed PPARa, y and S activities (Rau et al., 2006)§ 250 and 450 mg/kg of the aqueous extract of the roots decreased fasting blood glucose levels in alloxan induced diabetic rats (Aladodo et al., 2013)

Dysentry, Wound ulcers, Liver disorders, Hemorrhage, Antimicrobial, Analgesic

Seeds, Fruit, Leaves, Stem-bark, Root

Purgative, Cancer, Abortifacient, Diuretic, Hemostatic, Antipyretic, Inflammation, Convulsions, Wound healing, Anti-microbial, Insecticidal, Jaundice, STDs, Anti-parasitic, Skin diseases, Molluscicidal, Chewing stick, Irregular menses, Sciatica, Paralysis

Seeds, Leaves, Root Latex, Stem-bark

al., 2002); Ellagic acid, Caffeic acid, Scopoletin and 3,5-dicaffeoyl quinic acid (Terashima et al., 1991)

3-Friedelanone, Betulinic acid, Oleanolic acid, Methyl gallate, Trimethyl ellagic acid, Hardwickiic acid, 3-p-acetoxyursolic acid (Donfack et al., 2010);

Ellagic acid, Mono, Di and Tri-methyl ellagic acid and their glycosides, Galloyl ellagic acids, Ellagitannins, Kaempferol glucoside, Quercetin rhamnoside, Diosmetin (Sun and Chen, 2012)

Curcacycline A (van den Berg et al., 1995); Esterases, Lipase (Staubmann et al., 1999); Curcin, Curcain (Osoniyi and Onajobi, 2003); Scopaletin, Coumaroyl oleanolic acid, Methoxyanthraquinone, Heudelotinone, Tetradecyl ferulate, Podocarpatriene and Podocarpatrienone (Ravindranath et al., 2004);

Phospholipase D (Liu et al., 2010); Eicosadienoic, Oleic, Linoleic, Palmitic, Stearic and Eicosenoic acids; 12-deoxy-16-hydroxy phorbol, Riolozatrione, Jatrophol, Jatropholones A and B, Acetoxyjatropholone, Jatropherol 1, 2 and 3; Curcosones A-E, Palmarumycin, Caniojane, Heudolotione, Nobiletin,

Ingestion of the seeds caused severe vomiting and dehydration in children; and hemorrhage of the liver, lungs and stomach resulting in death at high doses in mice (Abdu-Aguye et al., 1986)

Administration of 10 mg of the methanol extract ofthe seeds daily to rats resulted in changes in their hematological indices (Oluwole and Bolarinwa, 1997) Ethanol extract of the root bark of the plant inhibited Cyt P450 3A4 and 3A7 enzymes (Agbonon et al., 2010)

Decoction

S/ Plant name Family Common Local

no. name Nigerian

name(s)

Region of Experimental evidence for use for its use in diabetes diabetes* management

68 Khaya ivorensis Meliaceae A.Chev.

African, Lagos Oganwo (Y), SW, SS, NC

or Red Ono (I)

mahogany

69 Khaya Meliaceae Dry-zone or Oganwo (Y), SW, SS,

senegalensis African Ono (I), NC, NW

(Desv.) AJuss. mahogany Madachi (H),

Okpen (Es), Ago (Ig)

An extract of the bark in buffer solution produced moderate inhibition of oc-amylase activity in-vitro (Funke and Melzig, 2006)

Other medicinal uses Plant part Traditional Identified active Other relevant Interaction/toxicity

(s) used preparation constituent(s) phytoconstituents studies

method identified in the plant

Arthritis, Fevers, Antiparasitic, Jaundice, SC anemia. Anti-tumour, Wound healing

Stem bark. Leaves

Maceration,

Decoction,

Infusion

Fevers, Sickle Cell, Anti- Stem bark. Infusion, parasitic, Anti- Leaves, Seeds Maceration,

microbial. Anti-tumour, Decoction

Hypertension, Insecticidal

Spirocurcasone, Ellagic acid, Jatrophalactam, Jatrogrossidione derivatives, ß-amyrin, Jatrophalactone, Caffeoyl aldehyde, Syringaldehyde, Jatrophadiketone, Uracil, ß-sitosterol, Jatrophalone, Taraxasterol, Stigmasterol, Daucasterol, Pyrrolidine, Curcamide, Tomentin, Coumarin compounds (Abdelgadir and Van Staden, 2013) 1 -0-deacetyl-6deoxy khayanolide E, 1-0-deacetyl-2a-hydroxy khayanolide E, 3-acetyl-khayalactone, 11a-acetoxy-2a-hydroxy-6-deoxy-

destigloylswietenine acetate, Swiemahogin, Khayalactol, Seneganolide, Khayanolide A and B, Khayanoside (Zhang et al., 2009a); Methyl angolensate, and its

6-hydroxy derivative, 3-deacetylkhivorin, 3,7-dideacetylkhivorin, 1,3,7-trideacetylkhivorin,

7-deacetylgedunin, 7-deacetoxy-7-oxogedunin, Swietenine, 3-0-detigloyl-3-0-acetylswietenine, 3-0-acetylswietenolide (Abdelgaleil et al., 2001); Proceranolide and its n-butyric derivative (Vanucci et al., 1992); Khivorin, Sitosterol, 3-deacetyl khivorin, 7-deacetyl khivorin. Methyl

6-hydroxyangolensate, Swietenolide acetate, Fissinolide, Methyl ivorensate. Esters of 6-deoxyswietenolide (Adesogan and Taylor, 1970)

Rutin, Catechin, Quercetin rhamnoside, Procyanidins (Atawodi et al., 2009); 3a,7a-dideacetylkhivorin, 1-O-acetylkhayanolide B

A herbal tonic containing a mix of extracts of the stem barks of Khaya ivorensis, Mitragyna stipulosa and Kigela africana modulated the activity of fat liver Cyt P450 enzymes (Martey et al., 2009) Aqueous extract of the stem bark modulates P-gp mediated efflux of Rhodamine-123 (Ezuruike et al., 2012)

S/ Plant name no.

Family

Common Local Region of Experimental evidence for Other medicinal uses Plant part Traditional Identified active

name Nigerian use for its use in diabetes (s) used preparation constituent(s)

name(s)* diabetes* management method

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

200 mg/kg aqueous extract of the bark produced only a 4% decrease in blood glucose levels after 2 h (Etuk and Mohammed, 2009); while the oil extract of the seeds decreased blood glucose levels by 20% after 2 h, which increased to 60% after 8hrs (Momoh and Muhammed, 2011), both in alloxan-induced diabetic rats. Antioxidant effects (Atawodi et al., 2009)

(Zhang et al., 2007); Khayanolides D and E, Khayanoside (Nakatani et al., 2002); Khayanolides A, B and C, Seneganolide, Methyl angolensate and its 6-hydroxy and 6-acetoxy derivatives (Abdelgaleil et al., 2001); Fissinolide, 2,6-dihydroxy fissinolide, Methyl-3ß-acetoxy-6-hydroxy-1-oxomeliac-14-enoate (Khalid et al., 1998); 2-hydroxy mexicanolide, 6-deoxy destigloyl swietenine, 2,3-dihydroxy-3-deoxymexicanolide, Mexicanolide, 3ß-hydroxy-3-deoxymexicanolide, 3ß-hydroxy-3-deoxycarapin, 3-acetyl-7-keto khivorin, 3-deacetyl khivorin (Govindachari and Kumari, 1998); Methyl 1a-acetoxy tri hydroxyl-2a-methoxy-2ß, 14ß-epoxy tricyclomeliac-7-oate, Methyl 1 a-acetoxy tetra hydroxyl-3-oxo-tricyclomeliac-7-oate, Scopoletin, ß-quercitrin (Olmo et al., 1997)

70 Lawsonia inermis L.

Lythraceae

Henna plant, Mehndi, Egyptian's priest

Laali (Y), Lelle SW

Alpha glucosidase inhibitory effects of the ethanol extract of the leaves (Prashanth et al., 2001 )§ Increased activity of in-vivo antioxidant enzymes (Dasgupta et al., 2003)§ Daily administration of graded doses (100800 mg/kg) of the ethanol extract of the leaves for 2 weeks decreased blood sugar levels in alloxan-induced diabetic rats (Inawati and Winarno, 2008)§ In vitro antioxidant effects of isolated constituents of the plant (Hsouna et al., 2011)§

Wound infection, Antimicrobial, Anti-parasitic, Jaundice, Nervous disorder, Arthritis, Analgesic, Ulcers, Diarrhea, Antipyretic, Hepato-protective, Leucorrhoea, Excessive ejaculation, Emmenagog, Skin diseases, STDs, Abortifacient, Sickle cell, Tumours, Tuberculosis, Splenomegaly, Menorrhagia

Lawsone and gallic acid isolated from the ethanol extract of the aerial parts inhibited the formation of glycated protein In vitro (Sultana et al., 2009)

ß-Sitosterol glucoside, Gallic acid, Coumarins, Xanthones, Lawsoniaside, Lalioside, Luteolin glucosides, 1,2-dihydroxy-

4-glucosyloxy naphthalene (Takeda and Fatope, 1988); Vomifoliol, Lawsonicin, Lawsonadeem (Siddiqui et al., 2003); Isoplumbagin, Hexenol, Linalool, ß-Ionone, a- and y-Terpineol, Terpinolene,

5-3-Carene, Benzaldehyde, Isocaryophyllene, Methyl salicylate, Naphthalene, Eugenol, Germacrene D, Farnesene, Bisabolene, ß-Elemene, Isophytol, S-Cadinene, Cadalene, Geranyl isobutyrate, Methyl cinnamate (Oyedeji et al., 2005);

Administration of henna leaf extract to mice for 21days resulted in increased activity of cytochrome b5 reductase enzyme and the phase 2 enzymes GST and DDT (Dasgupta et al., 2003) Topical application to skin lesions in G6PD deficient patients resulted in hemolytic anemia (Kôk et al., 2004)

Decoction

S/ Plant name no.

Family

Common Local Region of Experimental evidence for Other medicinal uses

name Nigerian use for its use in diabetes

name(s)* diabetes* management

Plant part Traditional Identified active (s) used preparation constituent(s) method

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

71 Mangifera indica Anacardiaceae L.

Manihot

esculenta Crantz, Syn: Manihot utilissima Pohl

Euphorbiaceae

Cassava, Tapioca

Mangoro SS, SE 1 g/kg of the aqueous extract of the leaves decreased blood glucose levels in normal and glucose loaded mice, but not in STZ-induced diabetic mice (Aderibigbe et al., 2001) Alpha glucosidase inhibitory effects of the ethanol extract of the bark (Prashanth et al., 2001 )§ 200 mg/kg aqueous extract of the leaves decreased blood glucose levels in alloxan-induced diabetic rats (Etuk and Mohammed, 2009) Dipeptidyl peptidase IV inhibitory activity of the methanol extract of the leaves (Yogisha and Raveesha, 2010)§ Antiooxidant effects (Badmus et al., 2011)

Gbaguda or SE, SW Increased intake of cassava Ege (Y), Akpu leaves in diet decreases the

or Abacha (I), risk of metabolic syndrome

Rogo (H) in Type-2 diabetic patients

(Mvitu Muaka et al., 2010)§ Antioxidant effects of the aqueous extract of the leaves (Tsumbu et al., 2011)§

Malaria, Analgesic, Inflammation, Antimicrobial, Anti-helminthic, Diarrhoea, Menorrhagia, Hypertension, Insomnia, Asthma, Scabies, STDs, Anemia, Malaria

Leaves Stem-bark, Kernel, Fruits

Arthritis, Gonorrhea, Burns, Ulcer

LeavesTubers Decoction

Mannitol, Hennatannic acid, Lawsone (2-hydroxy 1,4-naphtoquinone), Behenic, Oleic, Linolenic, Arachidic, Palmitic and Stearic acids, Laxanthone I, II and III, Apigenin glycosides, Stigmasterol, Acacetin, Cosmosiin, p-Coumaric acid, Fraxetin, Hennadiol, Scopoletin, Esculetin, Apiin, Lupeol, Betulin, Betulinic acid, Lawsoshamim, 2-methoxy-3-methyl naphthaquinone, 24ß-ethyl cholest-4-enol, Esters of Lawnermis acid (Chaudhary et al., 2010) Trihydroxy acetophenone and naphthalene gluco-pyranosides (Hsouna et al., 2011)

Tannic acid, Gallic acid, Epicatechin, Ellagic acid, Gallocatechin, n-butyl cyanidin (Arogba, 2000); 3,4-dihydroxy benzoic acid, Benzoic acid, Methyl gallate, Propyl gallate, Mangiferin, Catechin, Benzoic acid propyl ester (Nûnez Sellés et al., 2002) Violaxanthin dibutyrate, ß-Carotene, 9-cis- and trans-violaxanthin, Luteoxanthin, Mutatoxanthin, Neochrom, Xanthophyll palmitic and myristic acid esters (Pott et al., 2003); Isomangiferin, Quercetin and its glycosides, Kaempferol-3-O-glucoside, Rhamnetin-3-O-glycoside, Mangiferin and Isomangiferin gallate (Schieber et al., 2003; Berardini et al., 2005) ß-Sitosterol glucoside, Stigmast-4-en-3-one, Galactosyl diacylglyceride, Galactocerebroside, Scopoletin, Isoscopoletin, Scoparone, Esculetin, Ayapin, Umbelliferone, Scopolin, Esculin, ß-Carotene (Bayoumi et al.,

Stem bark extract of the plant, mangiferin and its metabolite norathyriol as well as quercetin, constituents of the plant showed dose-dependent modulation of P-gp activity in HK-2 and Caco-2 cell lines (Chieli et al., 2009) The stem bark extract also showed inhibitory effects for Cyp1A, 2D and 3A4 enzymes of human liver microsomes (Rodeiro et al., 2009)

Although intake of a cassava tuber rich diet has been implicated in the aetiology of pancreatitic diabetes (Kamalu, 1991); experiments have shown that it only aggravates diabetes in

Decoction

S/ Plant name Family Common Local

no. name Nigerian

name(s)

Region of Experimental evidence for Other medicinal uses use for its use in diabetes diabetes* management

73 Momordica Cucurbitaceae African Ejirin (Y), Ebe SW, SS, Daily administration of

charantia L. cucumber, isiugwu (Bi), NW 10 ml/kg of the fruit juice

Bitter melon, Urakhanye extract to STZ-induced

Bitter guord, (Es), Daddagu diabetic rats for lOwks

Bitter squash, (H) decreased blood glucose

Karela levels and increased plasma

insulin levels and the number of insulin positive islet cells. There was decreased glucose uptake by the brush border vessicles of the jejunum in extract treated rats compared to control. In vitro, 5 (ig/ml of the extract increased glucose transport into L6 myotubes (Ahmed et al., 2004) Several clinical studies in type-2 diabetic patients given extracts of the plant produced hypoglycaemic effects (Leung et al., 2009)§

Anti-fertility, Malaria, Anti-helminthic, Antimicrobial, Insecticidal, Weight loss, Abortifacient, Skin infections. Inflammation, Purgative, Dysentry, Fevers, Burns, Colic

Bitter melon

Momordica

foetida

Schumach.

Cucurbitaceae

Ebe isiugwu (Bi)

Ejinrin-wewe (Y)

500 mg/kg aqueous leaf extract decreased blood glucose levels in normal, high glucose fed and alloxan-induced diabetic rats (Osinubi et al., 2008) Antioxidant effects (Acquaviva et al., 2013)

Malaria

Malaria, Ulcer, GIT disorders. Antimicrobial, Antihelminthic, Hypertension, Abortifacient

Plant part Traditional (s) used preparation method

Identified active constituent(s)

Fruit, Leaves, Decoction, Root, Seeds Juice extract

Fruit, Leaves, Stem, Flower, Whole plant

Juice extract

Maceration, Decoction

2010); Cyanidin and Delphinidin 3-0-(6"-0-a-rhamno pyranosyl-p-glucopyranoside) (Byamukama et al., 2009); Rutin, Kaempferol-3-O-and 4/-0-rutinoside, Ferulic acid,

Amentoflavone (Ola et al., 2009); Caproic, Caprylic, Capric, Laurie, Myristic, Palmitic, Oleic, Linoleic, Arachidic, Behenic and Lignoceric acids (Raja and Ramakrishna, 1990); Linamarin, Lotaustralin (Ogunsua, 1980) Esters, Alcohols and Sugars of Cucurbitane triterpenoids, Kuguacins, Charantosides, Trinorcucurbitacin, Penta-norcucurbitacins, Octa-norcucurbitacin (Lee et al., 2009); Momorcharins, Momordin, Momordolol, Charantins, Momordenol, Momordicilin, Charine, Momordicosides, Momordicines, Diosgenin, Cryptoxanthin, Vicine, Cucurbitins, Cucurbitacins, Cucurbitanes, Erythrodiol, Cycloartenols, Gentisic, Elaeostearic, Galacturonic and Pipecolic acids; MAP 30, Goyaglycosides, Goyasaponins, P-insulin polypeptide, Ascorbigen, Multiflorinols, Luteolin, Laurie, Myristic, Palmitic, Stearic, Palmitoleic, Oleic, Linoleic and Linolenic acids (Paul and Raychaudhuri, 2010)

1 mg/kg foetidin isolated from the plant decreased blood glucose levels of normal fasted, but not alloxan-induced rats (Marquis et al., 1977)

low-protein diets (Yessoufou et al., 2006; Manwa et al., 2010) Risk of toxic effects on organs due to high cyanide content (Soto-Blanco and Gorniak, 2010)

Aqueous extract of the leaves inhibited GST enzyme in both rat and human liver cytosols and recombinant GSTs; as well as the activity of Cyp 2C9 supersomes but not Cyp 1A2, 2D6 and 3A4 (Appiah-Opong et al., 2008) A potentiated hypoglycaemic effect has been observed when extracts of the plant are coadministered with known anti-diabetic drugs (Nivitabishekam et al., 2009)

5,25-stigmastadiene-ol-glucoside, Foetidin, p-sitosterol glucoside (Marquis et al., 1977); p-Hydroxyfriedel-6( 7 )-ene-3-one, Octadecanoic acid, Stigmasterol-p-D-glucoside. Choline chloride (Olaniyi, 1980); Cucurbitacins (Chen et al..

S/ Plant name no.

Family

Common name

Nigerian

name(s)*

Region of use for diabetes#

Experimental evidence for its use in diabetes management

Other medicinal uses

Plant part (s) used

Traditional preparation method

Identified active constituent(s)

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

75 Mondia whiteii Apocynaceae (Hook.f.) Skeels

White ginger, Isirigun African ginger orAghuma orGbolo-gbolo (Y)

Morinda citrifolia L.

Rubiaceae

Indian

mulberry,

Aqueous extract of the roots did not show any inhibition against pancreatic alpha amylase and lipase enzymes (Etoundi et al., 2010)§

Infertility, Erectile dysfunction, Malaria, Gonorrhea, Anti-parasitic, Anti-depressant, Anti-spasmodic, Hemorrhoids, Inflammation, Memory loss, Cancer

Infusion, Decoction

300 mg/kg of a mixture of the aqueous fruit extract alongside that of Coccinia indica decreased blood glucose levels in alloxan-induced diabetic rats (Kumar and Verma, 2011)§ Administration of 2 ml/kg of the fruit juice extract twice a day to STZ-induced diabetic rats for twenty days resulted in a significant decrease in fasting blood glucose levels by the 5th day post administration (Nayak et al., 2011)§ Antioxidant effects for the methanol extract of roots and ethyl acetate extract of plant (Zin et al., 2002)§ Administration of 1ml/ 150mg body weight of Tahitian noni juice® for 4 weeks resulted in a prophylactic action against alloxan-induced diabetes in rats (Horsfal et al., 2008).

Malaria, Wound healing, Fruits, Roots,

Anti-microbial, Anti- Stems, Bark,

helminthic, Flower,

Inflammation, Immune Leaves

booster, Colds and Flu,

Ulcers, Tumours,

Analgesic, Arthritis,

Hypertension,

Tuberculosis

Decoction, Maceration

Hypoglycemic effects of the anthraquinones, damnacanthol-3-O-p-d-primeveroside and lucidin 3-O-p-d-primeveroside from the butanol fraction of the methanol extract at 100 mg/kg in STZ-induced diabetic mice. (Kamiya et al., 2008)

2005); 3p,7p-dihydroxyl-cucurbita-5,23,25-trien-19-al, Kaempferol-3-O-p-d-glucopyranoside (Odeleye et al., 2009) Isovanillin, 2-hydroxy-4-methoxy benzaldehyde and its -2-O-p-d-glucopyranose-(1 —6)-O-p-d-xylopyranoside (Koorbanally et al., 2000); Propacin, 5-methoxy propacin,

5-chloropropacin, Squalene, p-sitosterol, 3-methoxy-4-hydroxy benzaldehyde,

6-methoxy-7-hydroxycoumarin, 6-methoxy-7,8-dihydroxy coumarin (Patnam et al., 2005); Loliolide (Neergaard et al., 2010); Stigmasterol, 9-Hexacosene (Githinji et al., 2011); a and p-amyrin acetate (Watcho et al., 2012)

6-O-(p-d-glucopyranosyl)-1-O-octanoyl-p-d-gluco pyranose and 1-O-hexanoyl-p-d-glucopyranose, 3-methylbut-3-enyl 6-O-p-d-glucopyranosyl-p-d-glucopyranoside (Wang et al., 2000); Citrofolinin A and B, Kaempferol and Quercetin glycosides, Physcion, Ricinoleic, Octanoic, Hexanoic acids (Sang et al., 2001); Scopoletin, l-asperuloside, Alizarin, Asperulosidic, Caproic, Caprylic and Ursolic acids, Acubin, Rubiadin and its 1-methyl ether, Nordamnacanthal, Morindone, Rutin, 1-methoxy-2-formyl-3-hydroxy anthraquinone, Citrifolinoside, Proxeronine (Wang et al., 2002 ); Morenone-1 and 2, 6,8-dimethoxy-3-methyl anthraquinones 1-O-p-rhamnopyranosyl(1 —4) p-d-glucopyranoside, 6a-hydroxyadoxoside, 6p,7p-epoxy-8-epi-splendoside,

Risk of liver injury/ hepatitis (Millonig et al., 2005; Yuce et al., 2006; Mrzljak et al., 2013) Noni juice extract increased the activity of amino-pyrine N-demethylase (APND) and glutathione-S-transferase (GST) enzymes and decreased the activity of uridine diphosphoglucuronosyl transferase (UGT) enzyme of rat liver hepatocytes both in vitro and ex vivo (Mahfoudh et al., 2009) Co-incubation of noni juice and digoxin in Caco-2 monolayers did not change the net digoxin flux indicating no modulation of P-gp by noni juice (Engdal and Nilsen, 2008)

S/ Plant name Family Common Local

no. name Nigerian

name(s)

Region of Experimental evidence for Other medicinal uses use for its use in diabetes diabetes* management

77 Morinda lucida Benth.

Rubiaceae

Brimstone tree Oruwo (Y), Eze ogwu (I)

NC, SW Administration of the methanol extract of the leaves produced a dose dependent (50-400mg/kg) decrease in plasma glucose levels in both normal and STZ-induced diabetic rats (Olajide et al., 1999)

Malaria, Anti-microbial, Anti-parasitic, Antihelminthic, Analgesic, Laxative, Hypertension, Jaundice, Oligomenorrhea, Insomnia, Wound ulcers. Diuretic

78 Moringa oleifera Moringaceae Lam.

Drumstick Zogale (H), SE, SW, Aqueous extract of the leaves orHorseradish Okwe-oyibo NW, NC decreased blood glucose tree, Moringa or Okochi levels in normal, high glucose

egbu (I), fed and STZ-induced diabetic

Gergedi rats at doses between 100

(Igala), Ewe- and 300 mg/kg (Jaiswal et al.,

igbale or 2009)§ 200 mg/kg of the leaf

Gbogbo-nise powder improved glucose

(Y), tolerance in both normal

Konamarade wistar and spontaneously

(F) type-2 diabetic GK rats

(Ndong et al., 2007)§ Antioxidant effects (Siddhuraju and Becker, 2003)§

Antimicrobial, Antiparasitic, Anti-cancer, Inflammation, Diuretic, Anemia, Hypertension, Aphrodisiac, Antipyretic, Purgative, GIT disorders. Immune stimulant. Antispasmodic

Plant part Traditional Identified active (s) used preparation constituent(s) method

Leaves, Roots, Stem-bark

Decoction

Leaves, Pods

Infusion, Dried leaves

Borreriagenin, Deacetyl asperuloside, Dehydro methoxygaertneroside, 5,15-dimethyl morindol. Alizarin-1-methyl ether, Anthragallol- 1,3-dimethyl ether, Anthragallol-2-methyl ether, 6-hydroxy-anthragallol- 1,3-dimethyl ether, Morindone-5-methyl ether, Asuperlosidic acid, Deacetylasperulosidic acid, Morindacin (Kamiya et al., 2005);

Ursolic acid, Oleanolic acid (Cimanga et al., 2006) 1-Methylether alizarin, Soranjidiol, Damnacanthal, Nordamnacanthal, Lucidin, Rubiadin, Morindin, Munjistin, Purpuroxanthin, Digitolutein, Oruwalol, Oruwal (Lawal et al., 2012)

Isolated benzyl derivatives from the methanol extract of the fruits stimulated insulin release from the pancreatic p-cell line INS-1 (Francis et al., 2004)

Quercetin and Kaempferol glycosides, Chlorogenic acid. Rutin (Ndong et al., 2007); Isoquercitrin, Rhamnetin, Vanillin, ß-sitosterol, ß-sitostenone, Zeatin, 4-hydroxymellin, Niazirin, Niazicin A, Methyl 2,4-(oc-l-rhamnopyranosyl) phenyl acetate, N-[4-(ß-D-glucopyranosyl)benzyl ]-l -O-a-D-glucopyranosyl thiocarboxamide, 4-[(ß-D-glucopyranosyl)-( 1 3)-(a-L-rhamnopyranosyl) phenylacetonitrile, l-O-phenyl-a-L-rhamno pyranoside. Methyl N-(4 [(4'-0-acetyl-a-L-

Aqueous extract dose dependently (l-20mg/ ml) inhibited the P-gp mediated transport of digoxin across monolayers of Caco-2 cells (Oga et al., 2012) Aqueous extract and ethanol extract of the leaves moderately inhibited Cyp3A4 and 3A7 enzymes respectively (Agbonon et al., 2010) 0.5 mg/ml aqueous extract of the leaves inhibited the activity of the recombinant GST Ml-1 enzyme by > 70%, but not those of rat and human liver cytosols (Appiah-Opong et al., 2008)

Aqueous and methanol extracts of the leaves inhibited Cyp3A4 hydroxylation of testosterone in human liver microsomes (Monera et al., 2008) Hydroalcoholic extract of the drumsticks increased the activities of hepatic Cyt P450 and Cyt b5 enzymes as well as the antioxidant enzymes GST, GPx and GR (Bharali et al., 2003)

S/ Plant name Family Common Local Region of Experimental evidence for Other medicinal uses

no. name Nigerian use for its use in diabetes

name(s) diabetes* management

79 Morus alba L

White mulberry

Alpha glucosidase inhibitory effects of the aqueous extract of the leaves in Caco-2 cells (Hansawasdi and Kawabata, 2006)§ The leaf extract showed inhibitory effects against rat and human dissacharidase enzymes of the intestinal mucousa as well as decreased postprandial glucose levels in sucrose fed rats (Oku et al., 2006f 400 and 600 mg/kg ethanol extract of the leaves decreased blood glucose levels in STZ-induced diabetic rats and increased the number of p-cells in the islets of the pancreas (Mohammadi and Naik, 2008)§ Ingestion of the leaf extract by KK-Ay mice as part of the diet decreased blood glucose levels, improved glucose tolerance and increased plasma insulin levels (Tanabe et al., 2011 )§ Antioxidant effects (Yen et al., 1996)§

Anti-helminthic, Laxative, Emollient, Molluscicidal, Antimicrobial

Murraya koenigii Rutaceae (L.) Spreng.

Curry tree. Sweet neem

Methanol extract of the stem and leaves did not significantly decrease blood glucose levels in normal and alloxan-induced diabetic rats; while chloroform extract of the stems and isolated constituents decreased glucose mediated insulin release from INS cells (Adebajo et al., 2005) Hypoglycaemic effect of defatted ethanol extract of the leaves in STZ-induced diabetic rats and Antioxidant

Dysentry, Diarrhoea, Stimulant, Anti-venom, Hypertension, Antimicrobial, Inflammation, Antiparasitic

Plant part Traditional Identified active Other relevant Interaction/toxicity

(s) used preparation constituent(s) phytoconstituents studies

method identified in the plant

Leaves, Fruit, Bark

Infusion,

Decoction,

Maceration

Leaves, Seed, Stem

Powdered leaves as spice. Decoction

Administration of mahanimbine isolated from the petroleum ether fraction of the leaves decreased blood glucose levels in STZ-induced diabetic rats and had a dose-dependent alpha amylase and alpha glucosidase inhibitory effect (Dineshkumar et

rhamnopyranosyl)benzyl] carbamate. Methyl N-4-[ (a-L-rhamnopyranosyl) benzy] carbamate, 0-[2'-hydroxy-3'-2 "-heptenyl oxy)]-propyl undecanoate, methyl p-hydroxybenzoate, Moringine, Moringinine (Anwar et al., 2007) Morusin, Isomorusin, Compound A (Taro et al., 1978); Kuwanons K and L (Nomura et al., 1983); p-carotene, a-tocopherol (Yen et al., 1996); Isoquercitrin, Astragalin, Scopolin, Skimmin, Roseoside II, Benzyl d-glucopyranoside (Doi et al., 2001);

1-Deoxynojirimycin or Moranoline and its derivatives, Fagomine, Calystegin B1 and B2, (2R,3R,4R)-2-hydroxy methyl-3,4-dihydroxy pyrolidine-N-propionamide, 4-O-a-d-galactopyranosyl-calystegine B2, 3p,6p-dihydroxynortropane (Asano et al., 2001); Moralbanone, Kuwanon S, Mulberroside C, a-acetyl amyrin, Cyclomorusin, Eudraflavone-B hydroperoxide, Oxy dihydromorusin, Lechianone G (Du et al., 2003); Steppogenin-4'-0-/?-D-glucosiade, Mulberroside A, Moracin M (Zhang et al., 2009b) Indicolactone, 2",3"-epoxy indicolactone, Anisolactone (Adebajo et al., 1997); Xanthotoxin, Phellopterin, Isogosferol, Byakangelicol, Gosferol, Isobyakangelicol, Neobyakangelicol, Byakangelicin (Adebajo and Reisch, 2000); Bismurrayafoline, Euchrestine B, Mahanine, Mahaninebicine, O-methyl mahanine, Isomahanine, Bismahane, 8,10-

A sodium chloride extract of the leaves showed an insignificant dose dependent (2-6 mg/ml) inhibition of Cyp 3A4 enzyme activity in human liver microsomes (Pao et al., 2012)

Methanol extract of the leaves as well as isolated constituents of the plant inhibited Cyt P450 enzymes in rat liver microsomes. They also showed dose-dependent inhibitory effects against Cyp 1A2, 2C9, 2D6 and 3A4 enzymes (Pandit et al., 2012)

S/ Plant name no.

Family

Common Local Region of Experimental evidence for Other medicinal uses Plant part Traditional Identified active

name Nigerian use for its use in diabetes (s) used preparation constituent(s)

name(s)* diabetes* management method

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

Musa paradisiaca L., Syn: Musa sapientum L.

Plantain Banana

Ogede (Y), Abrika (I), Ayaba (H)

effects (Arulselvan and Subramanian, 2007)§

al., 2010) At a concentration of 1 mM, mangniferin showed 2-fold increase in glucose utilization in 3T3-L1 cells compared with untreated control (Dinesh Kumar et al., 2013)

250 mg/kg aqueous and methanol extract of the root decreased blood glucose levels in alloxan (Adewoye et al., 2009) and STZ-induced diabetic rats singly and in combination with the leaves of Coccinia indica (Mallick et al., 2007)§; as well as in vivo antioxidant effects. Dose dependent hypoglycaemic effect of the methanol extract of the mature fruits in normal and STZ-induced diabetic mice (Ojewole and Adewunmi, 2003)

Anemia, Hypertension, Ulcers

As a meal, Juice extract

tetrahydro dihydro tetramethyl bis(4-methyl-3-pentenyl)-bipyrano carbazole, Bispyrayafoline (Tachibana et al., 2003); Mahanimbilol, Grinimbine, Girinimbilol, Murrayanine, Isomahanimbine, Koenimbine, Murrayacine, Murrayaquinone-A, Murrayazolidine, Murrayazoline, Mahanimbine (Adebajo et al., 2005); Mahanimbilyl and Grinimbilyl acetate, Bicyclomahanimbiline (Adebajo et al., 2006); PI, PII, PIII (Ningappa and Srinivas, 2008) 14a-methyl cyclo-5a-ergost-24(28)-en-3p-ol (Knapp et al., 1972); a-glucan phosphorylase (Singh and Sanwal, 1975); Cycloeucalenol, 24-methyl cycloartanol, 31-nor cyclo laudenone, Trimethyl-5a-cholesta-dien-3p-ol (Dutta et al., 1983); Sitoindoside I, II, III and IV, Sitosterol gentiobioside, Myo-inosityl-p-d-glucoside, Sitosterol, Campesterol, Cycloartenol, Citrostadienol, Palmitic, Lauric, Myristic, Linoleic, Linolenic and Oleic acids; 24-ethyllophenol (Ghosal, 1985); Irenolone, Emenolone (Luis et al., 1993); Leucocyanidin, Leuco-anthocyanidin (Lewis et al., 1999); Polyphenol oxidase (Yang et al., 2000); Rel-(3S,4aR,10bR)-8-hydroxy-3-(4-hydroxy phenyl)-9-methoxy tetra hydro naphtopyran, 1,2-dihydro-trihydroxy-9-(4-methoxy phenyl) phenalene, Hydroxy anogorufone, 2-(4-hydroxyphenyl) naphthalic anhydride, 1,7-bis(4-hydroxy phenyl) hepta-4(£),6(£)-dien-3-one Clang et al., 2002)

Polyvalent cations present in the plant has been shown to form non-absorbable complexes with quinolone antibiotics, thus affecting their pharmacokinetics if co-administered (Nwafor et al., 2003)

Musaceae

S/ Plant name no.

Family

Common Local Region of Experimental evidence for Other medicinal uses

name Nigerian use for its use in diabetes

name(s)* diabetes* management

Plant part Traditional Identified active (s) used preparation constituent(s) method

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

Ocimum gratissimum L.

Lamiaceae

Scent leaf, African basil, Mint

Nchonwu (I), Efirin (Y), Daidoya (H)

SE, SS, SWa, NW

83 Parinari

curatellifolia Planch, ex Benth.

Chrysobalanaceae Mobola plum Ebere (Y)

84 Parkia biglobosa Leguminosae (Jacq.) G.Don

African locust Iru (Y), Ugba SW beanSoumbala (I),

Dawadawa

200 mg/kg aqueous extract of the leaves improved glucose tolerance in normal and neonatal STZ-induced diabetic rats (Oguanobi et al., 2012) In vitro antioxidant effects (Akinmoladun et al., 2010) (Awah and Verla 2010) 400 mg/kg methanol extract of the leaves decreased blood glucose levels in normal and alloxan-induced diabetic rats (Aguiyi et al., 2000) 150 ml of a (1:1:1) decoction mix of the leaves of Vernonia amygdalina, Ocimum gratissimum and Gongronema latifolium decreased baseline blood glucose levels in normal subjects when preadministered to normal subjects 45 min before an OGTT (Ejike et al., 2013)

Significant blood glucose lowering effects of 250 mg/ kg of the aqueous ethanolic extract of the seeds in alloxan-induced diabetic rats (Ogbonnia et al., 2008b)

Diarrhoea, Malaria, Anti-microbial, Anti-parasitic, Anxiolytic, Analgesic,

Inflammation, Wound healing, Cold symptoms, Hemorrhoids, Insect repellent, Anti-helminthic, Infant colic

Infusion, Food

vegetable

Malaria, Dysentry, Epilepsy, Toothache, STDs, Anti-cancer

Seeds, Root-bark

Diet supplementation with the aqueous and methanolic extract of the seeds (6 g/kg) resulted in > 60% decrease in fasting blood glucose levels in alloxan-induced diabetic rats (Odetola et al., 2006)

Hypertension, Analgesic, Inflammation, Antimicrobial, Snake venom, Fevers, Diarrhoea, Anti-plasmodial, Anti-helminthic

Leaves, Root, Bark

Infusion

Oleanolic acid (Njoku et al., 1997); Xanthomicrol, Cirsimaritin, Rutin, Kaempferol 3-O-rutinoside, Luteolin 5-O-and 7-O-glucosides, Vicenin-2, Isothymusin, Apigenin 7-O-glucoside, Vitexin, Isovitexin, Quercetin 3-O-glucoside (Grayer et al., 2000); Thymol, Eugenol, Luteolin, Cirsiliol, a-Camphene, p-Cymene, 1,8-Cineole, Geraniol, y-Caryophyllene, y-terpinene, y-terpineol, Terpinolene, a-Copaene, Methylchavicol, Anisole, y-Selinene, y-Murolene, Spathulenol (Vieira et al., 2001); Caffeic acid, Cichoric acid, Rosmarinic acid, Caffeoyl derivatives, Nevadensin (Ola et al.,

15-Oxozoapatlin and its 13-methoxy and 13-hydroxy derivatives (Lee et al., 1996); Quercetin-3-O-arabinoside, Quercetin-3-O-glucosyl galactoside, Quercetin-3-O-rhamnoside, Kaempferol-3,4-di-O-glucoside and glycoside, Kaempferol-3-O-glucoside, Quercetin-3-O-rutinoside, Kaempferol-3-O-rutinoside, Myricetin-3-O-rhamnoside, Myricetin-3-O-galactoside (Coradin et al., 1985) Epicatechin, Gallocatechin-O-glucuronide, Catechin-O-gallate-O-glucuronide and other catechin derivatives (Tala et al., 2013); Homogalacturonan, Arabinogalactan, Rhamnogalactans and Xylogalactans (El-Zoubair,

2010); Pyrazine derivatives, Dimethyl disulfide and trisulfide, Limonene, 2-Pentyl furan, Trimethyl oxazole, Indole, Methyl isothiazole, 4,4-Dihydro-2-methyl

Aqueous and ethanol extract of the leaves caused dose-dependent (400-3200 mg/kg) increase in AST and ALT enzyme levels, markers of hepatotoxicity (Ajibade et al., 2012; Onaolapo and Onaolapo, 2012)

S/ Plant name Family Common Local

no. name Nigerian

name(s)

Region of Experimental evidence for Other medicinal uses use for its use in diabetes diabetes* management

Persea americana Lauraceae Mill.

Avocado pear. Alligator pear

Ube bekee or SE, SS Übe oyibo (I), Igba or Apoka or Ipia (Y), Eben

mbakara (Ef), Piya (H)

Administration of 10 mg/kg aqueous extract of the leaves for 8weeks decreased plasma glucose levels of rats fed a high-cholesterol diet (Brai et al., 2007) Hypoglycaemic effect of the aqueous extract of the seeds in normal and alloxan-induced diabetic rats and protective effect on pancreatic islet cells (Edem et al., 2009)

Anemia, Analgesic, Antimicrobial, Hypertension, High cholesterol. Inflammation, Convulsions, Wound healing. Gastric ulcer. Arthritis, Cough, Insecticidal

Phyllanthus amarus

Phyllanthaceae

Pick-a-back, Stone breaker. Carry me seed. Black catnip

Eyin olobe (Y) SW

Apocynaceae

Akuamma plant

Abere (Y), Osu-igwe,

Antioxidant effects of constituents (Londhe et al., 2008) a-amylase inhibitory effects (Ali et al., 2006) Aqueous extract of the seeds and leaves showed a dose-dependent (150-600mg/kg) decrease in fasting blood glucose levels of normal rats (Adeneye et al., 2006) Dose dependent(200-1000 mg/ kg) decrease in blood sugar levels by methanol extract in alloxan-indued diabetic rats (Raphael et al., 2002f No evidence of a hypoglycaemic effect was observed with NIDDM patients taking 25 g of the powdered extract daily for 1 week as a substitute to their oral hypoglycaemic drugs (Moshi et al., 2001 )§

Hypoglycaemic effect of the glycosidic fraction (250mg/

Fevers, Ringworm, Gonorrhoea, Cancer, Anti-viral, Diuretic, Hypertension, Antimicrobial, Diarrhoea, Inflammation, Analgesic, Dropsy, Jaundice, Hepato-protective. Gastric ulcers. Kidney disorders

Hypertension, Anesthesia, Malaria,

Plant part Traditional (s) used preparation method

Identified active constituent(s)

Seeds,

Leaves, Root, Bark, Fruit

Whole plant Decoction

Infusion

Akuammicine isolated from the

thiazole, Trimethyl pyrazole, (Ouoba et al., 2005); Ferulic acid, Isoferuloyl alkanoyl glycerol, Feruloyl lignoceryl glycerol, Lupeol, Epicatechin-3-O-gallate, Epigallocatechin-3-O-gallate, 4-O-methyl-epi-gallocatechin, Epigallocatechin (Tringali et al., 2000)

Ept-dihydrophaseic acid p-D-glucoside, Hydroxy abscisic acid p-D-glucoside, (del Refugio Ramos et al.,

2004); 1,2,4-trihydroxy nonadecane derivatives, 1,2,4-trihydroxy heptadec-16-ene and hep tad ec-16-yne derivatives (Abe et al.,

2005); Persin ((Z,Z)-1-(acetyloxy)-2-hydroxy-12,15-heneicosadien-4-one) (Oelrichs et al., 1995) a- and p-pinene, Sabinene, a- and p-cubebene, p-caryophyllene, Valencene, a-humulene, Germacrene D, cis-y- and 8-cadinene, Caryophyllene oxide, Spathulenol (Ogunbinu et al., 2007)

Geraniin, Amariin, Amarulone, Corilagin, 1,6-digalloylglucopyranose, Quercetin-3-O-glucopyranoside, Gallic acid. Rutin, Gallocatechin, (Foo, 1993); Amariinic acid, l-O-galloyl-2,4-dehydro hexahydroxy diphenoyl glucopyranose elaeocarpusin, Geraniinic acid B, Repandusinic acid A, Phyllanthusiin D (Yeap Foo, 1995); Astragalin, Phyllanthin, Hypo-phyllanthin. Quercetin (Rajeshkumar et al., 2002); Ursolic acid, Oleanolic acid, Dotriacntanyl docosanoate, Triacontanol (Ali et al., 2006)

Pseudo-akuammidine, Akuammiline,

Ethanol extract of the leaves inhibited the activity of Cyp3A4, 3A5 and 3A7 enzyme supersomes (Agbonon et al., 2010)

Aqueous and Ethanol extracts of the aerial parts of the plant inhibited the activity of Cyp3A4, 3A5 and 3A7 enzyme supersomes (Agbonon et al., 2010) Aqueous extract of the whole plant inhibited the activity of Cyp 1A2, 2C9, 2D6 and 3A4 plasmids as well as GST enzyme in rat and human liver cytosols (Appiah-Opong et al., 2008) The inhibitory effect on Cyt P450 enzymes was also observed with the methanol extract and confirmed in vivo (Hari Kumar and Kuttan, 2006)

400 mg/kg of the stembark extract

S/ Plant name no.

Family

Common Local Region of Experimental evidence for Other medicinal uses Plant part Traditional Identified active

name Nigerian use for its use in diabetes (s) used preparation constituent(s)

name(s)* diabetes# management method

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

Picralima nitida (Stapf) T.Durand and H.Durand

Mkpokiri or Otosu (I)

SW, SE, NW, NC, SS

kg) of the methanol extract of Jaundice, Pneumonia,

88 Rauvolfia

vomitoria Afzel.

Apocynaceae

African or

Indian

snakeroot

Asofeyeje (Y), SW, SS Akanta (I), Wadda (H)

Sarcocephalus latifolius (Sm.) E. A.Bruce, Syn: Nauclea latifolia

Rubiaceae

African peach Ubulu inu (I) SE, NW

the leaves in normal and alloxan-induced diabetic rats (Okonta and Aguwa, 2007) 300 mg/kg hydro-ethanol extract of the leaves decreased blood glucose levels in STZ-induced diabetic mice and In vitro antioxidant effects (Teugwa et al., 2013b)§

875 mg of a mix of extracts of the fruit and Rauvolfia vomitoria foliage (RC tea) decreased serum glucose levels in diabetes type 2 model db/db mice and also decreased tissue lipid accumulation (Campbell et al., 2006)

In a pilot clinical study in type-2 diabetic patients, RC tea given daily for 4 months decreased post prandial and fasting plasma glucose levels with greater effects seen in patients with HbA1c levels < 7.3% (Campbell-Tofte et al., 2011)

200 mg/kg aqueous extract of the leaves decreased blood glucose levels in alloxan-induced diabetic rats but not normal rats (Gidado et al., 2005) Anti-hyperglycaemic effect of 200 mg/kg ethanol extract of the leaves preadministered to rats prior to the oral or intraperitoneal administration of 2 g/kg glucose and alpha glucosidase inhibitory effects (Gidado et al., 2012) Hypoglycaemic effect in alloxan-induced diabetic rats and icreased activity of glucose metabolising enzymes (Iwueke and Nwodo, 2008) In vitro antioxidant effects (Awah et al., 2012)

AsthmaTrypanosomiasis

Stem-bark, Seeds, Root, Fruit rind

chloroform extract of the seeds stimulated glucose uptake in 3T3-L1 adipocytes (Shittu et al., 2010)

Mental disorders, Root, Stem,

Sedative, Hypertension, Stem-bark, Snake bites, Skin Leaves

infections, Anti-parasitic, Oral infections, Rheumatism, Aphrodisiac, Purgative

Decoction, Maceration, Powdered root

In silico prediction of isosandwichine and ajmaline as potential DPP-IV inhibitors (Guasch et al., 2012)

Malaria, Anti-parasitic, Root, Bark, Anti-infective, Leaves

Hypertension, Jaundice, Infertility

Melinosime, Akuammine, Picracine, Akuammidine, Picra-phylline, Akuammigine, Akuammicine (Oliver-Bever, 1986); Alstonine, Picranitidine, Picratidine, Picraline, y-akuammigine (Okunji et al., 2005); 10-deoxyakuammine, Burnamine (Shittu et al.,

2010); Coumesan glycoside (Jacques et al.,

Lupeol, Ursolic acid, ß-stigmasterol, Betulinic acid, Sitosterol, Palmitic acid, 3ß-hexadecanoyloxy-lupeol (Fannang et al., 2011); Reserpine, Yohimbine, Ajmaline, Ajmalicine, Alstonine, Serpentine

Apigenin rhamnoside, Naringin (Campbell-Tofte et al., 2011)

Strictosamide, 21-O-methyl strictosamide aglycone, 21-O-ethyl strictosamide aglycone, Angustine, Nauclefine, Angustidine, Angustoline, 19-O-ethyl angustoline, Naucleidinal, 19-epi-naucleidinal, Quinovic acid-3p-O-a-l-rhamno pyranoside, Quinovic acid-3 p-O- p-d-fucopyranoside, Scopoletin, p-Sitosterol (Abreu and Pereira, 2001); Penta-O-benzoyl-a-d-fructo furanose, Penta-O-benzoyl-p-d-fructo furanose, Penta-O-benzoyl-p-d-fructo pyranose, Tetra-O-benzoyl-p-d-fructo pyranose, a- and p-d-pyranose forms of glucose, xylose and arabinose perbenzoates, Glycerol and d-Erythriol

produced hepato-toxic effects characterized by necrotic damage congestion of hepatic blood vessels (Fakeye et al., 2004) Methanol extract of the fruit rind administered daily for 6 weeks elevated AST, ALT and GSH levels in rats (Kouitcheu Mabeku et al., 2008)

Strictosamide binds to human serum albumin, which could in turn affect the bio-availability of highly protein bound drugs if co-administered (Pu et al., 2013)

S/ Plant name Family Common Local Region of Experimental evidence for Other medicinal uses

no. name Nigerian use for its use in diabetes

name(s)* diabetes* management

Plant part Traditional Identified active (s) used preparation constituent(s) method

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

90 Scoparia dulcis L. Plantaginaceae

Sweet broomweed

Roma-fada (H), Aiya (I), Mesen-mesen gogoro (Y)Ndiyang (Ef)

Bibimbelemo (Ij)

NC Administration of the

aqueous extract of the leaves for 45 days produced a dose dependent (150-450 mg/kg) decrease in glucose levels after an OGTT; as well as a hypoglycaemic effect in alloxan-induced diabetic rats. (Pari and Venkateswaran, 2002)§

200 mg/kg aqueous extract of the whole plant also produced a hypoglycaemic effect in STZ-induced diabetic rats, increased plasma insulin levels and protected against diabetes induced oxidative stress (Latha and Pari, 2004; Latha et al., 2004)§ A flavonoid rich fraction of the aqueous extract of the aerial plant increased glucose uptake in cells possibly by increasing expression and translocation of the GLUT4 receptor (Beh et al., 2010)§

Anti-infective, HIV, Abortifacient, Sickle cell, InflammationAnalgesic, Anti-tumour, Bronchitis, Hypertension, Gastric disorders, Sedative

Leaves, Whole plant

Infusion, Decoction

91 Securidaca Polygalaceae

longipedunculata Fresen

Violet tree, Rhodesian violet

Ipeta (Y), Sanya or Uwar

magunguna

(H), Ezeogwu

An extract of the root in buffer solution produced slight inhibition of a-amylase Cough, Inflammation, activity in-vitro (Funke and Anti-pyretic, Analgesic, Melzig, 2006) Dose-dependent (50-800 mg/kg) hypoglycaemic effect of the aqueous root bark extract in normal and STZ-induced diabetic rats (Ojewole, 2008)

Erectile dysfunction, Arthritis, Tumours,

Pesticide, Antimicrobial, Convulsions

Root, Stem-bark Leaves, Seeds

Decoction, Tinctures, Infusions, Powders

perbenzoates, Tetra-O-benzoy-fructo furanoside (Abreu et al., 2001); Betulinic acid (Yinusa et al., 2012)

Scoparol (30-O-methyl luteolin), Scoparoside (glycosyl scopanol), Amellin (Oliver-Bever, 1986); Scoparic acid A, B and C, Scopadulcic acid A and B (Hayashi et al., 1988)

Scopadulin (Hayashi et al., 1990); Scoparinol, Dulcinol, Benzoxazolinone, Betulinic acid, scutellarin, Sorbifolin (Ahmed and Jakupovic, 1990); Scopadulciol, Glutinol, Acacetin, 6-methoxy benzoxazoline (Hayashi et al., 1991); Adrenaline, Noradrenaline (Freire et al., 1996); Iso-dulcinol, Dulcidiol, 4-epi-scopadulcic acid B, Scopanolal, Scopadiol (Ahsan et al., 2003); ß-sitosterol-ß-d-gluc; side, Friedelan-3-one, Hispidulin (4,5,7-trihydroxy-6-methoxy flavone) (Osei-Safo et al.,

2009); Luteolin, P-coumarin, Apigenin, Quercetin (Beh et al.,

2010); Dulcinodal, Dulcinodiol, Scopadiol decanoate, (Ahsan et al., 2012)

Benzyl salicylate, Methyl paraben, Methyl vanillate, Methyl 2,6-dihydroxy benzoate, Lumiflavin (Costa et al., 1992); Methyl salicylate (Methyl-2-hydroxy benzoate), Methyl-2-hydroxy-6-methoxybenzoate, Benzyl-2-hydroxy-6-methoxy benzoate (Jayasekara et al., 2002); Securidaca xanthone (1,5-dihydroxy-2,3,6,7,8-penta

Nephrotoxic and hepatotoxic effects in rats administered 2 mg/ kg aqueous extract intra-peritoneally for 14 days (Dapar et al., 2007) Elevated levels of serum alkaline and acid phosphatase levels as well as decreased levels of antioxidant enzymes such as GSH and SOD in the liver and kidney (Ajiboye et al., 2010)

SW, NE, SE

S/ Plant name no.

Family

Common name

Nigerian

name(s)*

Region of use for

Experimental evidence for its use in diabetes

Other medicinal uses

Plant part (s) used

diabetes# management

Traditional preparation method

Identified active constituent(s)

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

92 Secamone afzelii Apocynaceae (Roem. and Schult.) K.Schum.

Secamone, Ringworm plant

Ailu (Y)

In vitro antioxidant effects (Mensah et al., 2004)

Hemorrhoids, Anti- Leaves, Pods, microbial, Purgative, Stems, Dysentery, Colic, Wound Whole plant healing, Aphrodisiac, Measles, STDs

93 Senna alata (L.) Leguminosae Roxb., Syn. Cassia alata (L.)

Ringworm plant, Candle bush

Asunwon oyibo (Y)

De-fatted methanol extract of Purgative, Ringworm, the leaves gave a slight dose- Eczema, Pruritus, Snake dependent (100-400 mg/kg) decrease in blood glucose levels in STZ-induced diabetic rats but not in normal rats (Palanichamy et al., 1988)§

bites, Analgesic, Constipation, Hypertension, Anti-infective, Inflammation

Leaves, Decoction,

Flower, Root, Juice extract Stem, Bark

Alpha glucosidase inhibitory effects of the flavonoids kaempferol and its 3-O-gentiobioside isolated from the methanol extract of the leaves (Varghese et al., 2013)

methoxyxanthone), 2-hydroxy-1,7-dimethoxy xanthone, 1,6-dihydroxy xanthone, 6-methoxy salicylic acid and its methyl ester, ß-d-(6-sinapoyl)-

glucopyranoside, ß-d-(3-sinapoyl)-fructofuranosyl-a-d-(6-sinapoyl)-gluco pyranoside (Meli Lannang et al., 2006); Methyl salicylate, a- and ß-pinene, 1,8-cineole, a-cadinol, p-cymene, ethyl salicylate (Adebayo et al., 2007); 1,4-dihydroxy-7-methoxy xanthone, Senegenic acid, Senegenin, Elymoclavine, Dehydroelymoclavine, 4,5-di-O-caffeic acid, 3,4,5-tri-O-caffeoyl quinic acid, Sinapic acid (Meyer et al.,

2008); Securidacaside A and B (Stevenson et al.,

2009); Gallic acid, Chlorogenic acid, Caffeic acid, Epicatechin, P-coumaric acid, Rutin, Quercetin, Cinnamic acid, Apigenin (Muanda et al.,

Alpha tocopherol (Mensah et al., 2004); Caffeic, Gentysic, Ferulic, Chlorogenic, a-resorcylic, Syryngic, Protocatechuic, Homoprotocatechuic, p-hydroxyphenylacetic, p-hydroxybenzoic, Synapic, Vanillic, Coumaric,

O-hydroxyphenylacetic and Salicylic acids (Nowak and Kawka, 1998) Linalool, a-terpineol, Borneol, Pentadecanal, ß-sitosterol, Stigmasterol, Daucosterol, Alarone, 2,6-dimethoxy bezoquinone, Dalbergin, 2,3,7 tri-O-methyl ellagic acid, Torachrysone, Alatonal, p-hydroxybenzoic acid, Adenine, Cassiaxanthone, Sennosides, Kaempferol, its 3-O-gentiobioside and

0.5 mg/ml aqueous extract of the leaves showed > 70% inhibition of GST enzymes in human and rat liver cytosols and recombinant GSTs; as well as inhibited Cyp 1A2, 2D6 and 3A4 supersomes but not 2C9 (Appiah-Opong et al., 2008).

S/ Plant name Family Common Local Region of Experimental evidence for Other medicinal uses Plant part Traditional Identified active Other relevant Interaction/toxicity

no. name Nigerian use for its use in diabetes (s) used preparation constituent(s) phytoconstituents studies

name(s)* diabetes* management method identified in the plant

occidentalis (L.) Synonym, (Cassia octidanaaiis)

Leguminosae

Coffee senna

Sanga-sanga or Rai dore

(H), Rere (Y), Akede-agbara

Senna singueana (Delile) Lock, Syn: Cassia goratensis

Leguminosae

Golden shower

Runfu (H)

In vitro antioxidant effects (Akinmoladun et al., 2010) Incorporation of the dry leaves 6.25% by weight into the diet of STZ-induced diabetic mice did not produce any hypoglycaemic effect after 9 days of treatment (Swanston-Flatt et al., 1989)§ Hypoglycaemic effect of 200 mg/kg aqueous extract of the leaves was observed in both normal and alloxan-induced diabetic rats, as well as partial restoration of the islet cells of the diabetic rats (Verma et al., 2010)§

Inflammation, Antipyretic, Analgesic, Purgative, Malaria, Anti-tumour, Anti-microbial, Hepato-protective, Insecticidal, GIT ailments

Leaves, Pods, Seeds

200 mg/kg aqueous extract of Inflammation,

the leaves decreased blood Analgesic, Malaria,

glucose levels by 53% in Gonorrhea, Heartburn,

alloxan-induced diabetic rats Convulsions,

(Etuk and Mohammed, 2009) Constipation, Wound

Root, Leaves Decoction

3-O-ß-d-glucopyranoside, Luteolin, Chrysoeriol-7-O-and Rhamnetin-3-O- (2"-O-ß-d-manno pyranosyl)-ß-d-allopyranoside, Aloe-emodin and its 8-O-ß-glucoside, Chrysophanol, Rhein, Physcion and its 1-O-glucoside, Alquinone, Isochrysophanol, Adenine, 1,3,8-trihydroxy-2-methyl anthraquinones (Hennebelle et al., 2009); Naringin, Apigenin (Okpuzor et al., 2009)

Achrosin, Aloe-emodin, Emodin, Apigenin, Chryso-obtusin, Aurantiobtusin, Campesterol, Cassiolin, Chrysarobin, Chrysophanic acid, Chrysophanol, Chrysoeriol, Funiculosin, Galactopyranosyl, Oleic, Linoleic, Linolenic and Lignoceric acids; Physcion, Islandicine,

Helminthosporine, Rhein, Kaempferol, Matteucinol, Obtusifolin, Quercetin, Rhamnosides, Rubrofusarin, Xanthorine, 3,2-dihydroxy-7,8,4'-tri methoxyflavon-5-O-ß-D-allopyranoside, 1,8-dihydroxy

anthraquinones, Pinseline, Occidentalols, Questin, Germichrysone, Methylgermitorosone, Singueanol, Vitexin, 7-methyltorosachrysone, N-methyl morpholine, 1,1-bi-4,4',5,5'-tetrahydroxy-2,2'-dimethyl anthraquinones, Metterucinol-7-O-a- l-rhamnoside,

Occidentalins, ß-sitosterol (Yadav et al., 2010) Torosachrysone, 7-methyl physcion, Germichrysone, Cassiamin A, Singueanol-I and II, Chrysophanol, Cassiamin A, Lupeol,

Ingestion of the seeds (beans) has been shown to cause acute hepato-myoencephalopathy in children and is also known to be toxic to animals (Vashishtha et al., 2009) Possible risk of renal impairment with chronic administration of anthraquinones glycosides from senna (Vanderperren et al., 2005)

NW, SW

Decoction

S/ Plant name no.

Family

Common Local Region of Experimental evidence for Other medicinal uses

name Nigerian use for its use in diabetes

name(s)* diabetes# management

Plant part Traditional Identified active (s) used preparation constituent(s) method

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

96 Solanum

aethiopicum L., misnamed Solanum incanum L.

Solanaceae

Garden egg

Osun (Y), Anara (I)

97 Solanum

melongena L.

Solanaceae

98 Sorghum bicolor Poaceae (L.) Moench,

(Sorghum caudatum)

African

Eggplant,

Aubergine

Sorghum

Igbagba or SW, SS Igba ijesu (Y), Mafowo-bomonu (I)

Okababa or SW Poroporo (Y), Sorgum (I), Jero (H)

ulcers, Snake bites, Skin cancer

The root and fruit extracts Convulsions, Colic, (200mg/kg) decreased blood Flatulence, Syphillis, glucose levels in both normal Hypertension, Anti-

Leaves, Fruit, Roots

Infusion, Juice extract

and STZ-induced diabetic rats. In addition, the fruit extract decreased weekly food consumption (Musabayane et al., 2006) Administration of 50 g of the leaves to normal volunteers prior to an oral glucose tolerance test produced a decrease in blood glucose levels (Okolie et al., 2009)

fungal, STDs, Hepatitis

in vivo antioxidant effects Cholesterol, Anti-viral, Leaves, Fruit Soup

(Sudheesh et al., 1999) Low a-amylase but high a-glucosidase inhibitory effects and in vitro antioxidant effects (Nwanna et al., 2013)

In vitro protein glycation inhibitory effects (Farrar et al., 2008)§ Alpha amylase and a-glucosidase inhibitors (Kim et al., 2011)§ 250 mg/kg sorghum extract decreased serum glucose and increased serum insulin levels in diabetic but not normal rats (Chung et al., 2011)§ In vitro antioxidant effects (Afify et al., 2012) Improved insulin sensitivity due to increased expression of PPARy receptors in rats fed a high fat diet followed by 0.5% and 1% sorghum meal (Park et al., 2012)§

Sedative, Analgesic, Fevers, Rheumatism, Skin diseases, Digestive tonic

condiment, Juice extract

Malaria, Fevers, Anemia, Leaves, Shaft Anti-microbial

Maceration, Infusion

Campesterol, p-sitosterol, Stigmasterol, Leuco-pelargonidin (Gebrelibanos, 2012) Diosgenin, Yamogenin (Gbile and Adesina, 1988) Solasodine, Solamargine, Solasonine, Ursolic acid, Carpesterol, p-sitosterol, Incanumine, Stigmasterol-p-d-glucoside, Khasianine (Lin et al., 1990) Chlorogenic acid, Trans-p-coumaric acid, Astragalin, Kaempferol, Quercetin, Isoquercitrin, Adenosine, Caffeic and Protocatechuic acids, Luteolin-7-O-p-d-glucopyranoside, Benzyl O-p-d-xylopyranosyl-p-d-glucopyranoside, Kaempferol glucosides, Isorhamnetin glucosides, Quercetin glucosides (Lin et al., 2000b) Solavetivone, Lubiminoic acid, Lubimin, Lubiminol, Aethione (Nagaoka et al., 2001)

Aethiosides A-C (Tagawa et al., 2003)

Polyphenol oxidase (Fujita and Tono, 1988); Solanidine (Keeler et al., 1990); Delphinidin (Nagase et al., 1998); a-solasoline, a-solamargine (Sanchez-Mata et al., 2010)

Procyanidin B1, Sinapic acid, Epicatechin gallate, Peonidin, Prodelphinidin, Luteolinidin, Fisetinidin, Pelagornidin, Cyanidin and Apigeninidin derivatives, Gallic, Caffeic, Gentisic, Chlorogenic, Syringic, p-hydroxy benzoic, Ferulic acids, Luteoforol, Apiforol, Luteolin, Naringenin, Eriodictoyl, Taxifolin, Sitosterol, Stigmasterol, Campesterol, Cholesterol (Awika and Rooney, 2004); Benzoic, p- o- and m-coumaric, p-resorcylic, Protocatechuic, Veratric, Vanillic, Homogentisic and

Possible inhibitory effect of steroidal alkaloids like solanidine on drug transport due to interaction with multi-drug resistant protein such as P-gp (Lavie et al., 2001)

SE, SW

S/ Plant name Family Common Local

no. name Nigerian

name(s)

Region of Experimental evidence for Other medicinal uses use for its use in diabetes diabetes* management

99 Sphenocentrum Menispermaceae jollyanum Pierre

Akerejupon (Y)

100 Spondias mombin L.

Anacardiaceae Hog plum

Iyeye or Olosan (Y), Tsada (H), Ngulungwu or Isikara (I)

In vitro (Nia et al., 2004) and in vivo antioxidant effects (Olorunnisola and Afolayan, 2013) Ethanol extract of the root decreased blood glucose levels in normal high glucose fed and alloxan-induced diabetic rabbits (Mbaka et al., 2009) Pre-administration of the aqueous extract of the roots for 7 days before induction of diabetes with alloxan had a protective effect against elevated sugar level and p-cell degeneration (Mbaka and Adeyemi, 2011) Hypoglycaemic effect of the methanol extract (lg/kg) of the leaves and its chloroform fraction was observed in glucose loaded (2 g/kg) and alloxan-induced diabetic rats (Fred-Jaiyesimi et al., 2009b) In vitro antioxidant effects (Akinmoladun et al., 2010)

Hypertension, Cough, Wounds, Fevers, Jaundice, Malaria, Emetic, Purgative, Aphrodisiac, Swollen breasts. Inflammation, Depression, Sickle cell, Anti-microbial, Analgesic, Anti-cancer, Anti-helminthic, Aphrodisiac, Constipation

Infertility, Child birth, Abortifacient, Inflammation, GIT disorders. Psychosis, Laxative, Anti-infective, Diuretic, Lactation, Anxiety

101 Stachytarpheta angustifolia (Mill.) Vahl

Verbenaceae

Ncha aji (I), SE, SW, Wutsiya bera NW (H), Iru alangba (Y)

750 mg/kg aqueous extract decreased blood glucose levels in normal and alloxan-induced diabetic rats (Isah et al., 2007) 250 mg/kg of a herbal mixture (Okudiabet®) made up of bark of Alstonia congensis, aerial parts of Stachytarpheta angustifolia and fruits of Xylopia aethiopica administered for 30 days produced a hypoglycaemic effect in

Immune modulatory, Anti-microbial, Diarrhoea, Abortifacient, Skin ulcers. Rheumatism, Cataract, Ear sores. Gonorrhea

Plant part Traditional Identified active (s) used preparation constituent(s) method

Root, Seed, Stem-bark, Fruit, Leaves

t-cinnamic acids. Vanillin, Pyrogallol, Resveratrol, Hesperidin, Rutin, Myricetin, Hesperetin, Formononetin, Quercetin, Biochanin A, Naringin (Chung et al., 2011); p-carotene, a-tocopherol, Apigenin, Kaempferol, Hypersoid, Catechin, Christin (Afify et al., 2012) Palmatine, Columbamine (Raji et al., 2006); Columbin, Isocolumbin, Fibleucine (Moody et al., 2006); Isocaryophyllene, a-Pinene, a-Eudesmol, 1,8-cineole (Aboaba and Ekundayo, 2010)

Extract of the leaves decreased the elevated levels of liver AST, ALT and ASP enzymes as well as increased GSH levels in rats infected with Plasmodium (Olorunnisola and Afolayan, 2013)

Leaves, Fruit Decoction

Maceration

Geraniin, Galloyl geranin, Chlorogenic acid, 2-0-caffeoylhydroxycitric acid (Corthout et al., 1992); Pelandjuaic acid, 6-(8'Z, ll'Z-heptadecadienyl)-salicylic acid, 6-(10'Z-heptadecenyl)-salicylic acid, 6-(12'Z-nona decenyl)-salicylic acid, 6-(15'Z-heneicosenyl)-salicylic acid (Corthout et al., 1994); Anacardic acid derivative (Coates et al, 1994); 3p-olean-12-en-3-yl (9Z)-hexadec-9-enoate, a-sitosterol (Fred-Jaiyesimi et al., 2009a) Ipolamide (Poser et al., 1997); Stachytarphine, p-(3',4' )-dihydroxyphenyl)-ethyl-O-a-L-

rhamnopyranosyl-( 1,3 )-p-D-(4-0-caffeoyl) glucopyranoside (Mohammed et al., 2012a, 2012b)

S/ Plant name no.

Family

Common Local Region of Experimental evidence for Other medicinal uses

name Nigerian use for its use in diabetes

name(s)* diabetes# management

Plant part Traditional Identified active (s) used preparation constituent(s) method

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

102 Strophanthus hispidus DC.

Apocynaceae

103 Syzygium guineense (Willd.) DC.

Myrtaceae

Poison arrow vine, Brown/ hairy

strophathus

Snake bean treeWater berryWater pear

Stem, Root, Leaves

alloxan-induced diabetic rats (Ogbonnia et al., 2010) In-vitro antioxidant effects (Awah et al., 2010) Sagere (Y), SW, SE, Administration of 2 mg and Aguru-ala or NW, NC 5 mg of various extracts of Osisi nke the plant produced a dose

aguru (I), dependent decrease in blood

Kwan-kwani glucose levels in normal

(H) rabbits (Ojiako and Igwe,

Malmo (H), SW, NW The hypoglycaemic effect of Hypertension Cardio- Seed, Stem, Decoction

Cardio-stimulant, Snake bites, Insecticidal, STDs, Inflammation, Constipation

Adere (Y), Ori (I), Mho (Ti), Asurahi (F)

104 Tamarindus indica L.

Leguminosae

Tamarind, Indian date

Tsamiya (H), Icheku oyibo (I), Ajagbon (Y), Tamsugu (Nu)

the butanol fraction of the aqueous extract of the leaves decreased blood glucose levels in normal and alloxan-induced diabetic rats (Worku, 2009)§

protective, Antimicrobial, Diarrhoea, Inflammation, Immune-modulatory, venom, Anti-cancer

Leaves

In vitro (Siddhuraju, 2007) and in vivo antioxidant effects (Bhutkar and Bhise, 2011)

800 mg/kg of the aqueous extract of the seed administered for 14 days decreased blood glucose levels and increased serum insulin levels in STZ-induced diabetic rats, resulting in increased glucose metabolism (Maiti et al., 2005)§

An extract of the leaves in buffer solution produced 90% inhibition of a-amylase activity in-vitro (Funke and Melzig, 2006)

Nutritional, Inflammation, Antimicrobial, Anti-parasitic, Fevers, Laxative, Alcohol detox, Anti-cancer, Anti-obesity, Hepato-protective

Stem-bark, Decoction, Fruits, Seed Maceration, Powder

Strophanthidin, Cymarin, Cymarol, Strophanthidol, Periplogenin, Emicymarin, (Heftmann et al., 1954); 9-hydroxyoctadec-12-enoic acid, Triglycerides, 2-mono glyceride (Gunstone and Qureshi, 1968)

Arjunolic acid, Ursolic acid, Asciatic acid, Terminolic acid, Betulinic acid, Oleanolic acid, 2-hydroxy oleanolic acid, 2-hydroxy ursolic acid, 6-hydroxy asiatic acid, Arjunolic acid 28-ß-gluco pyranosyl ester, Asiatic acid 28-ß-glucopyranosyl ester (Djoukeng et al., 2005)

Caryophyllene oxide, Benzyl benzoate, a-terpineol, Linalool, a and ß caryophyllene, a-cadinol, (Noudogbessi et al., 2008) Arabinogalactan-type pectic polysaccharides (Ghildyal et al., 2010) Methyl 3,4-dihydroxy benzoate, Epicatechin, 3,4-dihydroxy phenylacetate, 2-hydroxy-3',4'-dihydroxy acetophenone (Tsuda et al., 1994); Methyl salicylate, Eugenol, Vanillin; Lauric, Benzoic, Acetic, Myristic, Oleic, Linoleic, Linolenic and Palmitoleic acids (Wong et al., 1998); Apigenin, Eriodictyol, Narigenin, Procyanidin B2, Taxifolin, Procyanidin trimer, tetramer, pentamer and hexamer; Luteolin (Sudjaroen et al., 2005); Apigenin, Vitexin, ß-sitosterol, (+ )-Pinitol, 21-oxobehenic and Eicosanoic acid, Octocasoanyl ferulate, n-hexacosane (Jain et al., 2007); Lupeol,

100 and 200 mg/kg ethanol extract of the bark administered for 45 days increased previously depleted GSH levels in alloxan-induced diabetic rats (Bhutkar and Bhise, 2011) Bioavailability of aspirin increased in healthy adults co-administered a porridge meal containing the fruit extract of tamarind (Mustapha et al., 1996)

Decoction

SI Plant name no.

Family

Common Local Region of Experimental evidence for Other medicinal uses

name Nigerian use for its use in diabetes

name(s) diabetes* management

105 Tapinanthus bangwensis (Engl, and K. Krause) Danser, Syn Loranthus bangwensis Engl, and ICKrause, often misnamed Loranthus micranthus Hoolcf.

Loranthaceae

African mistletoe

An infusion of the leaves parasitic on citrus limon and Psidium guajava at a dose of 1.32mg//kg decreased blood glucose levels in normal and STZ-induced diabetic rats, but not that parasitic on Jatropha curcas (Obatomi et al., 1994) The blood glucose lowering effects of the methanol extract of the leaves was observed in alloxan-induced diabetic rats; an effect dependent on host plant and time of collection (Osadebe et al., 2004, 2010) in vitro antioxidant effects (Ogechukwu et al., 2012)

Anti-hypertensive, Antimicrobial, Immunomodulatory, Anti-cancer

106 Telfairia Cucurbitaceae Fluted Ugwu/Ugu (I), 250 mg/kg ethanol extract of occidentalis pumpkin Iroko or the leaves decreased blood Hoolcf. Apiroko (Y), glucose levels in normal and

Ubong (Ef), alloxan-induced diabetic

Umee rats; while 100 mg/kg

(Urhobo), ethanol extract of the seed

Umeke (Bi) decreased glucose levels in

alloxan-induced but not in normal or glucose-loaded rats (Eseyin et al., 2005, 2007a)

Alpha glucosidase and oc-amylase inhibitory effects of the hydro-ethanolic extract of the leaves as well as Antioxidant effects (Oboh et al., 2012b)

50 mg/kg globulin proteins extracted from the seeds decreased blood glucose levels when pre-administered to normal high glucose fed rats (Teugwa et al., 2013a)§

107 Terminalia Combretaceae Tropical Belebo SE, SS, SW Methanol extract of the catappa L almond, orlgifuruntu leaves decreased blood

Umbrella tree (Y), Ibulu (I) glucose levels in alloxan

induced diabetic mice by 59%

(Ezeigbo and Asuzu, 2010)

Convulsion, GIT disorders. Anemia, Hypertension, Anti-tumour, Immune modulating. Antiparasitic, Analgesia, Inflammation, High cholesterol. Anxiety

Aphrodisiac, Hepato-protective. Analgesic, Inflammation, Antimicrobial, Insomnia, Anti-cancer, Anti-viral

Plant part Traditional (s) used preparation method

Identified active constituent(s)

Infusion, Decoction

Leaves, Fruit, Seeds

Lupanone (Imam et al., 2007)

Catechin-3-O-rhamnoside, Catechin-7-O-rhamnoside, 4-methoxy-catechin-7-0-rhamnoside (Ogechukwu et al., 2012); 7p, 15a-dihydroxyl-lup-20(29)-ene-3p-palmitate, 7p, 15a-dihydroxyl-lup-20(29)-ene-3p-stearate, 7p, 15a-dihydroxyl-lup-20(29)-ene-3p-deca decanoate (Ogechukwu et al., 2011); Stigmast-7,20(21 )diene-3p-hdroxy-6-one, 3p-hdroxy-stigmast-23-ene, 7p, 15a-dihydroxyl-lup-20 (29)-ene-3p eicosanoate (Omeje et al., 2011); Linamarin gallate, Walsuraside, Catechin, Rutin, Epicatechin, Gallate derivatives of epicatechin, Quercet in- 3-O-/?- d- gluco pyranoside, Peltatoside (Agbo et al., 2013) Globulins, Carotenoids, y-amino butyric acid, 13-hydroxy-9Z, 11E-octadecatrienoic acid, a-and p-moschins. Pectin, MAP 2, MAP 4, MAP 11, MAP 28 (Caili et al., 2006)

Co-administration of the leaves prior to or alongside chloroquine tablets altered its pharnacokinetics (Eseyin et al., 2007b)

Leaves, Stem bark. Fruit, Seeds

Terminolic acid, p-sitosterol, p-sitosteryl palmitate (Idemudia, 1970); Terflavin A and B, Tercatain, Tergallagin,

Potential hepatic toxicity with high doses due to Punicalagin and punicalin (Lin et al., 2001)

S/ Plant name no.

Family

Common Local Region of Experimental evidence for Other medicinal uses

name Nigerian use for its use in diabetes

name(s)* diabetes* management

Plant part Traditional Identified active (s) used preparation constituent(s) method

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

Varying doses (40-78 mg/kg) of the aqueous, methanol and petroleum ether extracts of the fruits administered for 3 weeks also produced a hypoglycaemic effect in alloxan induced diabetic rats as well as regenerated the pancreas (Nagappa et al., 2003)§

TтeerapieeLaa telraptena (Schum. and Thonn.) Taub.

Leguminosae

Aridan (Y), Kpokrikpo or Mkpuruma oshosho (I)

SW, SE, SS, NC

1Q9 Treculia africana Decne, ex Trécu

Breadfruit

Ukwa (I), Afon (Y)

11Q Urena lobata L. Malvaceae

Caesar's weed Ilasa-omode SW or Ilasa-agborin (Y), Odoazezo (I), Rama rama (H)

800 mg/kg aqueous extract of the fruit produced a hypoglycaemic effect in normal and STZ-induced diabetic rats (Ojewole and Adewunmi, 2004) Aqueous extract of the fruit showed good antioxidant effects, moderate lipase inhibitory effects and little or no a-amylase inhibitory effects (Etoundi et al., 2010)§ Fractions of the hydro aceton extract of the bark decreased blood glucose levels at a dose of 10 mg/kg in alloxan-induced diabetic rats but not normal rats (Oyelola et al., 2007) Hypoglycemic effect of 500 mg/kg aqueous extract of the leaves in normal fasted glucose-loaded and STZ-induced diabetic rats (Ogbonnia et al., 2008c)

Fasting blood glucose lowering effects of 200 mg/ kg of the aqueous root extracts in normal rabbits (Omonkhua and Onoagbe, 2011) in vivo antioxidant effects (Omonkhua and Onoagbe, 2012)

Hemorrhoids, Insect repellent, Convulsions, Asthma, Cough, Insomnia, Poison antidote, Gonorrhoea, Rheumatism, Infertility, Bilharzia, Sickle cell, Lactation

Anti-microbial, Anti-helminth, Laxative, Skin diseases, Dental allergies, Depression

Pod, Bark

Decoction, Infusion

Anti-microbial, Colic, Skin diseases, Dysentry, Expectorant, Emollient, Malaria, Rheumatism, Wound healing, Analgesic, Inflammation

Root, Flower

Punicalagin, Punicalin, Chebulagic acid, Geranin, Granatin B, Corilagin, 1-desgalloyl eugenin (Tanaka et al., 1986); Isovitexin, Rutin, Vitexin, Isoorientin, Apigenin galloyl glucopyranosides (Lin et al., 2000a); Cyanidin-3-glucoside, Gallic acid, Ellagic acid, Brevifolin carboxylic acid, Euginic acid (Nagappa et al., 2003); Ursolic acid, Asiatic acid (Gao et al., 2004)

Aridanin, Glycosides of Olean-12-ene-28-oic acid, Echinocystic acid-3-O-sodium sulphate (Ngassapa et al., 1993); Butanoic acid derivatives, Myrcene, p-Cymene, 1,8-Cineol, Limonene, 2,4-dihydro-3,4-dimethylfuran, y-Terpinene, a-Terpinolene (Ngassoum et al., 2001) a- and p-Pinene, Camphene, Myrcene, Phellandrene, a- and y-Terpinene, p-Cymene, Limonene, Linalool oxide, Thujanol, Geranylacetone, p-Caryophyllene, Terpineol (Aboaba et al., 2007) ; Phyllocoumarin, 6,9-dihydroxy megastigmane-

3-one, Catechin (Kuete et al., 2008); 3-Prenyl-2/,4,4/-trihydroxy chalcone,

4-hydroxy benzoic acid, Bergapten, Morin, Epiphyllocoumarin, p-carotene, Riboflavin (Mueno et al., 2008) Tiliroside, Dihydro kaempferol 40-O-p-gluco pyranoside, Kaempferol and Quercetin 3-O-p-glucoside and 3-O-p-rutinoside, Luteolin-40-O-p-gluco pyranoside, Kaempferol-7-O-glucoside, Kaempferol, Quercetin (Matlawska and Sikorska, 1999); p-Sitosterol, stigmasterol,

Ethanol extract of the leaves given to rabbits for 10 days (50-150 mg/ kg) increased serum ALT levels (Odesanmi et al., 2009)

S/ Plant name Family Common Local

no. name Nigerian

name(s)

Region of Experimental evidence for Other medicinal uses use for its use in diabetes diabetes* management

111 Vernonia Compositae Bitter leaf Ewuro (Y), NW, NC, 80 mg/kg aqueous extract of amygdalina Shuwaka (H), SE, SS, SW the leaves produced a dose Delile Olugbu (I), dependent decrease in blood

Etidot (lb) glucose levels in normal and

alloxan-induced diabetic rabbits (Akah and Okafor, 1992); Antioxidant effects (Igile et al., 1994; Fasakin et al., 2011); Chronic intake of 400 mg/kg ethanolic extract of the fresh leaves significantly decreased fasting blood glucose levels, increased serum and pancreatic insulin levels, increased the activity of liver antioxidant enzymes as well as increased the expression and distribution of Glut 4 receptors in STZ-induced diabetic rats (Ong et al., 2011 )§; 150 ml of a (1:1:1) decoction mix of the leaves of Vernonia amygdalina, Ocimum gratissimum and Gongronema latifolium decreased baseline blood glucose levels in normal subjects when preadministered to normal subjects 45 min before an OGTT (Ejike et al., 2013)

112 Ximenia Olacaceae Sour plum, Tsaada (H), NW Graded doses (200,400 and americana L. Hog plum, Igo (Y) 600 mg/kg) of the extract

Yellow plum, produced significant blood

Sea lemon, glucose reduction to control

False sandal levels 6 h after

wood administration in alloxan-

induced hyperglycaemic rats (Siddaiah et al., 2011 )§

Hemorrhoids, Measles, Ringworm, Analgesic, Malaria, Pneumonia, Anti-microbial, Anticancer, Anti-feedant

Anti-parasitic, Antimicrobial, Inflammation, Pesticidal, Analgesic, Anti-pyretic, Anticancer, Hepato-protective. Ulcers, Skin infections. Purgative

Plant part Traditional (s) used preparation method

Identified active constituent(s)

Leaves, Roots Decoction, Juice extract

Imperatorin, Mangiferin, Quercetin, Palmitic and Linoleic acid triglycerides (Morelli et al., 2006); Syringic acid, Gluco-syringic acid. Salicylic acid, Protocatechuic acid and its methyl ester, CafFeic acid, Hexatriacontanoic acid, Pentadecanoic acid, Hexadecanoic acid, Maleic acid, Heptadecanoic acid, Diisobutyl phthalate (Lu et al., 2009); Ceplignan-4-O-p-D-glucoside, Urenoside A (Jia et al., 2010) Vernodalin, Vernolide, Vernomygdin, Vernolepin (Kupchan et al., 1969); Vernodalol, 11,13-dihydrovernodalin (Ganjian et al., 1983); Vernonioside Al, A2, A3, A4 and its aglycone, Bl, B2 and B3 (Jisaka et al., 1993); Luteolin, Luteolin 7-0-glucoside and 7-0-glucuronide (Igile et al., 1994); Vernonioside D and E (Igile et al., 1995); Luteolin 7-0- and 4'-0-rutinoside, Caffeoyl quinic acid, Chlorogenic acid. Rutin, 1,5-Dicaffeoyl quinic acid, Apigenin glucuronide, Luteolin (Ola et al., 2009)

Aqueous extract of the leaves inhibited P-gp efflux activity in Caco-2 cells (Oga et al., 2012)

Fruits, Stem,

Stem-bark,

Leaves

Mandelonitrile lyase (Kuroki and Conn, 1989); Xymenynic acid, Tariric acid (Fatope et al., 2000); Ximonicaine, Stigmastane (de Araujo et al., (2009)); Benzaldehyde, Hydroxy benzyl cyanide, Geraniol, Isophorone, Linalool, Caryophyllene oxide.

Aqueous extract of the stem bark and the root increased levels of hepatic enzymes ALT, AST and ALK-P significantly (James et al., 2008; Wurochekke et al., 2008); Inhibited P-gp mediated Rh-123

S/ Plant name no.

Family

Common Local Region of Experimental evidence for Other medicinal uses

name Nigerian use for its use in diabetes

name(s)* diabetes# management

Plant part Traditional Identified active (s) used preparation constituent(s) method

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

113 Xylopia

aethiopiea

(Dunal) A.Rich.

Ethiopian or Negro pepper, Long nose pepper

Erunje or Eeru (Y), Uda (I), Kimba (H)

Administration of 1 g/kg of a 1:1 mixture of a hydroethanolic extract of Alstonia congensis bark and Xylopia aethiopica fruits decreased blood glucose levels in normal mice (Ogbonnia et al., 2008a); 250 mg/kg of a herbal mixture Okudiabets) made up of bark of Alstonia congensis, aerial parts of Stachytarpheta angustifolia and fruits of Xylopia aethiopica administered for 30 days had a marked hypoglycaemic effect in alloxan-induced diabetic rats (Ogbonnia et al., 2010); Potent inhibitory effects against pancreatic lipase, a-amylase and a-glucosidase enzymes; Antioxidant effects (Etoundi et al., 2010; Adefegha and Oboh, 2012)

Purgative, Neuralgia, Amenorrhea, Anti-convulsant, Bronchitis, Stomach ache, Cough, Hemorrhoids, Asthma, Insect antifeedant, Antimicrobial, Diuretic

Fruit, Seeds

Methyl benzoate (Mevy et al., 2006); Hydrocyanic, Linolenic, Arachidonic, Erucic, Eicosatrienoic and Nervonic acids; Methyl-14,14-dimethyl-18-hydroxy hepta triacont-27,35-dienoate, Dimethyl-5-methyl-28,29-dihydroxy dotriacont-3,14,26-triendioate (Saeed and Bashier, 2010); Riproximin (Bayer et al., 2012); Sambunigrin, Gallic acid, Quercetin, p-glucogalline, 1,6-digalloyl-p-glucopyranose, Quercetin-3- O- (6-galloyl)- p-gluco pyranoside, Quercitrin, Avicularin, Quercetin-3-O-p-xylo pyranoside, Kaempferol-3-O-(600-galloyl)-p-glucopyranoside (Le et al., 2012)

efflux in Caco-2 cells (Ezuruike et al., 2012)

Xylopic acid (15ß-acetoxy kaur-16-en-19-oic acid) (Ekong and Ogan, 1968); Kauran-16a-ol, Kauran-16a, 19-diol, Kaur-16-en-19-oic acid (Leboeuf et al., 1980); a- and ß-pinene, 1,8-cineole, Cuminic aldehyde, a-terpineol, ß-caryophyllene, Limonene, Linalool, Ocimene, a- and ß-Phellandrene, Sabinene, a-murolene (Lamaty et al., 1987); Kaur-15-en-17-al-19-oic acid, 15-oxo-trachyloban-19-oic acid, 15-hydroxy-(-)-trachyloban-19-oic acid, 15ß-hydroxy-(-)-kaur-16-en-19-oic acid, 15-oxo-(-)-kaur-16-en-oic acid, Sitosterol glucoside (Harrigan et al., 1994a); Oxophoebine, Liriodenine, Oxoglaucine, O-methyl moschatoline, Lysicamine (Harrigan et al., 1994b); 7ß-acetoxy (-)-kaur-16-en-19-oic acid, E-3-(4-hydroxy-3-

Annonaceae

S/ Plant name Family Common Local Region of Experimental evidence for

no. name Nigerian use for its use in diabetes

name(s)* diabetes# management

Other medicinal uses

Plant part Traditional Identified active (s) used preparation constituent(s) method

Other relevant phytoconstituents identified in the plant

Interaction/toxicity studies

114 Zea mays L.

Agbado (Y), Oka (I), Masara (H)

115 Zingiber officinale Zingiberaceae Roscoe

Ginger

Atale (Y), SW Jinga(I), Chita (H)

0.2 g/d aqueous extract of corn silk improved kidney parameters in STZ-induced diabetic rats but no significant hypoglycaemic effect (Suzuki et al., 2005); 100 mg/L ethanol extract of the corn silk showed PPARa and y agonist activities (Rau et al., 2006)§; Inhibitory effects of the aqueous and ethanol extract of the maize kernels on a-glucosidase enzymes and antioxidant effects (Lee et al., 2010)§ Ethanol extracts of the rhizome reduced blood glucose levels dose dependently (50-800 mg/kg) in normal and STZ-induced diabetic rats (Ojewole, 2006); Alpha amylase and Alpha glucosidase inhibitory effects and In vitro antioxidant effects (Oboh et al., 2010); in vivo antioxidant effects (Morakinyo et al., 2011)

Hypertension, Analgesic, Inflammation, Contraceptive, Nose bleeds

Seed silk

Chrysoeriol 6-C-ß-boivino pyranosyl-7-O-ß-gluco pyranoside, Alternanthin (Suzuki et al., 2003)

Typhoid, Nausea, Cold symptoms, Asthma, Stimulant, Rheumatism, Hemorrhoids, Liver disorders, Obesity, Git disorders

Rhizome

6-, 8- and 10-Gingerols increased glucose uptake in L6 muscle cells primarily by an increased GLUT4 expression (Li et al., 2012); Aldose reductase

inhibitory effects of methoxy phenyl derivatives (Kato et al., 2006)

methoxy phenyl)-N-2-[4-hydroxy phenylethyl]-2-propenamide, E-3-(3,4-dihydroxyphenyl)-N-2-[4-hydroxyphenyl-ethyl]-2-propenamide, Grossamide, Demethylgrossamide, Cannabisin B and D (Lajide et al., 1995); 7a-hydroxy trachyloban-19ß-oic acid (Ngouela et al., 1998)

Glucose yield and glycaemic index of maize starch has been shown to be high, which may pose a problem for diabetic patients (Izuagie et al., 2007; Omoregie and Osagie, 2008)

2-(4-Hydroxy-3-methoxy phenyl) ethanol, 2-(4-hydroxy-3-methoxy phenyl) ethanoic acid, 2-(3,4-dimethoxyphenyl) ethanooic acid, 4-(4-hydroxy-3-methoxy phenyl)-2-butanone, (4-hydroxy-3-methoxy phenyl) methanol (Kato et al., 2006); Zingerone, Geraniol (Chen et al., 2007); Gingerols and its derivatives, Gingesulfonic acids, Shogasulfonic acids, Gingerdiols, Zingerone, Shogaols, Paradols and its derivatives, Zingiberene, Curcumene, p-bisabolene, Citral, Camphene, Neral, p-and Sesqui-phellandrene, Diarylheptanoids, Cineole, Gingerdiones, Geranial, Terpineol (Ali et al., 2008; Kubra and Rao, 2011)

Insufficient evidence for a possible interaction with warfarin or CYPs (Vaes and Chyka, 2000); 6-gingerol increased the accumulation of daunorubicin and rhodamine and decreased efflux of daunorubicine indicating possible P-gp modulatory effect (Nabekura et al., 2005)

Poaceae

Corn Maize

Decoction

* Bi-Bini, Ef-Efik, Es-Esan, F-Fulani, H-Hausa, I-Ibo, Ib-Ibibio, Id-Idoma, Ig-Igala, Ige-Igede, Ij-Ijaw, Nu-Nupe, Ti-Tiv, and Y-Yoruba.

# NC - North central, NE - North east, NW-North west, SE-South east, SS - South south, and SW-South west.

§ Experimental evidence involving plant samples not collected from within Nigeria.

other in vivo models used include spontaneous diabetic animal models obtained as a result of one or more genetic mutations such as obese zucker fatty rats, db/db mice and KK-Ay mice; as well as the use of high glucose or fructose-fed animals. This latter group simulate the development of diabetes from insulin resistance better as is more commonly found in patients with type-2 diabetes (Srinivasan and Ramarao, 2007).

Although most plants were only evaluated experimentally in a type-1 diabetes model, some of these have been shown to be effective hypoglycemic agents in type-2 diabetes patients, such as extracts of Bridelia ferruginea Benth. Daily administration of 15 mg of the leaves as an infusion to type-2 diabetic patients previously on insulin injections for eight weeks resulted in a significant decrease in their blood sugar levels (Iwu, 1983).

Only two out of the 96 plant species were ineffective in the in vivo experimental model of study, namely Zea mays L. (Suzuki et al., 2005) and Cucumeropsis mannii Naudin (Teugwa et al.). Despite its identified in in vitro PPARa and y agonist activities and a-glucosidase inhibitory effects (Lee et al., 2010), extracts of Zea mays failed to produce a significant hypoglycemic effect in vivo (Rau et al., 2006). This could possibly be as a result of the absence of the bioactive constituent(s) responsible for the hypoglycemic effect in the sample used for the in vivo study. The absence of an in-vivo hypoglycemic effect would however not 'eliminate' its use in the clinical management of diabetes, which also takes into account co-morbid conditions. In this regard, Zea mays could also provide protection against diabetic nephropathy, as it has been shown to improve kidney parameters in vivo (Suzuki et al., 2005).

In the case of Cucumeropsis mannii, its traditional use involves the ingestion of its ashes or its juice (Gbolade, 2009). This may indicate that its use is based on its oligo-elements and/or vitamins. In fact the supplementation of elements such as chromium, magnesium and vanadium is actively explored in the treatment of diabetes (Anderson et al., 1997; Halberstam et al., 1996; Rodriguez-Moran and Guerrero-Romero, 2003); some of which have been identified in the seeds of Cucumeropsis mannii (Badifu and Ogunsua, 1991).

3.2. In vitro pharmacological evidence

It is recommended that in vitro experiments are carried out to ascertain the mechanism of action for the plant. Certain plants produce their hypoglycemic effects as a side effect of their in vivo toxicity (Maries and Farnsworth, 1995). There is also the risk that the hypoglycemic effect is being mediated - at least in part -through an unwanted physical mechanism, rather than a physiological one, such as was observed with Gymnema sylvestre (Retz.) R. Br. Ex Sm (Persaud et al., 1999). This immediately eliminates the potential use of such a plant as a therapeutic hypoglycemic agent. In addition, due to the ethical considerations surrounding animal use (Festing and Wilkinson, 2007), it is advised that validation experiments are 'replaced' with non-animal models where possible.

Over one-third of the plants in our review have been studied for in vitro in models that could possibly explain some or all of their mechanism of action. Twenty-nine plants have inhibitory effects against either a-amylase or a-glucosidase enzymes; five plants have agonist activity on the PPARy receptor, whose activation enhances glucose metabolism; four plants increase insulin release from pancreatic cells; five plants increase glucose uptake in muscles or liver; while two plants increased the expression of the glucose transporter GLUT4, which in turn increases glucose uptake into muscles and adipose tissues. Two plants were identified as potential DPP-IV inhibitors, while six plants were identified as aldose reductase inhibitors (Fig. 1).

In vitro experiments are often designed to 'reflect' the mechanism of existing drugs used in diabetes management. Plants that possess alpha amylase or alpha glucosidase inhibitory effects reflect the action of acarbose, PPARy agonist activity reflect the thiazolidine-diones, while aldose reductase inhibitors are potential agents for preventing diabetic complications like the drug epalrestat. Thus with this identified mechanisms, researchers and healthcare professional alike can immediately identify the potential therapeutic benefit of the plant. This information could contribute to a more rational therapeutic regimen for diabetes patients, possibly benefitting from a synergistic effect with herbal remedies.

Plants that are a-amylase or a-glucosidase inhibitors-Abrus precatorius Aframomum melegueta Anacardium occidentale Annona muricata Anthocleista djalonensis Anthocleista vogelii Bixa orellana Capsicum annum Corchorus olitorius Ficus exasperata Ficus thonningii Garcinia kola Ipomoea batatas Khaya senegalensis Lawsonia inermis Mangifera indica Morus alba Murraya koenigii Phyllanthus amarus Sarcocephalus latifolius Securidaca longipedunculata Senna alata Solanum melongena Sorghum bicolor Tamarindus indica Telfairia occidentalis Xylopia aethiopicum Zeamays Zingiber officinale

Plants that promote insulin release-Azadirachta indica Bauhinia monandra Mardenia sylvestris Moringa oleifera

Plants which are PPARyagonists-Capsicum annum Curcuma longa Jatrophas curca Sorghum bicolor Zea mays

Plants which increase GLUT4 receptor

expression-Scoparia dulcís Vernonia amygdalina Zingiber officinale ¡

Fig. 1. Proposed molecular mechanisms of hypoglycemic effects for species studied so far.

The disadvantage of the molecular approach for experimental validation of plant activity is that the biological assays only explore known targets and do not take into account extracts that might be acting on unknown targets, possibly through innovative mechanisms. In addition, herbal medicines are often complex mixtures of various phytochemicals which work synergistically to achieve a desired therapeutic outcome (Campbell-Tofte et al., 2012). In such cases, a single end-point in vitro biological assay will not be sufficient in evaluating the clinical effect of the plant. For instance, the methanol extract of the root and stem of Gongronema latifolium Benth. produced a greater anti-hyperglycemic effect in glucose loaded rats than each of its fractions, indicating a syner-gistic effect of its constituents possibly acting through different molecular mechanisms (Adebajo et al., 2013).

There is also a holistic approach in the herbal management of diabetes such that plants which are not hypoglycemic themselves may be included in multi-component preparations because of their benefits in co-morbid conditions. Thus, in vitro studies might not immediately indicate the beneficial effect of the plant. A good example is the use of the aphrodisiac plant Mondia whiteii (Hook. f.) Skeels (Quasie et al., 2010). Despite not showing in vitro hypoglycemic effect (Etoundi et al., 2010), it is commonly included in multi-component preparations for diabetes management in men since erectile dysfunction is a common complication of the illness (personal communication during field work). This however does not preclude any in vivo activity which is yet to be evaluated.

3.3. Bioactive compounds

Over forty compounds from twenty three of the reviewed plants have been identified, either through an activity guided

fractionation or in silico studies as the bioactive constituents responsible for some or all of the plants' beneficial effects in diabetes. Some of these constituents are species-specific such as the alkaloid mahanimbine from Murraya koenigii (L.) Spreng (Dineshkumar et al., 2010), while others are known to be present in many plants like the alkaloid trigonelline, which is responsible for the hypoglycemic effect of Abrus precatorius L. (Monago and Nwodo, 2010) and Trigonella foenum-graecum L. (fenugreek), a plant whose use in diabetes management is popular across India and Europe (Bailey and Day, 1989). We hereby classify these compounds according to similar chemical features (which may not necessarily refer to similar biosynthetic pathways) as follows: compounds containing nitrogen (1-9) (Fig. 2), terpenes (10-16) (Fig. 3), phenolic compounds (17-33) (Figs. 4 and 5), and compounds containing hydroxyl groups including sugars (34-40) (Fig. 6).

3.3.1. Nitrogen containing compounds

A number of alkaloidal and non-alkaloidal active principles from plants used in diabetes management have been reported. Some of these were isolated from samples not collected from Nigeria such as hypoglycin A (1) and B (2) - from the fruit of Blighia sapida K.D.Koenig. (Chen et al., 1957). Murraya koenigii leaves are also used traditionally in Indian Ayurvedic system to treat diabetes. Mahanimbine (5) isolated from the Indian plant samples decreased blood glucose levels in STZ-induced diabetic rats and also produced a dose-dependent a-amylase and a-glucosidase inhibitory effect (Dineshkumar et al., 2010). Its cellular mechanism of action is also thought to be mediated by an increase in glucose utilization (Dinesh Kumar et al., 2013). Paradoxically, this and other related carbazole alkaloids isolated

Fig. 2. Nitrogen containing compounds with beneficial effects in diabetes.

Kolaviron (17) -Mixture of GB1 (R1=H, R2=H). GB2 (R1=OH, R2=H) & kolaflavanone (R1 =OH, R2=Me) Garcinia kola

Damnacanthol -3 -O-3-D-primeveroside (18) (R=OCH3) Lucidin-3-O-3-D-primeveroside(19) (R=OH ). Morinda citrifolia

R1=(CH2 )2OH, R2=OCH3, R3=OH (23) R1=CH2COOH, R2=OCH3, R3=OH (24) R1=(CH2)2COCH3, R,=OCH3, R3=OH (25) Zingiber officinale

Ellagic acid (26) Ipomoea batatas

Fig. 4. Phenolic compounds with beneficial effects in diabetes.

io OH I

6-Gingerol (34); [R= (CH2)4CH3] 8-Gingerol (35) ; [R= (CH2)6CH3] 10-Gingerol(36);[R= (CH2)8CH3] Zingiber officinale

D-3-O-methyl Chiroinositol(37) Bauhinia thonningii

1-O-phenyl a-L-rhamnopyranoside(38); (R=H, R1=H) Methylft/-{4-[(a-L-rhamnopyranosyl)benzyl]}carbamate (39); (R=H, R1=CH2-H-CO-Ome) Methyl N-{4-[(4'-O-acetyl-a-L-rhamnopyranosyl)benzyl]}carbamate (40); (R=CO-Me,R1=CH2-NH-CO-Ome) Moringa oleifera

Fig. 6. Other hydroxylated compounds with beneficial effects in diabetes.

from plant samples from Nigeria decreased the glucose-mediated insulin release from INS-l cells when compared to control, even though the amount of glucose released was dose dependent. This effect may however be explained by their known in vitro cytotoxicity (Adebajo et al., 2005).

The alkaloid trigonelline (4) isolated from the seeds of Abrus precatorius (L.) collected from the eastern part of Nigeria decreased blood glucose levels in alloxan-induced diabetic rats as well as reduced the activity of glucose-6-phosphatase and glycogen phosphorylase, two enzymes important for glucose production (Monago and Nwodo, 2010). Akuammicine (3) isolated from the chloroform extract of the seeds of Picralima nitida (Stapf) T.Durand and H.Durand stimulated glucose uptake in 3T3-L1 adipocytes (Shittu et al., 2010). It is also present in plants of the genus Alstonia such as Alstonia boonei De Wild. and Alstonia Congensis Engl. and

would most likely be contributing to their blood glucose lowering activity. Ajmaline (6) and isosandwichine (7) from Rauvolfia vomitoria Afzel. were identified as DPP-IV inhibitors using an in silico approach (Guasch et al., 2012).

Garlic and onions are commonly used as part of the diet in many Nigerian households and the hypoglycemic effect of plant samples collected from Nigeria has also been studied (Eyo et al., 2011). This hypoglycemic effect is possibly due to the presence of S-methylcysteine sulfoxide (8) (SMCS) in onions and S-allylcysteine sulfoxide (9) (SACS) in garlic, which have been isolated from Indian plant samples and have been shown to improve glucose tolerance in alloxan-induced diabetic rats (Sheela et al., 1995). Clinical studies in humans have shown that the supplementation of garlic to diabetic patients in combination with hypoglycemic drugs improves glycemic control in addition to

the reduction of cardiovascular risk (Sobenin et al., 2008). Although they both contain nitrogen, SMCS and SACS are primarily classed as sulfur containing compounds.

3.3.2. Terpenes

A number of terpenes have been isolated as bioactive constituents in plants used for diabetes management (Fig. 3). The leaves of Gongronema latifolium, otherwise known as 'utazi' or 'madu-maro' in Ibo and Yoruba respectively is commonly used as a food vegetable and is widely recognized for its traditional use in diabetes management. Lupenyl cinnamate (15), lupenyl acetate and a- and P-amyrin cinnamates (16) isolated from the combined root and stems of locally obtained samples have recently been identified as the bioactive compounds, possessing both anti-hyperglycemic effects in glucose-fasted rats as well as insulin stimulating effects in INS-1 cells (Adebajo et al., 2013).

Foetidin from the whole plant and the unripe fruits of Momor-dicafoetida collected in Nigeria also decreased blood glucose levels of normal fasted, but not alloxan-induced rats at only 1 mg/kg (Marquis et al., 1977). Acetylenic glucosides (10) and (11) from Bidens pilosa decreased blood glucose in the murine type 2 diabetes model C57BL/Ks-db/db mice (Ubillas et al., 2000), and inhibited the spontaneous development of diabetes in non-obese diabetic (NOD) mice by modulating the differentiation of T-helper cells (Chang et al., 2004).

The monoterpenes myrcene (12), citral (13) and geraniol (14) found in Cymbopogon citratus were identified as aldose reductase inhibitors using in-silico docking methods (Vyshali et al., 2011). They are also components of the essential oil of many medicinal plants used in Nigeria as shown in Table 1. This preliminary information warrants further in vitro and in vivo studies involving plant samples from Nigeria previously shown to contain these compounds, given that the beneficial effect of the essential oil of Cymbopogon citratus containing high amounts of these monoter-penes has now been validated in vivo in experimentally induced type-2 diabetic rats (Bharti et al., 2013).

3.3.3. Phenolic compounds

A wide range of phenolic compounds have been identified as active principle(s) in some of the plants here reviewed. Anthraquinone glycosides from Morinda citrifolia L, namely dam-nacanthol-3-O-P-D-primeveroside (18) and lucidin 3-O-P-D-prime-veroside (19), decreased blood glucose levels in STZ-induced diabetic mice at 100 mg/kg (Kamiya et al., 2008). Incidentally, this plant is not native to Nigeria and is not known to grow in Nigeria. However, the use of a registered herbal product of the juice extract, Tahitian noni juice® (TNJ) is quite popular in Nigeria for various ailments including diabetes. Administration of 1 ml/ 150 mg body weight of the rats twice daily for four weeks prior to and after the induction of diabetes with alloxan resulted in significant decrease in blood sugar levels, indicating a prophylactic effect of the extract against alloxan-induced diabetes (Horsfal et al., 2008). The presence of these phenolic compounds in the marketed product has however not been confirmed.

Kolaviron (17) is a mixture of flavanones isolated from the acetone extract of the edible nuts of Garcinia kola Heckel (bitter kola), which is valued in most parts of West Africa. It decreased blood sugar levels in normal and alloxan induced diabetic mice at a dose of 100 mg/kg, as well as inhibited rat lens aldose reductase (RLAR) activity (Iwu et al., 1990a).

Other phenolic compounds have been identified as bioactive constituents but not from plant samples collected in Nigeria. A diacylated anthocyanin peonidin 3-O-[2-O-(6-O-E-feruloyl-P-D-glucopyranosyl)-6-O-E-caffeoyl-P-D-glucopyranoside]-5-O-P-D-glucopyranoside isolated from the root of Ipomoea batatas (L.) Poir.

showed potent maltase inhibitory effects in vivo (Matsui et al., 2002), while ellagic acid (26) and 3,5-dicaffeoylquinic acid (27) isolated from the hot water extract of the leaves showed potent aldose reductase inhibitory effects (Terashima et al., 1991). Law-sone (20) (a naphtoquinone) and gallic acid (21) isolated from the ethanol extract of the aerial parts of Lawsonia inermis L. inhibited the formation of advanced glycated end products in vitro (Sultana et al., 2009). Some methoxy phenyl derivatives (22-25) isolated from the rhizomes of Zingiber officinale Roscoe have been identified as aldose reductase inhibitors both in vitro and in vivo, suppressing sorbitol accumulation in human erythrocytes as well as lens galactitol accumulation in 30% galactose-fed rats (Kato et al., 2006).

Several isolated flavonoids have also been identified as bioac-tive constituents. Isoscutellarein (8-hydroxy apigenin) (28) is a flavonoid isolated from the hot water extract of the leaves of Bixa orellana L., which was identified as an aldose reductase inhibitor (Terashima et al., 1991). Rutin (29) and quercetin (30) were isolated from the leaves of Bauhinia monandra Kurz as the anti-hyperglycemic constituents in alloxan-induced diabetic rats (Alade et al., 2011, 2012). A bioassay guided fractionation of the stem bark of Cassia fistula L. led to the identification of catechin (33) as the bioactive agent. It decreased plasma glucose levels in STZ-induced diabetic rats, with direct effects on glucose metabolizing enzymes and expression of the glucose transporter GLUT4 (Daisy et al., 2010). Fractionation of the methanol extract of the leaves of Senna alata (L.) Roxb. (syn- Cassia alata), which showed potent a-glucosidase inhibitory effects, identified kaempferol gentiobioside (31) and kaempferol (32) as the bioactive compounds (Varghese et al., 2013). Increased translocation of GLUT4 receptors to the plasma membrane of L6 myotubes was also observed with a flavonoid-rich fraction of Scoparia dulcis L. (Beh et al., 2010), although the bioactive constituent(s) was not identified.

The presence of aromatic hydroxyl groups in the benzo-y-pyran structure of flavonoids is associated with its antioxidant properties, particularly its free radical scavenging effects. These properties have been shown to protect pancreatic islet cells from oxidative stress as well as help in the regeneration of P-cells as shown with epicatechin found in green tea (Sabu et al., 2002) and quercetin (Coskun et al., 2005). More importantly, they can prevent the formation of advanced glycated end products (AGEs) and other diabetic complications associated with high oxidative stress conditions such as artherosclerosis, nephropathy, neuropathy, retinopathy and erectile dysfunction (Rahimi et al., 2005). Thus, the presence of quercetin and epicatechin as well as other potent antioxidant flavonoids in a wide range of plants such as Irvingia gabonensis, Khaya senegalensis, Mangifera indica, Securi-daca longipedunculata and Ocimum gratissimum, will contribute to - and in some cases may be the basis for - their use in the holistic management of diabetes which includes the prevention of diabetic complications.

Other flavonoids have also been shown to directly affect specific therapeutic targets in diabetes. For instance, supplementation of mice diet with naringin or hesperidin modulated the activity of glucose metabolizing enzymes, with an increase in hepatic glucokinase activity and decrease in hepatic glucose-6-phosphatase activity in diabetic db/db mice (Jung et al., 2004) and GK type-2 diabetic rats (Akiyama et al., 2009). These two flavo-noids are constituents of all citrus fruits and have also been identified in Senna alata (Hennebelle et al., 2009) and Rauvolfia vomitoria (Campbell-Tofte et al., 2011) and as such may account for some of their effects. Myricetin is another flavonoid that has shown direct beneficial effects in diabetes through enhanced glycogen metabolism (Ong and Khoo, 2000) and improved insulin sensitivity (Liu et al., 2007). It has been identified in some of the plants either in its aglycone form or as a glycoside. These are the

Allium species, Aloe vera, Azadirachta indica, Citrus species, Carica papaya, Bryophyllum pinnatum, Cassia sieberiana, Chrysophyllum albidum, Ipomoea batatas and Bridelia ferruginea.

3.3.4. Hydroxylated compounds including sugars

Some other non-phenolic hydroxylated cyclic compounds have been isolated and identified as bioactive agents. These include the gingerols (34-36) from Zingiber officinale, which were shown to enhance glucose uptake into muscles as a result of a direct increase in the expression of the GLUT4 receptor (Li et al., 2012). An inositol derivative, D-3-O-methyl chiroinositol (37) isolated from the methanol extract of the stem bark of Bauhinia thonningii Schum. produced a dose-dependent decrease in blood glucose levels in alloxan-induced diabetic rats (Asuzu and Nwaehujor, 2013).

Finally, a number of benzyl derivatives including carbamates and thiocarbamates have been isolated from fractions of the methanol extract of the fruits of Moringa oleifera Lam. These compounds have been shown to possess insulin secretory effects, stimulating > 15 ng insulin/mg protein in pancreatic INS-1 cells at 100 ppm. Some of these compounds were identified as 1-O-phenyl a-L-rhamnopyranoside (38), methyl N-{4-[(a-L-rhamnopyranosyl) benzyl]}carbamate (39), and methyl N-{4-[(4'-O-acetyl-a-L-rham-nopyranosyl)benzyl]}carbamate (40).

Many plant secondary metabolites have been associated with specific beneficial effects in diabetes, which might account for the therapeutic effect of the herbal drug (Qi et al., 2010; Singh et al., 2013). Thus, apart from a bioguided fractionation, the biologically active agent of a plant can also be inferred by evaluating the phytochemical constituents that have previously been isolated. These can thereafter be confirmed in specific pharmacologic experiments.

3.4. Clinical studies

The validation of biologically active plants in randomized, placebo-controlled clinical trials involving human subjects is a necessary step towards the possible integration of traditional herbal products into health systems. For these purposes, isolation of the active constituent may not be necessary. The European Directive of Traditional Herbal Medicinal Products is an example of how reports of traditional use and a sound safety profile are enough to regulate herbal medicines (Cox and Roche, 2004). However, knowing the identity of the active principle would be ideal in order to ensure a better quality control and perhaps a more defined dosage.

Fourteen of the plants reviewed in this paper have been clinically evaluated in human subjects, either singly or in combination. These are Bridelia ferruginea, Citrus aurantium, Gongronema latifolium, Ocimum gratissimum, Rauvolfia vomitoria, Vernonia amygdalina, Carica papaya, Curcuma longa, Ipomoea batatas, Irvin-gia gabonensis, Gymnema sylvestre, Phyllanthus amarus and Sola-num aethiopicum (Table 1), of which the first six involved plant samples collected from Nigeria. Only Phyllanthus amarus did not produce the desired clinical effect (Moshi et al., 2001).

Most of the clinical studies were not randomized, controlled trials but preliminary studies evaluating the therapeutic effect of the plant in human subjects. Exceptions to these were those carried out on Rauvolfia vomitoria and Citrus aurantium (Campbell-Tofte et al., 2011), Irvingia gabonensis (Ngondi et al., 2009) and Ipomoea batatas (Ludvik et al., 2004). Similarly, a meta-analysis by Leung et al. (2009) of all clinical studies carried out on Momordica charantia identified flaws in their study design, despite the extract consistently producing a hypoglycemic effect. As a result,

appropriate conclusions that will act as guidelines for their clinical use cannot be drawn.

A good knowledge of the traditional use of these plants based on ethnobotanical studies is very important in the design of a good clinical study. This is especially important for plants which are used as mixtures, as the individual components may be working synergistically to produce the overall desired effect. An example is the synergistic effect produced by a decoction mix of the leaves of Gongronema latifolium, Ocimum gratissimum and Vernonia amygdalina in modulating baseline blood glucose levels, which was not observed with the individual plants (Ejike et al., 2013). Given that many of these herbal remedies are currently being taken by diabetic patients alongside their prescription medicines, a concerted effort between clinicians and researchers would be an ideal way to recruit patients to such studies.

To ensure the reliability of conclusions drawn from any clinical study, they should always involve proper planning with appropriate controls and ought to be conducted within a reasonable time frame, in line with the guidelines of the Declaration of Helsinki. In addition, the recommendations for reporting randomized clinical trials, as defined in the 'Consolidated Standards of Reporting Randomized Clinical Trials (CONSORT) statement' (Schulz et al., 2010) should also be followed. Nonetheless, this relatively high 'success' rate amongst the various studies conducted highlights the potential of harnessing ethnobotanical information in enhancing patient therapy.

4. Toxicological evidence and considerations

The administration of whole plant extracts or fractions consisting of a myriad of compounds, can elicit different biological effects in the body, some of which may be harmful toxic effects. Sometimes, these toxic effects are only associated with certain parts of the plant. For example, the leaves of Senna occidentalis have hepatoprotective effects and are used traditionally for the treatment of liver disorders (Jafri et al., 1999). However, ingestion of toxins found in the seeds (beans) is thought to be the probable cause of acute hepato-myoencephalopathy (HMP) in children (Vashishtha et al., 2009). This risk of toxicity associated with the use of herbal products is one of the main reasons for the hesitance amongst healthcare practitioners towards promoting their integration into healthcare systems.

Adequate knowledge about the traditional use of such plants is very necessary as this often helps to forestall the ingestion of such toxic plants or plant parts. Sometimes the toxic component may have been identified such as abrin, a toxic protein found in the seeds of Abrus pecatorius, with an estimated human fatal dose of 0.1-1 mg/kg (Kirsten et al., 2003). In rare cases, the hypoglycemic agent in the plant could also be the toxic agent, such as with hypoglycin from Blighia sapida (Sherratt, 1986). Thus, the therapeutic use of such a plants as whole extracts is therefore not recommended.

Various plants in Table 1 have been associated with specific organ toxicity. Examples include the nephrotoxic effects of Alstonia congensis, Aristolochia spp., Cassia sieberiana, Ficus exasperata, Securidaca longipedunculata and the hepatotoxic effects of Cassia sieberiana, Ficus exasperata, Morinda citrifolia, Picralima nitida and Senna occidentalis. The hepatotoxic effects of some extracts such as Ocimum gratissimum and Sphenocentrum jollyanum are directly linked to their effect on the liver function enzymes. The cardio-toxic and neurotoxic effects of some other extracts have also been identified. Sometimes, these toxic effects are only seen at high doses, which would therefore not preclude their continued use as medicinal plants so long as there is appropriate information

about the safe dose ranges. The use of other more toxic plants would however need to be completely discontinued.

A thorough analysis of the plant's extracts as well as identified phytochemical constituents with respect to their safety/toxicity profile particularly in humans can ensure a critical assessment of its therapeutic potential. Previously, coumarins which are a component of a wide range of plants were identified as hepato-toxic based on various studies carried out in rodents. However, further studies have showed that certain animal species are resistant to coumarin-induced toxicity. The 7-hydroxylation metabolic pathway is the most favored in humans leading to the formation of non-toxic metabolites, whereas in rats the most favored pathway is a 3,4-epoxidation leading to the formation of toxic metabolites. Knowledge of this and a quantitative health risk assessment have now confirmed its safety in humans (Felter et al., 2006; Lake, 1999).

Evaluation of medicinal plants for potential herb-drug interactions is equally as important as its evaluation for efficacy and safety. Two types of herb-drug interactions exist: pharmaco-dynamic interactions and pharmacokinetic interactions. If a herbal plant alters the expected pharmacological effect of a drug as a result of its biochemical or physiological effect on the body, this is known as a 'pharmacodynamic interaction'. If the herb and the drug are both expected to produce the same pharmacological effect, there may be an increased therapeutic effect produced with their co-administration. This knowledge can be harnessed towards producing a synergistic effect between the two, which would possibly require a dose adjustment. Otherwise, the resulting effect could be detrimental if appropriate monitoring and evaluation is not done. A good example is the severe hypoglycemic that was observed in a female diabetic patient taking chlorpropamide and a meal containing Momordica char-antia and Allium sativum (Izzo and Ernst, 2001).

A synergistic effect should however not be assumed. It is sometimes advisable for patients not to take drugs alongside their herbal products due to negative drug interactions that may occur. For instance, the water soluble fraction of okra fruits has been shown to decrease the absorption of metformin (Khatun et al., 2011). Although both would otherwise be beneficial in diabetes management, taken together would result in a decrease in the therapeutic concentration of metformin, which in turn may not bring about the desired hypoglycemic effect in the patient.

Constituents of medicinal plants also undergo the four main pharmacokinetic processes of absorption, distribution, metabolism and elimination (ADME). There is therefore the possibility of an interaction with one of the different ADME parameters by the herb, which could invariably affect the fate/bioavailability of a co-administered drug and possibly, the resulting therapeutic benefit (s). This is known as a 'pharmacokinetic interaction'.

Out of the one hundred and fifteen plants reviewed in this paper, over thirty of them have shown in vitro and/or in vivo modulation of the activity of one or more of these ADME parameters (Fig. 7). Some of these interactions were on absorption, either by modulating the effect of P-glycoprotein (P-gp), an intestinal efflux transporter, or by direct effects on the intestinal tight junctions. Other pharmacokinetic interactions were on metabolism, by interacting with one or more cytochrome P450 enzymes responsible for phase 1 metabolism or either of the phase 2 metabolic enzymes (Table 1).

The role of P-gp in the intestinal epithelium is the extrusion of certain xenobiotics from the blood to the intestinal lumen as well as to minimize the entry of drugs in the lumen into the bloodstream, ultimately resulting in decreased absorption and decreased oral bioavailability (Sharom, 2007). For drugs that are P-gp substrates such as glibenclamide, this effect of the efflux transporter is one of the determinant factors in the recommended

Acacia nilotica Annona senegalensis Bauhinia thonningii Carica papaya Moringa oleifera Solanum melongena Vernonia amygdalina Ximenia americana Zingiber officinale

Bridelia ferruginea Catharanthus roseus Curcuma longa Khaya ivorensis Mangifera indica Morinda lucida

Aframomum melegueta Bixa orellana Citrus aurantiifolia Citrus aurantium Citrullus colocynthis Corchorus olitorius Ipomoea batatas Jatropha curcas Lawsonia inermis Momordica charantia Morus alba Murraya koenigii Persea americana Phyllanthus amarus Senna alata

Lawsonia inermis Momordica charantia Morinda citrifolia Morinda lucida Moringa oleifera Phyllanthus amarus Securidaca longipedunculata Senna alata__y

Fig. 7. In vitro pharmacokinetic herb-drug interactions identified based on the literature reviewed.

dose of the drug to ensure that an adequate therapeutic concentration is achieved in the bloodstream. Co-administration of the drug with a herb with inhibitory effects on P-gp such as Acacia nilotica, Annona senegalensis, Bauhinia thonningii, Bridelia ferrugi-nea, Carica papaya and Morinda lucida might result in increased plasma concentration of the drug.

The cytochrome P450 (CYP) family of enzymes are responsible for phase 1 oxidative, peroxidative and reductive metabolic transformations of drugs, environmental chemicals and natural compounds into less toxic, more water-soluble products, in order to facilitate their excretion from the body. They are most abundant in the liver, which is the primary site for metabolism. The activity of CYP enzymes can be modified either by induction or inhibition as seen with the extracts of Bixa orellana and Jatropha curcas respectively. The biological activity of the xenobiotics metabolized by these enzymes can be greatly altered as a result (Rendic and Carlo, 1997). St John's wort (Hypericum perforatum) is a very good example of a herbal product that has produced clinically significant effects as a result of its interactions with P-gp and CYP enzymes (Henderson et al., 2002).

In vitro interactions have also been identified with the phase 2 metabolizing enzymes, particularly with the glutathione trans-ferases (GSTs). As with P-gp and CYPs, such interactions can alter the plasma concentration and the resulting therapeutic effect of the co-administered substrate drug. In addition, GSTs directly control the levels of glutathione (GSH) within the cell. GSH also acts as an antioxidant within cells, and is particularly important in diabetic conditions characterized by oxidative stress. Unfortunately, plants such as Securidaca longipedunculata which decrease GSH levels might be counter-productive in diabetic patients.

For many of these plants in Fig. 7, the phytochemical constituents responsible for the pharmacokinetic interaction are still unknown. Polyphenols present in plants especially flavonoids have been the most implicated in herb-drug interactions, with direct effects seen with specific flavonoids on P-gp and drug metabolizing enzymes (Morris and Zhang, 2006) (Galati and O'Brien, 2004) (Hodek et al., 2002). It should however be taken into account that many of the in vitro pharmacokinetic interactions or alarming case studies published in primary literature fail to translate into significant clinical risks for the patients, as seen with many herbal remedies taken in Europe (Williamson et al., 2013). There is still an urgent need for effective pharmacovigilance of herbal medicines to ensure their safe and effective use in therapeutic management (Shaw et al., 2012).

5. Conclusions

Nigeria is endowed with a biodiversity of medicinal plants, many of which are currently used in the traditional management of diabetes. Our review shows that there is very good preclinical evidence for the efficacy of most of these plants, either as hypoglycemic agents or as useful agents in the management of diabetic complications. We have mapped their pharmacological mechanism of action as this can serve to promote a more rational use of these plants as herbal medicines based on the expected therapeutic outcome and their tabulated toxicological effects. Last but not least, we have also highlighted potential interactions with key parameters of the ADME process that can arise from the use of these plants in therapeutic management.

These available data can provide evidential support for the clinical development of a number of medicinal plants as adjuvant therapy. We believe that the criteria for selection should be based on social acceptance/frequency of use, efficacy and toxicity profile, and availability/sustainability of the supply chain, possibly tailored to each region. A set of quality parameters for the standardization

of these plants as herbal preparations (such as pharmacopoeial monographs) would be required to ensure the reproducibility of their therapeutic effects. Finally, as a means of giving credence to the pre-clinical experimental evidence, intervention or clinical studies with the standardised materials should be carried out in order to validate their usefulness in diabetes management. We hope that in this manner the therapeutic potential of these medicinal plants can be best harnessed, towards a possible integration into the healthcare system.

Acknowledgments

U.F. Ezuruike is grateful to the Commonwealth Scholarship Commission in the UK for the award of a DFID (Department for International Development) sponsored Ph.D. scholarship.

Appendix A. Supplementary information

Supplementary data associated with this article can be found in the online version at http://dx.doi.org/10.1016/jjep.2014.05.055.

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The use of plants in the traditional management of diabetes in Nigeria: Pharmacological and toxicological considerations Academic research paper on "Biological sciences"

Abstract of research paper on Biological sciences, author of scientific article — Udoamaka F. Ezuruike, Jose M. Prieto

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Academic research paper on topic "The use of plants in the traditional management of diabetes in Nigeria: Pharmacological and toxicological considerations"