Scholarly article on topic 'Leishmaniosis phytotherapy: Review of plants used in Iranian traditional medicine on leishmaniasis'

Leishmaniosis phytotherapy: Review of plants used in Iranian traditional medicine on leishmaniasis Academic research paper on "Chemical sciences"

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Abstract of research paper on Chemical sciences, author of scientific article — Mahmoud Bahmani, Kourosh Saki, Behrouz Ezatpour, Somayeh Shahsavari, Zohreh Eftekhari, et al.

Abstract Many native plants in traditional medicine have been used for the treatment of cutaneous leishmaniasis and the recent clinical trials have proven the efficacy of some of them. Researches conducted on these plants have shown that garlic, shallots, wormwood, yarrow, walnuts, thyme, henna plant, mimosa, aloe, wood betony, medlar, periwinkle, yeah, savory, black beans, etc. are effective on cutaneous leishmania. Synthetic agents in Iranian market have some disadvantages such as high cost and side effects and are painful in injections. Given the effectiveness of these plants, they can be a source of natural and safe compounds for the treatment of Leishmania. Therefore, more clinical researches should be done to determine the effectiveness and safety of these medicinal plants, their active ingredients and their possible toxic substances which can lead to the production of effective and safe drugs for leishmaniasis. It also might be an effective way to prepare herbal ointment on wound healing.

Academic research paper on topic "Leishmaniosis phytotherapy: Review of plants used in Iranian traditional medicine on leishmaniasis"

ELSEVIER

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Asian Pacific Journal of Tropical Biomedicine

journal homepage: www.elsevier.com/locate/apjtb

Review article http://dx.doi.org/10.1016/j.apjtb.2015.05.018

Leishmaniosis phytotherapy: Review of plants used in Iranian traditional medicine on leishmaniasis

Mahmoud Bahmani1, Kourosh Saki2, Behrouz Ezatpour3, Somayeh Shahsavari4, Zohreh Eftekhari5, Mahyar Jelodari6, Mahmoud Rafieian-Kopaei7*, Reza Sepahvand3

1Food and Beverages Safety Research Center, Urmia University of Medical Sciences, Urmia, Iran 2Shahid Beheshti University of Medical Sciences, Tehran, Iran

3Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran 4Young Researchers and Elite Club, Khorramabad Branch, Islamic Azad University, Khorramabad, Iran 5Research and Production Complex, Pasture Institute of Iran, Tehran, Iran 6Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

7Medical Plants Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran

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ARTICLE INFO

ABSTRACT

Article history: Received 16 Feb 2015 Received in revised form 25 May 2015

Accepted 30 May 2015 Available online 29 Jul 2015

Keywords:

Leishmania

Leishmaniasis

Native medicinal plants

Many native plants in traditional medicine have been used for the treatment of cutaneous leishmaniasis and the recent clinical trials have proven the efficacy of some of them. Researches conducted on these plants have shown that garlic, shallots, wormwood, yarrow, walnuts, thyme, henna plant, mimosa, aloe, wood betony, medlar, periwinkle, yeah, savory, black beans, etc. are effective on cutaneous leishmania. Synthetic agents in Iranian market have some disadvantages such as high cost and side effects and are painful in injections. Given the effectiveness of these plants, they can be a source of natural and safe compounds for the treatment of Leishmania. Therefore, more clinical researches should be done to determine the effectiveness and safety of these medicinal plants, their active ingredients and their possible toxic substances which can lead to the production of effective and safe drugs for leishmaniasis. It also might be an effective way to prepare herbal ointment on wound healing.

1. Introduction

Leishmaniasis is one of the six major infectious diseases in the world caused by various species of the genus Leishmania. Leishmaniasis is a public health problem in many tropical and subtropical countries like Iran [1]. Leishmania is the protozoan parasite whose family included Trypanosomatida. The disease is endemic in 81 countries. Annually, one to one and a half million new cases of the disease were reported in the world.

Corresponding author: Prof. Mahmoud Rafieian-Kopaei, Medical Plants Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran. Tel: +98 381 334 6692, +98 913 1811842 Fax: +98 381 3330709 E-mail: rafieian@yahoo.com

Peer review under responsibility of Hainan Medical University. Foundation Project: Supported by Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran (Grant No. 659-009).

Clinical features of leishmaniasis disease include cutaneous, mucocutaneous and visceral forms [2,3].

Cutaneous leishmaniasis (CL) is a parasitic disease spread by flies and common in many tropical and subtropical countries of the world. Probably about 12 million cases of CL in different parts of the world occur annually and 350 million people are at risk of developing the disease. Currently 88 countries in worldwide are infected with CL [4].

Several studies have shown that CL in the world is increasing. Annually, approximately 20 000 cases of leishman-iasis have been reported from different parts of the world and actual amount has estimated several times [5]. In Iran, approximately fifteen thousand people are infected with leishmaniasis. Based on existing researches, the actual incidence of leishmaniasis is four to five times of the current reports and incidence is 0.27 per thousand [6,7].

In this review study, related information was obtained from available ancient sources such as Iranian traditional books.

2221-1691/Copyright © 2015 Hainan Medical University. Production and hosting by Elsevier (Singapore) Pte Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Accordingly, a wide spectrum of plants was found to be useful for cleansing and protecting the liver. Finally, the obtained data was compared with those reported in modern medicinal databases covering all in vitro and in vivo leishmaniasis investigations. In the present article, the literature review was performed by using scientific information database focusing on the keyword of leishmaniasis.

2. Chemical agents in the treatment of leishmaniasis

At the present time, various chemical agents are used in the treatment of CL. Among them, the compounds of antimony (pentavalent), antimalarial drugs like chloroquine, quinacrine, emetine, metronidazole and minomycline antibiotics, tetracy-cline and rifampin are also used.

Treatment depending on the parasite species and determination of specification is important to plan control and prevention. Antimony compounds are the first line treatment of CL. Its two compounds, meglumine antimonate (glucantime) and sodium gluconate acetic (pantocetam), are commercially available and 5-valent antimony compounds, glucantime, the most common medications are used to treat CL in Iran and other parts of the world [8-10]. These drugs have side effects, including increased liver enzymes. Glucantime is an expensive and painful injection drug and its usage in patients with kidney and liver problems is not permitted [11-13]. The use of compounds that are free of these problems and disadvantages, is necessary [14-16]. The use of medicinal plants in the historical record rises increasingly [17-24].

Medicinal plant is an effective source of pharmaceutical products in Iran [25-31]. These drugs are inexpensive and proven to have health effects [32-34]. Iran currently produces about 820 herbal drugs [35-38]. Today, clinical research and empirical studies on the subject of medicinal plants have been done in different parts of the world especially in Iran [23,39-44].

3. The role of indigenous medicinal plants in the treatment of leishmaniasis

In different cultures and different countries, indigenous medicinal plants are used to treat diseases, especially leishmaniasis. Table 1 shows native medical plants in Iran and their effects are scientifically proven to be effective on leishmaniasis.

Leishmaniasis is a broad-spectrum parasitic disease reported worldwide. Until now no effective vaccine or drug for the inhibition of parasite has been reported and no effective chemicals for eradication of carriers are provided [66-69].

Natural substances or compounds derived from plants are widely used against pathogenic microorganisms [70].

Based on Figure 1, the family of native plants which has the best effect of anti-leishmania is the Asteraceae family. Plants of this family seem to have certain medicinal properties and chemicals that have the effect of imposing anti-leishmania. Plants of this family include Artemisia, and marigold. The bioactive compounds of Artemisia species including artemisinin and artemether are effective against leishmania. Because the Artemisia includes most plants of this family, we tried to introduce the different species of the genus that grow in Iran. In Iran, there are several species of the genus Artemisia, which include Turkish, Kermani and Caspian Artemisia.

In addition to antihelminthic activity of Artemisia, frequency of biological activities such as germicidal, anti-fungal, viral

wiring, antiparasitic and analgesic properties and antioxidant properties of the antibody and the dilation of blood vessels have been demonstrated [71-77].

Analysis has shown that the herb mountain Artemisia contains various compounds such as semen, sabinene, cineol, linalool, borneol, farnezole, esters and other compounds [71]. Artemisia aucheri (A. aucheri) has bioactive compounds such as flavonoids, santonian, coumarin compounds, bitter substances and volatile oils [78].

Siberian Artemisia contains bioactive substances including monoterpenes categories acid glycosides and 4-sezquitrepens derivatives of Oplonanon and germcran, derivatives bisabo-lene, salsolene ketones, camphor, 8,1 cineole of oxygenated monoterpene, sesquiterpene dehydroepiandrostrone, 1,8-cineole, b-thujon, thujon, alpha-dimethyl cyclopentane, carboxylic acid and camphor [79]. The combination of camphor, camphene, 1,8-cineole, alpha and beta-tojone, alpha-pinnene are components of Siberia Artemisia.

Pulmonary toxicity, anti-nutritional and repellent of Artemisia have already been demonstrated [80-82]. The main components of this plant include glycosides, santonins, coumarines, terpenoides and sterols, polyacetylene and flavonoids like quercetin and rotenoids which have antioxidant properties [83]. The composition of the essential oil of Artemisia is cineol and in extracts, tannins and flavonoids have an antiseptic effect [84-86].

Research has shown that the major compounds of A. aucheri include santonin, comphour and cineol [79,83,87,88]. Researches have proven that antiparasitic effects of santonin are based on paralysis of the parasites at low concentrations and poor stimulatory effect on the worms in high concentrations. Stimulatory or inhibitory action of santonin has been done through gabaergic and cholinergic stimulation mechanisms in the nervous system of worms [89]. In Artemisia annua, researches are more focused on terpene compounds that have antiparasitic activity, and less attention has been given to phenolic compounds of this plant, but recently antioxidant and anticancer effects of phenolic compounds has been discussed [90].

Active ingredients containing artemisinin (Figure 2) and artemether (Figure 3), two bioactive compounds against Leish-mania, are two different forms of the pharmaceutical composition (topical and injectable) which are both effective drugs against Leishmania.

Artemisinin has good antiparasitic and antimalarial effect. Artemisinin levels in different sepsis ranges from 0.01% to 1.5%. Because of naturally low levels of this substance in the plant, extraction of it is very expensive [91]. Artemisinin has low solubility in water and fat. Therefore, it is possible to use this compound as a commercial antiparasitic agent because it has not disadvantages [92-95]. Therefore, if we seek new and effective materials, we should be able to prepare drugs without disadvantages in those of artemisinin.

The bioactive substances in the pharmacological tests on leishmania have been investigated and effective compounds to produce efficient and safe drugs for parasitic consumption have been produced.

This paper presented a brief overview of leishmaniasis and effective native medicinal plants to treat the wound caused by leishmaniasis. The effectiveness of the plants in traditional medicine in wound healing and cutaneous infection cases has been proven.

Table 1

Medicinal plants and their effects on the leishmaniasis.

The scientific name of the plant

Family name

English name

Research result

Zajuria multiflora Boiss. Lawsonia inermis Calendula officinalis

Nerium oleander Capsicum annuum Amygdalus communis Ricinus communis L. Achillea millefolium Artemisia absinthium Juglans regia Allium hirtifolium Boiss.

Allium sativum

Aloe latex (Aloe emodin)

Arnebia euchroma Artemisia annua

A. aucheri Bioss. Berberis vulgaris Cassia fistula

Echinacea purpura

Eucalyptus globulus Artemisia dracunculus

Mimosa tenuiflora

Peganum harmala Alkanna tinctoria Satureia hortensis Nigella sativa

Scrophularia striata

Stachys lavandulifolia Mespilus germanica

Vinca major

Lamiaceae Lythraceae Asteraceae

Apocynaceae

Solanaceae

Rosaceae

Euphorbiaceae

Compositae

Compositae

Juglandaceae

Alliaceae

Alliaceae Aloaceae

Boraginaceae Asteraceae

Asteraceae

Berberidaceae

Leguminosa

Asteraceae

Myrtaceae Compositae

Fabaceae

Zygophyllaceae Boraginaceae Labiatae Ranunculaceae

Scrophulariaceae

Lamiaceae Rosaceae

Apocynaceae

Thyme Henna Marigold

Oleander Kapsa Almond Castor oil plant Yarrow

Grand wormwood Walnut Spring onion

Garlic Aloe

Sweet wormwood Artemisinin

Wormwood European berberry Amaltas

Purple coneflower

Blue gum Tarragon

Jurema

Harmal

Winter savory Blach seed

Snapdragon

Wood betony Dutch medlar

Periwinkle

Thyme and yarrow extract had positive effects on wound healing of cutaneous leishmaniasis [45].

The extraction of marigold at a concentration of 500 mg/mL killed all the parasites and in lower concentrations revealed anti-leishmania activity which was dose-dependent with LC50 of 17 mg/mL and 215 mg/mL, in alcoholic and water extracts, respectively [46].

The number of promastigotes of Leishmania reduced compared to control group. Significant reduction on the process of the formation of scars and cutaneous nodules at the base of the tail of the mice was also observed compared with the control group [47]. Increase in immobilization of parasites after 30 min compared to control group was observed and it was found that the effect of the extract was related to the time [48].

Concentrations of 0.01-0.1 mg/mL of the extract inhibited the parasites growth on the third day and the highest concentration was effective in the first day [49].

Garlic at the dose of 37 mg/mL in 48 h destroyed the existing promastigotes [50].

Aloe emodin had inhibitory effects on the growth of Leishmania promastigotes with LC50 of 52.8 mg/mL. Also, flow-cytometry results showed that it was able to induce apoptosis [51]. All tested concentrations (0.78, 1.5, 3.2, 6.5 and 12.5) reduced the number of leishmania parasites time dependently [52]. The concentrations of 10-100 mg/mL were effective against promastigote of L. major [53].

The inhibitory concentration (IC50) was 25 mg/L. The extract also caused DNA fragmentation on promastigotes of L. major [54].

The LC50 of the A. aucheri and Artemisia asafetida extracts were 4.7 and 7.5, respectively [55].

A concentration of 20% reduced the mean diameter of the lesions and the complete healing was observed in 27.7% in mice [56]. Significant improvement was observed in the length of patients lesions in both Cassia and glucantim groups. In both groups, the side effects such as itching and erythema were observed in 9 patients, and in this respect there was no difference between the two groups [57].

A significant improvement was seen compared to the control group [58].

Eucalyptus extract and tarragon extract caused complete healing of small wounds, complete removal of the lesions and Leishman bodies and prevented the expansion of large ulcers by reducing the number of parasites [59].

Extract of Mimosa at concentrations of 500 and 1 000 mg/L rapidly reduces parasite proliferation [60]. Peganum harmala plus Alkana were effective on L. major in in vitro situation and had inhibitory effect on promastigotes [61]. After 24 h, Satureia and Nigella extracts, in 8 percent concentration, significantly reduced the number of parasites in comparison to control group [62].

A concentration of 10 mg/mL control drug and a concentration of 25 mg/mL extract, on the third day, respectively caused complete elimination of L. major amastigotes within macrophages. Percentage of infected macrophages with increasing concentrations of the extract decreased and on the second and third days, the infected macrophages were not observed in the culture media [63].

The number of Leishmania promastigotes decreased dose-dependently with increasing concentrations of wood betony extract. Based on the results, there was not significant difference in the number of promastigotes in two concentration of Dutch medlar extract [64].

Purified extract of the plant Vinca caused significant reduction in the number of L. major promastigotes. Additionally, a purified extract of Vinca in the chloroform phase by injection form, prevented the development of ulcers caused by L. major in Balb/ C mice compared to the untreated controls [65].

L. major. Leishmania major.

Figure 1. The native plants with good effects on leishmaniasis.

substances [101,118-127]. Therefore, they might be a reliable source for preparation of new drugs.

Another important issue is the safety of natural remedies. Although natural immune therapy in different generations has been tested and approved, it is necessary to prove the overall pharmacological safety of the exact.

Chemical agents in Iranian market have disadvantages such as high cost, painful injections and side effects. Given the effectiveness of these plants, they can be a source of natural and safe agents for the treatment of Leishmania. Therefore, more clinical researches to determine the effectiveness and safety of medicinal plants and their active ingredients and possible toxic substances can lead to the production of efficient and safe drugs for leishmaniasis. Preparation of herbal ointment on wound healing is also an effective way of reducing injection pain and the treatment cost.

Figure 2. Artemisinin.

CH H "

Figure 3. Artemether.

Given the well documented effects, medicinal plants can be used as herbal supplements and even alone in the treatment of leishmaniasis.

Therefore, studies on plants and their active components are suggested. If the efficiency of plants and their active ingredients are proven by rigorous scientific studies, preparation of natural medicines due to the availability of raw materials will be much more effective and less expensive than buying imported chemical drugs.

Recent studies have proven their effects, not only on leish-maniasis, but also on other diseases such as Alzheimer [96-98], diabetes [99-102], atherosclerosis [103-106], cardiovascular diseases [107-110], cancer [111,112], wound healing [111,113] and other complication [114-117]. They also can be used in the treatment of or prevention from toxicities from other

Conflict of interest statement

We declare that we have no conflict of interest.

Acknowledgments

This study was financially supported by Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran (Grant No. 659-009).

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