Leishmania donovani: Assessment of leishmanicidal effects of herbal extracts obtained from plants in the visceral leishmaniasis endemic area of Bihar, India (original) (raw)

IN VITRO ANTILEISHMANIAL ACTIVITIES OF THREE MEDICINAL PLANTS: ARGEMONE MEXICANA, MURRAYA KOENIGII AND CINNAMOMUM TAMALA AGAINST MILTEFOSINE RESISTANT PROMASTIGOTES OF LEISHMANIA DONOVANI PARASITES Original Article

International Journal of Pharmacy and Pharmaceutical Sciences, 2021

Objective: Leishmaniasis is one of the neglected tropical diseases in terms of drug development and discovery. Non-responsiveness and resistance to the drug in Leishmania species need to develop new antileishmanial potentials; herbal medicines could be the alternative one. Methods: In the present study, semi-purified fractions were prepared from the traditionally used three medicinal plants of India: Argemone mexicana (aerial shoot), Murraya koenigii (stem), and Cinnamomum tamala (bark) by using multiple solvent systems (non-polar to polar, beginning with petroleum ether followed by n-hexane, benzene, and chloroform) and an effort was given to assess the leishmanicidal activities against Leishmania donovani miltefosine resistant HePC-R (Ld/MIL-30) promastigotes in vitro and the IC50 concentrations were estimated. Results: The study revealed that the semi-purified fractions of A. mexicana, M. koenigii, and C. tamala have effective antileishmanial activities and the 50% inhibitory concentrations (IC50) are 50 μg/ml, 98 μg/ml, and 200 μg/ml, respectively. At these (IC50) concentrations, these plant semipurified fractions were found to interfere in lipid and protein biosynthesis, alter cell morphology, DNA content, mitochondrial membrane potential, generating ROS, and apoptosis in promastigotes. The semi-purified fractions were also found noticeably non-toxic towards host splenocytes. Conclusion: These results could suggest that A. mexicana, M. koenigii, and C. tamala could carry potential novel compounds for the development of new drugs against Leishmaniasis.

Evaluation of antileishmanial activity of South Indian medicinal plants against Leishmania donovani

Experimental parasitology, 2012

Infections due to protozoa of the genus Leishmania are a major worldwide health problem, with high endemicity in developing countries. The aim of this study was to evaluate the in vitro antileishmanial activity of the acetone and methanol leaf extracts of Anisomeles malabarica, flower of Gloriosa superba, leaf of Ocimum basilicum, leaf and seed of Ricinus communis against promastigotes form of Leishmania donovani. Antiparasitic evaluations of different plant crude extracts were performed on 96 well plates at 37°C for 24-48 h. Out of the 10 experimental plant extracts tested, the leaf methanol extracts of A. malabarica, and R. communis showed good antileishmanial activity (IC(50)=126±19.70 and 184±39.33 μg/mL), respectively against promastigotes. Effective antileishmanial activity was observed making these plants as good candidates for isolation of antiprotozoal compounds which could serve as new lead structures for drug development.

Anti-leishmanial and toxicity activities of some selected Iranian medicinal plants

Parasitology Research, 2012

Leishmaniasis is caused by protozoan parasites belonging to the genus Leishmania. Cutaneous leishmaniasis is the most common form of leishmaniasis in Iran. As there is not any vaccine for leishmaniasis, treatment is important to prevent the spreading of parasites. There is, therefore, a need to develop newer drugs from different sources. The aim of this study was to assess anti-leishmanial activity of the ethanolic extracts of 17 different medicinal plants against Leishmania major promastigotes and macrophage cell line J774. The selection of the hereby studied 17 plants was based on the existing information on their local ethnobotanic history. Plants were dried, powdered, and macerated in a hydroalcoholic solution. Resulting extracts have been assessed for in vitro anti-leishmanial and brine shrimp toxicity activities. Four plants, Caesalpinia gilliesii, Satureia hortensis, Carum copticum heirm, and Thymus migricus, displayed high antileishmanial activity (IC50, 9.76±1.27, 15.625±3.76, 15.625 ±5.46, and 31.25±15.44 μM, respectively) and were toxic against the J774 macrophage cell line at higher concentrations than those needed to inhibit the parasite cell growth (IC50, 45.13 ± 3.17, 100.44 ± 17.48, 43.76 ± 0.78, and 39.67 ± 3.29 μM, respectively). Glucantime as positive control inhibited the growth of L. major promastigotes with IC500 254 μg/ml on promastigotes (1×10 6 /100 μ/well) of a log phase culture, without affecting the growth of J774 macrophages. These data revealed that C. gilliesii, S. hortensis, C. copticum heirm, and T. migricus extracts contain active compounds, which could serve as alternative agents in the control of cutaneous leishmaniasis. The activity of these herbs against L. major promastigotes and macrophage cell line J774 was reported for the first time in our study.

Evaluation of anti-leishmanial activity of selected Indian plants known to have antimicrobial properties

Parasitology Research, 2009

The severe toxicity, exorbitant cost and the emerging resistance of Leishmania spp. against most of the currently used drugs led to the urgent need for exploiting our traditional Ayurvedic knowledge to treat visceral leishmaniasis. The aim of this study was to evaluate the in vitro anti-leishmanial activity of various extracts from ten traditionally used Indian medicinal plants. The methanolic extract from only two plants, Withania somnifera Dunal (ashwagandha) and Allium sativum Linn. (garlic), showed appreciable activity against Leishmania donovani. Further active compounds from these two plants were isolated and purified based on bioactivity-guided fractionation. HPLC-purified fraction A6 of ashwagandha and G3 of garlic showed consistently high activity with 50% inhibitory concentration (IC50) of 12.5 ± 4 and 18.6 ± 3 μg/ml against promastigotes whereas IC50 of 9.5 ± 3 and 13.5 ± 2 μg/ml against amastigote form, respectively. The fraction A6 of ashwagandha was identified as withaferin A while fraction G3 of garlic is yet to be identified, and the work is in progress. Cytotoxic effects of the promising fractions and compounds were further evaluated in the murine macrophage (J774G8) model and were found to be safe. These compounds showed negligible cytotoxicity against J774G8 macrophages. The results indicate that fraction A6 of ashwagandha and fraction G3 of garlic might be potential sources of new anti-leishmanial compounds. The in vivo efficacy study and further optimization of these active compounds are in progress.

Screening of In Vitro Antileishmanial Activity of Extracts of Selected Medicinal Plants

National Academy Science Letters, 2015

The chemotherapeutic intervention for discovering drugs against leishmaniasis suffers from limitations as toxicity, high cost and development of resistant strains of Leishmania. As a result of unprecedented increase in the number of newly diagnosed cases against leishmaniasis, development of drugs from medicinal plants is gaining widespread interest. Different solvent extracts from ten plants were colorimetrically tested against the promastigotes. In the present study, aqueous extract of all the plants gave some level of activity against the promastigotes. The aqueous extract of Solanum xanthocarpum gave IC 50 value of 110 lg ml-1 followed by ethanolic extract of Tephrosia purpurea with IC 50 value of 141 lg ml-1. Moderate antipromastigote activity with inhibition of parasite growth in the range of 30-40 % was witnessed in the extracts of Asparagus racemosus, Boerhaavia diffusa, Citrullus colocynthis, Spilanthes acmella and Thuja occidentalis. For quality determination and reproducibility of results the aqueous extract of S. xanthocarpum and ethanolic extract of T. purpurea were analyzed through HPLC and general profile of the extract was recorded. The aqueous extract of S. xanthocarpum was also subjected to UV-Vis spectrophotometry and FTIR analysis. The results of this study advocate the promotion of medicinal plant products for the isolation of new natural molecules for the treatment of leishmaniasis.

Plants with anti-Leishmania activity: Integrative review from 2000 to 2011

Pharmacognosy Reviews, 2013

The search for more effective new drugs to treat Leishmaniasis is undoubtedly relevant. Our objective in this study was to investigate research publications addressing plants with anti-Leishmaniasis activity. An integrative review of the literature from 2000 to 2011 was carried out in the databases such as Latin-American and Caribbean Health Sciences (LILACS), Scientific Electronic Library Online (SciELO), and Medical Literature Analysis and Retrieval System Online (MEDLINE). In the initial search, 150 articles were found, with 25 based in LILACS, 68 in SciELO, and 46 in MEDLINE. From these data, after reading the abstracts that were available online, we excluded 12 from LILACS, 39 from SciELO, and 28 from MEDLINE for presenting article duplications. This left 61 articles to be read; however, only 18 of them answered the research questions and determined the final sample of this review. The results showed that research involving the search for new drugs against Leishmaniasis should be intensified, especially for the amastigote form, and studies with in vivo tests could become a great strategy for successfully finding new treatments for Leishmaniasis. It is believed that it is extremely important and urgent to conduct more trials in search of new effective drugs against Leishmaniasis that possess minimal adverse effects and that are easily accessible to the public.

In vitro antileishmanial activity of Mexican medicinal plants

Aim of the study: To evaluate the anti-leishmanial activity and cytotoxicity of aqueous and organic extracts of ten plants used in Mexican traditional medicine as anti-parasitics. Materials and methods: For the organic extracts, plant material was macerated in dichloromethane (CH 2 Cl 2) and dichloromethane/methanol (CH 2 Cl 2 /MeOH) (1:1) during two weeks; the aqueous extracts were prepared by infusion. The extracts were tested against promastigotes and intracellular amastigotes of Leishmania amazonensis. The cytotoxicity was assayed in parallel on peritoneal macrophages of BALB/c mice. Results: Four of the thirty extracts tested were active and selective against L. amazonensis promastigotes: Schinus molle (CH 2 Cl 2 and CH 2 Cl 2 /MeOH), Lantana camara (CH 2 Cl 2) and Prosopis laevigata (aqueous). These extracts had a median (http://creativecommons.org/licenses/by-nc-nd/4.0/). inhibitory concentration (IC 50) against intracellular amastigotes under 50 μg/mL and a selectivity index (SI) higher than 5, which indicates that they constitute valuable candidates to obtain secondary metabolites with leishmanicidal activity. Conclusions: The results derived from this study indicate that L. camara, P. laevigata, and S. molle might provide interesting new leads for the development of antileishmanial drugs.

In vitro evaluation of traditionally used Surinamese medicinal plants for their potential anti-leishmanial efficacy

Journal of Ethnopharmacology, 2016

Ethnopharmacological relevance: Plant-based preparations are extensively used in Surinamese folk medicine for treating leishmaniasis, but often without a scientific rationale. Aim of the study: To evaluate 25 Surinamese medicinal plants for their potential efficacy against leishmaniasis. Materials and methods: Concentrated plant extracts were evaluated for their effect on the viability of L. (V.) guyanensis AMC, L. (L.) major NADIM5, and L. (L.) donovani GEDII promastigotes, as well as intracellular amastigotes of L. (L.) donovani BHU814 in infected THP-1 cells. Selectivity was assessed by cytotoxicity against THP-1 cells. Results: The only plant extract that showed potentially meaningful anti-leishmanial activity was that from Solanum lycocarpum that displayed mean IC 50 values of about 51, 61, and o16 mg/mL against L. (V) guyanensis, L. (L) major, and L. (L) donovani promastigotes, respectively; about 374 mg/mL against L. (L) donovani amastigotes; and 4500 mg/mL against THP-1 cells. The Bryophyllum pinnatum, Inga alba, and Quassia amara extracts displayed moderate to high IC 50 values against promastigotes (about 51 to 4500 mg/mL) and/or amastigotes (about 224 to 4 500 mg/mL) but were relatively toxic to THP-1 cells (IC 50 values o16 to about 42 mg/mL). The remaining plant extracts exhibited in many cases IC 50 values close to, around, or above 500 mg/mL against promastigotes, amastigotes, and THP-1 cells. Conclusions: The S. lycocarpum preparation may be useful against leishmaniasis and may have a good safety index, warranting further investigations into its active constituents and mechanism(s) of action.

Leishmanicidal and Cytotoxic Activity of Algerian Medicinal Plants on Leishmania major and Leishmania infantum

Journal of Medical Microbiology and Infectious Diseases, 2019

Introduction: Leishmaniasis is a severe disease that presents a real public health problem worldwide. Antileishmanial therapy remains expensive with intolerable side effects; therefore, it is essential to develop tolerable antileishmanial medications with a selective efficacy. Methods: In this study, the leishmanicidal activities of seven Algerian plant extracts, selected based on either ethnobotanical or chemotaxonomical data, were screened for their antileishmanial activity against promastigotes and amastigotes of cutaneous leishmaniasis agent Leishmania major (MON 25), and visceral leishmaniasis agent Leishmania infantum (MON 1). The cytotoxic activity against human monocytes THP1 was also determined. Results: In both species, amastigotes showed more sensitivity to the extracts than promastigotes. Erica arborea flower (IC50=43,98 g/mL), Marrubium vulgare leaves (IC50=45,84 g/mL) and Artemisia herba-alba Asso aerial parts (IC50=55,21 g/mL) had an almost similar inhibitory effect on L. major promastigote. Marrubium vulgare leaves (IC50=35,63 g/mL) was most effective against L. infantum promastigotes. Besides, these extracts exhibited low selectivity indices. The best results were obtained with M. vulgare on both L. major and L. infantum promastigotes (IC50s of 45,84 µg/ml and 35,63 µg/ml), and amastigotes (IC50s of 32,15 µg/ml and 18,64 µg/ml). The selectivity index was above two (2.34 for L. major and 3.01 for L. infantum), calculated based on the acceptable cytotoxic effect of M. vulgare on human macrophage cell line (CC50=107,45 µg/ml). Conclusion: Out of the seven methanol extracts tested against promastigotes of L. major and L. infantum, three showed promising activity with potent leishmanicidal effect and acceptable selectivity indices on L. major and L. Infantum.

The potential role and apoptotic profile of three medicinal plant extracts on Leishmania tropica by MTT assay, macrophage model and flow cytometry analysis

Parasite Epidemiology and Control, 2021

Introduction: Treatment of leishmaniasis with conventional synthetic drugs is a major global challenge. This study was designed to explore the leishmanicidal activity and apoptotic profile of three leaf extracts on Leishmania tropica stages. Methods: The plants of Quercus velutina, Calotropis procera and Nicotiana tabacum were gathered from Anbarabbad county, in the southeastern part of Kerman province and extracted by maceration method using methanol alcohol. Various concentrations of the extracts (1, 10, 100 and 1000 μg/mL) were used against L. tropica stages to evaluate the inhibitory effect by colorimetric assay, macrophage model and flow cytometry. The MTT assay was conducted to determine the IC 50 and CC 50 values in promastigotes and J774-A1 macrophages, respectively. For intra-macrophage amastigotes, the leishmanicidal activity was evaluated by calculating the mean number of amastigotes in each macrophage and also IC 50 values. The promastigote or amastigote stages with no drug and complete medium without organisms were considered as positive and negative controls, respectively. Meglumine antimoniate (Glucantime) was also used as standard drug. Also, annexin V was used to assess the apoptotic profile. All treatment settings were incubated for a standard time of 72 h in triplicates. Data were analyzed by t-test and ANOVA. Results: The findings showed that all plant extracts inhibited the proliferation rate of promastigotes and amastigotes (P < 0.001); especially, Q. velutina represented the lowest IC 50 in both stages. Besides, Q. velutina showed the least number of amastigotes in each macrophage compared to the other groups (4.5 μg/mL). The percentage of parasitic apoptosis at 1000 μg/mL of Q. velutina, C. procera, N. tabacum and Glucantime® were 37.4, 18.6, 8.5 and 52.4, respectively. Amastigotes (clinical stage) were significantly more susceptible to extracts and also Glucantime® than promastigotes (P < 0.001). Conclusions: This study revealed that all three extracts of Q. velutina, C. procera and N. tabacum exhibited an effective antileishmanial activity and induced apoptosis against the L. tropica promastigotes. Further investigations are essential to isolate and analyze the chemical compositions and their biological properties.