1998

Cubukcu, B., Gasquet, M., Delmas, F., Favel, A., Mericli, A.H., Balansard, G., 1998.
Evaluation of antiprotozoal and antifungal activities of Turkish Artemisia santonicum
J. Fac. Pharm. Istanbul Univ. 32, 20–22.

Abstract

Extracts and eudesmanolides from Artemisia santonicum were tested for their antiprotozoal and antifungal activities. 8 a-hydroxytaurin was active against Leishmania donovani at 100 pg/ml.

2001

Hatimi, S., Boudouma, M., Bichichi, M., Chaib, N., Idrissi, N.G., 2001.
In vitro evaluation of antileishmania activity of Artemisia herba alba
Asso. Bull. Soc. Pathol. Exot. 94, 29–31

Texte de l’étude non disponible

Abstract

Aqueous extract and essential oil of Artemisia herba-alba Asso were tested for their antileshmanial activity again Leishmania tropica and Leishmania major. The strongest leishmanicidal activity was observed with the essential oil at 2 micrograms/ml as versus the other two strains tested. The aqueous extract showed an antileshmanial activity at 4 micrograms/ml.

2003

L.G. Rocha; J.R.G.S. Almeida; R.O. Macêdo; J.M. Barbosa-Filho
A review of natural products with antileishmanial activity
Phytomedicinevolume 12, issue 6-7 (2005)

Abstract

Infections caused by protozoa of the genus Leishmania are a major worldwide health problem, with high endemicity in developing countries. The incidence of the disease has increased since the emergence of AIDS. In the absence of a vaccine, there is an urgent need for effective drugs to replace/supplement those in current use. The plant kingdom is undoubtedly valuable as a source of new medicinal agents. The present work constitutes a review of the literature on plant extracts and chemically defined molecules of natural origin showing antileishmanial activity. The review refers to 101 plants, their families, and geographical distribution, the parts utilized, the type of extract and the organism tested. It also includes 288 compounds isolated from higher plants and microorganisms, classified into appropriate chemical groups. Some aspects of recent antileishmanial-activity-directed research on natural products are discussed.

2012

Emami SA, Zamanai Taghizadeh Rabe S, Ahi A, Mahmoudi M.
Inhibitory Activity of Eleven Artemisia Species from Iran against Leishmania Major Parasites
Iran J Basic Med Sci. 2012 Mar;15(2):807-11. PMID: 23493354; PMCID: PMC3586874.

Abstract

Objectives: Annual incidence of cutaneous leishmaniasis is increasingly growing and development of the alternative drugs against it is a major concern. Artemisia genus is a traditional medicinal plant in Iran. The aim of this study was to examine the leishmanicidal activity of various Iranian Artemisia species extracts.

Materials and methods: Different extracts were gathered from eleven Iranian Artemisia species. Their leishmanicidal activities against the growth of Leishmania major (L. major) promastigotes were examined as the half maximal inhibitory concentration (IC50) using MTT assay.

Results: Obtained results showed that ethanol extracts especially those taken from A. ciniformis, A. santolina and A. kulbadica have the strongest effects.

Conclusion: Looking for the effective leishmanicidal agents from natural resources in Iran, we found that the ethanol extract of collected Artemisia species had significant effect on in vitro leishmanicidal activity and may be suitable candidates in the treatment of leishmaniasis. Keywords: Artemisia; Leishmania major; Leishmanicidal activity; MTT assay; Promastigote.

Mohammad Islamuddin, Abdullah Farooque, Dwarakanath, Dinkar Sahal and Farhat Afrin
Extracts of Artemisia annua leaves and seeds mediate programmed cell death in Leishmania donovani
Journal of Medical Microbiology (2012), 61, 1709–1718

Abstract

Leishmaniasis is one of the major tropical parasitic diseases, and the condition ranges in severity from self-healing cutaneous lesions to fatal visceral manifestations. There is no vaccine available against visceral leishmaniasis (VL) (also known as kala-azar in India), and current antileishmanial drugs face major drawbacks, including drug resistance, variable efficacy, toxicity and parenteral administration. We report here that n-hexane fractions of Artemisia annua leaves (AAL) and seeds (AAS) possess significant antileishmanial activity against Leishmania donovani promastigotes, with GI50 of 14.4 and 14.6 mg μgml-1 , respectively, and the IC50 against intracellular amastigotes was found to be 6.6 and 5.05 μgml-11 , respectively. Changes in the morphology of promastigotes and growth reversibility analysis following treatment confirmed the leishmanicidal effect of the active fractions, which presented no cytotoxic effect on mammalian cells. The antileishmanial activity was mediated via apoptosis, as evidenced by externalization of phosphatidylserine, in situ labelling of DNA fragments by terminal deoxynucleotidyltransferase-mediated dUTP nick end labelling (TUNEL) and cell-cycle arrest at the sub-G0/G1 phase. High-performance thin-layer chromatography (HPTLC) fingerprinting showed that the content of artemisinin in crude bioactive extracts ( 1.4 mg per 100 mg n-hexane fraction) was too low to account for the observed antileishmanial activity. Characterization of the active constituents by GC-MS showed that a-amyrinyl acetate, b-amyrine and derivatives of artemisinin were the major constituents in AAL and cetin, EINECS 211-126-2 and artemisinin derivatives in AAS. Our findings indicate the presence of antileishmanial compounds besides artemisinin in the n-hexane fractions of A. annua leaves and seeds.

Abbreviations: AAL, n-hexane fraction of Artemisia annua leaves; AAS, n-hexane fraction of A. annua seeds; FITC, fluorescein sothiocyanate; PCD, programmed cell death; PI, propidium iodide; PS, phosphatidylserine; TdT, terminal deoxynucleotidyltransferase; TUNEL, TdTmediated dUTP nick end labelling;
VL, visceral leishmaniasis.

Schmidt TJ, Khalid SA, Romanha AJ, Alves TM, Biavatti MW, Brun R, Da Costa FB, de Castro SL, Ferreira VF, de Lacerda MV, Lago JH, Leon LL, Lopes NP, das Neves Amorim RC, Niehues M, Ogungbe IV, Pohlit AM, Scotti MT, Setzer WN, de N C Soeiro M, Steindel M, Tempone AG.
The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases - part I.
Curr Med Chem. 2012;19(14):2128-75. doi: 10.2174/092986712800229023. PMID: 22414103.

Abstract

Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical Diseases" (NTDs) defined as such by WHO due to the neglect of financial investment into research and development of new drugs by a large part of pharmaceutical industry and neglect of public awareness in high income countries. Another major tropical protozoan disease is malaria (caused by various Plasmodium species), which -although not mentioned currently by the WHO as a neglected disease- still represents a major problem, especially to people living under poor circumstances in tropical countries. Malaria causes by far the highest number of deaths of all protozoan infections and is often (as in this review) included in the NTDs. The mentioned diseases threaten many millions of lives world-wide and they are mostly associated with poor socioeconomic and hygienic environment. Existing therapies suffer from various shortcomings, namely, a high degree of toxicity and unwanted effects, lack of availability and/or problematic application under the life conditions of affected populations. Development of new, safe and affordable drugs is therefore an urgent need. Nature has provided an innumerable number of drugs for the treatment of many serious diseases. Among the natural sources for new bioactive chemicals, plants are still predominant. Their secondary metabolism yields an immeasurable wealth of chemical structures which has been and will continue to be a source of new drugs, directly in their native form and after optimization by synthetic medicinal chemistry. The current review, published in two parts, attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs.

Schmidt TJ, Khalid SA, Romanha AJ, Alves TM, Biavatti MW, Brun R, Da Costa FB, de Castro SL, Ferreira VF, de Lacerda MV, Lago JH, Leon LL, Lopes NP, das Neves Amorim RC, Niehues M, Ogungbe IV, Pohlit AM, Scotti MT, Setzer WN, de N C Soeiro M, Steindel M, Tempone AG.
The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases - part II.
Curr Med Chem. 2012;19(14):2176-228. PMID: 22414104.

Abstract

Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical Diseases" (NTDs) defined by the WHO. Furthermore, malaria (caused by various Plasmodium species) can be considered a neglected disease in certain countries and with regard to availability and affordability of the antimalarials. Living organisms, especially plants, provide an innumerable number of molecules with potential for the treatment of many serious diseases. The current review attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs. In part I, a general description of the diseases, the current state of therapy and need for new therapeuticals, assay methods and strategies applied in the search for new plant derived natural products against these diseases and an overview on natural products of terpenoid origin with antiprotozoal potential were given. The present part II compiles the current knowledge on natural products with antiprotozoal activity that are derived from the shikimate pathway (lignans, coumarins, caffeic acid derivatives), quinones of various structural classes, compounds formed via the polyketide pathways (flavonoids and related compounds, chromenes and related benzopyrans and benzofurans, xanthones, acetogenins from Annonaceae and polyacetylenes) as well as the diverse classes of alkaloids. In total, both parts compile the literature on almost 900 different plant-derived natural products and their activity data, taken from over 800 references. These data, as the result of enormous efforts of numerous research groups world-wide, illustrate that plant secondary metabolites represent an immensely rich source of chemical diversity with an extremely high potential to yield a wealth of lead structures towards new therapies for NTDs. Only a small percentage, however, of the roughly 200,000 plant species on earth have been studied chemically and only a small percentage of these plants or their constituents has been investigated for antiprotozoal activity. The repository of plant-derived natural products hence deserves to be investigated even more intensely than it has been up to present.

2014

Islamuddin M, Chouhan G, Tyagi M, Abdin MZ, Sahal D, Afrin F.
Leishmanicidal activities of Artemisia annua leaf essential oil against Visceral Leishmaniasis.
Front Microbiol. 2014 Nov 25;5:626. doi: 10.3389/fmicb.2014.00626.
Erratum in: Front Microbiol. 2015;6:1015. PMID: 25505453; PMCID: PMC4243575.

Abstract

Visceral leishmaniasis (VL), the second-most dreaded parasitic disease after malaria, is currently endemic in 88 countries. Dramatic increases in the rates of infection, drug resistance, and non-availability of safe vaccines have highlighted the need for identification of novel and inexpensive anti-leishmanial agents from natural sources. In this study, we showed the leishmanicidal effect of essential oil from Artemisia annua leaves (AALEO) against Leishmania donovani in vitro and in vivo. AALEO was extracted by hydrodistillation and characterized by GC-MS, the most abundant compounds were found to be camphor (52.06 %) followed by β-caryophyllene (10.95 %). AALEO exhibited significant leishmanicidal activity against L. donovani, with 50 % inhibitory concentration of 14.63 ± 1.49 μg ml(-1) and 7.3 ± 1.85 μg ml(-1), respectively, against the promastigotes and intracellular amastigotes. The effect was mediated through programmed cell death as confirmed by externalization of phosphatidylserine, DNA nicking by TdT-mediated dUTP nick-end labeling assay, dyskinetoplastidy, cell cycle arrest at sub-G0-G1 phase, loss of mitochondrial membrane potential and reactive oxygen species generation in promastigotes and nitric oxide generation in ex vivo model. AALEO presented no cytotoxic effects against mammalian macrophages even at 200 μg ml(-1). Intra-peritoneal administration of AALEO (200 mg/ kg.b.w.) to infected BALB/c mice reduced the parasite burden by almost 90% in the liver and spleen with significant reduction in weight. There was no hepato- or nephro-toxicity as demonstrated by normal levels of serum enzymes. The promising antileishmanial activity shown by camphor-rich AALEO may provide a new lead in the treatment of VL.

Keywords: Artemisia annua; apoptosis; essential oil; leishmaniasis; leishmanicidal; therapeutic efficacy; visceral.

2015

Islamuddin M, Chouhan G, Farooque A, Dwarakanath BS, Sahal D, Afrin F.
Th1-biased immunomodulation and therapeutic potential of Artemisia annua in murine visceral leishmaniasis.
PLoS Negl Trop Dis. 2015 Jan 8;9(1):e3321. doi: 10.1371/journal.pntd.0003321. PMID: 25568967; PMCID: PMC4287499.

Abstract

Background: In the absence of vaccines and limitations of currently available chemotherapy, development of safe and efficacious drugs is urgently needed for visceral leishmaniasis (VL) that is fatal, if left untreated. Earlier we reported in vitro apoptotic antileishmanial activity of n-hexane fractions of Artemisia annua leaves (AAL) and seeds (AAS) against Leishmania donovani. In the present study, we investigated the immunostimulatory and therapeutic efficacy of AAL and AAS.
Methodology/principal findings: Ten-weeks post infection, BALB/c mice were orally administered AAL and AAS for ten consecutive days. Significant reduction in hepatic (86.67% and 89.12%) and splenic (95.45% and 95.84%) parasite burden with decrease in spleen weight was observed. AAL and AAS treated mice induced the strongest DTH response, as well as three-fold decrease in IgG1 and two-fold increase in IgG2a levels, as compared to infected controls. Cytometric bead array further affirmed the elicitation of Th1 immune response as indicated by increased levels of IFN-γ, and low levels of Th2 cytokines (IL-4 and IL-10) in serum as well as in culture supernatant of lymphocytes from treated mice. Lymphoproliferative response, IFN-γ producing CD4+ and CD8+ T lymphocytes and nitrite levels were significantly enhanced upon antigen recall in vitro. The co-expression of CD80 and CD86 on macrophages was significantly augmented. CD8+ T cells exhibited CD62Llow and CD44hi phenotype, signifying induction of immunological memory in AAL and AAS treated groups. Serum enzyme markers were in the normal range indicating inertness against nephro- and hepato-toxicity.

Conclusions/significance: Our results establish the two-prong antileishmanial efficacy of AAL and AAS for cure against L. donovani that is dependent on both the direct leishmanicidal action as well as switching-on of Th1-biased protective cell-mediated immunity with generation of memory. AAL and AAS could represent adjunct therapies for the treatment of leishmaniasis, either alone or in combination with other antileishmanial agents.

2016

Azizi K, Shahidi-Hakak F, Asgari Q, Hatam GR, Fakoorziba MR, Miri R, Moemenbellah-Fard MD.
In vitro efficacy of ethanolic extract of Artemisia absinthium (Asteraceae) against Leishmania major L. using cell sensitivity and flow cytometry assays.
J Parasit Dis. 2016 Sep;40(3):735-40. doi: 10.1007/s12639-014-0569-5. Epub 2014 Sep 20. PMID: 27605775; PMCID: PMC4996182.

Abstract

Leishmaniasis is one of the most neglected human diseases with an estimated global burden ranking second in mortality and fourth in morbidity among the tropical infections. Chemotherapy involving the use of drugs like glucantime is the mainstay treatment in endemic areas of Iran. Drug resistance is increasingly prevalent, so search for alternative therapy is gathering pace. Medicinal herbs, like wormwood Artemisia, have chemical compounds effective against a number of pathogens. In this study, the efficacy of ethanol extract from Artemisia absinthium (Asteraceae) against Leishmania major L. was investigated in vitro. The outcome of different effective doses (1-40 mg/ml) of ethanol extracts from this medicinal herb, A. absinthium, on a standard Iranian parasite strain of L. major was examined. The L. major promastigote cell sensitivity and mortality or viability effects due to the addition of herbal extract were measured using the MTT assay and the flow cytometry technique, respectively. There was complete agreement between the two assays. The lethal concentration (LC50) was measured as 101 mg/ml. Some contrasting relationships between the medicinal herb concentrations and the viability of parasites were observed; so that there was an increased multiplication of the parasite at low concentrations of the drug, but an anti-parasitic apoptotic effect was seen at high concentrations of A. absinthium. It was concluded that there might be one or more chemical constituents within the herbal extract of wormwood which at high concentration controlled cell division and affected the relevant activity within the only one giant mitochondrion in this flagellate parasite. At low doses, however, it showed the opposite effect of leading to mitotic cell divisions.

Keywords: Artemisia; IC50; LC50; Leishmania; MTT; Viability assay; Wormwood.

Tariq A, Adnan M, Amber R, Pan K, Mussarat S, Shinwari ZK.
Ethnomedicines and anti-parasitic activities of Pakistani medicinal plants against Plasmodia and Leishmania parasites
Ann Clin Microbiol Antimicrob. 2016 Sep 20;15(1):52. doi: 10.1186/s12941-016-0170-0. PMID: 27647140; PMCID: PMC5029062.

Abstract

Background: Leishmaniasis and malaria are the two most common parasitic diseases and responsible for large number of deaths per year particularly in developing countries like Pakistan. Majority of Pakistan population rely on medicinal plants due to their low socio-economic status. The present review was designed to gather utmost fragmented published data on traditionally used medicinal plants against leishmaniasis and malaria in Pakistan and their scientific validation.
Methods: Pub Med, Google Scholar, Web of Science, ISI Web of knowledge and Flora of Pakistan were searched for the collection of data on ethnomedicinal plants. Total 89 articles were reviewed for present study which was mostly published in English. We selected only those articles in which complete information was given regarding traditional uses of medicinal plants in Pakistan.

Results: Total of 56 plants (malaria 33, leishmaniasis 23) was found to be used traditionally against reported parasites. Leaves were the most focused plant part both in traditional use and in in vitro screening against both parasites. Most extensively used plant families against Leishmaniasis and Malaria were Lamiaceae and Asteraceae respectively. Out of 56 documented plants only 15 plants (Plasmodia 4, Leishmania 11) were assessed in vitro against these parasites. Mostly crude and ethanolic plant extracts were checked against Leishmania and Plasmodia respectively and showed good inhibition zone. Four pure compounds like artemisinin, physalins and sitosterol extracted from different plants proved their efficacy against these parasites.

Conclusions: Present review provides the efficacy and reliability of ethnomedicinal practices and also invites the attention of chemists, pharmacologist and pharmacist to scientifically validate unexplored plants that could lead toward the development of novel anti-malarial and anti-leishmanial drugs.

Keywords: Ethnomedicines; In vitro activities; Leishmaniasis; Malaria; Phytochemicals.

Ullah N, Nadhman A, Siddiq S, Mehwish S, Islam A, Jafri L, Hamayun M.
Plants as Antileishmanial Agents: Current Scenario
Phytother Res. 2016 Dec;30(12):1905-1925. doi: 10.1002/ptr.5710. Epub 2016 Oct 5. PMID: 27704633.

Abstract

Leishmaniasis is a clinical manifestation caused by the parasites of the genus Leishmania. Plants are reservoirs of bioactive compounds, which are known to be chemically balanced, effective and least injurious as compared with synthetic medicines. The current resistance and the toxic effects of the available drugs have brought the trend to assess the antileishmanial effect of various plant extracts and their purified compound/s, which are summarized in this review. Moreover, it also highlights various traditional remedies used by local healers against leishmaniasis. A systematic cross-sectional study for antileishmanial activity of natural products was carried out using multiple literature databases. The records retrieved since 2000 till year 2016 were analysed and summarized in the form of comprehensive tables and graphs. Natural products are potential source of new and selective agents that can significantly contribute to primary healthcare and probably are promising substitutes of chemicals for the treatment of protozoan diseases like leishmaniasis. Where the researchers prefer to use alcoholic solvents for the extraction of antileishmanial agents from plants, most of the studies are limited to in vitro conditions majorly on using promastigote forms of Leishmania. Thus, there is a need to carry out such activities in vivo and in host macrophages. Further, there is a need of mechanistic studies that can help taking few of the promising pure compounds to clinical level.

Ogungbe IV, Setzer WN.
The Potential of Secondary Metabolites from Plants as Drugs or Leads against Protozoan Neglected Diseases-Part III: In-Silico Molecular Docking Investigations
Molecules. 2016 Oct 19;21(10):1389. doi: 10.3390/molecules21101389. PMID: 27775577; PMCID: PMC6274513.

Abstract

Malaria, leishmaniasis, Chagas disease, and human African trypanosomiasis continue to cause considerable suffering and death in developing countries. Current treatment options for these parasitic protozoal diseases generally have severe side effects, may be ineffective or unavailable, and resistance is emerging. There is a constant need to discover new chemotherapeutic agents for these parasitic infections, and natural products continue to serve as a potential source. This review presents molecular docking studies of potential phytochemicals that target key protein targets in Leishmania spp., Trypanosoma spp., and Plasmodium spp.

Keywords: Leishmania; Plasmodium; Trypanosoma; natural products drug discovery.

2017

Mesa LE, Vasquez D, Lutgen P, Vélez ID, Restrepo AM, Ortiz I, Robledo SM.
In vitro and in vivo antileishmanial activity of Artemisia annua L. leaf powder and its potential usefulness in the treatment of uncomplicated cutaneous leishmaniasis in humans
Rev Soc Bras Med Trop. 2017 Jan-Feb;50(1):52-60. doi: 10.1590/0037-8682-0457-2016. PMID: 28327802.

Abstract

Introduction: Cutaneous leishmaniasis (CL) is a tropical disease that affects millions of individuals worldwide. The current drugs for CL may be effective but have serious side effects; hence, alternatives are urgently needed. Although plant-derived materials are used for the treatment of various diseases in 80% of the global population, the validation of these products is essential. Gelatin capsules containing dried Artemisia annua leaf powder were recently developed as a new herbal formulation (totum) for the oral treatment of malaria and other parasitic diseases. Here, we aimed to determine the usefulness of A. annua gel capsules in CL.
Methods: The antileishmanial activity and cytotoxicity of A. annua L. capsules was determined via in vitro and in vivo studies. Moreover, a preliminary evaluation of its therapeutic potential as antileishmanial treatment in humans was conducted in 2 patients with uncomplicated CL.

Results: Artemisia annua capsules showed moderate in vitro activity in amastigotes of Leishmania (Viannia) panamensis; no cytotoxicity in U-937 macrophages or genotoxicity in human lymphocytes was observed. Five of 6 (83.3%) hamsters treated with A. annua capsules (500mg/kg/day) for 30 days were cured, and the 2 examined patients were cured 45 days after initiation of treatment with 30g of A. annua capsules, without any adverse reactions. Both patients remained disease-free 26 and 24 months after treatment completion.

Conclusion: Capsules of A. annua L. represent an effective treatment for uncomplicated CL, although further randomized controlled trials are needed to validate its efficacy and safety.

Soosaraei M, Fakhar M, Hosseini Teshnizi S, Ziaei Hezarjaribi H, Banimostafavi ES.
Medicinal plants with promising antileishmanial activity in Iran: a systematic review and meta-analysis
Ann Med Surg (Lond). 2017 Jul 27;21:63-80. doi: 10.1016/j.amsu.2017.07.057. PMID: 28794869; PMCID: PMC5536386.

Abstract

Background: Leishmaniasis is a major public health problem worldwide. The aim of the present study was to investigate medicinal plants with anti-Leishmania activity which used in Iran.
Methods: Data were systematically gathered from five English databases including Ebsco, Science Direct, PubMed, Google Scholar and Scopus, four Persian databases including Magiran, Iran doc, Iran medex and the Scientific Information Database (SID) from 1999 to April 2015. Information obtained included plant family, extraction method, concentrations of extracts, animal models and parasite strains.
Results: A total of 68 articles including 188 experiments (140 in vitro and 48 in vivo) between 1999 and 2015, met our eligibility criteria. Thoroughly, 98 types of plants were examined against three genera of Leishmania spp. For the heterogeneity study conducted, it was showed that there was a great deal of variation among studies. Based on random effect, meta-analysis pooled mean of IC50 was obtained 456.64 (95% CI: 396.15, 517.12).
Conclusion: The most Iranian plants used as anti-leishmanial activity were Artemisia species, Allium sativum, Achilleamille folium, Peganum harmala and Thymus vulgaris. The present systematic and meta-analysis review provide valuable information about natural products with anti-Leishmania activity, which would be examined in the future experimental and clinical trials and herbal combination therapy.

Keywords: Leishmania; herbal extracts; medicinal plants; natural products; systematic review.

2019

Moraes Neto RN, Setúbal RFB, Higino TMM, Brelaz-de-Castro MCA, da Silva LCN, Aliança ASDS.
Asteraceae Plants as Sources of Compounds Against Leishmaniasis and Chagas Disease
Front Pharmacol. 2019 May 8;10:477. doi: 10.3389/fphar.2019.00477. PMID: 31156427; PMCID: PMC6530400.

Abstract

Leishmaniasis and Chagas disease cause great impact on social and economic aspects of people living in developing countries. The treatments for these diseases are based on the same regimen for over 40 years, thus, there is an urgent need for the development of new drugs. In this scenario, Asteraceae plants (a family widely used in folk medicine worldwide) are emerging as an interesting source for new trypanocidal and leishmanicidal compounds. Herein, we provide a non-exhaustive review about the activity of plant-derived products from Asteraceae with inhibitory action toward Leishmania spp. and T. cruzi. Special attention was given to those studies aiming the isolation (or identification) of the bioactive compounds. Ferulic acid, rosmarinic acid, and ursolic acid (Baccharis uncinella DC.) were efficient to treat experimental leishmaniasis; while deoxymikanolide (Mikania micrantha) and (+)-15-hydroxy-labd-7-en-17-al (Aristeguietia glutinosa Lam.) showed in vivo anti-T. cruzi action. It is also important to highlight that several plant-derived products (compounds, essential oils) from Artemisia plants have shown high inhibitory potential against Leishmania spp., such as artemisinin and its derivatives. In summary, these compounds may help the development of new effective agents against these neglected diseases.

Keywords: Leishmania spp.; Trypanosoma cruzi; asteraceae plants; leishmanicidal activity; trypanocidal activity; trypanosomatids.

2020

Sánchez-Suárez J, Bernal FA, Coy-Barrera E. Colombian
Contributions Fighting Leishmaniasis: A Systematic Review on Antileishmanials Combined with Chemoinformatics Analysis
Molecules. 2020 Dec 3;25(23):5704. doi: 10.3390/molecules25235704. PMID: 33287235; PMCID: PMC7730898.

Abstract

Leishmaniasis is a parasitic morbid/fatal disease caused by Leishmania protozoa. Twelve million people worldwide are appraised to be currently infected, including ca. two million infections each year, and 350 million people in 88 countries are at risk of becoming infected. In Colombia, cutaneous leishmaniasis (CL) is a public health problem in some tropical areas. Therapeutics is based on traditional antileishmanial drugs, but this practice has several drawbacks for patients. Thus, the search for new antileishmanial agents is a serious need, but the lack of adequately funded research programs on drug discovery has hampered its progress. Some Colombian researchers have conducted different research projects focused on the assessment of the antileishmanial activity of naturally occurring and synthetic compounds against promastigotes and/or amastigotes. Results of such studies have separately demonstrated important hits and reasonable potential, but a holistic view of them is lacking. Hence, we present the outcome from a systematic review of the literature (under PRISMA guidelines) on those Colombian studies investigating antileishmanials during the last thirty-two years. In order to combine the general efforts aiming at finding a lead against Leishmania panamensis (one of the most studied and incident parasites in Colombia causing CL) and to recognize structural features of representative compounds, fingerprint-based analyses using conventional machine learning algorithms and clustering methods are shown. Abstraction from such a meta-description led to describe some function-determining molecular features and simplify the clustering of plausible isofunctional hits. This systematic review indicated that the Colombian efforts for the antileishmanials discovery are increasingly intensified, though improvements in the followed pathways must be definitively pursued. In this context, a brief discussion about scope, strengths and limitations of such advances and relationships is addressed.

Keywords: Colombia; Leishmania panamensis; chemoinformatics; leishmania parasites; leishmanicidal; machine learning; neglected tropical diseases.

Cortes S, Bruno de Sousa C, Morais T, Lago J, Campino L.
Potential of the natural products against leishmaniasis in Old World - a review of in-vitro studies
Pathog Glob Health. 2020 May 18;114(4):170-182. doi: 10.1080/20477724.2020.1754655. Epub 2020 Apr 27. PMID: 32339079; PMCID: PMC7448914.

Abstract

Leishmaniasis is a vector-borne disease among the 10 most Neglected Tropical Diseases with diverse clinical manifestations caused by protozoan parasites of the Leishmania genus. Around 80% of leishmaniasis cases are found in the Old World affecting populations mainly in low and middle-income countries. Its control relies mostly on chemotherapy which still presents many drawbacks. Natural products may offer an inexhaustible source of chemical diversity with therapeutic potential. Despite the lack of knowledge on traditional products with activity against Leishmania parasites, many reports describe the search for natural extracts and compounds with antileishmanial properties against promastigote and amastigote parasite forms. This review summarizes the research of 74 publications of the last decade (2008-2018) focused on the identification of endemic plant-derived products that are active against Old World Leishmania parasites responsible for cutaneous and visceral leishmaniasis. The present review combines data on antileishmanial activity of 423 plants species, belonging to 94 different families, including a large range of crude extracts which lead to the isolation of 86 active compounds. Most studied plants came from Asia and most promising plant families for antileishmanial activity were Asteraceae and Lamiaceae. From the chemical point of view, terpenoids were the most frequently isolated natural products. These studies suggest that natural products isolated from Old World flora are a rich source of new chemical scaffolds for future leishmaniasis treatment as well as for other Neglected Tropical Diseases warranting further investigation.

Keywords: Leishmaniasis; Old World Leishmania spp; antileishmanial activity; natural compounds; plants.