Les leishmanioses font partie des pathologies classées comme « maladies tropicales négligées » . Cette maladie parasitaire provoque des affections cutanées ou viscérales très invalidantes, voire mortelles si elles ne sont pas traitées. Elles sont dues à différents parasites protozoaires intracellulaire de la famille Leishmania transmis par la piqûre d’insectes infectés appelés phlébotomes. Cette maladie est endémique dans 98 pays des cinq continents. Selon l’OMS, 700 000 à 1 million de nouveaux cas se déclarent chaque année. La leishmaniose cutanée est la plus répandue et, bien que les traitements standards soient encore efficaces, ces médicaments ont des effets secondaires graves, de sorte que de nouveaux médicaments efficaces et plus sûrs sont nécessaires. La recension des études sur les propriétés antileishmaniennes de diverses Artemisia montre que certaines armoises et plus particulièrement Artemisia annua peuvent contribuer au traitement des leishmanioses.
Cet article recense l’ensemble des études relatives aux propriétés antileishmaniennes des Artemisia que nous avons pu identifier dans la littérature scientifique. Les études sont présentées dans l’ordre chronologique de leur publication.
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.Des extraits d’Artemisia santonicum ont été testés pour leurs activités antiprotozoaires et antifongiques. Le composé a-hydroxytaurine 8 s’est avéré actif contre Leishmania donovani à 100 pg/ml.
Résumé publié
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, 29–31Texte de l’étude non disponible
L’extrait aqueux et l’huile essentielle d’Artemisia herba-alba ont été testés pour leur activité antileishmanienne contre Leishmania tropica et Leishmania major. L’activité leishmanicide la plus forte a été observée avec l’huile essentielle à 2 microgrammes/ml par rapport aux deux autres souches testées. L’extrait aqueux a montré une activité antileishmanienne à 4 microgrammes/ml.
Résumé publié
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)Cet article est une revue de la littérature sur les extraits de plantes et les molécules d’origine naturelle présentant une activité antileishmanienne. 101 plantes sont présentées ainsi que leur famille, leur distribution géographique, les parties utilisées, le type d’extrait et les organismes cibles testés. Artemisia herba-alba et Artemisia santonicum font partie des plantes citées. Cette revue recense également 288 composés isolés. Les auteurs discutent certains aspects de la recherche orientée vers l’activité antileishmanienne des plantes.
Résumé publié
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.Un variété d’Artemisia font partie de la pharmacopée traditionnelle persane. Cette étude a permis d’examiner l’activité leishmanicide contre la croissance des promastigotes de Leishmania major d’extraits recueillis à partir de onze espèces iraniennes d’Artemisia : Artemisia. turanica, Artemisia annua, Artemisia absinthium, Artemisia fragrans, Artemisia kulbadica, Artemisia ciniformis, Artemisia santolina, Artemisia khorassanica, Artemisia kopedaghensis, Artemisia sieberi, Artemisia biennis. Les solvants utilisés étaient l’éthanol, l’éthyl acetate, le dichloromethane et l’hexane. Les auteurs ont montré que l’extrait éthanolique des espèces d’Artemisia collectées avait un effet significatif sur l’activité leishmanicide in vitro. Les auteurs considèrent que ces extraits pourraient être des candidats appropriés dans le traitement de la leishmaniose. Les extraits éthanoliques prélevés sur Artemisia ciniformis, Artemisia santolina et Artemisia kulbadica, ont eu les effets les plus forts.
Résumé publié
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, 1709–1718Cette étude a montré que des extraits de feuilles et de graines d’Artemisia annua médient la mort cellulaire programmée chez Leishmania donovani
Elle rapporte que les fractions n-hexane des feuilles et des graines d’Artemisia annua possèdent une activité antileishmanienne significative contre les promastigotes de Leishmania donovani, avec respectivement une CI50 de 14,4 et 14,6 mg μgml-1, et que la CI50 contre les amastigotes intracellulaires est de 6,6 et 5,05 μgml-1, respectivement. Les modifications de la morphologie des promastigotes et l’analyse de la réversibilité de la croissance après traitement ont confirmé l’effet leishmanicide des fractions actives, qui n’ont présenté aucun effet cytotoxique sur les cellules de mammifères. L’activité antileishmanienne a été médiée par l’apoptose et l’arrêt du cycle cellulaire. La teneur en artémisinine des extraits bioactifs bruts était trop faible pour expliquer l’activité antileishmanienne observée. La caractérisation des constituants actifs a montré que l’acétate d’a-amyrinyle, la b-amyrine et les dérivés de l’artémisinine étaient les principaux constituants de l’extrait de feuille et que la cétine, EINECS 211-126-2 et les dérivés de l’artémisinine étaient les principaux constituants de l’extrait de feuille. Ces résultats indiquent la présence de composés antileishmaniens autres que l’artémisinine dans les fractions n-hexane des feuilles et des graines d’Artemisia annua.Résumé publié
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.La présente revue, publiée en deux parties, expose le potentiel des substances d’origine végétale à fournir des pistes de recherches pour l’élaboration de médicaments antiprotozoaires dans la lutte contre les maladies tropicales négligées.
Résumé publié
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.Cet article est le deuxième volet d’une revue, publiée en deux parties, dédié au potentiel des produits naturels d’origine végétale en tant que pistes et/ou médicaments antiprotozoaires dans la lutte contre les maladies tropicales négligées.
Résumé publié
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.Cette étude expose l’effet leishmanicide de l’huile essentielle de feuilles d’Artemisia annua contre Leishmania donovani in vitro et in vivo inducteur de la leishmaniose viscérale, deuxième maladie parasitaire la plus redoutée après le paludisme, actuellement endémique dans 88 pays. Les composés identifiés comme les plus abondants dans les feuilles d’Artemisia annua étaient le camphre (52,06 %) suivi du β-caryophyllène (10,95 %). L’huile essentielle de feuilles d’Artemisia annua a présenté une activité leishmanicide significative contre L. donovani, avec une concentration inhibitrice de 50 % de 14,63 ± 1,49 μg ml(-1) contre les promastigotes, et de 7,3 ± 1,85 μg ml(-1) contre les amastigotes intracellulaires. L’effet a été médié par la mort cellulaire programmée. L’huile essentielle de feuilles d’Artemisia annua n’a présenté aucun effet cytotoxique contre les macrophages de mammifères, même à 200 μg ml(-1). L’administration intrapéritonéale d’huile essentielle de feuilles d’Artemisia annua (200 mg/ kg.p.c.) à des souris infectées a réduit la charge parasitaire de près de 90 % dans le foie et la rate avec une réduction significative du poids. Il n’y a pas eu d’hépatotoxicité ou de néphrotoxicité, comme le démontrent les niveaux normaux d’enzymes sériques. Pour les auteurs de cette étude, l’activité antileishmanienne prometteuse démontrée par l’huile essentielle de feuilles d’Artemisia annua riche en camphre pourrait fournir une nouvelle piste dans le traitement de la leishmaniose viscérale.
Résumé publié
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.Les auteurs de cet article contextualisent leur recherche de la manière suivante : « La leishmaniose viscérale est une maladie tropicale mortelle, transmise par des vecteurs, qui touche les couches les plus pauvres de la société. Les médicaments actuellement disponibles sont toxiques, coûteux et ont de graves effets secondaires. Le problème est encore aggravé par l’émergence de la co-infection leishmaniose viscérale-VIH et l’apparition de séquelles appelée « leishmaniose dermique post kala-azar » (PKDL) après une guérison apparente. En l’absence de vaccins et compte tenu de la résistance croissante aux médicaments, d’autres interventions thérapeutiques sont donc nécessaires. La leishmaniose viscérale se caractérise également par une grave dépression de l’immunité à médiation cellulaire qui complique l’efficacité des médicaments chimiothérapeutiques. La restauration du système immunitaire affaibli, associée à un effet antileishmanien, serait une approche rationnelle dans la recherche de médicaments antileishmaniens. Les métabolites secondaires dérivés de plantes ont été recommandés pour contenir les maladies antiparasitaires, y compris la leishmaniose, qui aident de manière synergique à lever la suppression immunitaire. »
Les auteurs de cette étude avaient précédemment rapporté l’activité antileishmanienne in vitro des fractions n-hexane des feuilles et des graines d’Artemisia annua qui était médiée par l’apoptose. Dans cette étude, ils ont montré que l’administration orale d’extrait n-hexane de feuilles et de graines d’Artemisia annua réduit de manière significative de la charge parasitaire du foie et de la rate des souris infectées par Leishmania donovani avec une immunostimulation concomitante et une induction de la mémoire immunologique. Les auteurs considèrent que ces résultats établissent l’efficacité antileishmanienne à deux volets des extraits n-hexane de feuilles et des graines d’Artemisia annua pour la guérison de leishmaniose viscérale qui dépend à la fois de l’action leishmanicide directe et de l’activation de l’immunité à médiation cellulaire protectrice basée sur Th1 avec la génération d’une mémoire immunologique. Les extraits n-hexane de feuilles et des graines d’Artemisia annua pourraient représenter des thérapies d’appoint pour le traitement de la leishmaniose, soit seuls, soit en association avec d’autres agents antileishmaniens.
Résumé publié
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.Dans cette étude, l’efficacité d’un extrait éthanolique d’Artemisia absinthium (Asteraceae) contre Leishmania major L. a été étudiée in vitro en mesurant la sensibilité des cellules promastigotes de L. major et les effets de mortalité ou de viabilité dus à l’ajout de l’extrait de plante. Les chercheurs ont observé des relations contrastées entre les concentrations d’herbes médicinales et la viabilité des parasites ont été observées ; ainsi, il y avait une multiplication accrue du parasite à de faibles concentrations du médicament, mais un effet apoptotique antiparasitaire a été observé à de fortes concentrations d’extrait d’Artemisia absinthium. Ces résultats montrent qu’ à forte concentration, un ou plusieurs constituants chimiques de l’extrait d’absinthe contrôlent la division cellulaire et affectent l’activité pertinente dans la seule mitochondrie géante de ce parasite flagellé. À faible dose, cependant, iles induisent l’effet inverse en entraînant des divisions cellulaires mitotiques.
Résumé publié :
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.La présente étude a été conçue pour rassembler les données publiées jusqu’aux plus fragmentaires sur les plantes médicinales utilisées traditionnellement contre la leishmaniose et le paludisme au Pakistan et sur leur validation scientifique. Cette revue montre que les plantes de la famille des Lamiaceae sont le plus souvent utilisées contre la leishmaniose quand celles de la famille des Asteraceae sont le plus fréquemment utilisées pour traiter la malaria. Les auteurs ont évalué l’activité antiplasmodium de 4 plantes, l’activité antileshmania de 11 plantes. La plupart des extraits de plantes bruts et éthanoliques ont montré une bonne zone d’inhibition. Quatre composés purs comme l’artémisinine, les physalines et le sitostérol extraits de différentes plantes ont prouvé leur efficacité contre ces parasites. Les auteurs concluent que revue démontre l’efficacité et la fiabilité des pratiques ethnomédicales pakistanises et invitent les chimistes, pharmacologues et pharmaciens à valider scientifiquement des plantes inexplorées qui pourraient conduire au développement de nouveaux médicaments antipaludiques et antileishmaniens.
Résumé publié
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.Cet article est une étude transversale systématique de l’activité antileishmanienne d’extraits de plantes a été réalisée en utilisant plusieurs bases de données de la littérature scientifique. Les auteurs ont été analysés et résumés les données qu’ils ont récupérées sous forme de tableaux et de graphiques détaillés. Ils considèrent que les extraits de plantes sont une source potentielle de nouveaux agents sélectifs qui peuvent contribuer de manière significative aux soins de santé primaires et sont probablement des substituts prometteurs des produits chimiques pour le traitement des maladies provoquées par des protozoaires comme la leishmaniose. Les auteurs notent que lorsque les chercheurs préfèrent utiliser des solvants alcooliques pour l’extraction d’agents antileishmaniens à partir de plantes, et que la plupart des études se limitent à des conditions in vitro, principalement en utilisant des formes promastigotes de Leishmania. Il est donc pour eux nécessaire de mener de mener des étude des activités in vivo et des études mécanistiques qui pourront aider à amener à entreprendre des essais cliniques des composés de plantes les plus prometteurs.
Résumé publié
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.Cet article est le troisième opus de deux autres publiées en 2012. Les auteurs relèvent que le paludisme, la leishmaniose, la maladie de Chagas et la trypanosomiase humaine africaine continuent de causer des souffrances et des décès considérables dans les pays en développement. Ils considèrent que les options thérapeutiques actuelles pour ces maladies parasitaires protozoaires ont généralement de graves effets secondaires, peuvent être inefficaces ou indisponibles, et relèvent que des résistances apparaissent. En conséquence, considèrent nécessaires nécessaires de découvrir de nouveaux agents chimiothérapeutiques pour ces infections parasitaires, et que les produits naturels peuvent en être une source potentielle. Cette revue présente des études de docking moléculaire de substances phytochimiques potentielles qui ciblent des protéines clés chez Leishmania spp., Trypanosoma spp. et Plasmodium spp.
Résumé publié
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.Les auteurs de cet articles ont étudié les effets de la poudre de feuilles d’Artemisia annua in vitro et in vivo sur des hamsters et avec deux sujets humains.
In vitro, la poudre de feuilles avaient une EC50 in vitro de 48,07 μg/mL contre les amastigotes de Leishmania panamensis avec un indice thérapeutique de 8,73. L’amphotéricine B avait un indice thérapeutique de 625 et une CE50 de 0,06 μg/mL. Les résultats in vivo de l’administration de 500 mg/kg/jour chez des hamsters ont induit 83,3% de guérison à 30 jours.
Les deux patients ont reçu de la poudre d’Artemisia annua comme suit : du 1er au 3e jour, 3 g/jour ; du 4e au 7e jour, 2 g/jour ; du 8e au 20e jour, 1 g/jour. La quantité totale d’A. annua administrée était de 30 g par patient sur 20 jours.
À la fin du traitement leurs ulcères avaient rétréci de 20 à 35 %. Ces lésions cutanées ont été totalement guéri avec une fermeture complète de l’ulcère 45 jours après la fin du traitement. Les ulcères des patients sont restés indemnes de résurgence de la maladie deux ans après le traitement. Pendant et après le traitement, aucun des patients n’a présenté d’effets indésirables, ce qui suggère que la poudre de feuilles d’Artemisia pourrait également s’avérer utile pour traiter la leishmaniose.Résumé publié
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.Soosaraei M et al. ont étudié les plantes médicinales à activité anti-Leishmania utilisées en Iran. Ils ont systématiquement recueillie les données disponibles de de 1999 à avril 2015 à partir des bases de données anglaises et persanes. A l’issue de cette recension, ils ont examiné manière approfondi l’activité de 98 espèces de plantes contre trois genres de Leishmania spp. Il ressort de cet exament que les plantes les plus utilisées pour leur activité anti-leishmanienne en Iran sont divreses espèces d’Artemisia, Allium sativum, Achilleamille folium, Peganum harmala et Thymus vulgaris. Pour ses auteurs, cette revue systématique et la méta-analyse associée fournissent des informations sur les produits naturels ayant une activité anti-Leishmania qui devraien être étudiées dans le cadre de futurs essais expérimentaux et cliniques.
Résumé publié
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.Les auteurs de cette publication ont procédé à une revue non exhaustive de l’activité des produits dérivés des Astéracées ayant une action inhibitrice sur Leishmania spp. et Trypanosoma cruzi. Ils ont accordé une attention particulière aux études axée sur l’isolation (ou l’identification) des composés bioactifs. Il ressort de cette revue que l’acide férulique, l’acide rosmarinique et l’acide ursolique (Baccharis uncinella DC.) ont été efficaces pour traiter la leishmaniose expérimentale, tandis que le désoxymikanolide (Mikania micrantha) et le (+)-15-hydroxy-labd-7-en-17-al (Aristeguietia glutinosa Lam.) ont montré une action anti-T. cruzi in vivo. Les auteurs soulignent que plusieurs produits dérivés de plantes (composés, huiles essentielles) comme l’artémisinine et ses dérivés provenant d’Artemisia sp.ont montré un potentiel inhibiteur élevé contre Leishmania spp. Les auteurs concluent que ces composés pourraient contribuer au développement de nouveaux agents efficaces contre la leishmaniose.
Résumé publié
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.Cette étude passe en revue les publications des chercheurs colombiens axées sur l’évaluation de l’activité antileishmanienne de composés naturels et synthétiques contre les promastigotes et/ou les amastigote au cours des trente-deux dernières années. son objectif étant de trouver des pistes de traitement contre Leishmania panamensis, l’un des parasites les plus étudiés et incidents en Colombie causant la leshmaniose cutanée. L’objectif plus spécifique des auteurs était d’identifier les caractéristiques structurelles des composés représentatifs. Cette méta-description a permis de décrire certaines caractéristiques moléculaires déterminant la fonction et de simplifier le regroupement d’occurrences isofonctionnelles plausibles.
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.Cet article passe en revue 74 publications de la décennie (2008-2018) axées sur l’identification de produits dérivés de plantes endémiques actifs contre les parasites Leishmania de l’Ancien Monde responsables de la leishmaniose cutanée et viscérale. La présente revue combine les données sur l’activité antileishmanienne de 423 espèces de plantes, appartenant à 94 familles différentes, y compris une large gamme d’extraits bruts qui ont conduit à l’isolement de 86 composés actifs. La plupart des plantes étudiées provenaient d’Asie et les familles de plantes les plus prometteuses pour l’activité antileishmanienne étaient les Asteraceae et les Lamiaceae. D’un point de vue chimique, les terpénoïdes étaient les produits naturels les plus fréquemment isolés.
Résumé publié
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.
6/10/2021
http://lavierebelle.org/artemisia-et-leishmanioses