In vitro efficacy of different concentrations of lupeol on old world Leishmania donovani
DOI:
https://doi.org/10.17420/ap7002.523Keywords:
lupeol, MTT assay, visceral leishmaniosis, IraqAbstract
Leishmaniosis is a tropical neglected parasitic disease that is endemic in many countries, including Middle East, with no existing effective vaccines. The bite of female sand-fly transmits the causative agent, Leishmania spp., to humans. High toxicity, resistance and treatment failure of the available chemotherapy against visceral leishmaniosis demands the investigation of new anti-leishmanial compounds. Lupeol is a form of triterpene isolated from several medicinal plants and possesses an antimicrobial property. In this study, cytotoxic effect of lupeol was screened against the mammalian amastigotes form and insect promastigote form of Leishmania donovani, following three cycles of incubation at different concentrations by MTT assay. Results revealed the in vitro anti-leishmanial effect of lupeol on both forms of the parasite where significant decline in promastigotes and amastigotes growth was observed. This was conducted along three times of follow up (24, 48, 72) hours, in comparison to the classical sodium stibogluconate treatment. Cell viability was calculated and the minimum IC50 was detected after 48 hours for amastigotes and 24 hours for promastigotes, 12.125 μM, 102.78 μM, respectively. Given the severity of visceral leishmaniosis and the toxicity of conventional chemotherapies, the anti-leishmanial activity of lupeol suggested a promising compound for additional clinical trials.
References
Majeed B., Sobel J., Nawar A., Badri S., Muslim H. 2013. The persisting burden of visceral leishmaniasis in Iraq: data of the National Surveillance System, 1990–2009. Epidemiology and Infection 141(2): 443–446. https://doi.org/10.1017/S0950268812000556
Cheghabaleki Z.Z., Yarahmadi D., Karampour M., Shamsipour A. 2019. Spatial dynamics of a Phlebotomine sand flies population in response to climatic conditions in Bushehr Province of Iran. Annals of Global Health 85(1): 60. https://doi.org/10.5334/aogh.30
Ending the neglect to attain the sustainable development goals: a road map for neglected tropical diseases 2021–2030. WHO. 28 January 2021. https://www.who.int/publications/i/item/978924001 0352
Knight C.A., Harris D.R., Alshammari S.O., Gugssa A., Young T., Lee C.M. 2023. Leishmaniasis: recent epidemiological studies in the Middle East. Frontiers in Microbiology 13: 1052478. https://doi.org/10.3389/fmicb.2022.1052478
Bayram D.M., Hassan G.M., Ali H.Z. 2022. Detection of some CC chemokine ligands in patients with cutaneous leishmaniasis. Iraqi Journal of Science 63(4): 1431–1437. https://doi.org/10.24996/ijs.2022.63.4.4
Moore E.M., Lockwood D.N. 2010. Treatment of visceral leishmaniasis. Journal of Global Infectious Diseases 2(2): 151–158. https://doi.org/10.4103/0974-777X.62883
Lockard R.D., Wilson M.E., Rodríguez N.E. 2019. Sex-related differences in immune response and symptomatic manifestations to infection with Leishmania Species. Journal of Immunology Research 2019: 4103819. https://doi.org/10.1155/2019/4103819
Helou D.G., Mauras A., Fasquelle F., Lanza J.S., Loiseau P.M., Betbeder D., Cojean S. 2021. Intranasal vaccine from whole Leishmania donovani antigens provides protection and induces specific immune response against visceral leishmaniasis. PLoS Neglected Tropical Diseases 15(8): e0009627. https://doi.org/10.1371/journal.pntd.0009627
Pradhan S., Schwartz R.A., Patil A., Grabbe S., Goldust M. 2022. Treatment options for leishmaniasis. Clinical and Experimental Dermatology 47(3): 516–521. https://doi.org/10.1111/ced.14919
de Jesus J.A., Laurenti M.D., Antonangelo L., Faria C.S., Lago J.H.G., Passero L.F.D. 2021. Related pentacyclic triterpenes have immunomodulatory activity in chronic experimental visceral leishmaniasis. Journal of Immunology Research 2021: 6671287. https://doi.org/10.1155/2021/6671287
Olías-Molero A.I., de la Fuente C., Cuquerella M., Torrado J.J., Alunda J.M. 2021. Antileishmanial drug discovery and development: time to reset the model?. Microorganisms 9(12): 2500. https://doi.org/10.3390/microorganisms9122500
Al-HAlbosiy M.M.F., Ali H.Z., Hassan G.M., Ghaffarifar F. 2020. Artemisinin efficacy against old world Leishmania donovani: in vitro and ex vivo study. Annals of Parasitology 63(3): 295–302. https://doi.org/10.17420/ap6603.267
Hassan G.M., Ali H.Z. 2020. Ex vivo study of anti- leishmanial activity of artemisinin against Leishmania tropica amastigote. Research Journal of Pharmacy and Technology 13(8): 3787–3787. https://doi.org/10.5958/0974-360x.2020.00670.8
Al Musayeib N., Mothana R., Gamal A., Al- Massarani S., Maes L. 2013. In vitro antiprotozoal activity of triterpenoid constituents of Kleiniaodora growing in Saudi Arabia. Molecules 18(8): 9207–9218. https://doi.org/10.3390/molecules18089207
Nikiéma J.B., Vanhaelen-Fastré R., Vanhaelen M., Fontaine J., De Graef C., Heenen M. 2001. Effects of antiinflammatory triterpenes isolated from Leptadeniahastata latex on keratinocyte proliferation. Phytotherapy Research 15(2): 131–134. https://doi.org/10.1002/ptr.700
Das A., Jawed J.J., Das M.C., Parveen S., Ghosh C., Majumdar S., Saha B., Bhattacharjee S. 2021. Lupeol and amphotericin B mediate synergistic anti-leishmanial immunomodulatory effects in Leishmania donovani-infected BALB/c mice. Cytokine 137: 155319. https://doi.org/1016/j.cyto.2020.155319
Sadiq M. Al‐Hamash. 2012. Study of visceral leishmaniasis (kala-azar) in children of Iraq. Mustansiriya Medical Journal 11(2): 15–19.
Neamah S.D., Ali H.Z., Al-Halbosiy M.M.F. 2023. Artemisinin efficacy on iNOS production in U937 cell-line infected with Leishmania donovani. Iraqi Journal of Science 46(2): 525–535. https://doi.org/10.24996/ijs.2023.64.2.3
Bates P.A. 1994. Complete development cycle of Leishmania mexicana in axenic culture. Parasitology 108: 1–9. https://doi.org/10.1017/s0031182000078458
Hassan G.M., Ali H.Z. 2019. Leishmanicidal activity of artemisinin against cutaneous leishmaniasis, in vitro. Journal of Biotechnology Research Center 13(1): 16–22. https://doi.org/10.24126/jobrc.2019.13.1.563
Das A., Jawed J.J., Das M.C., Sandhu P., De U.C., Dinda B., Akhter Y., Bhattacharjee S. 2017. Antileishmanial and immunomodulatory activities of lupeol, a triterpene compound isolated from Sterculia villosa. International Journal of Antimicrobial Agents 50(4): 512–522. https://doi.org/1016/j.ijantimicag.2017.04.022
Alvar J., den Boer M., Dagne D.A. 2021. Towards the elimination of visceral leishmaniasis as a public health problem in east Africa: reflections on an enhanced control strategy and a call for action. Lancet. Global Health 9(12): e1763–e1769. https://doi.org/10.1016/S2214-109X(21)00392-2
Colares A.V., Almeida-Souza F., Taniwaki N.N., Taniwaki N.N., Souza C.F., Martins da Costa J.G., Calabrese K., Abreu-Silva A.L. 2013. In vitro antileishmanial activity of essential oil of Vanillosmopsis arborea (Asteraceae) Baker. Evidence- Based Complementary and Alternative Medicine 2013: 727042. https://doi.org/10.1155/2013/727042
Machado M., Pires P., Dinis A.M., Santos-Rosa M., Alves V., Salgueiro L., Cavaleiro C., Sousa M.C. 2012. Monoterpenic aldehydes as potential anti- Leishmania agents: activity of Cymbopogon citratus and citral on L. infantum, L. tropica and L. major. Experimental Parasitology 130(3): 223–231. https://doi.org/10.1016/j.exppara.2011.12.012
Schmidt T.J., Khalid S.A., Romanha A.J., Alves T.M., Biavatti M.W., Brun R., Da Costa F.B., de Castro S.L., Ferreira V.F., de Lacerda M.V., Lago J.H., Leon L.L., Lopes N.P., das Neves Amorim R.C., Niehues M., Ogungbe I.V., Pohlit A.M., Scotti M.T., Setzer W.N., de N C Soeiro M., Steindel M., Tempone A.G. 2014. The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases – part II. Current Medicinal Chemistry 19(14): 2176–2228.
Chan-Bacab M.J., Peña-Rodríguez L.M. 2001. Plant natural products with leishmanicidal activity. Natural Products Report 18(6): 674–688. https://doi.org/10.1039/b100455g
Sen R., Chatterjee M. 2011. Plant derived therapeutics for the treatment of leishmaniasis. Phytomedicine 18(12): 1056–1069. https://doi.org/10.1016/j.phymed.2011.03.004
Machado V.R., Sandjo L.P., Pinheiro G.L., Moraes M.H., Steindel M., Pizzolatti M.G., Biavatti M.W. 2018. Synthesis of lupeol derivatives and their antileishmanial and antitrypanosomal activities, Natural Product Research 32(3): 275–281. https://doi.org/10.1080/14786419.2017.1353982
Hoet S., Pieters L., Muccioli G.G., Habib-Jiwan J.L., Opperdoes F.R., Quetin-Leclercq J. 2007. Anti- trypanosomal activity of triterpenoids and sterols from the leaves of Strychnos spinosa and related compounds. Journal of Natural Products 70(8): 1360–1363. https://doi.org/10.1021/np070038q
Kaur G., Chauhan K., Kaur S. 2019. Lupeol induces immunity and protective efficacy in a murine model against visceral leishmaniasis. Parasitology 146(11): 1440–1450. https://doi.org/10.1017/S0031182019000659
Saha S., Profumo E., Togna A.R., Riganò R., Saso L., Buttari B. 2020. Lupeol counteracts the proinflammatory signalling triggered in macrophages by 7-keto-cholesterol: new perspectives in the therapy of atherosclerosis. Oxidative Medicine and Cellular Longevity 2020: 1232816. https://doi.org/10.1155/2020/1232816
Sen N., Das B.B., Ganguly A., Mukherjee T., Tripathi G., Bandyopadhyay S., Rakshit S., Sen T., Majumder H.K. 2004. Camptothecin induced mitochondrial dysfunction leading to programmed cell death in unicellular hemoflagellate Leishmania donovani. Cell Death Differ 11(8): 924–936. https://doi.org/10.1038/sj.cdd.4401435