title: Molecular mechanisms of in vitro betulin-induced apoptosis of Leishmania donovani.
abstract: Although leishmanial infections of humans occur globally, the major health impact lies in developing nations, thus, leishmaniases remain "neglected" diseases for new drugs development. Multidrug resistance has been documented in most countries where leishmaniases is endemic. Betulin is a widely available and affordable natural product exerting leishmanicidal activity at micromolar concentration. In this study, the molecular mechanisms of death that contribute to the anti-leishmanial activity of betulin are investigated. In promastigotes, betulin stimulated reactive oxygen species generation at micromolar concentrations in Leishmania. Apoptosis was observed in betulin-treated promastigotes using flow cytometric analysis of treated cells stained with annexin V-FITC and propidium iodide. Furthermore, betulin treatment of promastigotes led to mitochondrial membrane damage, activation of caspase-like proteases, and DNA fragmentation in Leishmania donovani promastigotes. Betulin treatment of amastigotes cultured within macrophages, resulted in a reduced number of amastigotes, with no substantive cytotoxic damage to the host macrophage cells at leishmanicidal drug concentrations.
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Guwahati, Assam, India.
authors.forename: Prakash
authors.initials: P
authors.lastname: Saudagar
authors.forename: Vikash Kumar
authors.initials: VK
authors.lastname: Dubey
mesh_terms: D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D016054:DNA, Protozoan / Q000187:drug effects; D004587:Electrophoresis, Agar Gel; D006801:Humans; D007893:Leishmania donovani / Q000166:cytology / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D014315:Triterpenes / Q000627:therapeutic use*; D000094062:Betulinic Acid
chemical_list: D000981:Antiprotozoal Agents; D016054:DNA, Protozoan; D017382:Reactive Oxygen Species; D014315:Triterpenes; C002503:betulin; D000094062:Betulinic Acid