title: Iridoid glucosides from Nyctanthes arbortristis result in increased reactive oxygen species and cellular redox homeostasis imbalance in Leishmania parasite.
abstract: We report here the effect of iridoid glucosides, isolated from Nyctanthes arbortristis, on redox homeostasis of Leishmania parasite. These compounds led to an increase in reactive oxygen species by inhibiting a crucial enzyme of redox metabolism of the parasite. Our experiments clearly showed that these compounds are highly active as antileishmanial agents. The in vitro experiments on intra-macrophageal amastigotes showed significant killing of parasite even at very low concentration. Determination of mechanism of action of iridoid glucosides showed that increased ROS level leads to oxidative stress, cell membrane damage and apoptosis of Leishmania sp. Our cellular toxicity assays on Human embryonic kidney (HEK 293) and mouse macrophage (J774A.1) cell lines showed these compounds to be very safe for therapeutics application.
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India. s.anil@iitg.ernet.in
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Shukla
authors.forename: Sanjukta
authors.initials: S
authors.lastname: Patra
authors.forename: Vikash Kumar
authors.initials: VK
authors.lastname: Dubey
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D057809:HEK293 Cells; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D057888:Iridoid Glucosides / Q000494:pharmacology*; D007893:Leishmania donovani / Q000166:cytology* / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D008018:Life Cycle Stages / Q000187:drug effects; D051379:Mice; D029592:Oleaceae / Q000737:chemistry*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D000981:Antiprotozoal Agents; D057888:Iridoid Glucosides; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds