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A Novel Sterol Isolated from a Plant Used by Mayan Traditional Healers Is Effective in Treatment of Visceral Leishmaniasis Caused by Leishmania donovani
journal contributionposted on 2015-10-09, 00:00 authored by Gaurav Gupta, Kevin J. Peine, Dalia Abdelhamid, Heidi Snider, Andrew B. Shelton, Latha Rao, Sainath R. Kotha, Andrew C. Huntsman, Sanjay Varikuti, Steve Oghumu, C. Benjamin Naman, Li Pan, Narasimham L. Parinandi, Tracy L. Papenfuss, A. Douglas Kinghorn, Eric M. Bachelder, Kristy M. Ainslie, James R. Fuchs, Abhay R. Satoskar
Visceral leishmaniasis (VL), caused by the protozoan parasite Leishmania donovani, is a global health problem affecting millions of people worldwide. Treatment of VL largely depends on therapeutic drugs such as pentavalent antimonials, amphotericin B, and others, which have major drawbacks due to drug resistance, toxicity, and high cost. In this study, for the first time, we have successfully demonstrated the synthesis and antileishmanial activity of the novel sterol pentalinonsterol (PEN), which occurs naturally in the root of a Mexican medicinal plant, Pentalinon andrieuxii. In the experimental BALB/c mouse model of VL induced by infection with L. donovani, intravenous treatment with liposome-encapsulated PEN (2.5 mg/kg) led to a significant reduction in parasite burden in the liver and spleen. Furthermore, infected mice treated with liposomal PEN showed a strong host-protective TH1 immune response characterized by IFN-γ production and formation of matured hepatic granulomas. These results indicate that PEN could be developed as a novel drug against VL.
pentavalent antimonialshealth problemVisceral LeishmaniasisLeishmania donovaniVisceral leishmaniasisIFNamphotericin Bnovel drugparasite burdenparasite Leishmania donovaniPentalinon andrieuxiiBALBhepatic granulomasdrug resistanceliposomal PENantileishmanial activityNovel SterolTHnovel sterol pentalinonsterolVL