A Novel Sterol Isolated from a Plant Used by Mayan Traditional Healers Is Effective in Treatment of Visceral Leishmaniasis Caused by Leishmania donovani

作者：Gura Gaurav; Peine Kevin J; Abdehamid Dalia; Snider Heidi; Shelton Andrew B; Rao Latha; Kotha Sainath R; Huntsman Andrew C; Varikuti Sanjay; Oghumu Steve; Naman C Benjamin; Pan Li; Parinandi Narasimham L; Papenfuss Tracy L; Kinghom A Douglas; Bacheder Eric M; Ainslie Kristy M; Fuchs James R; Satoskar Abhay R^*

来源：ACS Infectious Diseases, 2015, 1(10): 497-506.

DOI：10.1021/acsinfecdis.5b00081

• visceral leishmaniasis
• liposome
• novel sterol synthesis
• antileishmanial

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-gamma production and formation of matured hepatic granulomas. These results indicate that PEN could be developed as a novel drug against VL.

• 出版日期2015-10