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Gupta G, Peine KJ, Abdelhamid D, et al. A Novel Sterol Isolated from a Plant Used by Mayan Traditional Healers Is Effective in Treatment of Visceral Leishmaniasis Caused by Leishmania donovani. ACS Infect Dis. 2015;1(10):497-506doi: 10.1021/acsinfecdis.5b00081.
Gupta, G., Peine, K. J., Abdelhamid, D., Snider, H., Shelton, A. B., Rao, L., Kotha, S. R., Huntsman, A. C., Varikuti, S., Oghumu, S., Naman, C. B., Pan, L., Parinandi, N. L., Papenfuss, T. L., Kinghorn, A. D., Bachelder, E. M., Ainslie, K. M., Fuchs, J. R., & Satoskar, A. R. (2015). A Novel Sterol Isolated from a Plant Used by Mayan Traditional Healers Is Effective in Treatment of Visceral Leishmaniasis Caused by Leishmania donovani. ACS infectious diseases, 1(10), 497-506. https://doi.org/10.1021/acsinfecdis.5b00081
Gupta, Gaurav, et al. "A Novel Sterol Isolated from a Plant Used by Mayan Traditional Healers Is Effective in Treatment of Visceral Leishmaniasis Caused by Leishmania donovani." ACS infectious diseases vol. 1,10 (2015): 497-506. doi: https://doi.org/10.1021/acsinfecdis.5b00081
Gupta G, Peine KJ, Abdelhamid D, Snider H, Shelton AB, Rao L, Kotha SR, Huntsman AC, Varikuti S, Oghumu S, Naman CB, Pan L, Parinandi NL, Papenfuss TL, Kinghorn AD, Bachelder EM, Ainslie KM, Fuchs JR, Satoskar AR. A Novel Sterol Isolated from a Plant Used by Mayan Traditional Healers Is Effective in Treatment of Visceral Leishmaniasis Caused by Leishmania donovani. ACS Infect Dis. 2015 Oct 09;1(10):497-506. doi: 10.1021/acsinfecdis.5b00081. Epub 2015 Sep 21. PMID: 27623316; PMCID: PMC5730984.
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ACS Infect Dis. 2015 Oct 09;1(10):497-506. doi: 10.1021/acsinfecdis.5b00081. Epub 2015 Sep 21.

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

ACS infectious diseases

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

Affiliations

  1. Department of Pathology, The Wexner Medical Center, The Ohio State University , 320 West 10th Avenue, Columbus, Ohio 43210, United States.
  2. Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of Sao Paulo , Av. Bandeirantes 3900, 14049-900 Ribeirão Preto, Brazil.
  3. Molecular, Cellular and Developmental Biology Graduate Program, The Ohio State University , 484 West 12th Avenue, Columbus, Ohio 43210, United States.
  4. Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina , 125 Mason Farm Road, Chapel Hill, North Carolina 27599, United States.
  5. Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University , 500 West 12th Avenue, Columbus, Ohio 43210, United States.
  6. Department of Medicinal Chemistry, Minia University , Minia, Egypt.
  7. Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Internal Medicine, The Wexner Medical Center, The Ohio State University , 473 West 12th Avenue, Columbus, Ohio 43210, United States.
  8. Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University , 1900 Coffey Road, Columbus, Ohio 43210, United States.
  9. Department of Pathology, WIL Research , Ashland, Ohio 55805, United States.
  10. Division of Pharmaceutics, College of Pharmacy, The Ohio State University , 500 West 12th Avenue, Columbus, Ohio 43210, United States.

PMID: 27623316 PMCID: PMC5730984 DOI: 10.1021/acsinfecdis.5b00081

Abstract

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.

Keywords: antileishmanial; liposome; novel sterol synthesis; visceral leishmaniasis

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