A Novel Sterol Isolated from a Plant Used by Mayan Traditional Healers Is Effective in Treatment of Visceral Leishmaniasis Caused by Leishmania donovani.
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.
Department of Pathology, The Wexner Medical Center, The Ohio State University , 320 West 10th Avenue, Columbus, Ohio 43210, United States.|Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of Sao Paulo , Av. Bandeirantes 3900, 14049-900 Ribeirão Preto, Brazil.
Gaurav
G
Gupta
Molecular, Cellular and Developmental Biology Graduate Program, The Ohio State University , 484 West 12th Avenue, Columbus, Ohio 43210, United States.|Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina , 125 Mason Farm Road, Chapel Hill, North Carolina 27599, United States.
Kevin J
KJ
Peine
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University , 500 West 12th Avenue, Columbus, Ohio 43210, United States.|Department of Medicinal Chemistry, Minia University , Minia, Egypt.
Dalia
D
Abdelhamid
Department of Pathology, The Wexner Medical Center, The Ohio State University , 320 West 10th Avenue, Columbus, Ohio 43210, United States.
Heidi
H
Snider
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.
Andrew B
AB
Shelton
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.
Latha
L
Rao
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.
Sainath R
SR
Kotha
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University , 500 West 12th Avenue, Columbus, Ohio 43210, United States.
Andrew C
AC
Huntsman
Department of Pathology, The Wexner Medical Center, The Ohio State University , 320 West 10th Avenue, Columbus, Ohio 43210, United States.
Sanjay
S
Varikuti
Department of Pathology, The Wexner Medical Center, The Ohio State University , 320 West 10th Avenue, Columbus, Ohio 43210, United States.
Steve
S
Oghumu
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University , 500 West 12th Avenue, Columbus, Ohio 43210, United States.
C Benjamin
CB
Naman
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University , 500 West 12th Avenue, Columbus, Ohio 43210, United States.
Li
L
Pan
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.
Narasimham L
NL
Parinandi
Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University , 1900 Coffey Road, Columbus, Ohio 43210, United States.|Department of Pathology, WIL Research , Ashland, Ohio 55805, United States.
Tracy L
TL
Papenfuss
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University , 500 West 12th Avenue, Columbus, Ohio 43210, United States.
A Douglas
AD
Kinghorn
Division of Pharmaceutics, College of Pharmacy, The Ohio State University , 500 West 12th Avenue, Columbus, Ohio 43210, United States.|Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina , 125 Mason Farm Road, Chapel Hill, North Carolina 27599, United States.
Eric M
EM
Bachelder
Division of Pharmaceutics, College of Pharmacy, The Ohio State University , 500 West 12th Avenue, Columbus, Ohio 43210, United States.|Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina , 125 Mason Farm Road, Chapel Hill, North Carolina 27599, United States.
Kristy M
KM
Ainslie
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University , 500 West 12th Avenue, Columbus, Ohio 43210, United States.
James R
JR
Fuchs
Department of Pathology, The Wexner Medical Center, The Ohio State University , 320 West 10th Avenue, Columbus, Ohio 43210, United States.
Abhay R
AR
Satoskar
antileishmanial; liposome; novel sterol synthesis; visceral leishmaniasis