title: A New Antileishmanial Preparation of Combined Solamargine and Solasonine Heals Cutaneous Leishmaniasis through Different Immunochemical Pathways.
abstract: Little has been done during the past 100 years to develop new antileishmanial drugs. Most infected individuals live in poor countries and have a low cash income to be attractive targets to pharmaceutical corporations. Two heterosidic steroids, solamargine and solasonine, initially identified as major components of the Brazilian plant Solanum lycocarpum, were tested for leishmanicidal activity. Both alkaloids killed intracellular and extracellular Leishmania mexicana parasites more efficiently than the reference drug sodium stibogluconate. A total of 10 μM each individual alkaloid significantly reduced parasite counts in infected macrophages and dendritic cells. In vivo treatment of C57BL/6 mice with a standardized topical preparation containing solamargine (45.1%) and solasonine (44.4%) gave significant reductions in lesion sizes and parasite counts recovered from lesions. Alkaloids present different immunochemical pathways in macrophages and dendritic cells. We conclude that this topical preparation is effective and a potential new and inexpensive treatment for cutaneous leishmaniasis.
authors.affiliation: Department of Pathology, OSUMC, The Ohio State University, Columbus, Ohio, USA lezama-davila@hotmail.com anpisaac@hotmail.com.
authors.forename: C M
authors.initials: CM
authors.lastname: Lezama-Dávila
authors.affiliation: Arbor Therapeutics LLC, Ironstone Separations Inc., Etta, Mississippi, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: McChesney
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: J K
authors.initials: JK
authors.lastname: Bastos
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: M A
authors.initials: MA
authors.lastname: Miranda
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: R F
authors.initials: RF
authors.lastname: Tiossi
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: J de C
authors.initials: Jde C
authors.lastname: da Costa
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: M V
authors.initials: MV
authors.lastname: Bentley
authors.affiliation: Centro de Investigaciones Biomédicas, Universidad Autonóma de Campeche, Campeche, México.
authors.forename: S E
authors.initials: SE
authors.lastname: Gaitan-Puch
authors.affiliation: Centro de Investigaciones Biomédicas, Universidad Autonóma de Campeche, Campeche, México lezama-davila@hotmail.com anpisaac@hotmail.com.
authors.forename: A P
authors.initials: AP
authors.lastname: Isaac-Márquez
mesh_terms: D000470:Alkaloids / Q000737:chemistry; D000818:Animals; D000967:Antimony Sodium Gluconate / Q000627:therapeutic use*; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D003713:Dendritic Cells / Q000469:parasitology; D005260:Female; D005434:Flow Cytometry; D005638:Fruit / Q000737:chemistry; D007894:Leishmania mexicana / Q000187:drug effects / Q000472:pathogenicity; D008264:Macrophages / Q000469:parasitology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010936:Plant Extracts / Q000737:chemistry / Q000627:therapeutic use*; D012991:Solanaceous Alkaloids / Q000627:therapeutic use*
chemical_list: D000470:Alkaloids; D000981:Antiprotozoal Agents; D010936:Plant Extracts; D012991:Solanaceous Alkaloids; C026608:alpha-solamargine; D000967:Antimony Sodium Gluconate