title: Oral metabolism and efficacy of Kalanchoe pinnata flavonoids in a murine model of cutaneous leishmaniasis.
abstract: Leishmaniasis is a parasitic disease that threatens 350 million people worldwide. In a search for new antileishmanial drugs, the in vitro activity of flavonoids from Kalanchoe pinnata (Crassulaceae) was previously demonstrated in infected cells. In order to demonstrate the safety and oral activity of K. pinnata, flavonoids were evaluated in vivo in a murine model of cutaneous leishmaniasis. Daily oral doses of quercetin 3-O-alpha-L-arabinopyranosyl (1-->2)-alpha-L-rhamnopyranoside, quercetin 3-O-alpha-L-rhamnopyranoside, and free quercetin (16 mg/kg body weight) all were able to control the lesion growth caused by Leishmania amazonensis and to significantly reduce parasite load. These flavonoids were as effective as the crude K. pinnata aqueous extract given at 320 mg/kg body weight. HPLC-DAD-MS analysis of the plasma of extract-treated mice suggested that quercetin and quercetin glucuronides are the main metabolites of K. pinnata quercetin glycosides. Our results indicate that K. pinnata quercetin glycosides are important active components of the aqueous extract and that they possess potent oral efficacy against cutaneous leishmaniasis.
authors.affiliation: Núcleo de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Michelle F
authors.initials: MF
authors.lastname: Muzitano
authors.forename: Camila A B
authors.initials: CA
authors.lastname: Falcão
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Cruz
authors.forename: Maria C
authors.initials: MC
authors.lastname: Bergonzi
authors.forename: Anna R
authors.initials: AR
authors.lastname: Bilia
authors.forename: Franco F
authors.initials: FF
authors.lastname: Vincieri
authors.forename: Bartira
authors.initials: B
authors.lastname: Rossi-Bergmann
authors.forename: Sônia S
authors.initials: SS
authors.lastname: Costa
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D047309:Flavones / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D031962:Kalanchoe / Q000737:chemistry*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D011794:Quercetin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000981:Antiprotozoal Agents; D047309:Flavones; D011794:Quercetin