Citrus limonoids are secondary metabolites and exhibit a variety of biological activities. In this study, we elucidated the suppression of adipogenesis by a Citrus limonoid kihadanin B and determined its molecular mechanism in mouse 3T3-L1 adipocytes. Kihadanin B was purified from the peels of immature Citrus unshiu by HPLC, and its chemical structure was determined by NMR and mass spectrometry. Kihadanin B reduced the lipid accumulation with the reduction of the expression levels of the adipogenic and lipogenic genes, but did not affect lipolysis in adipocytes. Phosphorylation levels of Akt and a forkhead transcriptional factor, FOXO1, a repressor of PPARγ, were lowered by kihadanin B. Furthermore, kihadanin B increased the binding level of FOXO1 to the PPARγ gene promoter in adipocytes. These results indicate that a Citrus limonoid kihadanin B repressed the adipogenesis by decreasing lipid accumulation through the suppression of the Akt-FOXO1-PPARγ axis in 3T3-L1 adipocytes.
Five new: 21,23-dihydro-21-hydroxy-23-oxonomilin (1), 21,23-dihydro-23-methoxy-21-oxonomilin (2), 21,23-dihydro-21-hydroxy-23-oxonomilinic acid methyl ester (3), 21,23-dihydro-23-methoxy-21-oxolimonin (4), and 21,23-dihydro-21-oxolimonin (5), and seven known limonoids were isolated from peels of satsuma orange (Citrus reticulata). The isolated compounds were evaluated for their inhibitory effects on macrophage activation by an inhibitory assay of nitric oxide (NO) production. Among them, compound (2) exhibited NO inhibitory activity without cytotoxicity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.