Pages PosterP-10-
We have identified the Chisocheton ceramicus(Meliaceae) extracts to possess in vitroanti-adipogenesis activity on MC3T3-G2/PA6 cells. Following research led to identification of 12 limonoids, ceramicines A-L. Their relative structures were elucidated by using 1D and 2D NMR data while the absolute structure of the most potent compound, ceramicine B was determined by X-ray crystallography and CD spectrum. Nine ceramicine B derivatives (CB 1-9) were synthesized for structure-activity relationship (SAR) studies. Preliminary SAR data indicated that the C-1 carbonyl, C-2/C-3 double bond, and furan ring at C-17 were essential features for anti-adipogenesis activity. Mechanistic studies on anti-adipogenesis activity showed that ceramicine B inhibited mRNA expression and subsequently protein expression of PPARγ. Further western-blot analysis indicated that ceramicine B may play a role in the inhibition of FoxO1 phosphorylation, resulting in down-regulation of PPARγ protein and finally affecting MC3T3-G2/PA6 differentiation into adipocyte.
