Anti-Differentiation Effect of B, D-Seco limonoids of Swietenia mahogani

BACKGROUND Obesity is a pathological state caused by abnormal or excessive accumulation of fat. Swietenia mahogani JACQ., known as West Indian mahogany, is a medium-sized semi-evergreen tree belonging to Meliaceae. Their seeds are used in Indonesian folk medicine as a treatment for hypertension, diabetes, malaria, and it also has anti-feedant activities. The major components of S. mahogani are B, D-seco limonoids, a type of irregular triterpenes are well known. OBJECTIVE We tried to find the bioactive components, which have the inhibitory activity on adipocyte differentiation from the seeds of S. mahogani. MATERIAL AND METHODS 3T3-L1 cells, derived from mouse preadipocyte, are widely used in studying adipogenesis process. In this study, we used 3T3-L1 cells to find natural products with the inhibitory activity on adipocyte differentiation. S. mahogani seeds were dried and extracted with 100% MeOH. RESULTS The methanolic extract was fractionated by bioassay-guided method to give nine B, D-seco limonoids (1-9) with slight structural modifications. Among nine compounds, compounds 4, 6 and 8 exhibited significant inhibitory effects of cell differentiation on 3T3-L1 cells. Those compounds have tigloyl residue at C-3 in common. Besides, compounds with no tigloyl residue at C-3 showed insignificant effect. Nevertheless, not all compounds with tigloyl residue at C-3 exerted significant inhibitory effect. CONCLUSION These results suggested that tigloyl residue at C-3 may play a role in the anti-proliferative activity on a dipogenesis and the refined extract of S. mahogani may have a potential to be developed as a therapeutic agent to treat obesity. SUMMARY Nine irregular seco-limonoids were isolated from Swietenia mahogani.Total extract and CHCl3 fraction of S. mahogani showed the significant inhibitory activities on 3T3-L1 cell differentiation.A tigloyl residue at C-3 in an aglycone may play a role in the anti-proliferative activity on adipogenesis.