Author(s): Cheppail Ramachandran, Karl-Werner Quirin, Anja Cawelius, Enrique Escalon and Steven J Melnick

Abstract: Obesity is one of the most common metabolic diseases that often lead to cardiovascular diseases, type II diabetes, cancer, and osteoarthritis. Inhibition of adipogenesis is a therapeutic target for reducing obesity and obesity-related disorders. We have investigated the anti-adipogenic effect of a supercritical ethanolic extract of dried fruits of Garcinia indica in-vitro. Chemical analysis of the high pressure ethanolic (HPE) extract showed that it has 36.7% hydroxy citric acid (HCA), 2.5% garcinol, 1.5% xanthochymol, 0.38% isogarcinol, and trace amounts of α-mangostin and cyaanidin-3-0-glucoside. G. indica HPE extract has an IC₅₀ values of 112 ug/ml in 3T3-L1 pre-adipocytes and 140 ug/ml in differentiated adipocytes in the cytotoxicity assays. The HPE extract inhibited the adipocyte differentiation significantly in a dose-dependent manner with increasing concentrations of extract in 3T3-L1 preadipocytes. Treatment of HepG2 liver cells with G. indica HPE extract down regulated mRNA expression of mTOR, GLUT3 and HIF-1α genes and up regulated AMPKα genes very significantly. Similarly, down regulation of mTOR, HIF-1α and AKT1 mRNA expression was noticed in extract-treated 3T3-L1 pre-adipocytes. On the other hand, SIRT1 and AMPKα mRNA mRNA expression were up regulated in 3T3-L1 pre-adipocytes. G. indica HPE extract also down regulated genes such as FXR and SHP, and up regulated PPAR- gene that are associated with fat metabolism in HepG2 cells. These results show that the anti-obesity effect of G. indica HPE extract is mainly through signaling pathways affecting the expression of genes associated with weight control and fat metabolism.