Biflavones from Ginkgo biloba as novel pancreatic lipase inhibitors: Inhibition potentials and mechanism.

Reduction of lipid absorption has been recognized as an attractive approach for the discovery of new drugs to treat obesity and overweight. The leave extract of Ginkgo biloba has been widely used for the treatment of metabolic diseases (such as hyperlipidemia) in both eastern and western countries, but the bioactive compounds in Ginkgo biloba and the underlying mechanism have not been fully characterized. This study aimed to investigate the inhibition potentials and mechanism of major biflavones from G. biloba on pancreatic lipase (PL), a key target regulating lipid absorption. The results clearly demonstrated that all tested biflavones in G. biloba including isoginkgetin, bilobetin, ginkgetin and sciadopitysin, displayed strong to moderate inhibitory effects on PL with the IC50 values ranging from 2.90 μM to 12.78 μM. Further investigations on both inhibition kinetic analyses and docking simulations demonstrated that isoginkgetin, bilobetin and ginkgetin were potent PL inhibitors (Ki < 2.5 μM), which could create strong interactions with the catalytic triad of PL via hydrogen bonding. These findings provided a new powerful evidence for explaining the hypolipidemic effects of G. biloba, while these newly identified PL inhibitors from G. biloba could serve as lead compounds for the development of biflavonoid-type PL inhibitors.