Molecular Biochemical Mechanism Of Interactions Between Saponins And Pancreatic Lipase

Obesity has become a serious disease among ten major diseases throughout the world, it seriously affects human health and life quality. Researches have demonstrated that inhibiting pancreatic lipase (PL) activity is the key proposal against obesity. Saponin compounds can effectively inhibit PL activity. However, the molecular biochemical mechanism of their interactions is still not clear so far. In this work, using 5 saponin compounds (TS, OA, B, Ro, and Rd) as materials, we will clarify interactiona molecular mechasnism between saponins and PL, providing a theoretical basis for the development of lipase inhibitor drugs. The main achievements are shown as follows:1. Saponin compounds inhibiting PL activity and inhibition type are dependent on saponin classification (TS, OA, B, Ro, Rd)PL, and the ligand in saponin structure plays a crucial role. TS show competitive inhibition of PL activity, while the other 4 kinds of tested saponin compounds show non-competitive inhibition of PL activity. PL inhibition efficiency of saponins is decreasing by the order of OA (69.8%)>B (68.6%)> (Ro) (40%)>TS (25.7%)>Rd (7.69%).2. Interaction molecular mechanisms between saponins and PL are elucidated from kinetics, thermodynamics and conformation. Saponins inhibit PL activity through PLstatic fluorescence quenchingPL, and their binding capacity is dependent on saponins molecular weight. The conformation and thermodynamic properties of PL protein can be changed in the presence of saponins.3. Morphology by AFM and solubility experiments shows that saponin compounds (TS, OA, B, RO, RD) can promote PL agglomeration with the soluble characters. The agglomeration properties of PL mediated by saponins are decreasing by the order of Rd=Ro> TS= OA> B.