The dry aerial part of Panax japonicus var. major is called “Zhuzishen Ye”, it is a characteristic Chinese herbal medicine in Qinba area. In order to rationally develop and utilize “Zhuzishen Ye” and clarify its chemical constituents, the main chemical constituents of the saponin fractions from “Zhuzishen Ye” were analyzed with HPLC, the inhibitory activities and inhibition types of the saponin fractions of “Zhuzishen Ye” on lipase were determined, and the lipase inhibition mechanisms and hypolipidemic effects were verified with molecular docking and animal experiments. The results were as follows: (1) The chemical constituents of saponin fractions from “Zhuzishen Ye” were 20(S)-ginsenoside Rg2, 20(R)-ginsenoside Rg2, ginsenoside Rb2, ginsenoside Rb3, ginsenoside Rd and ginsenoside Rh2. (2) The saponin fractions of “Zhuzishen Ye” and 20(R)-ginsenoside Rg2 had strong inhibitory effects on lipase with IC50 values of 0.14 and 2.30 μmol·L-1, respectively. (3) The saponin fractions of “Zhuzishen Ye”, 20(R)-ginsenoside Rg2 and ginsenoside Rb3 were all reversible inhibition, and the inhibition type was non-competitive inhibition. (4) The binding of ligands to ARG337B, ASP331B and ILE248B residues might help to improve the lipase inhibitory activity of ligands. (5) Saponins of “Zhuzishen Ye” could significantly reduce the content of cholesterol and triglyceride in serum of hyperlipidemia mice. This study provides the theoretical references for the further development and utilization of “Zhuzishen Ye”.
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