Molecular insight into the mechanism of lipid regulating effect of Alisma orientalis based on ACAT.

We studied the lipid-regulating effect and molecular mechanism of the medical components of Alisma orientalis: alisol A, alisol B, 23-acetyl alisol C (23C) and the 3 (alisol A): 1(alisol B):1(23C) and 2(alisol A):2(alisol B):1(23C) mixtures designed based on the ratio of them in Alisma orientalis from Fujian, Guangxi Province, China. The animal experiment and network pharmacology showed that ACAT was one of its lipid-regulating targets and alisols may reduce the level of TC by inhibiting ACAT activity. The molecular simulation and homologous modeling results suggested that the binding of alisol mixtures with ACAT was stronger than that of monomers because alisol monomers acted on different active regions of ACAT resulting in the superposition effect and caused the synergistic effect. The lipid-regulating effect of Fujian mixture was stronger than that of Guangxi mixture showing that 3:1:1 was a better ratio. The N-terminal lipid-regulating activity of ACAT was stronger than that of transmembrane domain 1.