Extensive studies have demonstrated that biochanin A (BCA) has a significant hypolipidemic effect. However, its mechanism of action is not clear. In this context, the effect of BCA on a high-fat diet (HFD)-induced hyperlipidemia in mice was determined. The results showed that treatment with a medium dose of biochanin A (BM) significantly decreased low-density lipoprotein cholesterol (LDL-C) 85% (from 1.196 ± 0.183 to 0.181 ± 0.0778 mM) and total cholesterol (TC) 39% (from 5.983 ± 0.128 to 3.649 ± 0.374 mM) levels, increased lipoprotein lipase (LPL) 96% (from 1.421 ± 0.0982 to 2.784 ± 0.177 U/mg protein) and hepatic triglyceride lipase (HTGL) 78% (from 1.614 ± 0.0848 to 2.870 ± 0.0977 U/mg protein) activities, significantly improved fecal lipid levels, and lowered the epididymal fat index in hyperlipidemic mice compared with the HFD control mice (p < 0.05). In vitro, the high antioxidant capacity of BCA was determined by the FRAP assay, ABTS•+ scavenging method, and an ROS assay. In RAW 264.7 macrophages, a dose of 10 μM BCA significantly increased the cholesterol efflux by 18.7% compared with the control cells. Moreover, molecular docking of BCA on cholesterol ester transfer protein (CETP) (Asn24 and Thr27 at the N-terminal; Ala274 and Phe270 at the C-terminal) gave new insights into the role of BCA in preventing cholesterol ester transport.
Keywords: CETP; antioxidant; biochanin A; cholesterol efflux; hypolipidemic.