Biochanin A Regulates Cholesterol Metabolism Further Delays the Progression of Nonalcoholic Fatty Liver Disease

Yan Fan,1,&ast; Long-Teng Yan,2,&ast; Zheng Yao,2 Guang-Yi Xiong2 1Department of Anatomy, Histology, and Embryology, School of Basic Medical Science, Kunming Medical University, Kunming, Yunnan, 650500, People’s Republic of China; 2Key Laboratory of Microcosmic Syndrome Differentiation, School of Basic Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, 650500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zheng Yao; Guang-Yi XiongKey Laboratory of Microcosmic Syndrome Differentiation, School of Basic Medicine, Yunnan University of Chinese Medicine, No. 1076, Yuhua Road, Chenggong District, Kunming, Yunnan, 650500, People’s Republic of ChinaTel/Fax +86 189 0871 9365Email zhengyaomail@126.com; 307924002@qq.comPurpose: To discover the possible target of biochanin A (BCA) in the lipid metabolism pathway and further explore its mechanism to nonalcoholic fatty liver disease (NAFLD).Methods: We adopted a high-fat and high-glucose diet for 12 weeks to build the NAFLD rat model, which was then treated with different proportions of BCA for 4 weeks. General condition, body weight, Lee index, and liver index were then evaluated. Furthermore, blood lipid level and insulin resistance (IR) were detected. Moreover, hematoxylin and eosin and oil red O staining were used to observe the pathological changes in the liver. Finally, Western blotting was used to detect the protein expression levels of CYP7A1, HMGCR, LDLR, PPAR-α, PPAR-γ, and SREBP-1c in the liver.Results: The vital signs of rats in each group were stable. The treatment with BCA effectively reduced Lee index and liver index (F = 104.781, P < 0.05); however, the weight was not effected in each group. Additionally, BCA effectively reduced the related lipid metabolism indexes of NAFLD, such as total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), blood glucose, insulin, IR (F =12.463 (TC), 6.909 [TG], and 15.3 effected 75 [LDL], P < 0.05), and increased HDL (F = 11.580, P < 0.05). We observed that BCA could significantly improve steatosis and inflammatory cell infiltration in liver slices. Furthermore, BCA significantly increased the CYP7A1, LDLR, and PPAR-α protein expression in the liver and downregulated the HMGCR, SREBP-1c, and PPAR-γ protein expression.Conclusion: BCA could delay the liver damage of NAFLD induced by a high-fat diet, regulate the blood lipid level, and improve the expression of lipid metabolism-related genes in rats.Keywords: biochanin A, nonalcoholic fatty liver disease, NAFLD, cholesterol metabolis