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

Abstract

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), lowdensity 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.

Natural compounds proposed for the management of non-alcoholic fatty liver disease

“…Biochanin A ( C2 ), an O -methylated isoflavone belonging to the phytochemical class of flavonoids, has several pharmacological effects, including anti-inflammatory, lipid-lowering, and cholesterol-lowering effects as well as cancer chemoprevention-related effects [ 63 , 64 ]. In diabetic rats, biochanin A, as a potent activator of both PPAR-γ and PPAR-α receptors, has shown promising and interesting effects in lowering glycemia and improving insulin sensitivity [ 65 , 66 ].…”

Chemical and Biological Properties of Biochanin A and Its Pharmaceutical Applications

“…By analysing the pancreatic tissue from BCA-treated/non-BCA-treated streptozotocin diabetic rats, it was found that the BCA-treated rats had reduced fat in normal pancreatic islet cells, indicating that BCA could act as a preventative measure against weight loss in diabetic animals (Figure 3) [22]. As a fatty acid amide hydrolase inhibitor, BCA can slow down the progression of nonalcoholic fatty liver disease (NAFLD) by regulating cholesterol metabolism [23,24]. BCA as a β-Site App-Cleaving Enzyme 1 (Bace1) inhibitor also has the potential to be developed into preventive and therapeutic agents for Alzheimer's disease [25].…”

Intervention of Shugan Xiaozhi Decoction on Nonalcoholic Fatty Liver Disease via Mediating Gut-Liver Axis

“…In addition, IR, a possible pathogenesis of NAFLD, had positive correlation with the raised plasma levels of apoB48-containing lipoproteins, which might be due to impaired hepatic ability of clearing TG-rich lipoproteins caused by excessive production of intestinal chylomicrons (CMs) and accumulation of serum CM remnants [ 13 , 14 ]. On the other hand, cholesterol absorption is mainly accomplished by the endocytosis of exogenous cholesterol through peroxisome proliferator activated receptors (PPARs) and low-density lipoprotein receptor (LDL-R), while cholesterol excretion is through the bile acid pathway [ 15 ]. PPARs exist in a variety of tissues with active metabolism such as the liver and participate in regulating the absorption and metabolism of cholesterol, phospholipids, and FFAs [ 16 ].…”