Palmatine regulates bile acid cycle metabolism and maintains intestinal flora balance to maintain stable intestinal barrier

Palmatine (PAL) is a natural isoquinoline alkaloid that has been widely used in the pharmaceutical field. The current study aimed to investigate the function of PAL in improving hyperlipidemia induced by high-fat diet (HFD) in rats. Biochemical analysis of triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDLC) was performed on rats. Total bile acid (TBA) and stool TC and TBA were also measured to assess the changes in total bile acid excretion. RT-qPCR was employed to detect the expression of genes related to bile acid metabolism, and the Western blot assay was used to detect the levels of CYP7A1, ZO-1, ZO-2, and Claudin-1. The siRNA experiment was employed to further investigate whether PAL regulated CYP7A1 through PPARα. Lipopolysaccharide (LPS) and FITC-dextran (FD-4) were also tested to assess the intestinal permeability. AL-treated rats had lower TC, TG, LDL-C levels, lower serum TBA levels, and increased fecal TBA and TC levels. Furthermore, CYP7A1 protein expression was up-regulated in PAL-treated rats. Additionally, PAL regulated bile acid metabolism by up-regulating the expression of CYP7A1 and PPARα and down-regulating the expression of FXR. Besides, the area of plasma FD-4 and LPS content in the PAL group were reduced, and the expression of proteins ZO-1, ZO-2 and Claudin-1 related to intestinal permeability was increased. All in all, PAL could mediate the PPARα-CYP7A1 pathway to maintain the balance of intestinal flora, regulate the bile acid metabolism, and reduce the blood lipids of rats, thereby protecting against hyperlipidemia.