Oroxin A from Oroxylum indicum improves disordered lipid metabolism by inhibiting SREBPs in oleic acid-induced HepG2 cells and high-fat diet-fed noninsulin-resistant rats

Abstract

Abstract Background Lipid metabolism disorders have become a major global public health issue. Due to the complexity of these diseases, much more research and many more drugs are needed to address them. Oroxin A, the major component of Oroxylum indicum (L.) Kurz (Bignoniaceae), can improve the lipid profiles of diabetic and insulin-resistant (IR) rats. Since insulin resistance is highly correlated with lipid metabolism, improving insulin resistance may also be an effective way to improve lipid metabolism. Thus, more research on the efficacy and mechanism of oroxin A under non-IR conditions is needed. Method In this research, we established lipid metabolism disorder rats by high-fat diet feeding and fatty HepG2 cell lines by oleic acid induction and evaluated the therapeutic effect and mechanism of oroxin A in vitro and in vivo by biochemical indicators, pathological staining, immunoblotting, and immunofluorescence staining. Results Oroxin A improved disordered lipid metabolism under non-IR conditions, improved plasma and hepatic lipid profiles, and enhanced the lipid-lowering action of atorvastatin. Additionally, oroxin A reduced the total triglyceride (TG) level by inhibiting SREBP1 expression and reducing the expression of ACC and FASN in vivo and in vitro. Oroxin A also reduced the total cholesterol (TC) level by inhibiting SREBP2 expression and reducing HMGCR expression in vivo and in vitro. In addition, oroxin A bound LDLR and increased AMPK phosphorylation. Conclusion Our results suggested that oroxin A may modulate the nuclear transcriptional activity of SREBPs by binding to LDLR proteins and increasing AMPK phosphorylation, thereby reducing lipid synthesis for lipid metabolism disorder treatment and prevention.