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

BACKGROUND

Lipid metabolism disorders have become a major global public health issue. Due to the complexity of these diseases, additional research and drugs are needed. Oroxin A, the major component of (L.) Kurz (Bignoniaceae), can improve the lipid profiles of diabetic and insulin-resistant (IR) rats. Because insulin resistance is strongly correlated with lipid metabolism, improving insulin resistance may also constitute an effective strategy for improving lipid metabolism. Thus, additional research on the efficacy and mechanism of oroxin An under non-IR conditions is needed.

METHODS

In this study, we established lipid metabolism disorder model rats by high-fat diet feeding and fatty HepG2 cell lines by treatment with oleic acid and evaluated the therapeutic effect and mechanism of oroxin A and through biochemical indicator analysis, pathological staining, immunoblotting, and immunofluorescence staining.

RESULTS

Oroxin A improved disordered lipid metabolism under non-IR conditions, improved the plasma and hepatic lipid profiles, and enhanced the lipid-lowering action of atorvastatin. Additionally, oroxin A reduced the total triglyceride (TG) levels by inhibiting sterol regulatory element-binding protein 1 (SREBP1) expression and reducing the expression of acetyl coenzyme A carboxylase (ACC) and fatty acid synthase (FASN) and . Oroxin A also reduced the total cholesterol (TC) levels by inhibiting SREBP2 expression and reducing HMGCR expression and . In addition, oroxin A bound to low-density lipoprotein receptor (LDLR) and increased AMPK phosphorylation.

CONCLUSIONS

Our results suggested that oroxin A may modulate the nuclear transcriptional activity of SREBPs by binding to LDLR proteins and increasing AMPK phosphorylation. Oroxin A may thus reduce lipid synthesis and could be used for the treatment and prevention of lipid metabolism disorders.