Integrating network analysis and experimental validation to reveal the mechanism of pinocembrin in alleviating high glucose and free fatty acid-induced lipid accumulation in HepG2 cells

Abstract

Hepatocyte lipid accumulation in type 2 diabetes mellitus (T2DM) promotes the development of metabolic dysfunction-associated steatosis liver disease (MASLD), whereas no specific drug treatment is available. Pinocembrin assists in the treatment of many diseases, however, little is known about its protective effect on hepatic lipid metabolism disorders induced by T2DM. In this study, the ameliorative effects of pinocembrin on T2DM-induced hepatocyte lipid accumulation were investigated by in vitro experiments combined with a comprehensive analysis strategy of network pharmacology and molecular docking. High glucose and free fatty acid co-cultured HepG2 cell line was used. The results indicated that pinocembrin reduced lipid deposition by modulating the release of Cyclooxygenase-2 (COX-2)-mediated inflammatory factors and improving insulin resistance (IR) in HepG2 cells. Overall, the findings of this study suggested that pinocembrin ameliorated lipid accumulation and IR in vitro, and thus may be a potential therapeutic agent for the treatment of T2DM-induced hepatic steatosis.

Keywords

• Pinocembrin
• Metabolic dysfunction-associated steatosis liver disease
• Type 2 diabetes mellitus
• Network pharmacology
• Lipid metabolism
• Anti-inflammatory