Gynura procumbens (Lour.) Merr. and Its Active Compound Attenuate Oleic Acid-Induced Hepatocyte Steatosis and Modulate Cholesterol Metabolism-Related Gene Expression

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterised by excessive lipid accumulation in hepatocytes and often accompanied by dyslipidaemia. Gynura procumbens, a medicinal plant native to Southeast Asia, exhibits lipid-lowering and hepatoprotective properties. However, its effects on hepatic lipid accumulation and cholesterol metabolism-related gene regulation remain unclear. This study evaluated the effects of G. procumbens extract (GPCE) and stigmasterol on oleic acid-induced hepatocyte steatosis and cholesterol metabolism-related gene expression. GPCE was assessed for HMG-CoA reductase (HMGCR) inhibition, lipid accumulation, and expression of cholesterol metabolism-related genes (HMGCR, SREBP2, LDLR, and PCSK9). Bioassay-guided fractionation identified stigmasterol as a constituent of the highly active fractions and its structure was characterised by LC-TOF-MS and NMR. GPCE and stigmasterol inhibited HMGCR activity by 86.31 ± 5.3% and 56.59 ± 7.6%, respectively. Both treatments reduced lipid accumulation in hepatocytes and modulated the mRNA expression of selected cholesterol homeostasis-related genes, including transcriptional downregulation of SREBP2 and PCSK9. These findings suggest that G. procumbens possesses lipid-lowering activity and that stigmasterol may represent one of the bioactive constituents contributing to its observed biological effects. Further studies involving protein level validation, functional assays and in vivo studies are warranted to fully elucidate the mechanisms and establish the biological relevance of these findings in MASLD.