Hispidulin can improve lipid parameters in the HepG2 cell line with metabolic dysfunction-associated steatotic liver disease

Purpose: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant health issue. Although its pathogenesis remains unclear, insulin resistance, steatosis, and inflammation play crucial roles. Research on alternative treatment agents is ongoing. This is the first study to investigate the effect of hispidulin, a flavonoid, in a MASLD model. Materials and Methods: Non-toxic concentrations of hispidulin and oleic acid were determined using the MTT cytotoxicity assay. Cells were first treated with hispidulin, followed by the addition of oleic acid two hours later. The cells were incubated for 24 hours to induce lipolysis. The intracellular lipids were demonstrated both qualitatively and quantitatively using Oil Red O staining. Triglyceride and total cholesterol levels, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and adenosine monophosphate-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) levels were measured. Results: Hispidulin at 40 µM significantly reduced triglyceride levels by 67%, total cholesterol levels by 53%, ALT levels by 66%, and AST levels by 36%. However, no increase in AMPK or SIRT1 levels was observed compared to the model group. Conclusion: Hispidulin can reduce cellular lipid accumulation, improve lipid parameters, and lower aminotransferase enzyme levels in MASLD. However, this effect may not occur via the AMPK-SIRT1 pathway but rather through other mechanisms. Further studies are needed to elucidate the mechanisms of hispidulin's action in MASLD.