The Bioactive Flavonoid Taxifolin Inhibits Differentiation and the Production of the Inflammatory Cytokine Interleukin-6 in Cultured Human Adipocytes

Background: Taxifolin, a bioactive flavonoid that possesses potent antioxidant activity, has been reported to show multiple pharmacological properties, including protective effects against obesity-related diabetic nephropathy and diabetic cardiomyopathy. However, knowledge regarding the effects of taxifolin on adipocytes, which are closely associated with obesity and diabetes, is insufficient. Objective: This study aimed to explore the direct effects of taxifolin on differentiation and inflammation adipocytes by culturing human preadepocytes (HPAds). Methods: HPAds were cultured for 16 days in a differentiation medium with or without taxifolin to examine its effect on differentiation. On day 16, levels of lipid and differentiation-related gene expression (PPARγ, C/EBPα, adiponectin, CD36, and GLUT4 mRNAs) in adipocytes were measured using the Oil Red O assay and the real-time polymerase chain reaction assay, respectively. Adiponectin levels in the medium were measured using an enzyme-linked immunosorbent assay (ELISA). The taxifolin effect on inflammation was assessed using mature adipocytes differentiated for 15 days. After incubating mature adipocytes in a differentiation medium containing tumor necrosis factor-α (TNF-α) or TNF-α + taxifolin for three hours, the level of interleukin-6 (IL-6), an inflammatory cytokine in the medium, was measured using ELISA. Results: Exposure of taxifolin to adipocytes during differentiation decreased the levels of lipid in adipocytes and adiponectin in the medium. It also decreased the expression levels of C/EBPα, adiponectin, CD36, and GLUT4 mRNAs, but not PPARγ mRNA. Taxifolin inhibited the increase in IL-6 levels in the medium induced by TNF-α in mature adipocytes. Conclusion: These results suggest that taxifolin has anti-differentiation and anti-inflammatory effects on adipocytes. Additionally, taxifolin is expected to have the potential as a therapeutic drug for obesity and metabolic syndrome.