Abstract
Cardiovascular diseases (CVD) affect millions of people and spend a lot of medical costs around the world each year. Taxifolin is a natural anti-oxidative reagent obtained from multiple plants and exhibits a wide range of pharmacological effects. High mobility group box protein 1 (HMGB1) is expressed in multiple types of cells in the extracellular environment, regulating the pro-inflammatory process. Here, we detected the viability of cells using MTT assay, and the expression of each target protein was detected using western blotting analysis. The expression of each target mRNA was detected using the qPCR method, and the concentration of each cytokine in serum samples was detected using the ELISA method. In this study, we found that taxifolin could decrease the expression of hypoxia-inducible factor-1α (HIF-1α) while increasing the expression of endothelial nitric oxide synthase (eNOS), presented a protective role. Besides, taxifolin could also increase the expression of vascular endothelial growth factor-α (VEGF-α), transforming growth factor-β (TGF-β) and fibroblast growth factor21 (FGF21), resulting in viability rate increasing. And these effects were mediated by phosphatidylinositol 3-hydroxy kinase (PI3K)/AKT/mTOR signaling pathway; a similar trend was also observed in HMGB1 knockdown mice. We also found that inhibition of HMGB1 could enhance the cardioprotective effect of taxifolin and might be a new therapeutic strategy for cardiovascular disease.