Anti-inflammatory effect of taxifolin in TNF-α/IL-17A/IFN-γ induced HaCaT human keratinocytes

Abstract

AbstractTaxifolin, a bioactive flavonoid, has been attracting attention as a beneficial and valuable phytochemical due to its antioxidant, anticancer, and anti-inflammatory properties. Recently, an improvement effect of taxifolin against psoriasis has been reported in an animal experimental model. However, its exact mechanism of action at molecular and cellular levels is not known. Thus, the purpose of this study was to verify the anti-inflammatory effect of taxifolin on psoriasis at cellular/molecular level using HaCaT human keratinocytes. First, a CCK-8 assay was performed to evaluate cytotoxicity of taxifolin. Results revealed that taxifolin was a relatively safe material, showing no cytotoxicity at concentrations up to 300 μg/mL. In TNF-α-induced HaCaT cells, taxifolin significantly inhibited mRNA expression levels of pro-inflammatory cytokines (IL-1α, IL-1-β, and IL-6) and chemokines (CXCL8 and CCL20). The ability of taxifolin to regulation expression of inflammatory cytokine genes was associated with phosphorylation of IκB/STAT3 protein. In addition, taxifolin inhibited expression levels of IL-1α/β, IL-6, CXCL8, and CCL20 by inhibiting IκB/STAT3 protein phosphorylation upon stimulation of TNF-α, IL-17A, and IFN-γ. These results show that taxifolin has the potential to be developed as a treatment for psoriasis and skin inflammation.