Quercetin regulates proliferation,inflammation,and oxidative stress in psoriatic keratinocytes via the NF-κB signaling pathway
Objective:Quercetin holds promising potential in the treatment of psoriasis,yet its specific mechanisms of action remain unclear.This study investigates whether quercetin can regulate the proliferation,inflammation,and oxidative stress of psoriatic keratinocytes via the nuclear transcription factor kappa B(NF-κB)signaling pathway.Methods:Human epidermal keratinocytes(HaCaT)were cultured and induced with tumor necrosis factor α(TNF-α)to establish a psoriasis cell damage model(TNF-α group).The cells were then treated with low,medium,and high doses of quercetin(concentrations of 0,3.75,7.50,15.00,30.00,60.00,120.00 μmol/L),and categorized into TNF-α+quercetin low,medium,and high dose groups,with untreated HaCaT cells serving as the control group.In the TNF-α+high-dose quercetin group,cells were further treated with dimethyl sulfoxide(DMSO)(TNF-α+high-dose quercetin+DMSO group)and NF-κB pathway activator(NF-κB activator 1)(TNF-α+high-dose quercetin+NF-κB activator 1 group).The cell counting kit-8(CCK-8)assay was used to determine the minimal concentration of quercetin affecting TNF-α-induced cell proliferation.Enzyme-linked immunosorbent assay(ELISA),biochemical staining,and Western blotting were employed to detect inflammatory cytokines,oxidative stress markers,and NF-κB signaling pathway-related proteins in HaCaT cells.Results:Compared to TNF-α+quercetin 0 μmol/L cells,the proliferation of TNF-α+quercetin 3.75,7.50,15.00,and 30.00 μmol/L cells showed no significant differences(all P>0.05),while TNF-α+quercetin 60.00 and 120.00 μmol/L cells exhibited significantly inhibited proliferation(both P<0.05).Compared to the control group,the TNF-α group showed significantly elevated levels of interleukin(IL)-6,IL-1β,intercellular cell adhesion molecule-1(ICAM-1),malondialdehyde(MDA),and phosphorylation-65(p-p65)/p65(all P<0.001),and a significantly decreased level of glutathione peroxidase(GSH-Px)activity(P<0.001).Compared to the TNF-α group,the TNF-α+medium-dose quercetin and TNF-α+high-dose quercetin groups showed significantly reduced levels of IL-6,IL-1β,ICAM-1,and MDA in cell supernatants(all P<0.001),and significantly increased level of GSH-Px activity(P<0.001),with a notable reduction in p-p65/p65 levels in the TNF-α+high-dose quercetin group(P<0.001).Compared to the TNF-α+high-dose quercetin+DMSO group,the TNF-α+high-dose quercetin+NF-κΒ activator 1 group showed significantly elevated p-p65/p65 levels and increased concentrations of IL-6,IL-1β,ICAM-1,and MDA in cell supernatants(all P<0.001),and significantly decreased GSH-Px activity(P<0.001).Conclusion:Quercetin regulates the proliferation,inflammation,and oxidative stress in psoriatic keratinocytes by inhibiting the NF-κB signaling pathway.
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