基于NF-кB信号通路探讨加味小陷胸汤抗动脉粥样硬化的作用机制OA

Objective Building upon prior network pharmacology findings,this study aimed to elucidate the mechanism by which Modi-fied Xiaoxianxiong Decoction(加味小陷胸汤,MXXD)attenuates atherosclerosis,focusing on its role in modulating the NF-κB signal-ing pathway.Methods Drug-containing serum was obtained from SPF-grade male SD rats(n=48)administered low-dose,medium-dose,or high-dose MXXD.An in vitro foam cell model was established by stimulating RAW264.7 macrophages with oxidized low-density lipoprotein(ox-LDL).Cells were divided into control,model(ox-LDL),and ox-LDL+MXXD serum(low,medium,high dose)groups.Cell viability was assessed using CCK-8 assay.Foam cell formation was visualized by Oil Red O staining.Intracellular total cholesterol(TC)and free cholesterol(FC)levels were quantified enzymatically.Inflammatory cytokine(IL-1β,IL-6,IL-10,TNF-α)secretion was measured by ELISA.mRNA and protein expression of key NF-κB pathway components(NF-κB,IκB-α,IKKα)were analyzed using RT-PCR and Western blot(WB),respectively.Results Varying concentrations of MXXD serum did not signifi-cantly affect RAW264.7 cell proliferation.However,20%MXXD serum notably enhanced cell viability under ox-LDL stress(P<0.01).Oil Red O staining revealed a marked reduction in lipid droplets and improved cell morphology across all MXXD treatment groups.MXXD serum significantly decreased intracellular TC(P<0.01)and FC(P<0.01)content.It also suppressed the ox-LDL-induced secretion of pro-inflammatory cytokines IL-1β(P<0.01),IL-6(P<0.05),and TNF-α(P<0.05),while promoting the release of anti-inflammatory IL-10(P<0.05).At the molecular level,MXXD treatment downregulated mRNA and protein expression of NF-κB and IKKα,and upregulated IκB-α expression.Conclusion Our findings demonstrate that MXXD inhibits ox-LDL-induced mac-rophage foam cell formation by suppressing NF-κB pathway activation.This effect is associated with improved intracellular cholesterol metabolism and a shift in the inflammatory profile,highlighting its potential therapeutic mechanism against atherosclerosis.