Integrated serum pharmacochemistry and network pharmacology validate Qiangli Dingxuan Tablets ameliorates metabolic hypertension via TLR4/MyD88/NF-κB pathwayOA

Background:Modified Qiangli Dingxuan Tablets(ZYSJ)is an optimized formulation derived from the classic Chinese patent medicine Qiangli Dingxuan Tablet.It targets the pathological features associated with metabolic hypertension(MH)and metabolic disorders,although its antihypertensive mechanism remains unclear.Methods:A rat model of metabolic hypertension was established using a high-sugar,high-fat diet combined with progressively increasing concentrations of ethanol.Blood pressure,serum lipids,inflammatory cytokines,and endothelial function markers were assessed.Serum pharmacochemistry combined with network pharmacology was employed to predict key targets and pathways,followed by in vivo validation using qRT-PCR,Western blotting,immunofluorescence,and immunohistochemistry.Results:ZYSJ significantly reduced blood pressure and serum lipid levels in model rats.Thirty absorbed bioactive components were identified.Mechanistic studies revealed that ZYSJ downregulated the TLR4/MyD88/NF-κB signaling pathway at both the mRNA and protein levels,upregulated endothelial nitric oxide synthase(eNOS)expression,and decreased the levels of inflammatory cytokines(TNF-α,IL-1β,IL-6),thereby improving vascular endothelial function.Conclusion:ZYSJ effectively lowers blood pressure and serum lipids in rats with metabolic hypertension.Its mechanism of action is closely associated with regulation of the TLR4/MyD88/NF-κB signaling pathway,improvement of vascular endothelial function,and alleviation of inflammation.