Study on mechanism of Simiao Yong'an Decoction in treating MSU-induced gouty arthritis through MEK1/2-ERK1/2 pathway
Objective To investigate the effect of Simiao Yong'an Decoction on gouty arthritis rats induced by monosodium urate(MUS)and its possible mechanism.Methods The target of Simiao Yong'an Decoction in the intervention of gouty arthritis was predicted by network pharmacology,and the relationship network of active ingredient-target and target-pathway was constructed.Totally 48 male SD rats were randomly divided into control group,model group,Simiao Yong'an Decoction low,medium and high dose group(6.075,12.150,and 24.300 g·kg-1),with eight rats in each group.Prophylactic ig administration once a day for seven days.On the 3rd day of ig administration,except for the control group,the GA rat model was established according to the classical modeling method.The different doses of Simiao Yong'an Decoction were injected into the stomach to measure and calculate the degree of ankle swelling,and the histopathological changes of ankle synovium and the levels of inflammatory factors in serum of rats in each group were detected.Finally,real-time quantitative fluorescent PCR(qRT-PCR)and Western blotting were used to detect the mRNA and protein expression levels of MEK1/2-ErK1/2 pathway genes in joint tissues.Results The network pharmacology results show that AKT1,ALB,TNF,HSP90AAl,EGFR,SRC,VEGFA,CCND1,and HRAS may be the key targets of Simiao Yong'an Decoction for the treatment of gouty arthritis;β-sitosterol,kaempferol,quercetin,and lutein may be the more important effective components for the treatment of gouty arthritis;the enriched genes in biological processes(BP)are mainly related to inflammatory responses,positive regulation of cell migration,negative regulation of responses to external stimuli,and regulation of small molecule metabolic processes;the enriched genes in cellular components(CC)include secretory granules,cytoplasmic vesicles,endoplasmic reticulum,Golgi,and platelet granules;the enriched genes in molecular functions(MF)include transcription factor binding,protein kinase activity,and kinase regulatory activity at the front;the KEGG metabolic pathways are mainly enriched in MAPK signaling pathway,PI3K-Akt signaling pathway,IL-17 signaling pathway,and Ras signaling pathway.Compared with the model group,Simiao Yong'an Decoction at high dose can significantly improve the degree of ankle edema(P＜0.05);at medium and high doses,it can alleviate the inflammatory infiltration of synovial tissue in rats with gouty arthritis;at medium and high doses,the levels of inflammatory factors are significantly lower(P＜0.05,0.01);at medium and high doses,the gene mRNA expression of MAPK3 and MAP2K1 is significantly downregulated(P＜0.01);at high dose,the expression of ErK1/2 and MEK1/2 proteins is significantly downregulated(P＜0.01).Conclusion Simiao Yong'an Decoction has a certain intervention effect on GA rats,and its active components may inhibit the expression of inflammatory factors such as TNF-α and IL-1β by inhibiting the expression of key targets in MAPK signaling pathway,and alleviate the inflammatory response,so as to play a therapeutic role in gouty arthritis.
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