Effects of Huangqi Guizhi Wuwu(黄芪桂枝五物)Decoction in the Treatment of Exercise-Induced Fatigue Based on Network Pharmacology,Molecular Docking and Animal Experiments
Objective:To investigate the mechanism of action of Huangqi Guizhi Wuwu(黄芪桂枝五物)Decoction in the treatment of exercise-in-duced fatigue(EF)by using network pharmacology and molecular docking,and to validate and analyze it through animal experiments.Meth-ods:The active ingredients,core targets and signaling pathways of Huangqi Guizhi Wuwu Decoction in the treatment of EF were obtained by network pharmacology tools.An EF rat model was constructed,and HE staining,ELISA,and PCR experiments were performed to verify the principal targets and therapeutic effects predicted by network pharmacology.Results:A total of 43 active ingredients and 242 potential targets in Huangqi Guizhi Wuwu Decoction were screened out,and 1002 potential targets for EF.A total of 104 targets was observed at the intersec-tion of drug and disease,including AKT1,IL6,TNF,IL1B,PPARG,PTGS2,etc.The results of KEGG enrichment analysis showed that AGE-RAGE,TNF,IL-17,TNF,IL-17and HIF-1 signaling pathways were involved.The molecular docking results showed that the active ingredi-ents,such as leguminol,prickly aristolochicin and proto-opiomelanocarpine hadgood binding activities with key targets,such as PTGS2,PTGS1,CHRM1,etc.Huangqi Guizhi Wuwu Decoction affected the expression of target proteins,such as AKT1,IL-6,TNF,IL-1B,PPARG,PTGS2,etc.,and thus regulated inflammatory response and apoptosis.Animal experiment results showed that Huangqi Guizhi Wuwu Decoc-tion could induce rat muscle fibers more closely aligned,enhance rat limb muscle strength,exercise endurance,cardiac blood supply,and alle-viate the cardiac overcompensation.Compared with the control group,the swimming exhaustion time and limb grip strength were significantly reduced in the model group.The serum levels of creatine kinase(CK),blood lactate(BLA),interleukin 6(IL-6),tumor necrosis factor-α(TNF-α),and hypoxia-inducible factor-1α(HIF-1α)were significantly elevated.The levels of vascular endothelial growth factor(VEGF)and erythropoietin(EPO)were significantly reduced(P＜0.01).The mRNA expression of estrogen receptor 1(ESR1)was down regulated,and the mRNA expressions of prostaglandin endometriosis synthase 2(Ptgs2),threonine kinase 1(Akt 1),peroxisome proliferator-activated receptor γ(Pparg),and fructooligosaccharides(Fos)were up regulated(P＜0.05).Compared with the model group,the swimming exhaus-tion time and limb grip strength was significantly increased in the Huangqi Guizhi Wuwu Decoction group,the serum levels of BLA,CK,IL-6,TNF-α,and HIF-1α were significantly decreased,and the levels of VEGF and EPO were significantly increased(P＜0.01).The mRNA ex-pression of Esr1 was up regulated,while the mRNA expressions of Ptgs2,Akt1,Pparg,and Fos were down regulated(P＜0.05).Conclusion:Quercetin,β-sitosterol,kaempferol and other compounds in Huangqi Guizhi Wuwu Decoction played a key role in the prevention and treatment of EF by affecting the expression of target proteins,such as PTGS2,PTGS1 and ADRB2,and participating in the signaling pathways,such as AGE-RAGE,TNF and IL-17 signaling pathways.
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