Clinical And Network Pharmacology Study On The Treatment Of Liver And Kidney Deficiency Syndrome Of Knee Osteoarthritis By Busui Qianggu Decoction

Objective: To observe the clinical efficacy and safety of Busuiqianggu Decoction in improving the degree of knee dysfunction in patients with deficiency syndrome of liver and kidney of knee osteoarthritis,relieving pain,and discussing its clinical application value.At the same time,the method of network pharmacological research was used to conduct a systematic bioinformatics analysis of Busuiqianggu Decoction,so as to deeply explore the mechanism of action of Busuiqianggu Decoction in the treatment of knee osteoarthritis.Methods: 1.The clinical trial observation part selected 60 patients with knee osteoarthritis and liver and kidney deficiency syndrome who met the inclusion criteria in the micro-orthopaedic clinic of Shandong Hospital of Traditional Chinese Medicine from December 2021 to December 2022.They were randomly divided into experimental group and control group,with 30 cases in each group.The control group was given glucosamine sulfate capsules,2 capsules,3 times a day,orally;Experimental group was given Bupi Qianggu decoction on the basis of conventional treatment,one dose a day,orally.Patients in the two groups were treated for 12 weeks.VAS and WOMAC before,6 weeks and 12 weeks after treatment were recorded respectively.Finally,TCM efficacy of patients in the two groups was statistically analyzed.2.TCMSP database was used to search the active ingredients and related targets of Busuiqianggu Decoction in the part of network pharmacology.Genecards,OMIM,Drug Bank and TTD databases were used to search the related targets of knee osteoarthritis,and the network between Busuiqianggu Decoction and knee osteoarthritis was constructed to screen out the targets between them.String,David6.8,Cytoscape3.8.0 websites and software were used to conduct biofunctional and pathway analysis on the target of Busuiqianggu Decoction in the treatment of knee osteoarthritis,so as to explore the potential mechanism of Busuiqianggu Decoction in the treatment of knee osteoarthritis.Finally,Auto Dock Tools software was used to conduct molecular docking of active ingredients and key targets,in order to further prove the feasibility of Busuiqianggu Decoction in the treatment of knee osteoarthritis from the molecular level.Results: 1.Results of clinical trials1.1 Comparison of general data before treatment: Statistical results showed that there was no significant difference in gender composition between the two groups(P=0.602 >0.05),which was comparable;There were no significant differences in age(P=0.439 > 0.05)and course of disease(P=0.509 > 0.05),which were also comparable.1.2 VAS and WOMAC scores: VAS and WOMAC scores were lower in both groups after treatment than before treatment.The two indexes were compared at 6 weeks and 12 weeks after treatment,and the differences were statistically significant(P < 0.05).1.3 Clinical efficacy and safety: at the end of 12 weeks of treatment,the total effective rates of subjects in the experimental group and the control group were 90% and 63.3%,respectively,with statistically significant differences between groups(P=0.015 < 0.05).In the experimental group,1 patient had fever and 1 patient had loss of appetite during treatment(P > 0.05),and no serious adverse reactions occurred in both groups.2.Network pharmacological resultsA total of 129 active ingredients were obtained from Bumedi Qianggu formula after database screening,involving 213 potential targets.A total of 2390 disease targets were identified after screening for knee osteoarthritis.There are 123 targets at the intersection of drugs and diseases.Eleven key targets of bumyeljinju prescription for the treatment of knee osteoarthritis were identified,including tumor necrosis factor(TNF),leukocyte meso-6(IL6),rac-α-serine/threonine protein kinase(AKT1),leukocyte meso-1b(IL1B),vascular endothelial growth factor(VEGFA)and cell tumor antigen p53(TP53)Point.KEGG pathway enrichment analysis identified 136 signaling pathways,among which TNF signaling pathway and IL-17 signaling pathway are important pathway hubs.Molecular docking model showed that 5 compounds with better active components had higher binding energy with 2 key targets.Conclusions: 1.Busuiqianggu Decoction has good therapeutic effect on the syndrome of liver and kidney deficiency of knee osteoarthritis.Combined with conventional western medicine glucosamine sulfate capsules,Busuiqianggu Decoction can significantly improve the activity dysfunction at the knee joint of patients and significantly reduce the pain of patients,showing good clinical efficacy and safety.2.The potential mechanism of action of Busuiqianggu Decoction in the treatment of knee osteoarthritis involves multiple active ingredients,multiple targets and multiple pathways,which mainly plays a synergistic role through mediating inflammatory immune response and improving vascular function.Molecular docking results showed that β-sitosterol,luteolin,quercetin,naringenin,kaempferol and other active ingredients had good binding with the key targets of AKT and MMP9.