Network Pharmacological Study And Clinical Effect Observation Of Bushen Huoxue Decoction In The Treatment Of Knee Osteoarthritis With Kidney Deficiency And Blood Stasis

Knee osteoarthritis(KOA)is a common chronic disease and multiple diseases in clinic,especially incidence rate in elderly population.According to the data from the China Health and Elderly Care Follow-up Survey database,8.1% of KOA patients diagnosed in China need to cure a doctor,and the proportion of women is higher than men.Nowadays,OA has become the second largest disease after heart disease,which makes patients lose the ability to work,and brings economic burden to society and families.Traditional Chinese medicine divides it into categories such as "bi syndrome" and "gubi".Kidney deficiency and blood stasis type KOA discussed in this paper is the most common type of clinical syndrome,which is based on deficiency of liver and kidney and based on qi stagnation and blood stasis.The treatment of Bushen Huoxue Decoction(BHD)in Dacheng of Traumatology written by Zhao Zhuquan in the Qing Dynasty was performed with the combination of 11 traditional Chinese herbs,such as Rehmannia Glutinosa,Fructus Psoraleae,Semen Cuscutae,Cortex Eucommiae,Medlar,Angelica Sinensis,Fructus Comi,Cistanches,Myrrh,Archangelica and Safflower.In this paper,the effective chemical components,targets and possible mechanisms of action of BHD in the treatment of knee osteoarthritis were analyzed through network pharmacological study.Qualitative analysis was used to determine its biological activity and obtain the existing compounds.The clinical efficacy of BHD in the treatment of KOA was further confirmed by clinical observation.Objective:Experiment 1:Main to explore the key target and effect of BHD in the treatment of KOA with kidney deficiency and blood stasis.Experiment 2:The chemical constituents of BHD were qualitatively analyzed by ultra performance liquid chromatography-tandem time of flight mass spectrometry.Experiment 3:The aim is to explore the clinical efficacy of BHD in the treatment of KOA with kidney deficiency and blood stasis through clinical observations.Methods:Experiment 1:The target of main active compounds in BHD was searched by Swiss Target Prediction.The disease targets of KOA were collected through Genecards database,and the intersection of the two was obtained to obtain a common target,Protein interaction(PPI)network was plotted using STRING database,and GO enrichment analysis and KEGG pathway enrichment analysis were performed on key targets.Experiment 2:A Waters ACQUITY UPLC high performance liquid chromatography(HPLC)was used to determine the chromatographic and mass spectrum conditions;The samples were processed and analyzed to obtain the positive and negative ion mode mass spectra;The chemical components in the peak of the mass spectrum were analyzed and identified.Experiment 3:Methods from June 2020 to March 2021,33 patients with koa were selected from the Department of orthopedics and ward of the First Affiliated Hospital of Tianjin University of traditional Chinese medicine.During the observation period,the patients were given BHD,and the conditions and changes of the patients before treatment,3 weeks after treatment and 6 weeks after treatment were observed.The main outcome measures were visual analogue scale(VAS)and TCM syndrome classification and quantitative score of knee osteoarthritis.Secondary outcome measures were Lequesne Knee Index Function Scale and its pain or discomfort,walking ability,living ability,and adverse reactions.Statistics and analysis of the results.Results:Experiment 1:There are 82 active components and 615 potential targets of BHD.There were 482 targets for KOA diseases and 533 drug diseases.GO enrichment analysis obtained119 cell biological items;95 related signaling pathways were obtained by KEGG pathway enrichment analysis.Experiment 2:A total of 62 compounds,including 17 lactones,were identified in the positive and negative ion mode,of which 14 were coumarins,11 iridoids,5 flavonoids,4 ketones,and 4 Phenolics,3 aldehydes,3 phenylpropanoids,3glycosides,3 terpenes,2 chalcones,1chalcone glycosides,1 phenylpropionic acid,1 Phenolic acids,1 carboxylic acid,1 lignin and 2undetermined compounds.Experiment 3:In the third week of treatment,the total effective rate was 53.57%;At the6 th week of treatment,the total effective rate was 92.86%.After 3 weeks of treatment and 6weeks of treatment,there were statistically significant differences in joint pain,joint swelling,walking ability,life aspects,knee and eye tenderness,joint clicking,waist and knee pain and weakness,fatigue and fatigue,dizziness and tinnitus(P<0.05).Before treatment and 3 weeks of treatment and 3 weeks of treatment and 6 weeks of treatment,there was no significant difference in Lequesne severity and activity index scores of 28 patients with knee osteoarthritis before and after treatment(P>0.05).The quantitative scores of TCM syndrome grading and VAS scores of 28 patients with knee osteoarthritis before and after treatment were analyzed,and the differences were statistically significant(P<0.05).Conclusion:Experiment 1:The molecular mechanism of BHD in multi-component,multi-channel and multi-target treatment of KOA is elaborated,which provides basis for follow-up research and clinical practice.Experiment 2:The application of this method can comprehensively and efficiently analyze the chemical components in BHD,and provide evidence at the molecular level for the efficacy of BHD;at the same time,it verifies the drug target of the network pharmacology analysis.Experiment 3:BHD can significantly improve the patients with kidney deficiency and blood stasis type KOA,relieve their discomfort and restore their joint function,and no adverse reactions were found,which is worthy of further exploration.