| Objective The clinical efficacy of Lu’s fumigation decoction in the treatment of knee osteoarthritis with kidney deficiency and stasis was observed by randomized control experiment,and its potential mechanism of action was explored based on network pharmacology and molecular docking technology.Methods 1.From January to December 2022,80 outpatients who met the diagnostic criteria of knee osteoarthritis of kidney deficiency and stasis in our community hospital were selected as the research objects,and they were divided into control group and treatment group by random number table method,with 40 cases in each group.The control group was treated with topical flurbiprofen gel plaster,and the treatment group was treated with Lu’s fumigation formula.The TCM syndrome score,pain index,WOMAC score,12-SCT score and safety were observed before and after treatment in the two groups.Through the traditional Chinese medicine system pharmacology database and analysis platform TCMSP,drug likeness(DL)≥0.18,molecular weight(MW)<500,and logarithm of lipid and water partition coefficient(AlogP)1-3 were set.To screen out the active components and corresponding targets of Lu’s fumigation recipe.The target proteins corresponding to the active components of the screened drugs were standardized into gene names through Uniport database.GeneCards and OMIM databases were used to obtain the disease targets of KOA.The target genes of the two were interposed to draw a Venn diagram.Cytoscape software was used to construct the TCM regulatory network of"TCM-component-target".The common targets of drugs and diseases were imported into the DAVID database for GO and KEGG enrichment analysis and plotted for visualization.The protein interaction network was constructed by STRING database,and the key genes of intersection target PPI were screened by Cytoscape.Using molecular docking technology,the main active ingredients of core traditional Chinese medicine and the main key targets were docked to obtain the combination of the two,so as to verify the reliability of the mechanism prediction.Results 1.The clinical efficacy observation study was finally completed in 75 cases,38 cases in the control group,37 cases in the treatment group,and 5 cases dropped out.Before treatment,the two groups were comparable in terms of general data such as age,gender,course of disease and efficacy indicators such as TCM syndrome score,pain index,osteoarthritis index,12-SCT score(P>0.05).After treatment,the scores of TCM syndromes in the treatment group were significantly lower than those before treatment(P<0.01),and the improvement degree of joint pain,swelling,stiffness,activity disadvantage,waist and knee soreness and other aspects in the treatment group were significantly better than those in the control group(P<0.05).After treatment,the total TCM syndrome scores of the two groups were significantly improved compared with those before treatment(P<0.01),and the improvement degree of the treatment group was significantly better than that of the control group(P<0.01).The total effective rate of the treatment group was 89.19%,which was significantly higher than 63.16%of the control group(P<0.05).The pain index of the two groups was significantly reduced after treatment(P<0.01),and the improvement degree of the treatment group was significantly better than that of the control group(P<0.01).The WOMAC scores of the two groups after treatment were significantly lower than those before treatment(P<0.01),and the improvement in the treatment group was significantly better than that in the control group(P<0.05).The 12-SCT scores of the two groups after treatment were significantly lower than those before treatment(P<0.01),and the improvement degree of the treatment group was better than that of the control group.No adverse reactions such as allergy and rash or other serious adverse events occurred in the two groups during the whole study period,and there were no obvious abnormalities in vital signs,three routine tests,liver and kidney function and other indicators of the two groups.2.In the preliminary study of Lu’s fumigation recipe for the treatment of KOA based on network pharmacology and molecular docking,the results showed that 68 effective active ingredients were obtained after screening and deweighing,which corresponded to 864 target genes,and 141 overlapping target genes with KOA.The visualization of the traditional Chinese medicine regulatory network showed that there were 184 nodes and 490 edges.The main active ingredients involved in the regulation included quercetin,apigenin,luteolin,daidzein,kaempferol,etc.The PPI network showed a total of 141 nodes and 607 edges,with an average number of nodes of 8.61,and 14 core target proteins such as STAT3,MAPK1,JUN,EP300,and MAPK14 were obtained.GO enrichment results showed that BP may be related to the response to peptides,oxidative stress,chemical stress,extracellular stimulation,lipopolysaccharide and bacterial-derived molecules.CC may be related to membrane raft,membrane microregion,transcription regulatory complex,vesicle cavity,etc.MF may be related to DNA-transcription factor binding,RNA polymerase II specific DNA-transcription factor binding,cytokine receptor binding,etc.KEGG enrichment analysis showed that a total of 149 pathways were involved,among which the top 30 pathways were most likely related to blood lipids and atherosclerosis,PI3K-Akt signaling pathway,AGE-RAGE signaling pathway in diabetic complications,etc.Molecular docking was performed using the core target proteins STAT3,mapkl and Jun with their corresponding small molecule ligands of the active ingredients myricetin,quercetin and kaempferol.The molecular docking results showed that the lowest binding energies of each were-7.3(kcal/mol),-9.0(kcal/mol)and-5.8(kcal/mol),respectively,suggesting that each of the three possessed a better binding activity and stable binding conformation.Conclusion 1.Lu’s fumigation decoction has a good effect on patients with knee.osteoarthritis of kidney deficiency and blood stasis.After 2 weeks of treatment,it can effectively reduce the level of inflammatory factors,significantly relieve the pain of patients,inhibit the inflammatory response,and is safe and has no obvious adverse reactions,which can be further applied in clinical practice.2.Lu’s fumigation decoction has the characteristics of multi-component,multi-target,multi-pathway and multi-pathway in the treatment of knee joint of kidney deficiency and stasis,and predicts its possible targets and mechanisms of action.It is suggested that Lu’s fumigation decoction mainly has anti-inflammatory,anti-oxidation,inhibition of chondrocyte apoptosis and protection of articular cartilage. |
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