To Explore The Efficacy And Mechanism Of Yulinzhu In The Treatment Of Polycystic Ovary Syndrome Based On Meta-analysis And Network Pharmacology

Objective:1.To systematically evaluate the clinical efficacy and safety of Yulinzhu in the treatment of polycystic ovary syndrome,and provide evidence-based medical evidence for the clinical application of Yulinzhu in the treatment of polycystic ovary syndrome;2.To explore the mechanism of Yulinzhu in the treatment of polycystic ovary syndrome by using network pharmacology technology.Methods:1.Search each database: China Biomedical Literature Database(Sino Med),China Journal Full Text Database(CNKI),Wanfang(Wanfang)database,Vip(VIP)database,Pub Med,US Science Citation Database(Web of Science),Cochrane Library,from the beginning of the build The clinical randomized controlled trials of yohimbe for the treatment of PCOS published in China and abroad until December 31,2022,duplicate literature was excluded,and then the title,abstract and full text were read,and literature that did not meet the inclusion and exclusion criteria were also excluded,data extraction was performed on the final obtained literature,and quality assessment was performed using the Cochrane Risk of Bias Assessment Tool literature,and the Revman 5.4 software was used to conduct Meta-analysis of the literature.2.Search the TCMSP database,BATMAN-TCM,Herb database,and Huayuan.com,and combine the published literature on the ingredients of traditional Chinese medicine,and the platforms complement each other to obtain their CAS number,active ingredients or structural formula;The oral bioavailability of the obtained active ingredients was predicted through the Swiss ADME platform,and the published and verified literature reports were retrieved from the relevant documents of the Chinese Biomedical Literature Database(CBM),the Chinese Journal Full-text Database(CNKI),the Wanfang database and the VIP database to supplement the unpredictable ingredients in the database and establish the Yulinzhu ingredient target database.Combine the target obtained above,remove the weight,and carry out gene correction through Uniprot database to obtain the target information of the potential active ingredients of Yulinzhu.Retrieve the disease targets of PCOS in Gene Cards database,OMIM database and Drug Bank database,construct Wayne map,obtain the intersection targets of PCOS treatment,obtain the protein-protein interaction data in STRING database,and use Cytoscape software for visual analysis to obtain the key targets of PCOS treatment,In the Metascape database,the gene ontology(GO)enrichment analysis and the Kyoto Encyclopedia of Genes and Genome(KEGG)pathway enrichment analysis are carried out for the key targets,and the results are visualized through the micro-signal platform.Results:(1)Meta analysis results:This study comprehensively searched the relevant literature of Yulinzhu in the treatment of PCOS,discussed the clinical efficacy of Yulinzhu in the treatment of PCOS,a total of 126 relevant literature was retrieved in Chinese and foreign language databases,and after screening by inclusion and exclusion criteria,6 articles were finally included,and the Jadad score table was used for inclusion risk evaluation,so as to lay the foundation for obtaining higher quality evidence,a total of 485 patients were included,the maximum number of cases was 54,the minimum was 30,and the sample size of various studies varied greatly.The control group was treated with western medicine alone,and the experimental group added Yulin beads on the basis of the control group or simply used Yulin beads to add and subtract.The included literature adopts the principle of randomized controlled trials,and the meta-analysis results tend to be more effective than Western medicine for PCOS in combination with Western medicine basic treatment,and Yulinzhu has a certain effect on ovulation rate,pregnancy rate,serum sex hormones,and TCM syndrome points in PCOS patients.The results of the Mete analysis of Yulinbead for the treatment of PCOS are as follows:In terms of total clinical response rate,a total of 6 articles were included,and the results of meta-analysis showed that OR=3.04,95% CI(1.80,5.14),P<0.00001,the difference was statistically significant,indicating that the addition and subtraction of Yulinzhu or combination with western medicine for the prevention and treatment of PCOS was better than that of the western drug treatment group alone.In terms of ovulation rate,a total of 3 articles were included,and the results of meta-analysis showed that OR=2.34,95% CI(1.33,4.14),P<0.05,the difference was statistically significant,suggesting that Yulinzhu combined with Western medicine treatment had a higher ovulation rate than pure Western medicine treatment for PCOS.In terms of pregnancy rate,a total of 3 articles were included,and the meta-analysis results showed that OR=3.80,95% CI(1.96,7.34)P<0.0001,the difference was statistically significant,indicating that Yulinzhu combined with Western medicine treatment had a higher pregnancy rate than pure Western medicine treatment for PCOS.n terms of TCM syndrome scores,4 articles reported on them,and the meta-analysis results showed that MD=-3.64,95%CI(-6.37,-0.92),P=0.009,<0.05,the difference was statistically significant,indicating that Yulinzhu combined with Western medicine was better than the control group in improving TCM symptoms.Among them,3 subjects were patients with renal deficiency PCOS,and the TCM symptoms observed were basically the same,including symptoms such as waist and knee soreness,dizziness,tinnitus and loss of libido.Through sensitivity analysis,it can be concluded that Yulinzhu combined with Western medicine is stronger than Western drugs alone in reducing the medical syndrome score of patients with renal deficiency PCOS,and it can be considered that Yulinzhu has a better therapeutic effect in the treatment of renal deficiency PCOS,and can effectively reduce the symptoms of waist and knee soreness,dizziness,tinnitus and loss of libido in women with PCOS.In terms of testosterone,a total of 4 articles were included,and the results of meta-analysis showed that SMD =-1.07,95% CI(-1.83,-0.32),P<0.05,the difference was statistically significant,indicating that the Yulinzhu combined with Western medicine group was better than the control group in improving testosterone.In terms of luteinizing hormone,a total of 5 articles were included,and the results of meta-analysis showed that SMD=-2.35,95%CI=(-3.42,-1.28),P<0.0001,the difference was statistically significant,suggesting that both groups could improve serum LH levels,and Yulinzhu combined with western medicine group was better than the control group.In terms of estradiol,a total of 5 articles were included,and the results of meta-analysis showed that SMD=0.64,95%CI=(0.41,0.86),P<0.0001,the difference was statistically significant,suggesting that both groups could improve serum E2 levels,and Yulinzhu combined with western medicine was better than the control group.For LH/FSH,one study was included,and meta-analysis showed MD=-0.86,95%CI=(-0.89,-0.83),Z=66.70,P < 0.00001,the difference was statistically significant,suggesting that the group of Yulinzhu combined with western medicine was better than the control group in improving LH/FSH.But the study included only one article,and the results were not very convincing.In terms of follicle-stimulating hormone,a total of 5 articles were included,and the meta-analysis results showed that SMD =-0.47,95% CI =(-2.59,1.65),P>0.05,there was no significant difference,which could indicate that there was no significant difference in the effect of using Yulinzhu combined with western medicine versus western medicine alone in the treatment of patients with PCOS.(2)Network pharmacology:The results obtained from the active ingredients of Yulinzhu are as follows,with a total of 275 active ingredient information and 755 drug-related targets.There are 1559 target genes associated with PCOS,and 155 common targets of drugs and diseases are obtained through the Wayne diagram.The core targets of the PPI network were selected as MAPK1,ESR1,VEGFA,and AR.GO enrichment showed PCOS-related entries including 967 bioprocesses,866 for BP analysis,64 for MF analysis,and 37 for CC analysis.KEGG pathway enrichment analysis yielded a total of 145 pathways,mainly involving m TOR,PI3K/Akt,TNF,MAPK,Fox O and other signal pathways.Conclusion(s):1.Meta analysis:(1)The total clinical effective rate of Yulinzhu plus or minus or combined with conventional western medicine in the treatment of PCOS was better than that of conventional western medicine control group.(2)The addition or subtraction of Yulinzhu or the combination of conventional western medicine for the treatment of PCOS can significantly improve the ovulation rate,pregnancy rate,TCM syndrome score,serum LH,E2,T,LH/FSH levels in PCOS patients,but there is no significant improvement in serum FSH levels.(3)According to the results of TCM syndrome points,Yulinzhu combined with Western medicine treatment is stronger than Western drugs alone in reducing the medical syndrome points of patients with renal deficiency PCOS compared with Western drugs alone,and it can be considered that Yulinzhu has a better therapeutic effect in the treatment of renal deficiency PCOS,and can effectively reduce the symptoms of waist and knee soreness,dizziness,tinnitus and loss of libido in women with PCOS.2.Network pharmacology:Based on the research mode of network pharmacology,the research and analysis of Yulinzhu was carried out,and it was found that the treatment of PCOS by Yulinzhu may act on core targets such as STAT3,CTNNB1,MAPK1,ESR1,VEGFA,EGF,TNF,AR,etc.through quercetin,kaempferol,β-sitosterol,isorhamnetin,plant sterols and other components,and reduce insulin resistance,anti-inflammatory,and oxidative stress by regulating signal pathways such as PI3K/Akt,TNF,MAPK,and Fox O Promote follicle development,regulate lipid metabolism,regulate hormone levels,etc.,thereby treating and improving PCOS.