Study On The Effect And Mechanism Of Zuogui Pill In The Treatment Of Premature Ovarian Failure

Objective（1）With the help of Cite Space 5.8.R3 application software,the relevant literature of traditional Chinese medicine（TCM）in the treatment of premature ovarian failure（POF）was visually analyzed using bibliometric methods to explore the research status,hot topics and emerging trends in this field.（2）The data mining method is used to analyze the medication rules of the clinical prescriptions of traditional Chinese medicine collected in the literature for the treatment of POF,so as to provide ideas for guiding clinical medication.（3）Based on the previous research,it was found that the traditional Chinese medicine compound Zuogui Pill（ZGP）was favored in the treatment of POF.The effectiveness and safety of ZGP in the treatment of POF were systematically evaluated with the method of evidence-based medicine.（4）Combining the network pharmacology method and molecular docking technology to jointly study the mechanism of ZGP in the treatment of POF.Method（1）Bibliometric methodThe documents related to the treatment of POF by traditional Chinese medicine were collected from CNKI and Web of Science（WOS）databases and entered into Cite Space 5.8.R3 application software to better analyze and explore its relevant knowledge.（2）Data mining methodsCollect clinical prescriptions of traditional Chinese medicine for the treatment of POF from literature,establish a prescription database of"Traditional Chinese Medicine for POF"using Excel tables,and perform frequency,efficacy,taste,meridian tropism,clustering,association rules,and complex network analysis on its data to better display its characteristic information.（3）Evidence-based medicine analysis methodThrough searching CNKI,VIP,WANFANG,CBM,PUBMED and other databases,we collected randomized controlled trials on ZGP treatment of POF,screened and sorted the literature,extracted effective data,and analyzed them with Rev Man5.3application software.（4）Network pharmacology methodThe active components of Rehmannia glutinosa,Cornus officinalis,Lycium barbarum,Cuscuta chinensis,Yam and Achyranthes bidentata in ZGP were searched by using the Systems pharmacology analysis platform（TCMSP）.Obtain target proteins related to POF from the Online Mendelian Inheritance in Man（OMIM）and Gene Cards databases.Venn analysis was performed on the active compound targets and POF disease targets in ZGP.The common targets at the intersection were also known as potential targets.A protein interaction network diagram of potential targets was constructed using the String database and Cytoscape 3.9.1 application software,and the core targets were obtained through corresponding conditional screening.Then,with the help of Auto Dock 4.2.6 application software,the small molecules of the active compound are docked with the core target proteins of the disease.Finally,GO function and KEGG analysis were conducted on its potential targets using a genome annotation database.Result（1）The research progress of traditional Chinese medicine in the treatment of POF was explored by using the literature metrology method.A total of 1468 articles were included,including 1251 in Chinese and 217 in English.Among the international studies,Human Reproduction has the largest number of published articles（11,5.07%）.Since its research in 1989,the research on traditional Chinese medicine in the treatment of POF has been increasing year by year,with most of the research coming from higher education institutions in China.In this field of research,several authors such as Feng Yixuan,Ren Yulan,and Ling Lele have published a large number of literature in China,while Betterle C is the author with the highest number of published literature in the international research field.Through analysis,it is further concluded that ZGP,expression,cells,genes,models,etc.are currently hot topics;Acupuncture and moxibustion,activation,data mining,oxidative stress,and systematic evaluation may become emerging trends in the future.（2）Through data mining analysis,it was found that traditional Chinese medicine has the main efficacy in treating POF,such as tonifying deficiency,promoting blood circulation,and resolving blood stasis;The medicinal properties of drugs are commonly found in warm,calm,and cold type drugs;The medicinal taste of drugs is mostly sweet,pungent,and bitter,and their meridians mainly lie in organs such as the liver,kidney,spleen,heart,and lungs.The study found that the core drugs such as prepared rehmannia,Chinese yam,wolfberry,dodder,and cornus were used more frequently,which was related to the kidney deficiency of POF patients,taking into account the deficiency of heart,liver,and spleen,and was consistent with the addition and subtraction of ZGP,to achieve the effect of nourishing yin and kidney,filling the marrow,which fully reflected the unique idea of Chinese medicine.（3）The results of evidence-based medicine meta-analysis showed that there were significant differences in clinical efficacy and adverse reactions,as well as diagnostic indicators such as luteinizing hormone（LH）,serum follicle stimulating hormone（FSH）,and estradiol(E₂)levels between the Chinese medicine experimental group（Zuogui pill combined with hormone therapy）and the Western medicine control group（hormone therapy alone）,but there was no significant difference in the syndrome score level between the two groups.（4）Through network pharmacology analysis,ZGP mainly treats POF by regulating pathways such as cell apoptosis,angiogenesis,and inflammatory response.Moreover,a large number of literature studies have shown that POF is associated with MAPK,PI3K/AKT,TNF,IL-17,and H1L-1 signaling pathways.By regulating these signaling pathways,it reduces ovarian inflammatory response,inhibits apoptosis of follicular granulosa cells,and improves follicular growth and development,thereby achieving a protective effect on ovarian function.Due to the complex composition of traditional Chinese medicine,the combination of network pharmacology methods and molecular docking techniques can effectively elucidate its mechanism of action,thus providing a favorable basis for subsequent research.