Study On The Molecular Mechanism Of Wuziyanzong Pill Against Premature Ovarian Failure Based On Network Pharmacology And Molecular Docking

OBJECTIVE: To discuss the mechanism of action of Wuziyanzong pill in the treatment of premature ovarian failure by network pharmacology method,and to verify the binding activity of key intersection protein targets and drug active components,the stability of docking complex,and the strength of matching and binding effect by molecular docking method.METHODS: The major chemical constituents of Wuziyanzong pill were screened by searching published and verified literature reports from TCMSP database and related literature,and the Gene Symbol of the target genes of the corresponding chemical constituents was searched on Uniprot protein database platform to obtain the protein target information of the corresponding active components.The "active ingredient-target" network of Wuziyanzong pill was constructed by using Cytoscape3.6.0 software,and the more important active ingredients,targets and the relationship between them were obtained.The keyword "Premature Ovarian Failure" was retrieved from the Pub Med Mesh vocabulary.Potential targets of Premature Ovarian Failure were searched in Genecards database and OMIM database,and the first-line Western drug action targets for clinical treatment of Premature Ovarian Failure were searched in Ddrugbank database as supplements to get potential targets of Premature Ovarian Failure.Access to medicines in intersection with disease targets,using Cytoscape3.6.0 build abital yan zong pill composition-ovarian premature aging diseases of PPI network target proteins interacting with each other,to identify its internal protein Module,the various PPI network score in the first three of the Module is analyzed,and the candidate gene targets KEGG and GO analysis,using Metascape platform used after screening the key pathway and mechanism of core Cyto Scape 3.6.0 abital yan zong pill component-ovarian premature aging targets-biological pathways network diagram,Select target node Degree value is the top five compounds and nodes as the core protein targets and core active ingredients of compound,in bank PDB database to find the key targets of PDB ID,to obtain their crystal structure,using the Docking module in the Application to the key target of the optimized structure,and then according to the target protein complexes of ligand parts choose the active site of Docking,using SYBYL X2.1molecular mechanics program Minimize activity into small molecular structure to optimize the distribution of body to get stable conformation.Surflex-dock function module of Sybyl X2.1 software was used for molecular docking,and the results were shown by the scoring function,Total Score.Py Mo L software was used to visualize the results of the joint verification,and a 3D pattern was drawn,while the Proteins Plus online mapping tool(https://proteins.plus/)was used to draw a 2D pattern.RESULTS: 1.The main active compounds of Wuziyanzong pill in the treatment of premature ovarian failure were quercetin,kaempferol,beta-sitosterol,ellagic acid and daidzein;The main targets were PGR,NCOA2,PTGS2,PPARG and Rel A.2.The main biological processes involved in the treatment of premature ovarian failure by Wuziyanzong pill include: active oxygen metabolism,reaction to lipopolysaccharide,cell apoptosis,cell proliferation and differentiation;The related signaling pathways mainly include cancer pathway,AGE-RAGE signaling pathway,IL-17 signaling pathway,cell senescence and progesterone mediated oocyte maturation.The main functions of the targets are protein kinase binding,protein domain-specific binding,transcription factor binding,cytokine receptor binding,protein kinase activity,protein homodimerization activity,and nuclear receptor activity.3.The molecular docking method verified that most of the key protein targets had good binding activity with drug active components,and the docking complex was stable with good matching and binding effect.Conclusion: This study found that the influence mechanism of Wuzi Yanzong Pill on premature ovarian failure mainly includes the following aspects:(1)through the mitochondrial pathway and death receptor pathway to improve the activity of antioxidant enzymes,lower levels of ROS,reduce oxidative stress reaction,and inhibit apoptosis,promote the mature oocytes,follicle stimulating hormone generated and successful fertilisation(2)affect the hormone receptor expression,improve cell adhesion force,improve the ability of implantation(3)the damage to the ovaries(4)reduce inflammation medium inhibit lipid over oxidation,improve glucolipid metabolic disturbance,delay ovarian aging,regulate immune function(5)play a class estrogen-like effect,promote the proliferation of osteoblast differentiation and mineralization ability,inhibiting osteoclast function,adjust the balance of bone metabolism,anti osteoporosis.