Study On The Mechanism Of Liuwei Dihuang Pills In Treating Parkinson’s Disease Based On Network Pharmacology

BackgroundParkinson’s disease(PD)is one of the common neurodegenerative diseases in middle-aged and elderly people.With the development of my country’s aging population,it is expected that the number of Parkinson’s disease patients in my country will increase to 5 million by 2030.At present,the pathogenesis of Parkinson’s disease is not clear,conventional treatment methods cannot cure Parkinson’s disease,and long-term medication will The prevention and control of Parkinson’s disease has become a huge challenge in the field of health due to problems such as reduced drug efficacy and adverse drug reactions.Liuwei Dihuang Pill has a good effect on the treatment of Parkinson’s disease,but its mechanism of action is still unclear.Network pharmacology is the product of the combination of basic theories and research methods of medicine,biology,computer science,bioinformatics and other disciplines.Relying on existing databases,it can systematically,comprehensively and save manpower and material resources to explore the role of drugs in disease networks.Mechanism,especially suitable for the study of traditional Chinese medicine.MethodThe main components of six Chinese herbal medicines in Liuwei Dihuang Pills were obtained through the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP),and the active components were screened according to the parameters of absorption,distribution,metabolism and excretion(ADME);target.Parkinson’s disease-related targets were obtained from the Gencards,OMIM,TTD and DRUGBANK 4 databases.The active ingredient targets were mapped with the Parkinson’s disease targets to obtain Liuwei Dihuang Pills candidate targets for the treatment of Parkinson’s disease.Cytoscape software was used to build the network model of "drug-ingredient-target" and the protein interaction(PPI)network model of Liuwei Dihuang Pill for the treatment of Parkinson’s disease.Topological analysis of the constructed network was conducted to screen the core components and core targets of Liuwei Dihuang Pill in the treatment of Parkinson’s disease.The Metascape platform was used for GO functional and KEGG pathway enrichment analysis.Finally,molecular docking is applied to verify whether the active ingredient has good affinity with the target.ResultAfter screening and deduplication,69 active ingredients,204 active ingredient targets,4333 Parkinson’s disease-related disease targets and 162 Liuwei Dihuang Pills for Parkinson’s disease candidate targets were obtained.We constructed a "drug-ingredient-target" network model and a PPI network model of Liuwei Dihuang Pill’s candidate targets for the treatment of Parkinson’s disease.According to the results of network topology analysis,we predict that the core components of Liuwei Dihuang Wan are quercetin,stigmasterol,kaempferol and β-sitosterol;the core targets are AKT1,VEGFA,IL6,TP53,and CASP3.GO function and KEGG pathway enrichment analysis showed that Liuwei Dihuang Pill’s candidate target for Parkinson’s disease was involved in neuronal death,G protein-coupled amine receptor activity,reactive oxygen species metabolic process,MAPK signaling pathway,cell senescence and other biological process.Molecular docking results showed that the binding affinity between the core components and the targets targets was good.Conclusion1.Quercetin,stigmasterol,kaempferol and β-sitosterol are the core components of Liuwei Dihuang Pills in the treatment of Parkinson’s disease.They have antioxidant properties,improve mitochondrial function,resist neuroinflammation,protect and repair neurons,and regulate cell apoptosis.These functions can effectively alleviate the progression of Parkinson’s disease and are the material basis for Liuwei Dihuang Pills to treat Parkinson’s disease.2.AKT1,VEGFA,IL6,TP53 and CASP3 are the core targets of Liuwei Dihuang Pill in the treatment of Parkinson’s disease.3.On the one hand,Liuwei Dihuang Pill directly targets corresponding target proteins such as AKT1,VEGFA and IL6 through its active ingredients such as quercetin,stigmasterol,kaempferol and β-sitosterol,thereby exerting its antioxidant properties,Improve mitochondrial function,resist neuroinflammation,protect and repair the physiological functions of nerves.On the other hand,it can play a medicinal role by regulating PI3K/Akt,IκB/NF-κB,MAPK and other signaling pathways through target proteins.