Systematic Pharmacological Study On The Molecular Mechanism Of Shaoyaogancao Decoction In Treating Of Parkinson’s Disease

ObjectiveParkinson’s disease(PD)is the second most common progressive neurodegenerative disease.It is characterized by the absence of dopaminergic neurons in the melanin substantia nigra,which leads to motor dysfunction.In addition,cognitive decline,mood disorders,sleep dysfunction,gastrointestinal problems and autonomic dysfunction also occur in the later stages of the disease.Parkinson’s disease seriously affects the physical health,quality of life,and social functions of elderly people at home and abroad,while western medicine treatment has many side effects.Traditional Chinese Medicine(TCM)has been treating thousands of complex diseases,including PD,for thousands of years.ShaoyaoGancao Decoction(SGD)has a good neuroprotection and has a good clinical effect in the practice of PD treatment as a classic Chinese medicine in the Shang Han Lun – Sun chapter.However,due to the complex nature of Chinese herbal medicines with multiple components and multiple targets,it is difficult to clearly explain their therapeutic mechanism using traditional experimental methods.Therefore,this study intends to use a systematic pharmacological approach to explore the active ingredients,potential targets and related pathways of ShaoyaoGancao Decoction for the treatment of Parkinson’s disease,explaining its mechanism of action.In order to provide the basis for the clinical study of SGD,improving the quality of life and social function of PD patients,and extend their survival period.MethodsThis study used systematic pharmacology to systematically explore the compounds and possible therapeutic targets of SGD against Parkinson’s disease,as well as the overall mechanism of action pathways.Collecting all components of Baishao and Gancao in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)by "Herb name" searching and screening active compounds used OB ≥ 50% and DL ≥ 0.18.Candidate targets for active compounds were obtained using the SysDT model prediction method.Known targets related to Parkinson’s disease were obtained by integrating the Therapeutic Target Database(TTD),the International Genetic Pharmacology Database(PharmGKB),Genetic Association Database(GAD),DrugBank,and Comparative Toxicogenomics Database(CTD).By mapping drug target and disease target,we can get the target of SGD against PD.The STRING database was used to analyze the relationship between candidate target proteins.The network model was constructed using Cytoscape software,and key target proteins and key active ingredients were obtained through network topology analysis.Then,the functional annotation and regulatory pathways of SGD anti-PD target proteins were performed through Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis using Database for Annotation,Visualization and Integrated Discovery(DAVID).Finally,iGEMDOCK software was used to verify the binding ability between active ingredients and key target proteins through molecular docking.ResultsIn this study,383 compounds in SGD were collected,50 active ingredients and 100 targets regulated by active ingredients were obtained by screening with two parameters.A total of 200 PD-related target proteins were collected in five databases.After deduplication and intersection processing,44 candidate targets for SGD treatment of PD were finally obtained.Through the construction of the network model and the analysis of the network topology,it was found that kaempferol,β-sitosterol,cantharidin and other active components play a role in the treatment of PD by regulating prostaglandin G/H synthase 2(PTGS2),estrogen receptor(ESR1),estrogen receptor beta(ESR2),racalpha serine/threonine protein kinase(AKT1)and other pivotal nodes.These target proteins,through binding with enzymes,acetylcholine,and heme,exert biological processes such as cholinergic synaptic transmission,positive regulation of vasoconstriction,and positive regulation of peptidylserine phosphorylation,regulating the PI3K-Akt signaling pathway,the neuroactive ligand receptor interaction and the calcium signaling pathway,and finally achieves the therapeutic effect on Parkinson’s disease.Conclusion1.The iridoid glycosides,flavonoids and phytosterols active compounds of SGD,such as paeoniflorin,kaempferol,β-sitosterol,and formononetin have anti-inflammatory,antioxidant and neuroprotective effects,which may be the active substance basis of SGD against PD2.PTGS2,ESR1,ESR2,AKT1 and other hub nodes are the core targets of SGD against PD.3.The target proteins of SGD against PD is combined with enzymes,acetylcholine and heme,and exerts biological processes such as cholinergic synaptic transmission,positive regulation of vasoconstriction,and positive regulation of peptidylserine phosphorylation,which regulate the PI3K-Akt signaling pathway,the neuroactive ligand receptor interaction and calcium signaling pathways ultimately achieve the effect of treating Parkinson’s disease.4.ShaoyaoGancao Decoction can treat Parkinson’s disease through mechanisms such as antioxidant stress,anti-neuritism and inhibition of abnormal protein aggregation.