Researching The Mechanism Of Zanthoxylum Bungeanum Maxim In Analgesia And Improvement Of Cognitive Dysfunction Based On Network Pharmacology And Molecular Docking Technology

Objectives:The aim of this study is to investigate the active ingredients,action targets and possible mechanisms of Zanthoxylum bungeanum Maxim in analgesia and improvement of cognitive dysfunction.The goal of the study is to provide a new perspective for the development of novel anesthetic drugs,especially those with postoperative cognitive dysfunction improvement effects.Methods:The components in Zanthoxylum bungeanum Maxim were obtained by searching the TCMSP and related literature.Screening the components by drug-like properties(DL)≥ 0.18 was aimed at obtaining the active ingredients of Zanthoxylum bungeanum Maxim.TCMSP was used to predict and analyze the effective target components in Zanthoxylum bungeanum Maxim.The Genecards database,OMIM database,Drugbank database,Pharm Gkb database and TTD database were searched to gain the relevant targets for pain and cognitive dysfunction respectively.The targets of the active ingredients of Zanthoxylum bungeanum Maxim and the relevant targets of pain and cognitive dysfunction were each taken to intersection to gain the targets of Zanthoxylum bungeanum Maxim for analgesia and improvement of cognitive dysfunction respectively.Through these steps we can obtain protein-protein interaction(PPI)networks with effective targets,and complete the construction of relevant networks with the help of STRING database.Then based on the visual analysis of the component-target network and the PPI network,the core targets of Zanthoxylum bungeanum Maxim for analgesia and improvement of cognitive dysfunction were screened.Bioconductor R was used for Gene Ontology(GO)analysis and Kyoto Encyclopedia of Gene and Genomes(KEGG)pathway enrichment analysis.Finally,Auto Dock 4.2.6 is used to map the core targets and active ingredients contained therein one by one,and analyze and study their binding potential.Results:1.A total of 8 active ingredients were obtained from Zanthoxylum bungeanum Maxim,among which 6 active ingredients can exert analgesia and improved cognitive dysfunction.They are eta-sitosterol,quercetin,Diosmetin,Diosmin,Skimmianin and Hyperin.2.We obtained 58 targets of Zanthoxylum bungeanum Maxim for analgesia,of which AKT1,IL1 B,CASP3,TP53 and PTGS2 were the core targets.54 targets of Zanthoxylum bungeanum Maxim that can improve cognitive dysfunction cover 3 core targets(AKT1,IL1 B and CASP3).3.AGE-RAGE signaling pathway,IL-17 signaling pathway,and TNF signaling pathway play important roles in the analgesia exerted by Zanthoxylum bungeanum Maxim.The response to drugs and the regulation of the metabolic process of reactive oxygen species are closely related to the analgesic effect of Zanthoxylum bungeanum Maxim.4.Response to lipopolysaccharide and modulation of multicellular organism processes are relevant to the role of Zanthoxylum bungeanum Maxim in improving cognitive dysfunction.Zanthoxylum bungeenum Maxim can improve cognitive dysfunction by 3 more significant signaling pathways(AGE-RAGE signaling pathway,HIF-1 signaling pathway and IL-17 signaling pathway).Conclusions:Zanthoxylum bungeanum Maxim may affect AGE-RAGE,HIF-1 and other signaling pathways through the regulation of AKT1,IL1 B,CASP3 and other targets.After these signaling pathway are activated,Some pathological processes including anti-inflammatory,antioxidant,inhibition of excessive accumulation of β-amyloid and abnormal phosphorylation of tau protein will begin to take place.These changes help relieve pain and improve cognitive dysfunction.The study found that flavonoids are the most critical component.