摘要
Background:Gout is an inflammatory joint disease.Modern pharmacological studies have shown that Zanthoxylum bungeanum(Z.bungeanum)has significant anti-inflammatory and osteoprotective effects.This study is aimed to explore the therapeutic effect of Z.bungeanum on gouty arthritis.Methods:Firstly,the compounds in the water extract of Z.bungeanum(WZB)were analyzed by UPLC-QE-Orbitrap-MS/MS.The compounds and disease targets were predicted using SwissTargetPrediction platform and GeneCards database,and the candidate targets were acquired by taking the intersection.Next,the protein interaction network was constructed and the hub genes were screened using String platform and Cytoscape software.Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes analysis of hub genes were performed using Metascape platform.Finally,the disease-pathway-target-drug-component network diagram was constructed to obtain the active components and targets for treating disease,and the affinity between components and targets were predicted by applying Discovery Studio software.In vitro,using an acute gout model of RAW 264.7 macrophages induced by Monosodium Urate to evaluate the anti-inflammatory effect of WZB on Gout.Meanwhile,we established a mice model of hyperuricemia and measured the serum xanthine oxidase(XOD)activity and uric acid(UA)contents.Results:A total of 20 chemical components were identified from WZB,mainly alkaloid components.The network pharmacology results showed that Dihydrobungeanool,Quercetin,Hydroxy-α-sanshool and Hydroxy-ɛ-sanshool were the main active components of WZB against gout.MAPK1,PIK3CA,EGFR and TLR1 proteins were the main targets of WZB in the treatment of gout.Pathways in cancer,PI3K/Akt signaling pathway,Th17 cell differentiation and MAPK signaling pathway were closely related to anti-gout.Molecular docking results have shown that Dihydrobungeanool may be the main active ingredient of WZB for gout treatment,and PIK3CA is the main potential target.The cellular gout model showed that WZB significantly reduced IL-1βand TNF-αinflammatory factor levels and influenced the expression of PI3K protein.In addition,WZB administration effectively reduced UA levels and XOD activity in the serum of mice with hyperuricemia.Conclusion:Our study results suggest that WZB could treat gout by acting on PIK3CA gene target to reduce the level of inflammatory factors,and reduce XOD activity to lower UA levels.
基金
This work was supported by the Project of State Administration of Traditional Chinese Medicine of Sichuan Province of China(No.2020HJZX001)。
