基于网络药理学和动物实验探讨葛根素治疗类风湿关节炎的作用机制
Mechanism of puerarin in treatment of rheumatoid arthritis based on network pharmacology and animal experimental verification
摘要
Abstract
Objective To investigate the mechanism of puerarin in the treatment of rheumatoid arthritis(RA)by network pharmacology and animal experiments.Methods Traditional Chinese Medicine Systems Pharmcolog Data-base(TCMSP)and SwissTargetPrediction database were used to collect puerarin targets,and the targets of RA were obtained from GeneCards database and OMIM database.The PPI network was established by Cytoscape 3.7.2 software.Gene ontology(GO)function and Kyotoencyclopedia of genes(KEGG)enrichment analysis were per-formed through the Metascape database.RA rat-collagen-induced arthritis(CIA)model was reproduced using typeⅡ collagen emulsion,49 Wistar rats were randomly assigned to seven groups:control group,CIA model group,low-dose,medium-dose and high-dose puerarin group,methotrexate group,Tripterysium Glycosides Tablets group.Except for the control group,the other groups were given continuous gavage for 28 days after the CIA in rats model were prepared.The redness and swelling of the joints and ankle joint pathological changes were observed in each group.Western blot was used to detect the expression of Glycogen synthase kinase3 β(GSK-3 β),beta-catenin(β-catenin)proteins in the synovium.Real-time quantitative polymerase chain reaction(qPCR)was used to detect the expression of GSK-3β,β-catenin and c-Myc mRNA in the synovium.Results Puerarin had 134 targets genes,RA had 5 821 target genes,and there were 102 overlapping target genes of puerarin and RA.It involved 184 signa-ling pathways,including JAK-STAT signaling pathway,NF-κB signaling pathway,Wnt signaling pathway,et al.The results of animal experiments showed that after the intervention of M-puerarin and MTX,the symptoms of red-ness and swelling of the hind foot were alleviated,the inflammatory cell infiltration in the synovium of the joint was significantly reduced,and the damage of cartilage and bone tissue was reduced.Compared with CIA group,the ex-pressions of GSK-3 β,β-catenin protein and GSK-3β,β-catenin and c-Myc mRNA in synovial tissue of rats after M-puerarin intervention decreased(P＜0.05).Conclusion Puerarin has the characteristic of multi-components,multi-targets and multi-pathway intervention in RA.Puerarin may alleviate synovial hyperplasia,reduce articular cartilage erosion and bone destruction in CIA in rats by inhibiting Wnt/β-catenin signaling pathway.关键词
葛根素/类风湿关节炎/CIA大鼠/网络药理学/Wnt/β-catenin信号通路/滑膜增生Key words
puerarin/rheumatoid arthritis/CIA in rats/network pharmacology/Wnt/β-catenin signaling path-way/synovial hyperplasia分类
医药卫生引用本文复制引用
高月,唐芳,马武开,兰维娅,蒋总,金泽旭..基于网络药理学和动物实验探讨葛根素治疗类风湿关节炎的作用机制[J].安徽医科大学学报,2025,60(1):22-31,10.基金项目
国家自然科学基金(编号:82160917) （编号:82160917）
贵州省科技计划项目(编号:黔科合基础-ZK[2023]一般435) （编号:黔科合基础-ZK[2023]一般435）
贵州省高等学校重点实验室建设项目(编号:黔教技[2023]017号) （编号:黔教技[2023]017号）
贵州省中医药管理局中医药、民族医药科学技术研究项目(编号:QZYY-2020-005) National Natural Science Foundation of China(No.82160917) （编号:QZYY-2020-005）
Project of the Scientific and Technology Department of Guizhou Province(Official Document of Guizhou Basic Scientific Research,2023,Gen-eral No.435) （Official Document of Guizhou Basic Scientific Research,2023,Gen-eral No.435）
Key Laboratory Project in Universities of Guizhou Province(Official Document of Guizhou Educa-tion and Technology,2023,No.017) （Official Document of Guizhou Educa-tion and Technology,2023,No.017）
Chinese Medicine,Ethnic Medicine Science and Technology Research Pro-ject of Guizhou Administration of Traditional Chinese Medicine(No.QZYY-2020-005) （No.QZYY-2020-005）
