Scholarlink

Background <p>Osteoarthritis (OA) is a degenerative joint disease characterized by progressive articular cartilage loss, osteophyte formation, and synovial inflammation. For OA, most of the Western medical treatments are surgery, drugs, etc. However, the effects of these methods are limited, and there are many side effects. Studies have confirmed that astragaloside (AST) can reduce the pathological changes of OA, but the molecular mechanism is still unclear. Therefore, we investigated the mechanism of AST in the treatment of OA based on network pharmacology, molecular docking simulation, and animal experiments.</p> Methods <p>First, search the related target of AST and OA in the database. Then the target genes of AST and OA were intersected to construct the interaction between target protein–protein interaction (PPI) network. Through software analysis, PPI core subnetwork modules and top 10 key targets were obtained and enriched for analysis. Molecular docking simulation was used to predict the binding pattern and binding ability between AST and key target proteins. AST and saline were injected into the knee cavity of osteoarthritis rabbits, respectively, labeled as AST group and OA group. After 4&#xa0;weeks, the therapeutic effect of OA in the two groups was compared by histological staining, MRI, and qRT-PCR to detect and verify the expression of key target genes.</p> Results <p>The top 10 key intersection target genes were obtained. GO enrichment analysis obtained 625 annotation items, KEGG enrichment analysis obtained 111 signal pathways. Molecular docking simulation showed that AST and key target proteins showed good binding force. Animal experiments displayed that AST had obvious therapeutic effect on OA; knee fluid accumulation and bone marrow injury were significantly reduced. qRT-PCR results showed that, compared with OA group, the expressions of SRC and TLR4 in AST group were significantly increased, while the expressions of ALB and ESR1 were decreased; the expression of other genes had no significant difference.</p> Conclusions <p>AST treatment of OA is characterized by multi-target and multi-pathway interactions, and its key target genes act on OA by affecting endothelial cell permeability, regulating synovial, chondrocyte survival, proliferation, and extracellular matrix synthesis, etc., and its molecular mechanism involves the Src/PI3K/Akt, NF-κB, MAPK, and TLRs signaling pathways.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Exploring the mechanism of action of astragaloside in the treatment of osteoarthritis based on network pharmacology

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月10日

查看全文
  • Daiying Song,
  • Juncen Li,
  • Yanfeng Sun,
  • Baihui Li,
  • Xiangming Lin,
  • Wei Xu,
  • Yajie Wang,
  • Di Wang,
  • Guangdong Zhou,
  • Yu Liu

摘要

Background

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive articular cartilage loss, osteophyte formation, and synovial inflammation. For OA, most of the Western medical treatments are surgery, drugs, etc. However, the effects of these methods are limited, and there are many side effects. Studies have confirmed that astragaloside (AST) can reduce the pathological changes of OA, but the molecular mechanism is still unclear. Therefore, we investigated the mechanism of AST in the treatment of OA based on network pharmacology, molecular docking simulation, and animal experiments.

Methods

First, search the related target of AST and OA in the database. Then the target genes of AST and OA were intersected to construct the interaction between target protein–protein interaction (PPI) network. Through software analysis, PPI core subnetwork modules and top 10 key targets were obtained and enriched for analysis. Molecular docking simulation was used to predict the binding pattern and binding ability between AST and key target proteins. AST and saline were injected into the knee cavity of osteoarthritis rabbits, respectively, labeled as AST group and OA group. After 4 weeks, the therapeutic effect of OA in the two groups was compared by histological staining, MRI, and qRT-PCR to detect and verify the expression of key target genes.

Results

The top 10 key intersection target genes were obtained. GO enrichment analysis obtained 625 annotation items, KEGG enrichment analysis obtained 111 signal pathways. Molecular docking simulation showed that AST and key target proteins showed good binding force. Animal experiments displayed that AST had obvious therapeutic effect on OA; knee fluid accumulation and bone marrow injury were significantly reduced. qRT-PCR results showed that, compared with OA group, the expressions of SRC and TLR4 in AST group were significantly increased, while the expressions of ALB and ESR1 were decreased; the expression of other genes had no significant difference.

Conclusions

AST treatment of OA is characterized by multi-target and multi-pathway interactions, and its key target genes act on OA by affecting endothelial cell permeability, regulating synovial, chondrocyte survival, proliferation, and extracellular matrix synthesis, etc., and its molecular mechanism involves the Src/PI3K/Akt, NF-κB, MAPK, and TLRs signaling pathways.