盐酸青藤碱通过抑制 PI3K-Akt 信号通路缓解类风湿关节炎：基于网络药理学、分子对接和实验验证的研究。
Sinomenine Alleviates Rheumatoid Arthritis by Suppressing the PI3K-Akt Signaling Pathway, as Demonstrated Through Network Pharmacology, Molecular Docking, and Experimental Validation.
机构信息
Department of Clinical Laboratory, Wuxi Ninth People's Hospital Affiliated to Soochow University, Wuxi, Jiangsu, 214000, People's Republic of China.
Department of Orthopedics, Wuxi Ninth People's Hospital Affiliated to Soochow University, Wuxi, Jiangsu, 214000, People's Republic of China.
出版信息
Drug Des Devel Ther. 2024 Aug 6;18:3523-3545. doi: 10.2147/DDDT.S475959. eCollection 2024.
PURPOSE
Sinomenine (SIN) is commonly used in Traditional Chinese Medicine (TCM) as a respected remedy for rheumatoid arthritis (RA). Nevertheless, the therapeutic mechanism of SIN in RA remains incompletely understood. This study aimed to delve into the molecular mechanism of SIN in the treatment of RA.
METHODS
The potential targets of SIN were predicted using the TCMSP server, STITCH database, and SwissTarget Prediction. Differentially expressed genes (DEGs) in RA were obtained from the GEO database. Enrichment analyses and molecular docking were conducted to explore the potential mechanism of SIN in the treatment of RA. In vitro and in vivo studies were conducted to validate the intervention effects of SIN on rheumatoid arthritis, as determined through network pharmacology analyses.
RESULTS
A total of 39 potential targets associated with the therapeutic effects of SIN in RA were identified. Enrichment analysis revealed that these potential targets are primarily enriched in PI3K-Akt signaling pathway, and the molecular docking suggests that SIN may act on specific proteins in the pathway. Experimental results have shown that exposure to SIN inhibits cytokine secretion, promotes apoptosis, reduces metastasis and invasion, and blocks the activation of the PI3K-Akt signaling pathway in RA fibroblast-like synoviocytes (RA-FLS). Moreover, SIN treatment alleviated arthritis-related symptoms and regulated the differentiation of CD4+ T cells in the spleen of collagen-induced arthritis (CIA) mice.
CONCLUSION
By utilizing network pharmacology, molecular modeling, and in vitro/in vivo validation, this study demonstrates that SIN can alleviate RA by inhibiting the PI3K-Akt signaling pathway. These findings enhance the understanding of the therapeutic mechanisms of SIN in RA, offering a stronger theoretical foundation for its future clinical application.
目的
盐酸青藤碱（SIN）是一种常用于传统中药（TCM）治疗类风湿关节炎（RA）的药物。然而，SIN 治疗 RA 的机制尚不完全清楚。本研究旨在深入探讨 SIN 治疗 RA 的分子机制。
方法
使用 TCMSP 服务器、STITCH 数据库和 SwissTarget Prediction 预测 SIN 的潜在靶点。从 GEO 数据库中获取 RA 中的差异表达基因（DEGs）。进行富集分析和分子对接，以探讨 SIN 治疗 RA 的潜在机制。通过网络药理学分析，进行体内和体外研究，验证 SIN 对类风湿关节炎的干预作用。
结果
共鉴定出 39 个与 SIN 治疗 RA 疗效相关的潜在靶点。富集分析表明，这些潜在靶点主要富集在 PI3K-Akt 信号通路中，分子对接表明 SIN 可能作用于该通路中的特定蛋白。实验结果表明，SIN 抑制细胞因子分泌，促进细胞凋亡，减少转移和侵袭，并阻断 RA 成纤维样滑膜细胞（RA-FLS）中 PI3K-Akt 信号通路的激活。此外，SIN 治疗减轻了胶原诱导关节炎（CIA）小鼠的关节炎相关症状，并调节了脾脏中 CD4+T 细胞的分化。
结论
本研究通过网络药理学、分子建模和体内/体外验证，表明 SIN 可以通过抑制 PI3K-Akt 信号通路来缓解 RA。这些发现加深了对 SIN 治疗 RA 机制的理解，为其未来的临床应用提供了更坚实的理论基础。
Zotero 插件