生物信息学分析结合实验验证探讨仙灵骨葆胶囊治疗骨关节炎的作用机制。
Bioinformatics analysis combined with experimental validation to explore the mechanism of XianLing GuBao capsule against osteoarthritis.
机构信息
1st School of Medicine, Guangzhou University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou, 510405, PR China; The Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, PR China.
Department of Orthopaedics, First Affiliated Hospital, Guangzhou University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou, 510405, PR China.
出版信息
J Ethnopharmacol. 2022 Aug 10;294:115292. doi: 10.1016/j.jep.2022.115292. Epub 2022 Apr 18.
ETHNOPHARMACOLOGICAL RELEVANCE
XianLing GuBao Capsule (XLGB) is often used to treat osteoarthritis (OA), osteoporosis, fractures, and other musculoskeleton disorders. However, the molecular mechanism of XLGB for treating OA is still unclear.
AIM OF THE STUDY
This study set out to uncover the molecular mechanism underlying the treatment of osteoarthritis with XLGB.
MATERIALS AND METHODS
Disease genes were obtained from CTD, DisGeNET, and GeneCards databases, and XLGB drug targets were obtained from ETCM and target genes predicted by XLGB metabolic components reported in the literature. Then we used the Venn diagram viewer to extract disease and drug intersection genes as potential therapeutic genes for Protein-protein interaction (PPI), GO terminology, and KEGG pathway analysis. Subsequently, we performed qRT-PCR, Western blot and histological analysis to validate the therapeutic effect of XLGB against OA and its molecular mechanism.
RESULTS
A total of 1039 OA genes and 949 XLGB target genes were collected, and finally 188 potential therapeutic target genes were obtained. PPI network analysis indicated that the main target genes for XLGB to treat OA include Akt1, Mapk3, Il-6, Il-1β, Ptgs2, Mmp9, etc. The results of KEGG and GO enrichment analysis suggested that XLGB may treat OA by anti-inflammatory and reducing extracellular matrix degradation. In vitro, XLGB down-regulated the expressions of Mmp3, Mmp9, Mmp12, Mmp13, Cox-2, Il-6, increased the expression of Collagen II and Sox9. Mechanistically, XLGB inhibits the activation of PI3K/AKT/NF-κB and MAPK pathways. Moreover, the results of animal experiments indicated that XLGB reduced cartilage destruction, bone resorption, and synovitis in osteoarthritic rats.
CONCLUSIONS
XLGB has a protective effect against OA by suppressing PI3K/AKT/NF-κB and MAPK signaling. Our study provides a theoretical basis for XLGB in the treatment of osteoarthritis.
民族药理学相关性
仙灵骨葆胶囊（XLGB）常用于治疗骨关节炎（OA）、骨质疏松症、骨折和其他肌肉骨骼疾病。然而，XLGB 治疗 OA 的分子机制尚不清楚。
研究目的
本研究旨在揭示 XLGB 治疗 OA 的分子机制。
材料和方法
从 CTD、DisGeNET 和 GeneCards 数据库中获得疾病基因，从 ETCM 中获得 XLGB 药物靶点，并从文献中报道的 XLGB 代谢成分预测的靶基因。然后，我们使用 Venn 图查看器提取疾病和药物的交集基因，作为治疗 OA 的潜在治疗基因，进行蛋白质-蛋白质相互作用（PPI）、GO 术语和 KEGG 通路分析。随后，我们进行 qRT-PCR、Western blot 和组织学分析，以验证 XLGB 治疗 OA 的疗效及其分子机制。
结果
共收集到 1039 个 OA 基因和 949 个 XLGB 靶基因，最终获得 188 个潜在治疗靶基因。PPI 网络分析表明，XLGB 治疗 OA 的主要靶基因包括 Akt1、Mapk3、Il-6、Il-1β、Ptgs2、Mmp9 等。KEGG 和 GO 富集分析结果表明，XLGB 可能通过抗炎和减少细胞外基质降解来治疗 OA。在体外，XLGB 下调了 Mmp3、Mmp9、Mmp12、Mmp13、Cox-2、Il-6 的表达，增加了 Collagen II 和 Sox9 的表达。机制上，XLGB 抑制了 PI3K/AKT/NF-κB 和 MAPK 通路的激活。此外，动物实验结果表明，XLGB 减轻了骨关节炎大鼠的软骨破坏、骨质吸收和滑膜炎。
结论
XLGB 通过抑制 PI3K/AKT/NF-κB 和 MAPK 信号通路对 OA 具有保护作用。本研究为 XLGB 治疗骨关节炎提供了理论依据。
Zotero 插件