The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Futian District, Shenzhen, Guangdong Province, China.
Guangzhou University of Chinese Medicine, Baiyun District, Guangzhou, Guangdong Province, China.
Medicine (Baltimore). 2022 Aug 12;101(32):e29844. doi: 10.1097/MD.0000000000029844.
Epimedium has gained widespread clinical application in Traditional Chinese Medicine, with the functions of promoting bone reproduction, regulating cell cycle and inhibiting osteoclastic activity. However, its precise cellular pharmacological therapeutic mechanism on osteoporosis (OP) remains elusive. This study aims to elucidate the molecular mechanism of epimedium in the treatment of OP based on system bioinformatic approach. Predicted targets of epimedium were collected from TCMSP, BATMAN-TCM and ETCM databases. Differentially expressed mRNAs of OP patients were obtained from Gene Expression Omnibus database by performing Limma package of R software. Epimedium-OP common targets were obtained by Venn diagram package for further analysis. The protein-protein interaction network was constructed using Cytoscape software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were carried out by using clusterProfiler package. Molecular docking analysis was conducted by AutoDock 4.2 software to validate the binding affinity between epimedium and top 3 proteins based on the result of protein-protein interaction. A total of 241 unique identified epimedium targets were screened from databases, of which 62 overlapped with the targets of OP and were considered potential therapeutic targets. The results of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that these targets were positive regulation of cell cycle, cellular response to oxidative stress and positive regulation of cell cycle process as well as cellular senescence, FoxO, PI3K-Akt, and NF-kappa B signaling pathways. Molecular docking showed that epimedium have a good binding activity with key targets. Our study demonstrated the multitarget and multi-pathway characteristics of epimedium on OP, which elucidates the potential mechanisms of epimedium against OP and provides theoretical basis for further drug development.
淫羊藿在中医药中得到了广泛的临床应用，具有促进骨再生、调节细胞周期和抑制破骨细胞活性的功能。然而，其对骨质疏松症（OP）的确切细胞药理学治疗机制仍不清楚。本研究旨在通过系统生物信息学方法阐明淫羊藿治疗 OP 的分子机制。从 TCMSP、BATMAN-TCM 和 ETCM 数据库中收集淫羊藿的预测靶点。通过 R 软件的 Limma 包从基因表达综合数据库中获得 OP 患者的差异表达 mRNA。通过 Venn 图包获得淫羊藿-OP 共同靶点，以便进一步分析。使用 Cytoscape 软件构建蛋白质-蛋白质相互作用网络。使用 clusterProfiler 包进行基因本体论和京都基因与基因组百科全书途径富集分析。通过 AutoDock 4.2 软件进行分子对接分析，验证蛋白质-蛋白质相互作用结果中基于前 3 个蛋白质的淫羊藿结合亲和力。从数据库中筛选出 241 个独特的淫羊藿靶点，其中 62 个与 OP 靶点重叠，被认为是潜在的治疗靶点。基因本体论和京都基因与基因组百科全书富集分析的结果表明，这些靶点是细胞周期的正调控、细胞对氧化应激的反应以及细胞周期过程和细胞衰老的正调控，以及 FoxO、PI3K-Akt 和 NF-kappa B 信号通路。分子对接表明淫羊藿与关键靶点具有良好的结合活性。本研究表明淫羊藿对 OP 具有多靶点、多途径的作用特点，阐明了淫羊藿防治 OP 的潜在机制，为进一步开发药物提供了理论依据。
