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基于网络药理学探讨二十五味骨折丸治疗骨折的作用机制。

Understanding the mechanism of twenty-five ingredient decoction for setting a fracture in the treatment of fractures based on network pharmacology.

机构信息

College of First Clinical Medical, Shandong University of Traditional Chinese Medicine, Jinan, P.R. China.

Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, P.R. China.

出版信息

Medicine (Baltimore). 2023 Feb 3;102(5):e32864. doi: 10.1097/MD.0000000000032864.

Abstract

To study the mechanism of 25 ingredient decoction for setting a fracture (TDSF) in fracture treatment using network pharmacology. The TCMSP, BATMAN-TCM, HERB, and Uniprot protein databases were used to identify the active ingredients and targets of TDSF. Fracture-related targets were collected from the gene cards and the online mendelian inheritance in man databases. The acquisition of common genes of active compounds of TDSF and disease fractures was carried out using the Venny software. The Cytoscape 3.7.1 software and String database were used to construct a network diagram of drug-active ingredient-target-disease and the main core targets were obtained by protein interaction analysis. The Metascape platform was used to perform gene oncology functional and Kyoto encyclopedia of genes and genomes pathway enrichment analyses for common drug-disease targets. A total of 311 active ingredients and 348 targets were associated with TDSF, with 5197 targets related to fractures and 224 common targets between the 2 keywords. Key targets included serine/threonine protein kinase 1, tumor necrosis factor, interleukin 6, tumor protein 53, and vascular endothelial growth factor. Important roles of the following pathway were identified: cancer, lipid, and atherosclerosis; AGE-RAGE signaling pathway in diabetic complications; chemical carcinogenesis - receptor activation; PI3K -Akt signaling pathway; platinum drug resistance; cAMP signaling pathway; transcriptional mis regulation in cancer; serotonergic synapse; and malaria. TDSF mainly treats fractures by acting on multiple targets, such as serine/threonine protein kinase 1, tumor necrosis factor, interleukin 6, tumor protein 53, and vascular endothelial growth factor, and regulating the PI3K/AKT and cAMP signaling pathways.

摘要

运用网络药理学研究二十五味接骨散治疗骨折的作用机制。利用 TCMSP、BATMAN-TCM、HERB 和 Uniprot 蛋白质数据库来识别二十五味接骨散的活性成分和靶点。从基因卡片和在线 Mendelian 遗传在线人类数据库中收集与骨折相关的靶点。使用 Venny 软件获取二十五味接骨散活性化合物与疾病骨折的共同基因。使用 Cytoscape 3.7.1 软件和 String 数据库构建药物-活性成分-靶点-疾病网络图,并通过蛋白质相互作用分析获得主要核心靶点。使用 Metascape 平台对共同药物-疾病靶点进行基因肿瘤学功能和京都基因与基因组百科全书通路富集分析。与二十五味接骨散相关的有 311 种活性成分和 348 个靶点,与骨折相关的靶点有 5197 个,这两个关键词之间有 224 个共同靶点。关键靶点包括丝氨酸/苏氨酸蛋白激酶 1、肿瘤坏死因子、白细胞介素 6、肿瘤蛋白 53 和血管内皮生长因子。鉴定出以下重要通路:癌症、脂质和动脉粥样硬化;糖尿病并发症中的 AGE-RAGE 信号通路;化学致癌作用-受体激活;PI3K-Akt 信号通路;铂类药物耐药性;cAMP 信号通路;癌症转录失调;5-羟色胺能突触;疟疾。二十五味接骨散主要通过作用于丝氨酸/苏氨酸蛋白激酶 1、肿瘤坏死因子、白细胞介素 6、肿瘤蛋白 53 和血管内皮生长因子等多个靶点,调节 PI3K/AKT 和 cAMP 信号通路来治疗骨折。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57dd/9901973/ceb5c57ff2b3/medi-102-e32864-g001.jpg

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