Wang Ying, Ding Shuang, Gao Feng, Jia Yuyan, Wang Xukai
The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, China.
Medicine (Baltimore). 2024 Dec 6;103(49):e40798. doi: 10.1097/MD.0000000000040798.
Jie-gu capsules are widely used for the treatment of fractures in China. However, the core active pharmaceutical ingredients of Jie-gu capsules and the potential mechanisms for treating fractures remain unclear. This study aims to preliminarily elucidate the potential mechanisms of Jie-gu capsules in the treatment of fractures through network pharmacology and mendelian randomization methods. Data of fracture patients were obtained from the GEO database (GSE93215), and the active pharmaceutical ingredients and therapeutic targets of Jie-gu capsules were retrieved from the TCMSP and TCMID databases to identify the intersection genes. Subsequently, a protein-protein interaction network of the intersection genes was constructed using the STRING database. Then, GO and KEGG analyses were conducted on the intersection genes. In addition, mendelian randomization was employed to identify core targets. Finally, molecular docking techniques were used to perform molecular docking of the core active pharmaceutical ingredients and core targets for Jie-gu capsules in the treatment of fractures. In this study, a total of 65 intersection genes involved in Jie-gu capsule treatment of fractures were identified. GO and KEGG results indicated that these 65 intersection genes were primarily associated with biological processes such as response to tumor necrosis factor and are involved in signaling pathways, especially the regulation of the MAPK signaling pathway. We identified 5 core active ingredients of Jie-gu capsules (quercetin, baicalein, kaempferol, luteolin, and succinic acid). Mendelian randomization confirmed 2 core targets (ALOX12 and EGF). Molecular docking results demonstrated that the core active pharmaceutical ingredients (quercetin, baicalein, kaempferol, luteolin, and succinic acid) exhibit high affinities with the core targets (ALOX12 and EGF). This study has unveiled the core active pharmaceutical ingredients and potential action targets of the Jie-gu capsules in treating fractures, offering valuable insights for subsequent foundational research and the development of new medications.
接骨胶囊在中国被广泛用于治疗骨折。然而，接骨胶囊的核心活性药物成分以及治疗骨折的潜在机制仍不清楚。本研究旨在通过网络药理学和孟德尔随机化方法初步阐明接骨胶囊治疗骨折的潜在机制。骨折患者的数据从GEO数据库（GSE93215）中获取，接骨胶囊的活性药物成分和治疗靶点从TCMSP和TCMID数据库中检索以确定交集基因。随后，使用STRING数据库构建交集基因的蛋白质-蛋白质相互作用网络。然后，对交集基因进行GO和KEGG分析。此外，采用孟德尔随机化来确定核心靶点。最后，使用分子对接技术对接骨胶囊治疗骨折的核心活性药物成分和核心靶点进行分子对接。在本研究中，共鉴定出65个参与接骨胶囊治疗骨折的交集基因。GO和KEGG结果表明，这65个交集基因主要与对肿瘤坏死因子的反应等生物学过程相关，并参与信号通路，特别是MAPK信号通路的调控。我们确定了接骨胶囊的5种核心活性成分（槲皮素、黄芩素、山奈酚、木犀草素和琥珀酸）。孟德尔随机化确定了2个核心靶点（ALOX12和EGF）。分子对接结果表明，核心活性药物成分（槲皮素、黄芩素、山奈酚、木犀草素和琥珀酸）与核心靶点（ALOX12和EGF）表现出高亲和力。本研究揭示了接骨胶囊治疗骨折的核心活性药物成分和潜在作用靶点，为后续的基础研究和新药开发提供了有价值的见解。
