Peng Jiafeng, Zhang Hongxing, Wang Huaize, Meng Qianqian, Li Danyang, Gao Minglei, Li Yingchun, Ma Xingfu, Xia Li, Xu Ran, Zhu Junchen
The Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China.
Graduate School of Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China.
Medicine (Baltimore). 2025 Mar 21;104(12):e41917. doi: 10.1097/MD.0000000000041917.
The ancient Chinese medical texts have recorded Guizhi Fuzi decoction (GZFZT) as a therapeutic intervention for lumbar disc herniation (LDH), and its clinical efficacy has been validated in medical practice. This research endeavor is specifically designed to delve into and elucidate its precise underlying mechanisms of action, leveraging the sophisticated methodologies of network pharmacology and bioinformatics. In this study, we used the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform to extract active compounds and targets from the traditional Chinese medicine GZFZT. Subsequently, we integrated LDH disease target information from DisGeNET, GeneCards, OMIM, and GEO database. By combining this with drug-effective targets, we screened for common targets. Based on these, we conducted protein-protein interaction network analysis and performed gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses on core targets to explore LDH treatment pathways. Finally, we used molecular docking to evaluate potential targets and compounds, identifying the optimal core protein-compound complex. Our study identified 154 active compounds and 230 corresponding targets of GZFZT. Additionally, we collected a total of 1492 LDH disease targets. Topological analysis of the protein-protein interaction network for common drug-disease targets revealed 6 core targets: TNF, STAT3, MAPK1, IL6, MAPK3, and AKT1. Gene ontology enrichment analysis indicated that the mechanism of action of GZFZT is associated with inflammatory responses, apoptotic processes, and oxidative stress states. Kyoto Encyclopedia of Genes and Genomes enrichment analysis suggested that the mechanism of action of GZFZT is closely related to genes involved in the AGE-RAGE and IL-17 signaling pathways. Molecular docking results demonstrated that the selected compounds exhibit strong binding affinity to the targets, indicating their good biological activity. This study unveils novel insights into the active ingredients, targets, and signaling pathways of Guizhi Fuzi decoction in the treatment of lumbar disc herniation. Furthermore, this study suggests that the 3 bioactive components of Guizhi Fuzi decoction (naringenin, β-sitosterol, and stigmasterol) may exert their therapeutic effects on lumbar disc herniation by specifically targeting MAPK3.
中国古代医学典籍已将桂枝附子汤（GZFZT）记载为腰椎间盘突出症（LDH）的一种治疗手段，其临床疗效已在医疗实践中得到验证。本研究旨在利用网络药理学和生物信息学的精密方法，深入探究并阐明其确切的作用机制。在本研究中，我们使用中药系统药理学数据库及分析平台从中药桂枝附子汤中提取活性成分和靶点。随后，我们整合了来自DisGeNET、GeneCards、OMIM和GEO数据库的LDH疾病靶点信息。通过将其与药物有效靶点相结合，我们筛选出共同靶点。在此基础上，我们进行了蛋白质-蛋白质相互作用网络分析，并对核心靶点进行基因本体论和京都基因与基因组百科全书通路富集分析，以探索LDH的治疗途径。最后，我们使用分子对接来评估潜在靶点和化合物，确定最佳的核心蛋白-化合物复合物。我们的研究确定了桂枝附子汤的154种活性成分和230个相应靶点。此外，我们共收集了1492个LDH疾病靶点。对共同的药物-疾病靶点进行蛋白质-蛋白质相互作用网络的拓扑分析，发现了6个核心靶点：TNF、STAT3、MAPK1、IL6、MAPK3和AKT1。基因本体论富集分析表明，桂枝附子汤的作用机制与炎症反应、凋亡过程和氧化应激状态有关。京都基因与基因组百科全书富集分析表明，桂枝附子汤的作用机制与参与AGE-RAGE和IL-17信号通路的基因密切相关。分子对接结果表明，所选化合物对靶点具有很强的结合亲和力，表明它们具有良好的生物活性。本研究揭示了桂枝附子汤治疗腰椎间盘突出症的活性成分、靶点和信号通路的新见解。此外，本研究表明，桂枝附子汤的3种生物活性成分（柚皮素、β-谷甾醇和豆甾醇）可能通过特异性靶向MAPK3对腰椎间盘突出症发挥治疗作用。
