基于网络药理学与分子对接技术探讨六味地黄丸抗骨质疏松症的机制研究

目的基于网络药理学及分子对接方法探讨六味地黄丸在治疗骨质疏松症(osteoporosis,OP)过程中的有效成分及作用机制。方法通过TCMSP数据库获得六味地黄丸组方的药物有效成分及其预测靶点;利用疾病数据库筛选骨质疏松症相关疾病作用靶点;将获得的关键靶点上传至STRING数据库完成PPI网络分析;利用DAVID数据库完成关键靶点的富集分析;通过Auto Dock Vina等软件完成化学有效药物成分与关键靶点的分析对接验证。结果共获得六味地黄丸组方化学有效成分69个、药物靶点蛋白128个及药物与骨质疏松症共同相关靶点81个;获得了IL6、TP53、VEGFA、TNF、JUN、MAPK1、EGF、EGFR、ESR1、CAT等PPI网络中的关键靶点。富集分析结果显示,其通过参与细胞增殖与凋亡过程、药物代谢、雌激素反应调节与细胞抗缺氧、抗衰老等生物学进程,调控TNF、药物代谢过程、HIF-1、VEGF、雌激素调节等信号通路,参与骨质疏松症的治疗过程;分子对接结果显示,调控网络中的关键靶点与相关有效成分之间具有较高的结合活性。结论借助生物信息学手段和分子对接技术,初步揭示了六味地黄丸抗骨质疏松症的作用机制,为后续进一步的机制研究及实验验证提供了目标与思路。

Study on anti-osteoporotic mechanism of Liuwei Dihuang Pills based on network pharmacology and molecular docking technology

Objective Based on network pharmacology and molecular docking methods, the effective ingredients and mechanism of Liuwei Dihuang Pills in the treatment of osteoporosis were discussed. Method Obtain the active ingredients of Liuwei Dihuang Pills and their predicted targets through the TCMSP database; Use the disease database to screen the targets of osteoporosis-related diseases; Upload the obtained key targets to the STRING database to complete the PPI network analysis; Use DAVID database to complete the enrichment analysis of key targets; Use Auto Dock Vina and other software to complete the analysis and docking verification of chemically effective pharmaceutical ingredients and key targets. Results A total of 69 chemical active ingredients in Liuwei Dihuang Pill formula, 128 drug target proteins, and 81 drug and osteoporosis common related targets were obtained. Key targets in the PPI network such as IL6, TP53, VEGFA, TNF, JUN, MAPK1, EGF, EGFR, ESR1, CAT, etc. have been obtained. Enrichment analysis results show that it regulates TNF signaling pathway, drug metabolism process signaling pathway, and HIF-1 signaling by participating in biological processes such as cell proliferation and apoptosis, drug metabolism, estrogen response regulation, and cell anti-anoxia and anti-aging. Pathways, VEGF signaling pathways, estrogen regulatory signaling pathways and other signaling pathways, which are involved in the treatment of osteoporosis. The results of molecular docking show that the key targets in the regulatory network have high binding activity with relevant active ingredients. Conclusion With the help of bioinformatics methods and molecular docking technology, the anti-osteoporotic mechanism of Liuwei Dihuang Pills is initially revealed, which provides goals and ideas for subsequent further mechanism research and experimental verification.