基于网络药理学方法探讨蛇床子治疗骨质疏松可能的分子途径

Study on Potential Molecular Pathways for Anti-osteoporosis of Cnidii Fructus Based on Network Pharmacology

目的采用网络药理学方法探讨蛇床子抗骨质疏松的可能分子途径。方法利用中药系统药理学数据库(TCMSP)筛选蛇床子活性成分,预测靶蛋白和相互作用蛋白;用TTD和CTD数据库查询骨质疏松靶蛋白,预测相互作用蛋白,构建药物–靶蛋白–疾病交互网络;用DAVID数据库富集并分析靶蛋白信号通路;通过Systems Dock软件将蛇床子活性成分与重要的靶蛋白进行分子对接验证。结果筛选得到蛇床子活性成分19个、靶蛋白72个、骨质疏松疾病靶蛋白118个;经相互作用蛋白(PPI)网络交集后,获得药物和疾病共同靶蛋白91个;富集得到26条信号通路;β-谷固醇、豆甾醇、24-epicampesterol、poriferast-5-en-3β-ol与SRC、ESR1靶蛋白具有良好的分子对接活性。结论蛇床子可能通过激活甲状腺激素信号通路中的SRC和ESR1起到治疗骨质疏松的作用。

Objective To explore the possible molecular mechanism of Cnidii fructus on anti-osteoporosis based on network pharmacology.Methods The active components of Cnidii fructus were screened by Traditional Chinese Medicine Systems Pharmacology Database(TCMSP)to predict the target proteins and interaction proteins.Osteoporosis target proteins were derived from CTD and TTD databases,and their interaction proteins were predicted.Then the drug-target protein-disease correlation network was constructed.The signal pathways of targeted proteins were enriched and analyzed with DAVID database.Molecular docking of the active ingredients of Cnidii fructus with important target proteins was verified by Systems Dock software.Results Nineteen active ingredients of Cnidii fnictus and 72 target proteins were retrieved,118 target proteins of osteoporosis were selected,and 91 common target proteins of Cnidii fructus and osteoporosis were obtained.Then 26 signaling pathways were enriched.High molecular docking scores between active components(β-Sitosterol,Stigmasterol,24-epicampesterol and poriferast-5-en-3β-ol)and ESR1,SRC were obtained.Conclusion The results show that Cnidii fructus may play a key role in the treatment of osteoporosis by activating SRC and ESR 1 in thyroid hormone signaling pathway.