[关键词]
[摘要]
目的 基于网络药理学和生物信息学研究骨碎补治疗骨关节炎(OA)可能的分子机制。方法 通过中药系统药理学数据库和分析平台(TCMSP)对骨碎补可能的生物活性成分和靶点进行筛选和预测,通过TTD等5个数据库挖掘骨关节炎相关的作用靶点,采用ClueGo分析骨碎补治疗OA可能的分子机制。结果 从TCMSP检索出71个骨碎补相关成分,根据口服生物利用度(OB)和药物相似性(DL)值筛选获得生物活性成分18个,同时预测出92个可能的作用靶点;通过相关数据库共检索到与OA密切相关的靶点168个;拓扑分析筛选出骨碎补治疗OA的99个关键靶点;ClueGO分析显示,骨碎补治疗OA的关键靶点主要涉及细胞周期、炎症、感染、癌症相关等31条信号通路。结论 骨碎补治疗OA具有多系统、多成分、多靶点的特点;其可能的作用机制包括直接参与骨重建的细胞增殖、凋亡及分化,调节成骨、破骨代谢平衡,以及调节免疫、炎症反应等干预和影响骨微环境以达到控制疾病发生发展的目的,与目前治疗OA的作用机制相符合。
[Key word]
[Abstract]
Objective To investigate the potential molecular mechanism of Drynariae Rhizoma in the treatment of osteoarthritis based on network pharmacology and bioinformatics. Methods The potential active constituents and targets of Drynariae Rhizoma were screened and predicted through the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP). Using TTD and four other osteoarthritis related disease databases, combining the topological analysis, the specific target of Drynariae Rhizoma in the treatment of osteoarthritis was filtered. And the further possible molecular mechanism of Drynariae Rhizoma was analyzed through ClueGo method. Results Seventy-one corresponding compounds of Drynariae Rhizoma were retrieved from TCMSP. According to the values of oral bioavailability (OB) and drug likeness (DL), 18 possible bioactive components were screened out, and 92 potential targets were obtained by using the related target prediction technique. A total of 168 known targets closely related to the development of osteoarthritis were retrieved from the disease-related databases. A total of 99 key genes were screened out through network topological analysis. The ClueGo analysis showed that the action mode of Drynariae Rhizoma in treating osteoarthritis was mainly working on 31 signaling pathways related to cell cycle, inflammation, infection and cancer etc. Conclusion Drynariae Rhizoma has the characteristics of multisystem, multiple targets, and multicomponent in the treatment of osteoarthritis. Through analysis, the possible mechanism includes not only directly acting on proliferation, apoptosis, differentiation of cells related to bone reconstruction and regulation of the balance of bone metabolism, but also affecting and interfering the bone and cartilage microenvironment through regulating immunity, inflammation, and other systems, which is consistent with the current mechanism of osteoarthritis treatment.
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[基金项目]
国家自然科学基金资助项目(81774333);山东省重点研发计划(2016GSF202022)