基于网络药理学和分子对接探究青蒿素及其衍生物治疗骨质疏松症的潜在机制。
Exploring the Potential Mechanism of Artemisinin and Its Derivatives in the Treatment of Osteoporosis Based on Network Pharmacology and Molecular Docking.
机构信息
Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China.
出版信息
Comput Math Methods Med. 2022 Dec 22;2022:3976062. doi: 10.1155/2022/3976062. eCollection 2022.
OBJECTIVE
This study is aimed at predicting and contrasting the mechanisms of artemisinin (ARS), dihydroartemisinin (DHA), artesunate (ART), artemether (ARM), and arteether (ARE) in the treatment of osteoporosis (OP) using network pharmacology and molecular docking.
METHODS
The targets of ARS, DHA, ART, ARM, and ARE were obtained from the SwissTargetPrediction. The targets related to OP were obtained from the TTD, DrugBank, Genecards, and DisGeNet databases. Then, the anti-OP targets of ARS, DHA, ART, ARM, and ARE were obtained and compared using the Venn diagram. Afterward, the protein-protein interaction (PPI) networks were built using the STRING database, and Cytoscape was used to select hub targets. Moreover, molecular docking validated the binding association between five molecules and hub targets. Finally, GO enrichment and KEGG pathway enrichment were conducted using the DAVID database. The common pathways of five molecules were analysed.
RESULTS
A total of 28, 37, 36, 27, and 33 anti-OP targets of ARS, DHA, ART, ARM, and ARE were acquired. EGFR, EGFR, CASP3, MAPK8, and CASP3 act as the top 1 anti-OP targets of ARS, DHA, ART, ARM, and ARE, respectively. MAPK14 is the common target of five molecules. All five molecules can bind well with these hubs and common targets. Meanwhile, functional annotation showed that MAPK, Serotonergic synapse, AMPK, prolactin, and prolactin signaling pathways are the top 1 anti-OP pathway of ARS, DHA, ART, ARM, and ARE, respectively. IL-17 signaling pathway and prolactin signaling pathway are common anti-OP pathways of five molecules. Besides, GO enrichment showed five biological processes and three molecular functions are common anti-OP mechanisms of five molecules.
CONCLUSION
ARS, DHA, ART, ARM and ARE can treat OP through multi-targets and multi pathways, respectively. All five molecules can treat OP by targeting MAPK14 and acting on the IL-17 and prolactin signaling pathways.
目的
本研究旨在利用网络药理学和分子对接技术预测和对比青蒿素（ARS）、双氢青蒿素（DHA）、青蒿琥酯（ART）、蒿甲醚（ARM）和青蒿醚（ARE）治疗骨质疏松症（OP）的作用机制。
方法
从 SwissTargetPrediction 中获取 ARS、DHA、ART、ARM 和 ARE 的靶点；从 TTD、DrugBank、Genecards 和 DisGeNet 数据库中获取与 OP 相关的靶点。然后，利用 Venn 图获取 ARS、DHA、ART、ARM 和 ARE 的抗 OP 靶点，并进行比较。之后，利用 STRING 数据库构建蛋白质-蛋白质相互作用（PPI）网络，并用 Cytoscape 选择枢纽靶点。此外，利用分子对接验证五种分子与枢纽靶点的结合关系。最后，利用 DAVID 数据库进行 GO 富集和 KEGG 通路富集，分析五种分子的共同通路。
结果
共获得 ARS、DHA、ART、ARM 和 ARE 的 28、37、36、27 和 33 个抗 OP 靶点。EGFR、EGFR、CASP3、MAPK8 和 CASP3 分别为 ARS、DHA、ART、ARM 和 ARE 的 top1 抗 OP 靶点。MAPK14 是这五种分子的共同靶点。这五种分子均能与这些枢纽靶点和共同靶点很好地结合。同时，功能注释显示，MAPK、5-羟色胺能突触、AMPK、催乳素和催乳素信号通路分别为 ARS、DHA、ART、ARM 和 ARE 的 top1 抗 OP 通路；IL-17 信号通路和催乳素信号通路是这五种分子的共同抗 OP 通路。此外，GO 富集显示，这五种分子有五个生物过程和三个分子功能是共同的抗 OP 机制。
结论
ARS、DHA、ART、ARM 和 ARE 可通过多靶点、多通路治疗 OP。这五种分子均可通过靶向 MAPK14 作用于 IL-17 和催乳素信号通路治疗 OP。
Zotero 插件