Guangxi University of Traditional Chinese Medicine, Nanning City, Guangxi Zhuang Autonomous Region 530001, China.
Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine, Nanning City, Guangxi Zhuang Autonomous Region 530011, China.
Biomed Res Int. 2022 Jul 23;2022:8080679. doi: 10.1155/2022/8080679. eCollection 2022.
To investigate the main pharmacological basis and mechanism of action of Gujiansan in the treatment of steroid-induced avascular necrosis of the femoral head (SANFH).
The active constituents and targets of Gujiansan were screened by using TCMSP and other databases, and relevant disease targets were obtained by analyzing the microarray of SANFH in the GEO database. The intersection of the two was taken to obtain the potential targets of Gujiansan for the treatment of SANFH, and key active constituents were screened with the "active constituent-target" network constructed by the Cytoscape software; then, the STRING database was used to construct the protein interaction network to screen the key targets. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of key targets were performed by the DAVID database, and the relationship between the "key active constituent-key target-key signaling pathway" was explored. Finally, the molecular docking between key active constituents and key targets was verified. In addition, qPCR detection technology was used to evaluate the preventive and therapeutic effects of key active constituents of Gujiansan in a rat osteoblast model of SANFH to verify the possible mechanism of the effect of Gujiansan in the treatment of SANFH.
(1) 106 active constituents and 55 targets were obtained for the treatment of SANFH. (2) Quercetin, luteolin, kaempferol, cryptotanshinone, and naringenin were the key active constituents for the treatment of SANFH. (3) IL1B, STAT3, CAT, PTGS2, and MAPK3 were the key targets for the treatment of SANFH. (4) IL1B, STAT3, CAT, PTGS2, MAPK3, and HMOX1 are key targets in the protein interaction network. (5) DAVID enrichment analysis mainly covers the regulation of DNA-binding transcription factor activity, positive regulation of cytokine production, and response to oxidative stress and other biological processes, involving IL-17, AGE-RAGE, C-type lectin receptor, and other signaling pathways. (6) Gujiansan is a multitarget and multisignaling pathway for the treatment of SANFH. (7) Good binding activity exists between key active constituents and key targets.
This study analyzes the potential mechanism of action of Gujiansan in the treatment of SANFH with network pharmacology, which can provide a reference for the further study of its pharmacological basis and targets.
探讨龟芪骨肽治疗激素性股骨头坏死（SANFH）的主要药理基础和作用机制。
利用 TCMSP 等数据库筛选龟芪骨肽的活性成分和靶点，通过分析 GEO 数据库中 SANFH 的微阵列获得相关疾病靶点。取两者的交集，获得龟芪骨肽治疗 SANFH 的潜在靶点，并利用 Cytoscape 软件构建的“活性成分-靶点”网络筛选关键活性成分；然后利用 STRING 数据库构建蛋白质相互作用网络，筛选关键靶点。利用 DAVID 数据库对关键靶点进行基因本体论和京都基因与基因组百科全书富集分析，探讨“关键活性成分-关键靶点-关键信号通路”之间的关系。最后，通过分子对接验证关键活性成分与关键靶点之间的关系。此外，还采用 qPCR 检测技术评估龟芪骨肽关键活性成分在 SANFH 大鼠成骨细胞模型中的预防和治疗作用，以验证龟芪骨肽治疗 SANFH 的可能作用机制。
（1）获得了治疗 SANFH 的 106 种活性成分和 55 个靶点。（2）槲皮素、木樨草素、山奈酚、隐丹参酮和柚皮苷是治疗 SANFH 的关键活性成分。（3）IL1B、STAT3、CAT、PTGS2 和 MAPK3 是治疗 SANFH 的关键靶点。（4）IL1B、STAT3、CAT、PTGS2、MAPK3 和 HMOX1 是蛋白质相互作用网络中的关键靶点。（5）DAVID 富集分析主要涵盖 DNA 结合转录因子活性的调节、细胞因子产生的正调节以及对氧化应激等生物过程的反应，涉及 IL-17、AGE-RAGE、C 型凝集素受体等信号通路。（6）龟芪骨肽是治疗 SANFH 的多靶点、多信号通路药物。（7）关键活性成分与关键靶点之间存在良好的结合活性。
本研究采用网络药理学分析龟芪骨肽治疗 SANFH 的潜在作用机制，可为进一步研究其药理基础和靶点提供参考。
