Jia Jiangwei, Liu Bo, Wang Xin, Ji Fenglan, Wen Fuchun, Song Lianlian, Xu Huibo, Ding Tao
Pharmacodynamic and Toxicological Evaluation Center, Jilin Academy of Chinese Medicine Sciences, Changchun, Jilin, China.
School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun, Jilin, China.
Curr Comput Aided Drug Des. 2025;21(3):333-347. doi: 10.2174/0115734099298932240308104437.
Diabetic Retinopathy (DR) is one of the common chronic complications of diabetes mellitus, which has developed into the leading cause of irreversible visual impairment in adults worldwide. The Compound Qilian Tablets (CQLT) were developed in China for the treatment and prevention of DR, but their mechanism of action still needs to be clarified.
In the present study, network pharmacology, molecular docking, and in vivo validation experiments were used to investigate the active components and molecular mechanisms of CQLT against DR.
The active components and targets of CQLT were collected through the TCSMP database, and the targets of DR were obtained from GeneCards, OMIM, and Drugbank databases. We established a protein-protein interaction network using the STRING database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the Metascape database. Molecular docking using AutoDock Vina was performed to investigate the interactions between components of CQLT and core targets. Moreover, we selected ZDF rats to establish a DR model for the experimental studies.
39 active components and 448 targets in CQLT were screened, among which 90 targets were shared with DR. KEGG pathway enrichment analysis identified 181 pathways. The molecular docking results demonstrated that the main active components had strong binding ability to the core targets. The results from animal experiments indicate that the mechanism of CQLT against DR is associated with inhibiting the retinal mTOR/HIF-1α/VEGF signaling pathway, alleviating the inflammatory response, suppressing retinal neovascularization, and protecting the function and morphology of the retina.
The present study preliminarily explored the mechanism of CQLT in treating DR and demonstrated that CQLT exerts anti-DR effects through multiple components, multiple targets, and multiple pathways. These findings suggest that CQLT shows promise as a potential therapeutic agent for DR and could contribute to developing novel treatments.
糖尿病视网膜病变(DR)是糖尿病常见的慢性并发症之一,已成为全球成年人不可逆视力损害的主要原因。复方芪连片(CQLT)在中国研发用于治疗和预防DR,但其作用机制仍需阐明。
本研究采用网络药理学、分子对接和体内验证实验,探讨CQLT抗DR的活性成分和分子机制。
通过TCSMP数据库收集CQLT的活性成分和靶点,从GeneCards、OMIM和Drugbank数据库获取DR的靶点。使用STRING数据库建立蛋白质-蛋白质相互作用网络。利用Metascape数据库进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析。使用AutoDock Vina进行分子对接,以研究CQLT成分与核心靶点之间的相互作用。此外,选用ZDF大鼠建立DR模型进行实验研究。
筛选出CQLT中的39种活性成分和448个靶点,其中90个靶点与DR共有。KEGG通路富集分析确定了181条通路。分子对接结果表明,主要活性成分与核心靶点具有较强的结合能力。动物实验结果表明,CQLT抗DR的机制与抑制视网膜mTOR/HIF-1α/VEGF信号通路、减轻炎症反应、抑制视网膜新生血管形成以及保护视网膜的功能和形态有关。
本研究初步探讨了CQLT治疗DR的机制,表明CQLT通过多种成分、多个靶点和多条途径发挥抗DR作用。这些发现表明,CQLT有望成为治疗DR的潜在药物,并有助于开发新的治疗方法。