School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China.
Capital Medical University Affiliated Beijing Traditional Chinese Medicine Hospital, Beijing 100010, China.
Biosci Rep. 2023 Jan 31;43(1). doi: 10.1042/BSR20220893.
Diabetic retinopathy (DR) is the leading cause of blindness in the working population worldwide, with few effective drugs available for its treatment in the early stages. The Zhujing pill (ZJP) is well-established to enhance the early symptoms of DR, but the mechanism underlying its therapeutic effect remains unclear. In the present study, we used systems biology and multidirectional pharmacology to screen the main active ingredients of ZJP and retrieved DrugBank and Genecards databases to obtain 'drug-disease' common targets. Using bioinformatics analysis, we obtained the core targets, and potential mechanisms of action of ZJP and its main components for the treatment of DR. Molecular docking was used to predict the binding sites and the binding affinity of the main active ingredients to the core targets. The predicted mechanism was verified in animal experiments. We found that the main active ingredient of ZJP was oleanolic acid, and 63 common 'drug-disease' targets were identified. Topological analysis and cluster analysis based on the protein-protein interaction network of the Metascape database screened the core targets as PRKCA, etc. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that these core targets were significantly enriched in the pro-angiogenic pathway of the VEGF signaling pathway. Molecular docking and surface plasmon resonance revealed that ZJP and its main active component, oleanolic acid had the highest binding affinity with PKC-α, the core target of the VEGF signaling pathway. Animal experiments validated that ZJP and oleanolic acid could improve DR.
糖尿病视网膜病变（DR）是全球工作人群致盲的主要原因，早期可用的治疗药物很少。竹精丸（ZJP）已被证实可改善 DR 的早期症状，但其治疗效果的机制尚不清楚。在本研究中，我们使用系统生物学和多向药理学筛选 ZJP 的主要活性成分，并从 DrugBank 和 Genecards 数据库中检索“药物-疾病”共同靶点。通过生物信息学分析，我们获得了 ZJP 及其主要成分治疗 DR 的核心靶点和潜在作用机制。分子对接用于预测主要活性成分与核心靶点的结合位点和结合亲和力。预测机制在动物实验中得到了验证。我们发现 ZJP 的主要活性成分为齐墩果酸，鉴定出 63 个共同的“药物-疾病”靶点。基于 Metascape 数据库的蛋白质-蛋白质相互作用网络的拓扑分析和聚类分析筛选出的核心靶点有 PRKCA 等。基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析表明，这些核心靶点在 VEGF 信号通路的促血管生成途径中显著富集。分子对接和表面等离子体共振显示，ZJP 和其主要活性成分齐墩果酸与 VEGF 信号通路的核心靶点 PKC-α具有最高的结合亲和力。动物实验验证了 ZJP 和齐墩果酸可以改善 DR。
