Department of Ophthalmology, Inner Mongolia Autonomous Region People's Hospital, Hohhot, China.
J Chin Med Assoc. 2024 Aug 1;87(8):789-798. doi: 10.1097/JCMA.0000000000001113. Epub 2024 May 23.
Diabetic retinopathy (DR) is one of the most well-known microvascular complications of diabetes mellitus. As a traditional Chinese medicine, Huangqi (HQ), has been used for treating DR for a long time. However, its anti-DR active ingredients and mechanism are still unknown. Therefore, we designed this study to explore the active components and mechanism of HQ against DR via network pharmacology analysis.
The ingredients of HQ, and potential targets of HQ and DR were obtained from public databases. We used the protein-protein interaction (PPI) network, Kyoto Encyclopedia of Genes and Genomes (KEGGs) pathway enrichment, and Gene Ontology (GO) analysis to identify core targets and pathways of HQ against DR. Finally, molecular docking and vitro experiments were applied to validate our results.
A total of 34 potential targets of HQ against DR were obtained. Based on PPI network, VEGFA, PTGS2, Interleukin-6 (IL-6), and CCL2 were considered as core targets. GO analysis involved 692 biological processes, 21 cellular components, and 35 molecular functions. KEGG enrichment analysis manifested that the anti-DR effect of HQ was mainly mediated via the AGE-RAGE signaling pathway in diabetic complications. The molecular docking results indicated that kaempferol had higher affinity with CCL2, IL-6, VEGFA, and PTGS2. The vitro experiments showed that the mRNA expressions of CCL2, IL-6, VEGFA, and PTGS2 in ARPE-19 cells were differentially decreased after kaempferol treatment.
This study preliminarily unveiled that the therapeutic efficacy of HQ against DR might be attributed to the reduced expression of CCL2, IL-6, VEGFA, and PTGS2.
糖尿病视网膜病变（DR）是糖尿病最著名的微血管并发症之一。黄芪（HQ）作为一种中药，长期以来一直用于治疗 DR。然而，其抗 DR 的活性成分和机制尚不清楚。因此，我们设计了这项研究，通过网络药理学分析探讨 HQ 治疗 DR 的活性成分和机制。
HQ 的成分以及 HQ 和 DR 的潜在靶点从公共数据库中获得。我们使用蛋白质-蛋白质相互作用（PPI）网络、京都基因与基因组百科全书（KEGGs）通路富集和基因本体论（GO）分析来确定 HQ 治疗 DR 的核心靶点和通路。最后，应用分子对接和体外实验来验证我们的结果。
共获得 34 个 HQ 治疗 DR 的潜在靶点。基于 PPI 网络，VEGFA、PTGS2、白细胞介素-6（IL-6）和 CCL2 被认为是核心靶点。GO 分析涉及 692 个生物过程、21 个细胞成分和 35 个分子功能。KEGG 富集分析表明，HQ 对 DR 的治疗作用主要通过糖尿病并发症中的 AGE-RAGE 信号通路介导。分子对接结果表明，山奈酚与 CCL2、IL-6、VEGFA 和 PTGS2 具有更高的亲和力。体外实验表明，山奈酚处理后 ARPE-19 细胞中 CCL2、IL-6、VEGFA 和 PTGS2 的 mRNA 表达均有差异下降。
本研究初步揭示了 HQ 治疗 DR 的疗效可能归因于 CCL2、IL-6、VEGFA 和 PTGS2 的表达降低。
