Sun Wentao, Wang Rui, Gong Ke, Wang Liping, Li Fengzhi, Deng Jin
Shaanxi Eye Hospital, Xi'an People's Hospital (Xi'an Fourth Hospital), Affiliated People's Hospital of Northwest University, 21 Jiefang Road, Xi'an, 710004, China.
Tongchuan Wuguan Hospital, Tongchuan, 712100, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr;398(4):4571-4582. doi: 10.1007/s00210-024-03562-1. Epub 2024 Nov 7.
Diabetic retinopathy (DR) is a leading cause of blindness globally. Buyang Huanwu decoction (BHD) is a traditional Chinese medicine for treating DR, but its therapeutic mechanisms are not fully understood. This study aimed to elucidate and validate the underlying mechanisms of BHD in DR treatment through network pharmacology and in vitro experiments. We identified active compounds in BHD and their associated targets using the TCMSP and SwissTargetPrediction. DR-related targets were sourced from GeneCards, NCBI, and OMIM databases. The protein-protein interaction (PPI) network and enrichment analyses were employed to predict common targets and pathways. Subsequent molecular docking and in vitro experiments, including cell viability assays, RT-qPCR, flow cytometry, and Western blot, were conducted to validate the anti-DR mechanism of BHD. Network pharmacology identified paeoniflorin as a key active compound in BHD for treating DR, with VEGFA emerging as a central target. Molecular docking suggested a strong binding affinity between paeoniflorin and VEGFA. In vitro experiments confirmed that paeoniflorin attenuated high glucose-induced increases in cell viability, migration, apoptosis, and inflammatory cytokine expression in retinal pigment epithelial cells. The therapeutic effect of paeoniflorin was primarily mediated through the downregulation of VEGFA expression. Our study demonstrates that paeoniflorin, a key active compound in BHD, effectively mitigates DR by downregulating VEGFA expression and reducing high glucose-induced cellular alterations, thereby highlighting its potential as a therapeutic agent for DR.
糖尿病视网膜病变（DR）是全球失明的主要原因。补阳还五汤（BHD）是一种用于治疗DR的中药，但其治疗机制尚未完全明确。本研究旨在通过网络药理学和体外实验阐明并验证BHD治疗DR的潜在机制。我们使用中药系统药理学数据库与分析平台（TCMSP）和瑞士靶点预测工具确定了BHD中的活性化合物及其相关靶点。DR相关靶点来源于基因卡片（GeneCards）、美国国立医学图书馆（NCBI）和在线孟德尔人类遗传数据库（OMIM）。采用蛋白质-蛋白质相互作用（PPI）网络和富集分析来预测共同靶点和通路。随后进行了分子对接和体外实验，包括细胞活力测定、逆转录-定量聚合酶链反应（RT-qPCR）、流式细胞术和蛋白质免疫印迹法，以验证BHD的抗DR机制。网络药理学确定芍药苷是BHD治疗DR的关键活性化合物，血管内皮生长因子A（VEGFA）是核心靶点。分子对接表明芍药苷与VEGFA之间具有很强的结合亲和力。体外实验证实，芍药苷可减轻高糖诱导的视网膜色素上皮细胞活力、迁移、凋亡及炎性细胞因子表达的增加。芍药苷的治疗作用主要通过下调VEGFA表达介导。我们的研究表明，芍药苷作为BHD中的关键活性化合物，通过下调VEGFA表达和减少高糖诱导的细胞改变，有效减轻DR，从而突出了其作为DR治疗药物的潜力。
