Department of Ophthalmology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China.
Medicine (Baltimore). 2023 Sep 8;102(36):e35034. doi: 10.1097/MD.0000000000035034.
In this study, the potential mechanism of the Hu-Zhang Qing-Mai Formulation (HZQMF) on diabetic retinopathy (DR) in inhibiting oxidative stress was explored through network pharmacology analysis and in vitro experiments.
The Traditional Chinese Medicine Systematic Pharmacology Analysis Platform was used to retrieve the active pharmaceutical ingredients and targets of HZQMF. DR-related genes and oxidative stress-related genes were obtained from PharmGKB, TTD, OMIM, GeneCards, and Drugbank. STRING was used to construct a protein-protein interaction network to screen core targets. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses were performed using R 4.0.3. Network topology analysis was carried out using Cytoscape 3.8.2. Finally, we looked into how well the main API protected human retinal pigment epithelial cells from damage brought on by hydrogen peroxide (H2O2).
Quercetin (Que) was identified as the primary API of HZQMF through network pharmacology analysis, while JUN, MAPK1, and STAT3 were identified as the primary hub genes. Kyoto encyclopedia of genes and genomes enrichment analysis showed that the AGE-RAGE signaling pathway may be crucial to the therapeutic process. In vitro experiments confirmed that Que increased cell vitality and inhibited apoptosis.
Que might significantly reduce H2O2-induced ARPE-19 cell injury by inhibiting apoptosis-related genes of the AGE-RAGE pathway (JUN, MAPK1, STAT3). This study lays the foundation for further research on HZQMF in treating DR.
本研究采用网络药理学分析和体外实验，探讨胡璋青麦配方（HZQMF）抑制氧化应激治疗糖尿病视网膜病变（DR）的潜在作用机制。
利用中药系统药理学分析平台检索 HZQMF 的活性成分和作用靶点；从 PharmGKB、TTD、OMIM、GeneCards 和 Drugbank 中获取 DR 相关基因和氧化应激相关基因；利用 STRING 构建蛋白质-蛋白质相互作用网络，筛选核心靶点；利用 R 4.0.3 进行基因本体和京都基因与基因组百科全书富集分析；采用 Cytoscape 3.8.2 进行网络拓扑分析。最后，研究主要 API 对过氧化氢（H2O2）诱导的人视网膜色素上皮细胞损伤的保护作用。
通过网络药理学分析，鉴定出 HZQMF 的主要 API 为槲皮素（Que），而 JUN、MAPK1 和 STAT3 被鉴定为主要枢纽基因。京都基因与基因组百科全书富集分析表明，AGE-RAGE 信号通路可能是治疗过程的关键。体外实验证实，Que 可通过抑制 AGE-RAGE 通路的凋亡相关基因（JUN、MAPK1、STAT3），显著提高 H2O2 诱导的 ARPE-19 细胞活力，抑制细胞凋亡。
Que 可能通过抑制 AGE-RAGE 通路的凋亡相关基因（JUN、MAPK1、STAT3），显著降低 H2O2 诱导的 ARPE-19 细胞损伤，为进一步研究 HZQMF 治疗 DR 奠定了基础。
