Hu-Zhang Qing-Mai Formulation anti-oxidative stress alleviates diabetic retinopathy: Network pharmacology analysis and in vitro experiment

Abstract

Background: 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. Methods: 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). Results: 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. Conclusion: 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.