Mechanisms of Qing-Gan Li-Shui Formulation in Ameliorating Primary Open Angle Glaucoma: An Analysis Based on Network Pharmacology.

Objective: In this study, we investigated the mechanism of Qing-Gan Li-Shui formulation (QGLSF) in treating primary open glaucoma (POAG) by network pharmacology and experiments.

Methods: The active pharmaceutical ingredients (APIs) of GLQSF (prepared with vulgaris, Kudzu root, , and ) were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Yet Another Traditional Chinese Medicine database (YATCM). The targets of POAG were screened out with GeneCards, OMIM, PharmGKB, Therapeutic Target Database (TTD), and DrugBank databases. The Venny platform was used to summarize the core targets. Topological analysis was performed using Cytoscape3.8.0. A protein-protein interaction network was plotted by STRING online. The key targets were subjected to GO and KEGG enrichment analyses. Finally, the effects of APIs were verified by a model of chloride hexahydrate (CoCl)-induced retinal ganglion cells-5 (RGC-5).

Results: The main APIs were selected as quercetin (Que) by network pharmacology. Nine clusters of QGLSF targets were obtained by the PPI network analysis, including AKT-1, TP53, and JUN. KEGG enrichment analysis showed that these targets were mainly involved in the AGE-RAGE signaling pathway. By experiments, Que promoted cell proliferation. The secretion of AKT-1, TP53, JUN, AGE, and RAGE in the cell culture supernatant decreased, as shown by ELISA. The mRNA levels of AKT-1, TP53, JUN, and RAGE decreased, as shown by RT-PCR. QGLSF may employ the AGE-RAGE signaling pathway to counter POAG.

Conclusion: This study preliminarily elucidates the efficacy and mechanism of QGLSF in the treatment of POAG.