Cataract is a common eye disease, which is caused by many reasons and is also the main cause of blindness. Shihu Yeguang Pill is one of the ancient and commonly used Chinese patent medicines. It has a certain curative effect in the treatment of cataracts and glaucoma. However, the action mechanism remains unclear. In this study, network pharmacology, molecular docking, and cell experiment were used to explore the underlying molecular mechanism of Shihu Yeguang Pill in treating cataracts. The active components and targets of Shihu Yeguang Pill were screened by TCMSP, PubChem, SuperPred, and BATMAN-TCM databases. The targets related to cataracts were obtained from GeneCards, CTD, Malacards, DisGeNET and
OMIM database, and the intersected targets were obtained by Venny2.1.0. Then, an active component-target network was constructed using Cytoscape software. And the protein-protein interaction (PPI) network was drawn through the String database and Cytoscape software, and the core targets were obtained. Next, KEGG pathway enrichment analyses were performed by Bioconduct database. Molecular docking was conducted using Autodock Vina. Finally, cell experiments were conducted to verify the effect of active compounds. Results showed that according to the screening criteria, a total of 1 511 active compounds and 576 potential targets of Shihu YeGuang Pill were chosen. Through the online database, 10 133 cataract-related targets were identified, and 449 overlapping targets were obtained. In an active component-target network, isorhamnetin, naringenin, and quercetin were the important active components. In the PPI network, MAPK3, MAPK1, STAT3, TP53, and AKT1 were the core targets. KEGG analyses showed that the main pathways of Shihu Yeguang Pill in treating
cataracts involved PI3K-AKT, TNF, and MAPK signaling pathways. In molecular docking, the active compounds of Shihu Yeguang Pill had a good affinity with the core targets. Cell survival tests showed that QUE(quercetin), Naringenin (NAR), and ISO (Isorhamnetin) can improve B-3 cell injury induced by H2O2. The determination of total reactive oxygen species in B-3 cells showed that NAR, ISO, and QUE could treat H2O2-induced oxidative damage. In this study, the main active components, targets, and signaling pathways of Shihu Yeguang Pill in the treatment of cataracts have been preliminarily predicted, providing new ideas for further research on the protective mechanism and clinical application of Shihu Yeguang Pill against cataracts.