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Objective. This study is designed to find out the molecular targets of effective Chinese medicine Ziyin Mingmu pills (ZMPs) in treating age-related macular degeneration (AMD) based on network pharmacology and experimental data. Methods. A comprehensive network pharmacology strategy that consists of three sequential modules (drug-disease target molecular docking, enrichment analysis, and external verification) was carried out to identify potential targets of ZMPs acting on AMD. Results. The active ingredients of ZMPs targeting 66 genes have effects on the process of AMD. GO and KEGG pathway enrichment analyses suggested that response to oxidative stress, regulation of angiogenesis, and lipid and atherosclerosis might serve as the most important signaling pathways in ZMPs for AMD treatment. Combined with the GSE29801 dataset for further analysis, two key genes, EGFR and VEGFA, were identified. Immune infiltration analysis showed that there was a strong association between EGFR and immune cell content. In addition, images were acquired following 24 h in the scratch experiment showed that ZMPs can reduce the percentage of wound healing distance. The Western blot assay found that ZMPs increased the expression of EGFR and decreased the expression of VEGFA. Conclusion. This study sheds light on some mechanisms of ZMP therapy for AMD, particularly the effect of ZMP on the oxidative stress in RPE and cell survival and angiogenesis in AMD. We propound ZMPs as a promising strategy to intervene in the process of AMD. [ABSTRACT FROM AUTHOR]

The use of 5-fluorouracil (5-FU) has been proven benefits, but it also has adverse events in colorectal cancer (CRC) chemotherapy. In this study, we explored the mechanism of 5-FU resistance by bioinformatics analysis of the NCBI public dataset series GSE81005. Fifteen hub genes were screened out of 582 different expressed genes. Modules of the hub genes in protein-protein interaction networks gathered to TOP2α showed a decrease in HCT-8 cells but an increase in 5-FU-resistant HCT-8/5-FU cells with 5-FU exposure. Downregulation of TOP2α with siRNA or miR-494 transfection resulted in an increase of cytotoxicity and decrease of cell colonies to 5-FU for HCT-8/5-FU cells. Moreover, we found that an ethanol extract of Spica Prunellae (EESP), which is a traditional Chinese medicine with clinically beneficial effects in various cancers, was able to enhance the sensitivity of 5-FU in HCT-8/5-FU cells and partly reverse the 5-FU resistance effect. It significantly helped suppress cell growth and induced cell apoptosis in HCT-8/5-FU cells with the expression of TOP2α being significantly suppressed, which increased by 5-FU. Consistently, miR-494, which reportedly regulates TOP2α, exhibited reverse trends in EESP/5-FU combination treatment. These results suggested that Spica Prunellae may be beneficial in the treatment of 5-FU-resistant CRC patients. [ABSTRACT FROM AUTHOR]