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Context: Yi-Qi Cong-Ming (YQCM) decoction has been widely used to prevent age-related hearing loss (ARHL), the most prevalent neurodegenerative disease in the elderly. Objective: To explore the mechanism of YQCM decoction in the treatment of ARHL. Materials and methods: The chemical constituents of YQCM were screened from the Traditional Chinese Medicine Systems Pharmacology Database. Potential targets of YQCM against ARHL were predicted by DrugBank, GeneCards, and OMIM database. Protein-protein network and enrichment analysis were used for exploring possible molecular mechanisms. Molecular docking and an in vitro model of ARHL by exposing auditory cells with 100 μM H2O2 for 3 h were applied. Cell viability and mitochondrial membrane potential (ΔΨM) were detected by CCK-8 and high-content analysis. γH2AX and cleaved caspase-3 were detected by Western blot. Results: The main compounds have good affinities with hub targets, especially AKT1, PTGS2, and CASP3. GO and KEGG analysis showed that the main biological process and key targets were related to negative regulation of the apoptotic process. H2O2 treatment could reduce the cell viability by 68% and impaired ΔΨM, while 90 μg/mL YQCM pre-treatment could restore the cell viability by 97.45% and increase ΔΨM (2-fold higher). YQCM pre-treatment also reduced γH2AX and cleaved caspase-3 protein levels. Conclusions: Our study suggested that YQCM prevents ARHL by modulating the apoptosis process in auditory hair cells. Moreover, this study proved that bioinformatics analysis combined with molecular docking and cell model is a promising method to explore other possible pharmacological interventions of ARHL. [ABSTRACT FROM AUTHOR]

Weisiensin B, a new ent-kaurane diterpenoid, was isolated from traditional Chinese herb Rabdosia weisiensis C.Y. Wu. In this study, cytotoxicity of weisiensin B was tested on four different tumor cell lines and the effect of growth inhibition and apoptosis in BEL-7402 cell line were investigated in vitro. The results indicated that weisiensin B had significant antiproliferation activity on the four cell lines. Further study on BEL-7402 cells involving Hoechst 33258 stain and DNA fragmentation assay revealed the characteristic apoptotic features of nuclear and DNA ladder formation. Flow cytometric (FCM) analysis with propidium iodide (PI) staining demonstrated that BEL-7402 cells treated with weisiensin B were arrested in G2/M phase. The results demonstrated that a significant fraction of weisiensin B-treated cells died by an apoptotic pathway in BEL-7402 cells. [ABSTRACT FROM AUTHOR]

Reactive oxidative compounds including superoxide anions and nitric oxide are believed to play a central role in many blinding eye diseases. In the present study, we examine the effect of ischemia on human retinal pigment epithelial (RPE) cells in an unusual clinical case. We show that ischemia leads to extensive nitrotyrosine deposition in the RPE and choroid, thus indicating NO-dependent oxidative stress. We also show for the first time the in vivo translocation of glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) to the nuclei of RPE cells. This enzyme's nuclear translocation has previously been demonstrated in vitro where it is a marker of apoptosis. Furthermore, nitrotyrosine deposition and GAPDH translocation have been duplicated in vitro using human RPE cells. Thus, nitrotyrosine formation and GAPDH trafficking to the nucleus may be observed during ischemic conditions. [ABSTRACT FROM AUTHOR]