School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Experimental Teaching Center, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Pharm Biol. 2022 Dec;60(1):1478-1490. doi: 10.1080/13880209.2022.2101671.
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.
To explore the mechanism of YQCM decoction in the treatment of ARHL.
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 model of ARHL by exposing auditory cells with 100 μM HO 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.
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. HO 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.
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.
益智聪明汤已广泛用于预防与年龄相关的听力损失（ARHL），这是老年人最常见的神经退行性疾病。
探讨益智聪明汤治疗 ARHL 的作用机制。
从中药系统药理学数据库中筛选益智聪明汤的化学成分。通过 DrugBank、GeneCards 和 OMIM 数据库预测益智聪明汤治疗 ARHL 的潜在靶点。利用蛋白质-蛋白质网络和富集分析探讨可能的分子机制。应用分子对接和 100μM HO 暴露听觉细胞 3 小时建立 ARHL 模型。通过 CCK-8 和高内涵分析检测细胞活力和线粒体膜电位（ΔΨM）。通过 Western blot 检测 γH2AX 和 cleaved caspase-3。
主要化合物与关键靶标，特别是 AKT1、PTGS2 和 CASP3 具有良好的亲和力。GO 和 KEGG 分析表明，主要的生物学过程和关键靶标与细胞凋亡过程的负调控有关。HO 处理可使细胞活力降低 68%，并损害 ΔΨM，而 90μg/mL 益智聪明汤预处理可使细胞活力恢复 97.45%，并增加 ΔΨM（增加 2 倍）。益智聪明汤预处理还降低了 γH2AX 和 cleaved caspase-3 蛋白水平。
本研究表明，益智聪明汤通过调节听觉毛细胞的凋亡过程来预防 ARHL。此外，本研究证明，生物信息学分析结合分子对接和细胞模型是探索 ARHL 其他可能药理干预的有前途的方法。
