Quercetin attenuates cisplatin-induced muscle atrophy via Hippo/YAP1 signaling pathway

IF 2.6 4区医学 Q3 CHEMISTRY, MEDICINAL

Journal of Natural Medicines Pub Date : 2026-07-20 DOI:10.1007/s11418-026-02062-1

Jingchun Lv, Jianwei Lin, Xiaojing Chen, Qi Wu, Zhiyao Cao, Dapeng Jiang

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引用次数: 0

Abstract

Muscle wasting is a common event among cancer patients receiving chemotherapy treatment and has been reported to affect their survival. However, current therapies for counteracting this side effect are ineffective. This study investigates quercetin’s efficacy against cisplatin-induced muscle atrophy and its mechanism. Using both C2C12 myotube and mouse models, we found quercetin pretreatment significantly alleviates cisplatin-induced muscle wasting. Mechanistically, transcriptome analysis identified that the Hippo signaling pathway was involved in cisplatin-induced muscle atrophy. Quercetin restored the activity of this pathway, including the expression and nuclear localization of its effector YAP1. Furthermore, quercetin mitigated cisplatin-induced muscle damage by improving mitochondrial membrane quality and function. Molecular docking revealed a direct interaction between quercetin and YAP1. Additionally, the possible interaction between YAP1 and mitochondrial function was revealed. Our findings demonstrate that quercetin attenuates cisplatin-induced muscle atrophy by modulating the Hippo/YAP1 pathway and preserving mitochondrial homeostasis, highlighting its therapeutic potential.

Graphical abstract

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槲皮素通过Hippo/YAP1信号通路减轻顺铂诱导的肌肉萎缩。

在接受化疗的癌症患者中，肌肉萎缩是一种常见的现象，据报道，肌肉萎缩会影响患者的生存。然而，目前对抗这种副作用的疗法是无效的。本研究探讨槲皮素抗顺铂所致肌肉萎缩的作用及其机制。通过C2C12肌管模型和小鼠模型，我们发现槲皮素预处理可显著缓解顺铂诱导的肌肉萎缩。机制上，转录组分析确定Hippo信号通路参与顺铂诱导的肌肉萎缩。槲皮素恢复了这条通路的活性，包括其效应物YAP1的表达和核定位。此外，槲皮素通过改善线粒体膜质量和功能减轻顺铂诱导的肌肉损伤。分子对接揭示了槲皮素与YAP1之间的直接相互作用。此外，还揭示了YAP1与线粒体功能之间可能存在的相互作用。我们的研究结果表明，槲皮素通过调节Hippo/YAP1通路和保持线粒体稳态来减轻顺铂诱导的肌肉萎缩，突出了其治疗潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Natural Medicines 医学-药学

CiteScore

6.90

自引率

3.00%

发文量

审稿时长

1.7 months

期刊介绍： The Journal of Natural Medicines is an international journal publishing original research in naturally occurring medicines and their related foods and cosmetics. It covers: -chemistry of natural products -biochemistry of medicinal plants -pharmacology of natural products and herbs, including Kampo formulas and traditional herbs -botanical anatomy -cultivation of medicinal plants. The journal accepts Original Papers, Notes, Rapid Communications and Natural Resource Letters. Reviews and Mini-Reviews are generally invited.