Salidroside Alleviates Mobocertinib-Induced Cardiotoxicity by Improving Cardiac Electrophysiology

作者：Yan Chi, Xiaohong Liu, Xiaoyan Zhang, Pei Wei, Xuefang Li, Dongxu Li, Guhao Zhang, Meng Li, Xiayan Zang, Guangjian Lu, Fei Lin · 发表于：Cardiovascular Toxicology · 年份：2026 · DOI：10.1007/s12012-026-10169-w · 研究领域：Medicinal Plants and Bioactive Compounds、Nigella sativa pharmacological applications、Antioxidants, Aging, Portulaca oleracea

Mobocertinib, a tyrosine kinase inhibitor approved for EGFR exon 20 insertion-mutated non-small cell lung cancer, induces cardiotoxicity manifesting as QT prolongation. Salidroside, a bioactive compound from Rhodiola rosea, exhibits cardioprotective properties. We investigated electrophysiological mechanisms underlying mobocertinib cardiotoxicity and salidroside's protective efficacy using Langendorff-perfused rat hearts and neonatal rat cardiomyocytes (NRCMs). Hearts were treated with escalating mobocertinib concentrations (214, 428, 856 nM) with or without salidroside (20 μM) pretreatment; cardiac parameters including heart rate, PR, JT, QTc intervals and conduction were mapped via high-resolution multichannel electrophysiology. NRCMs underwent chronic mobocertinib exposure with/without salidroside, followed by transcriptomic sequencing, qRT-PCR, and western blot validation. Mobocertinib concentration-dependently prolonged PR, JT, QTc intervals, increased conduction time/heterogeneity, reduced heart rate/velocity, and JT/QTc prolongation persisted after washout. Salidroside pretreatment markedly attenuated these abnormalities. In NRCMs, mobocertinib prolonged field potential duration and impaired conduction; salidroside normalized parameters. Transcriptomic analysis identified enrichment in calcium signaling, aldosterone synthesis, cGMP-PKG, and adrenergic pathways. Notably, Atp2b2 was upregulated in mobocertinib group but downregulated in salidroside combination group, whe...