Li Yingxiao, Hsu Chao-Tien, Yang Ting-Ting, Cheng Kai-Chun
Department of Anatomy, College of Medicine, I-Shou University, Kaohsiung 824005, Taiwan.
Department of Pathology, E-Da Hospital, I-Shou University, Kaohsiung 824005, Taiwan.
Pharmaceuticals (Basel). 2025 Jan 16;18(1):110. doi: 10.3390/ph18010110.
Cardiac hypertrophy is a significant complication of diabetes, often triggered by hyperglycemia. Glucagon-like peptide-1 (GLP-1) receptor agonists alleviate cardiac hypertrophy, but their efficacy diminishes under GLP-1 resistance. Syringaldehyde (SA), a natural phenolic compound, may activate GLP-1 receptors and mitigate hypertrophy. This study explores SA's therapeutic potential in hyperglycemia-induced cardiac hypertrophy in H9c2 cardiomyocytes. H9c2 cells were exposed to high glucose to induce hypertrophy. Cells were treated with varying SA concentrations, and hypertrophic biomarkers were analyzed using ELISA, qPCR, and Western blot. SA reduced cell size and hypertrophic biomarkers in a dose-dependent manner while increasing GLP-1 receptor expression and cAMP levels. These effects were attenuated in GLP-1-resistant cells, highlighting the role of GLP-1 receptor activation. AMPK activation was essential, as its inhibition abolished SA's effects. SA also decreased O-linked N-acetylglucosamine transferase (OGT) expression via AMPK activation, contributing to reduced hypertrophy. SA alleviates hyperglycemia-induced cardiac hypertrophy in H9c2 cells by activating the GLP-1 receptor and AMPK signaling pathway.
心脏肥大是糖尿病的一种重要并发症，通常由高血糖引发。胰高血糖素样肽-1（GLP-1）受体激动剂可减轻心脏肥大，但在GLP-1抵抗情况下其疗效会降低。丁香醛（SA）是一种天然酚类化合物，可能激活GLP-1受体并减轻肥大。本研究探讨SA在高血糖诱导的H9c2心肌细胞心脏肥大中的治疗潜力。将H9c2细胞暴露于高糖环境以诱导肥大。用不同浓度的SA处理细胞，并使用酶联免疫吸附测定（ELISA）、定量聚合酶链反应（qPCR）和蛋白质免疫印迹法分析肥大生物标志物。SA以剂量依赖方式减小细胞大小并降低肥大生物标志物，同时增加GLP-1受体表达和环磷酸腺苷（cAMP）水平。在GLP-1抵抗细胞中这些作用减弱，突出了GLP-1受体激活的作用。腺苷酸活化蛋白激酶（AMPK）激活至关重要，因为其抑制会消除SA的作用。SA还通过激活AMPK降低O-连接的N-乙酰葡糖胺转移酶（OGT）表达，有助于减轻肥大。SA通过激活GLP-1受体和AMPK信号通路减轻高血糖诱导的H9c2细胞心脏肥大。
