Syringaldehyde Alleviates Cardiac Hypertrophy Induced by Hyperglycemia in H9c2 Cells Through GLP-1 Receptor Signals

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 18; no. 1; p. 110
• Main Authors: Li, Yingxiao, Hsu, Chao-Tien, Yang, Ting-Ting, Cheng, Kai-Chun
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.01.2025; MDPI
• Subjects: Aldehydes; AMPK; Biomarkers; cardiac hypertrophy; Cardiomyocytes; Cardiomyopathy; Care and treatment; Cellular signal transduction; Complications and side effects; Diabetes; diabetes complications; Diabetic angiopathies; GLP-1 receptor agonists; GLP-1 resistance; Glucose; Health aspects; Heart attacks; Heart enlargement; Heart failure; Hyperglycemia; Kinases; O-linked N-acetylglucosamine transferase (OGT); Oxidative stress; Peptides; Physiology; Proteins; syringaldehyde; Testing; Taiwan; AMPK; O-linked N-acetylglucosamine transferase (OGT); syringaldehyde; diabetes complications; cardiac hypertrophy; GLP-1 resistance
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph18010110

Background: 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. Methods: 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. Results: 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. Conclusions: SA alleviates hyperglycemia-induced cardiac hypertrophy in H9c2 cells by activating the GLP-1 receptor and AMPK signaling pathway.