Syringaldehyde Alleviates Cardiac Hypertrophy Induced by Hyperglycemia in H9c2 Cells Through GLP-1 Receptor Signals
<b>Background:</b> 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 phenol...
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2025-01-01
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| author | Yingxiao Li Chao-Tien Hsu Ting-Ting Yang Kai-Chun Cheng |
| author_facet | Yingxiao Li Chao-Tien Hsu Ting-Ting Yang Kai-Chun Cheng |
| author_sort | Yingxiao Li |
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| description | <b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> SA alleviates hyperglycemia-induced cardiac hypertrophy in H9c2 cells by activating the GLP-1 receptor and AMPK signaling pathway. |
| format | Article |
| id | doaj-art-67c004b2fb144c0bae436059bd8ff7e5 |
| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Pharmaceuticals |
| spelling | doaj-art-67c004b2fb144c0bae436059bd8ff7e52025-01-24T13:45:25ZengMDPI AGPharmaceuticals1424-82472025-01-0118111010.3390/ph18010110Syringaldehyde Alleviates Cardiac Hypertrophy Induced by Hyperglycemia in H9c2 Cells Through GLP-1 Receptor SignalsYingxiao Li0Chao-Tien Hsu1Ting-Ting Yang2Kai-Chun Cheng3Department of Anatomy, College of Medicine, I-Shou University, Kaohsiung 824005, TaiwanDepartment of Pathology, E-Da Hospital, I-Shou University, Kaohsiung 824005, TaiwanSchool of Chinese Medicine for Post Baccalaureate, College of Medicine, I-Shou University, Kaohsiung 824005, TaiwanDepartment of Pharmacy, College of Pharmacy and Health Care, Tajen University, Pingtung 90741, Taiwan<b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> SA alleviates hyperglycemia-induced cardiac hypertrophy in H9c2 cells by activating the GLP-1 receptor and AMPK signaling pathway.https://www.mdpi.com/1424-8247/18/1/110AMPKcardiac hypertrophydiabetes complicationsGLP-1 resistanceO-linked N-acetylglucosamine transferase (OGT)syringaldehyde |
| spellingShingle | Yingxiao Li Chao-Tien Hsu Ting-Ting Yang Kai-Chun Cheng Syringaldehyde Alleviates Cardiac Hypertrophy Induced by Hyperglycemia in H9c2 Cells Through GLP-1 Receptor Signals Pharmaceuticals AMPK cardiac hypertrophy diabetes complications GLP-1 resistance O-linked N-acetylglucosamine transferase (OGT) syringaldehyde |
| title | Syringaldehyde Alleviates Cardiac Hypertrophy Induced by Hyperglycemia in H9c2 Cells Through GLP-1 Receptor Signals |
| title_full | Syringaldehyde Alleviates Cardiac Hypertrophy Induced by Hyperglycemia in H9c2 Cells Through GLP-1 Receptor Signals |
| title_fullStr | Syringaldehyde Alleviates Cardiac Hypertrophy Induced by Hyperglycemia in H9c2 Cells Through GLP-1 Receptor Signals |
| title_full_unstemmed | Syringaldehyde Alleviates Cardiac Hypertrophy Induced by Hyperglycemia in H9c2 Cells Through GLP-1 Receptor Signals |
| title_short | Syringaldehyde Alleviates Cardiac Hypertrophy Induced by Hyperglycemia in H9c2 Cells Through GLP-1 Receptor Signals |
| title_sort | syringaldehyde alleviates cardiac hypertrophy induced by hyperglycemia in h9c2 cells through glp 1 receptor signals |
| topic | AMPK cardiac hypertrophy diabetes complications GLP-1 resistance O-linked N-acetylglucosamine transferase (OGT) syringaldehyde |
| url | https://www.mdpi.com/1424-8247/18/1/110 |
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