Small-molecule 7,8-dihydroxyflavone counteracts compen-sated and decompensated cardiac hypertrophy via AMPK activation
Peng-Zhou HANG1
Pei-Feng LI2
Jie LIU2
Feng-Feng LI3
Ting-Ting CHEN2
Yang PAN2
Man-Ru ZHANG4
Hua-Qing YU4
Hong-Yu JI2
Zhi-Min DU5
Jing ZHAO6
1.Institute of Clinical Pharmacology,the Second Affiliated Hospital of Harbin Medical University(University Key Labor-atory of Drug Research,Heilongjiang Province),Harbin,China;Department of Pharmacy,Clinical Medical College,Yangzhou University,Northern Jiangsu People's Hospital,Yangzhou,China2.Institute of Clinical Pharmacology,the Second Affiliated Hospital of Harbin Medical University(University Key Labor-atory of Drug Research,Heilongjiang Province),Harbin,China3.Department of Pharmacology,Harbin Medical University,Harbin,China4.Department of Pharmacy,Clinical Medical College,Yangzhou University,Northern Jiangsu People's Hospital,Yangzhou,China5.Institute of Clinical Pharmacology,the Second Affiliated Hospital of Harbin Medical University(University Key Labor-atory of Drug Research,Heilongjiang Province),Harbin,China;State Key Laboratory of Quality Research in Chinese Medicines,Macau Uni-versity of Science and Technology,Macau,China6.Department of Pharmacy,Clinical Medical College,Yangzhou University,Northern Jiangsu People's Hospital,Yangzhou,China;Department of Cardiology,the First Affiliated Hospital of Harbin Medical University,Harbin,China
摘要：BACKGROUND Pathological cardiac hypertrophy is a compensated response to various stimuli and is considered a key risk factor for heart failure. 7,8-Dihydroxyflavone (7,8-DHF) is a flavonoid derivative that acts as a small-molecule brain-derived neur-otrophic factor mimetic. The present study aimed to explore the potential role of 7,8-DHF in cardiac hypertrophy.METHODS Kunming mice and H9c2 cells were exposed to transverse aortic constriction or isoproterenol (ISO) with or without 7,8-DHF, respectively. F-actin staining was performed to calculate the cell area. Transcriptional levels of hypertrophic markers, including ANP, BNP, and β-MHC, were detected. Echocardiography, hematoxylin-eosin staining, and transmission elec-tron microscopy were used to examine the cardiac function, histology, and ultrastructure of ventricles. Protein levels of mitochon-dria-related factors, such as adenosine monophosphate-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), were detected. RESULTS 7,8-DHF inhibited compensated and decompensated cardiac hypertrophy, diminished the cross-sectional area, and alleviated the mitochondrial disorders of cardiomyocytes. Meanwhile, 7,8-DHF reduced the cell size and repressed the mRNA levels of the hypertrophic markers of ISO-treated cardiomyocytes. In addition, 7,8-DHF activated AMPK and PGC-1α signals without affecting the protein levels of mitochondrial dynamics-related molecules. The effects of 7,8-DHF were eliminanted by Compound C, an AMPK inhibitor. CONCLUSIONS These findings suggest that 7,8-DHF inhibited cardiac hypertrophy and mitochondrial dysfunction by activ-ating AMPK signaling, providing a potential agent for the treatment of pathological cardiac hypertrophy.
机标关键词：flavoneampkactivationcardiaccompen-satedcounteractsdecompensatedhydroxy
论文发表日期：2022-11-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：14( 853-866 )