Hesperetin post-treatment prevents rat cardiomyocytes from hypoxia/reoxygenation injury in vitro via activating PI3K/Akt signaling pathway

• Published in: Biomedicine & pharmacotherapy Vol. 91; pp. 1106 - 1112
• Main Authors: He, Shangfei, Wang, Xianbao, Zhong, Yongkang, Tang, Lu, Zhang, Ya, Ling, Yuanna, Tan, Zhipeng, Yang, Pingzhen, Chen, Aihua
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.07.2017
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Cardiomyocytes; Cardiotonic Agents - pharmacology; Caspase 3 - metabolism; Cell Survival - drug effects; Hesperetin (HPT); Hesperidin - pharmacology; Hypoxia - drug therapy; Hypoxia - metabolism; Hypoxia/reoxygenation (H/R); Internal Medicine; Medical Education; Myocardial Reperfusion Injury - drug therapy; Myocardial Reperfusion Injury - metabolism; Myocytes, Cardiac - drug effects; Phosphatidylinositol 3-Kinases - metabolism; PI3K/Akt; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Sprague-Dawley; Signal Transduction - drug effects; Cardiomyocytes; Hesperetin (HPT); Hypoxia/reoxygenation (H/R); Apoptosis; PI3K/Akt
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2017.05.003

Abstract Hesperidin (HES), a citrus fruit extract, has beneficial effects on various ischemia/reperfusion (I/R) models. Here, we investigated the possible positive effect of hesperetin (HPT), an active metabolite of HES, and identified the potential molecular mechanisms involved in cardiomyocytes H/R-induced injury. To construct the cardiomyocyte model of hypoxia/reoxygenation (H/R) injury, cultured neonatal rat cardiomyocytes were subjected to 3 h of hypoxia followed by 3 h of reoxygenation. Cell viability and apoptosis were detected. The levels of Apoptosis-related proteins and PI3K/Akt proteins were detected by western blot. Our results showed that HPT post-treatment significantly inhibited apoptosis by elevating the expression of Bcl-2, decreasing the expression of Bax and cleaved caspase-3, and diminished the apoptotic cardiomyocytes ratio. Mechanism studies demonstrated that HPT post-treatment up-regulated the expression levels of p-PI3K, and p-Akt. Co-treatment of the cardiomyocytes with the PI3K/Akt-specific inhibitor LY294002 blocked the HPT-induced cardioprotective effects. Taken together, these data suggested that HPT post-treatment prevented cardiomyocytes from H/R injury in vitro most likely through the activation of PI3K/Akt signaling pathway.