The protective effect of hispidin against hydrogen peroxide-induced apoptosis in H9c2 cardiomyoblast cells through Akt/GSK-3β and ERK1/2 signaling pathway

Dae Eun Kim, Bokyung Kim, Hwa Sup Shin, Ho Jeong Kwon, Eun Seok Park

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51 Citations (Scopus)


Hispidin, a phenolic compound from Phellinus linteus (a medicinal mushroom), has been shown to possess strong anti-oxidant, anti-cancer, anti-diabetic, and anti-dementia properties. However, the cardioprotective efficacy of hispidin has not yet been investigated. In the present study, we investigated the protective effect of hispidin against oxidative stress-induced apoptosis in H9c2 cardiomyoblast cells and neonatal rat ventricular myocytes. While the treatment of H9c2 cardiomyoblast cells with hydrogen peroxide caused a loss of cell viability and an increase in the number of apoptotic cells, hispidin significantly protected the cells against hydrogen peroxide-induced cell death without any cytotoxicity as determined by XTT assay, LDH release assay, Hoechst 33342 assay, and Western blotting of apoptosis proteins such as caspase-3, Bax, and Bcl-2. Our data also shows that hispidin significantly scavenged intracellular ROS, and markedly enhanced the expression of antioxidant enzymes such as heme oxygenase-1 and catalase, which was accompanied by the concomitant activation of Akt/GSK-3β and ERK1/2 phosphorylation in H9c2 cardiomyoblast cells. The effects of hispidin on Akt and ERK phosphorylation were abrogated by LY294002 (a PI3K/Akt inhibitor) and U0126 (an ERK1/2 inhibitor). The effect of hispidin on GSK-3b activities was also blocked by LY294002. Furthermore, inhibiting the Akt/GSK-3β and ERK1/2 pathway by these inhibitors significantly reversed the hispidin-induced Bax and Bcl-2 expression, apoptosis induction, and ROS production. These findings indicate that hispidin protects against apoptosis in H9c2 cardiomyoblast cells exposed to hydrogen peroxide through reducing intracellular ROS production, regulating apoptosis-related proteins, and the activation of the Akt/GSK-3β and ERK1/2 signaling pathways.

Original languageEnglish
Pages (from-to)264-275
Number of pages12
JournalExperimental Cell Research
Issue number2
Publication statusPublished - 2014 Oct 1

Bibliographical note

Funding Information:
This work was supported by Kyungbok University , National Research Foundation of Korea 322 (NRF) grant funded by the Korea government (MSIP; 2009-0092964 , 2009-0083522 , 2010-323 0017984 , and 2012M3A9D1054520 ), Center for Food and Drug Materials of Agriculture Science and Technology Development 324 ( PJ0079772012 ), Rural Development Administration 325 , the National R&D Program, Ministry of Health and Welfare ( 0620360-1 ), and the Brain Korea 21 Plus Project, Republic of Korea .

Publisher Copyright:
© 2014 Elsevier Inc.

All Science Journal Classification (ASJC) codes

  • Cell Biology


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