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KMID : 1234920150150020093
Journal of Korean Oriental Association for Study of Obesity
2015 Volume.15 No. 2 p.93 ~ p.103
Protective Effects of Isorhamnetin against Hydrogen Peroxide-Induced Apoptosis in C2C12 Murine Myoblasts
Choi Yung-Hyun

Abstract
Objectives: It was investigated the cytoprotective efficacies of isorhamnetin, a flavonoid originally derived from Hippophae rhamnoides L., against oxidative stress-induced apoptosis in C2C12 myoblasts.

Methods: The effects of isorhamnetin on cell growth, apoptosis and reactive oxygen species (ROS) generation were evaluated by trypan blue dye exclusion assay, 4¡¯,6-diamidino-2-phenylindole staining and flow cytometry. The levels of apoptosis-regulatory and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway-related proteins, and caspase activities (caspase-3 and -9) were determined by Western blot analysis and colorimetric assay, respectively.

Results: Our results revealed that treatment with isorhamnetin prior to hydrogen peroxide (H2O2) exposure significantly increased the C2C12 cell viability and, indicating that the exposure of C2C12 cells to isorhamnetin conferred a protective effect against oxidative stress. Isorhamnetin also effectively attenuated H2O2-induced apoptosis and ROS generation, which was associated with the restoration of the upregulation of Bax and downregulation of Bcl-2 induced by H2O2. In addition, H2O2 enhanced the activation of caspase-9 and -3, and degradation of poly (ADP- ribose)-polymerase, a typical substrate protein of activated caspase-3; however, these events were almost totally reversed by pretreatment with isorhamnetin. Moreover, isorhamnetin increased the levels of heme oxygenase-1, a potent antioxidant enzyme, associated with the induction of Nrf2.

Conclusions: Our data indicated that isorhamnetin may potentially serve as an agent for the treatment and prevention of muscle disorders caused by oxidative stress.
KEYWORD
3-methylquercetin, Oxidative stress, Reactive oxygen species, Apoptosis, Nuclear factor erythroid 2-related factor 2/heme oxygenase-1
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