Improvement of Oxidative Stress-induced Cytotoxicity of Angelica keiskei (Miq.) Koidz. Leaves Extract through Activation of Heme Oxygenase-1 in C2C12 Murine Myoblasts

다국어 초록 (Multilingual Abstract)

Angelica keiskei, (Miq.) Koidz. has been traditionally used as a food and medicinal resource in Asia including Korea. Although extracts or components of this plant are known to possess various pharmacological activities, studies on their antioxidant activity are still lacking. In this study, we evaluated whether an ethanol extract of A. keiskei leaves (AK) can protect oxidative damage by in C2C12 murine myoblasts. For this purpose, we exposed C2C12 cells to hydrogen peroxide (H 2 O 2 ) to mimic oxidative stress and evaluated the effects of AK on H 2 O 2 -induced cell survival inhibition, reactive oxygen species (ROS) generation, DNA damage, mitochondrial dysfunction and apoptosis. Our results showed that AK could inhibit H 2 O 2 -induced cytotoxicity and DNA damage while blocking the generation of ROS. AK also protected C2C12 cells from induction of apoptosis associated with mitochondrial impairment caused by H 2 O 2 treatment. In addition, AK enhanced the activity and expression of heme oxygenase-1 (HO-1) as well as phosphorylation of nuclear factor-erythroid-2 related factor 2 (Nrf2) in H 2 O 2 -treaetd C2C12 myoblasts, suggesting that AK acted as an Nrf2 activator. However, the ROS scavenging ability of AK and its protective effect on H 2 O 2 -induced oxidative damage were largely abolished by the HO-1 inhibitor, indicating that AK could increase Nrf2-mediated activity of HO-1 to protect C2C12 myoblasts from oxidative stress. Taken together, our findings demonstrate that AK may be promising for the treatment of oxidative damage-mediated muscle diseases in the future.

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