Antcin C from Antrodia cinnamomea Protects Liver Cells Against Free Radical-Induced Oxidative Stress and Apoptosis In Vitro and In Vivo through Nrf2-Dependent Mechanism

M Gokila Vani; K J Senthil Kumar; Jiunn-Wang Liao; Shih-Chang Chien; Jeng-Leun Mau; Shen-Shih Chiang; Chin-Chung Lin; Yueh-Hsiung Kuo; Sheng-Yang Wang

doi:10.1155/2013/296082

Antcin C from Antrodia cinnamomea Protects Liver Cells Against Free Radical-Induced Oxidative Stress and Apoptosis In Vitro and In Vivo through Nrf2-Dependent Mechanism

Evid Based Complement Alternat Med. 2013:2013:296082. doi: 10.1155/2013/296082. Epub 2013 Dec 11.

Authors

M Gokila Vani¹, K J Senthil Kumar², Jiunn-Wang Liao³, Shih-Chang Chien⁴, Jeng-Leun Mau⁵, Shen-Shih Chiang⁵, Chin-Chung Lin⁶, Yueh-Hsiung Kuo⁷, Sheng-Yang Wang⁸

Affiliations

¹ Department of Forestry, National Chung Hsing University, Taichung 402, Taiwan.
² Department of Cosmeceutics, China Medical University, Taichung 40402, Taiwan.
³ Graduate Institute of Veterinary Pathology, National Chung Hsing University, Taichung 402, Taiwan.
⁴ The Experimental Forest Management Office, National Chung-Hsing University, Taichung 402, Taiwan.
⁵ Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 402, Taiwan.
⁶ Taiwan Leader Biotech Company, Taipei 24747, Taiwan.
⁷ Graduate Institute of Chinese Pharmaceutical Science, China Medical University, Taichung 40402, Taiwan ; Department of Biotechnology, Asia University, Taichung 41354, Taiwan.
⁸ Department of Forestry, National Chung Hsing University, Taichung 402, Taiwan ; Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan.

Abstract

In this study, we investigated the cytoprotective effects of antcin C, a steroid-like compound isolated from Antrodia cinnamaomea against AAPH-induced oxidative stress and apoptosis in human hepatic HepG2 cells. Pretreatment with antcin C significantly protects hepatic cells from AAPH-induced cell death through the inhibition of ROS generation. Furthermore, AAPH-induced lipid peroxidation, ALT/AST secretion and GSH depletion was significantly inhibited by antcin C. The antioxidant potential of antcin C was correlated with induction of antioxidant genes including, HO-1, NQO-1, γ -GCLC, and SOD via transcriptional activation of Nrf2. The Nrf2 activation by antcin C is mediated by JNK1/2 and PI3K activation, whereas pharmacologic inhibition of JNK1/2 and PI3K abolished antcin C-induced Nrf2 activity. In addition, AAPH-induced apoptosis was significantly inhibited by antcin C through the down-regulation of pro-apoptotic factors including, Bax, cytochrome c, capase 9, -4, -12, -3, and PARP. In vivo studies also show that antcin C significantly protected mice liver from AAPH-induced hepatic injury as evidenced by reduction in hepatic enzymes in circulation. Further, immunocytochemistry analyses showed that antcin C significantly increased HO-1 and Nrf2 expression in mice liver tissues. These results strongly suggest that antcin C could protect liver cells from oxidative stress and cell death via Nrf2/ARE activation.