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

• Published in: Evidence-based complementary and alternative medicine Vol. 2013; no. 2013; pp. 1 - 17
• Main Authors: Kuo, Yueh-Hsiung, Wang, Sheng-Yang, Gokila Vani, M., Lin, Chin-Chung, Chiang, Shen-Shih, Mau, Jeng-Leun, Kumar, K. J. Senthil, Liao, Jiunn-Wang, Chien, Shih-Chang
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Puplishing Corporation 01.01.2013; Hindawi Publishing Corporation; Hindawi Limited
• Subjects: 1-Phosphatidylinositol 3-kinase; Activation; Animal tissues; Antioxidants; Apoptosis; Cell culture; Cell death; Cytochrome c; Cytotoxicity; Deoxyribonucleic acid; DNA; Enzymes; Free radicals; Hepatocytes; Immunocytochemistry; Inhibition; Kinases; Lipid peroxidation; Lipids; Liver; Liver diseases; Metabolism; Mice; Oxidative stress; Penicillin; Peroxidation; Phytochemicals; Poly(ADP-ribose) polymerase; Pretreatment; Secretion; Toxicology; Transcription activation
• ISSN: 1741-427X; 1741-4288
• DOI: 10.1155/2013/296082

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.