title: 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.
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.
authors.affiliation: Department of Forestry, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: M
authors.initials: M
authors.lastname: Gokila Vani
authors.affiliation: Department of Cosmeceutics, China Medical University, Taichung 40402, Taiwan.
authors.forename: K J Senthil
authors.initials: KJ
authors.lastname: Kumar
authors.affiliation: Graduate Institute of Veterinary Pathology, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Jiunn-Wang
authors.initials: JW
authors.lastname: Liao
authors.affiliation: The Experimental Forest Management Office, National Chung-Hsing University, Taichung 402, Taiwan.
authors.forename: Shih-Chang
authors.initials: SC
authors.lastname: Chien
authors.affiliation: Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Jeng-Leun
authors.initials: JL
authors.lastname: Mau
authors.affiliation: Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Shen-Shih
authors.initials: SS
authors.lastname: Chiang
authors.affiliation: Taiwan Leader Biotech Company, Taipei 24747, Taiwan.
authors.forename: Chin-Chung
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Graduate Institute of Chinese Pharmaceutical Science, China Medical University, Taichung 40402, Taiwan ; Department of Biotechnology, Asia University, Taichung 41354, Taiwan.
authors.forename: Yueh-Hsiung
authors.initials: YH
authors.lastname: Kuo
authors.affiliation: Department of Forestry, National Chung Hsing University, Taichung 402, Taiwan ; Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Sheng-Yang
authors.initials: SY
authors.lastname: Wang