title: Fruiting Bodies of Antrodia cinnamomea and Its Active Triterpenoid, Antcin K, Ameliorates N-Nitrosodiethylamine-Induced Hepatic Inflammation, Fibrosis and Carcinogenesis in Rats.
abstract: Antrodia cinnamomea (A. cinnamomea), a popular medicinal mushroom in Taiwan, is widely used to prevent or treat liver diseases. Systematic studies on the anti-inflammatory effect of A. cinnamomea and its molecular mechanisms have not yet been fully investigated. HPLC fingerprint analysis identified seven ergostane-type triterpenoids from A. cinnamomea water extract (ACW), including high amounts of Antcin K (AC), Antcin C, Antcin H, Dehydrosulphurenic acid, Antcin B, Antcin A and Dehydroeburicoic acid. Here, we explored the effects and mechanisms of ACW and the highest content AC on N-nitrosodiethylamine (DEN) induced liver inflammation, fibrosis and carcinogenesis in rats. In the in vitro study, we measured how ACW and AC dose-dependently scavenged O[Formula: see text], H2O2and HOCl by a chemiluminescence analyzer. In the in vivo experiment, oral intake ACW and AC significantly inhibited DEN-enhanced hepatocellular inflammation, fibrosis and carcinoma by pathologic observation, the elevated bile and liver reactive oxygen species (ROS) amounts, plasma [Formula: see text]-glutamyl transpeptidase, and oxidative stress including 3-nitrotyrosine, 4-hydroxynonenal and Kuppfer cell infiltration (ED-1 stains) in the inflammatory livers. DEN enhanced nuclear factor-[Formula: see text]B (NF-[Formula: see text]B) translocation, whereas ACW and AC suppressed DEN-enhanced NF-[Formula: see text]B translocation through the inhibition of its upstream signaling of p85/phosphoinositide-3-kinase, mitogen activated protein kinase and CYP2E1 expression. In conclusion, DEN can induce hepatocellular inflammation, fibrosis and carcinoma by increasing NF-[Formula: see text]B translocation to the nucleus, and oxidative injury. ACW and its active component, Antcin K, counteract DEN-induced hepatic injury and inflammation by the protective and therapeutic mechanisms of a direct scavenging ROS activity and an upregulation of anti-oxidant defense mechanisms.
authors.affiliation: * Department of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan, R.O.C.
authors.forename: An-Jan
authors.initials: AJ
authors.lastname: Tien
authors.affiliation: † Department of Surgery, Mackay Memorial Hospital and Mackay Medical College, Taipei 10449, Taiwan, R.O.C.|‡ Mackay Junior College of Medicine, Nursing and Management, New Taipei City 252, Taiwan, R.O.C.
authors.forename: Chen-Yen
authors.initials: CY
authors.lastname: Chien
authors.affiliation: * Department of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan, R.O.C.
authors.forename: Yueh-Hsi
authors.initials: YH
authors.lastname: Chen
authors.affiliation: § Department of Internal Medicine, Kuang-Tien General Hospital, Taichung City 433, Taiwan, R.O.C.
authors.forename: Lung-Chin
authors.initials: LC
authors.lastname: Lin
authors.affiliation: * Department of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan, R.O.C.
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chien
mesh_terms: D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D055491:Antrodia; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D063646:Carcinogenesis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000517:prevention & control*; D002782:Cholestenes / Q000494:pharmacology*; D004052:Diethylnitrosamine / Q000633:toxicity; D048690:Fruiting Bodies, Fungal; D006505:Hepatitis / Q000209:etiology / Q000517:prevention & control*; D006861:Hydrogen Peroxide / Q000378:metabolism; D006997:Hypochlorous Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000517:prevention & control*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000187:drug effects / Q000378:metabolism
chemical_list: D000477:Alkylating Agents; D002782:Cholestenes; D017382:Reactive Oxygen Species; C000602429:antcin K; D013481:Superoxides; D004052:Diethylnitrosamine; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D005723:gamma-Glutamyltransferase
keywords: Antcin K; Antrodia cinnamomea; Fibrosis; Hepatic Inflammation; Hepatocarcinogenesis; N-Nitrosodiethylamine; Reactive Oxygen Species