title: ERK Signaling Pathway Plays a Key Role in Baicalin Protection Against Acetaminophen-Induced Liver Injury.
abstract: Acetaminophen (APAP) overdose causes hepatocytes necrosis and acute liver failure. Baicalin (BA), a major flavonoid of Scutellariae radix, has potent hepatoprotective properties in traditional medicine. In the present study, we investigated the protective effects of BA on a APAP-induced liver injury in a mouse model. The mice received an intraperitoneal hepatotoxic dose of APAP (300[Formula: see text]mg/kg) and after 30[Formula: see text]min, were treated with BA at concentrations of 0, 15, 30, or 60[Formula: see text]mg/kg. After 16[Formula: see text]h of treatment, the mice were sacrificed for further analysis. APAP administration significantly elevated the serum alanine transferase (ALT) enzyme levels and hepatic myeloperoxidase (MPO) activity when compared with control animals. Baicalin treatment significantly attenuated the elevation of liver ALT levels, as well as hepatic MPO activity in a dose- dependent manner (15-60[Formula: see text]mg/kg) in APAP-treated mice. The strongest beneficial effects of BA were seen at a dose of 30[Formula: see text]mg/kg. BA treatment at 30[Formula: see text]mg/kg after APAP overdose reduced elevated hepatic cytokine (TNF-[Formula: see text] and IL-6) levels, and macrophage recruitment around the area of hepatotoxicity in immunohistochemical staining. Significantly, BA treatment can also decrease hepatic phosphorylated extracellular signal-regulated kinase (ERK) expression, which is induced by APAP overdose. Our data suggests that baicalin treatment can effectively attenuate APAP-induced liver injury by down-regulating the ERK signaling pathway and its downstream effectors of inflammatory responses. These results support that baicalin is a potential hepatoprotective agent.
authors.affiliation: * Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|† College of Medicine, Chang Gung University, Taoyuan, Taiwan.|‡ Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chia-Chih
authors.initials: CC
authors.lastname: Liao
authors.affiliation: * Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|† College of Medicine, Chang Gung University, Taoyuan, Taiwan.|‡ Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Yuan-Ji
authors.initials: YJ
authors.lastname: Day
authors.affiliation: * Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|† College of Medicine, Chang Gung University, Taoyuan, Taiwan.|‡ Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Hung-Chen
authors.initials: HC
authors.lastname: Lee
authors.affiliation: * Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|† College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Jiin-Tarng
authors.initials: JT
authors.lastname: Liou
authors.affiliation: * Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|† College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: An-Hsun
authors.initials: AH
authors.lastname: Chou
authors.affiliation: * Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|† College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Fu-Chao
authors.initials: FC
authors.lastname: Liu
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000410:Alanine Transaminase / Q000187:drug effects / Q000378:metabolism; D018712:Analgesics, Non-Narcotic / Q000633:toxicity*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D062787:Drug Overdose; D005419:Flavonoids / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D009195:Peroxidase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
chemical_list: D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005419:Flavonoids; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; C038044:baicalin; D000082:Acetaminophen; D009195:Peroxidase; D000410:Alanine Transaminase
keywords: Acetaminophen; Baicalin; ERK/JNK MAPK; Inflammation; Liver Injury