title: Chlorogenic acid prevents acetaminophen-induced liver injury: the involvement of CYP450 metabolic enzymes and some antioxidant signals.
abstract: Chlorogenic acid (CGA), a polyphenolic compound, is abundant in fruits, dietary vegetables, and some medicinal herbs. This study investigated the prevention of CGA against acetaminophen (AP)-induced hepatotoxicity and its engaged mechanisms. CGA reversed the decreased cell viability induced by AP in L-02 cells in vitro. In addition, CGA reduced the AP-induced increased serum levels of alanine/aspartate aminotransferase (ALT/AST) in vivo. The effect of CGA on cytochrome P450 (CYP) enzymatic (CYP2E1, CYP1A2, and CYP3A4) activities showed that CGA caused very little inhibition on CYP2E1 and CYP1A2 enzymatic activities, but not CYP3A4. The measurement of liver malondialdehyde (MDA), reactive oxygen species (ROS), and glutathione (GSH) levels showed that CGA prevented AP-induced liver oxidative stress injury. Further, CGA increased the AP-induced decreased mRNA expression of peroxiredoxin (Prx) 1, 2, 3, 5, 6, epoxide hydrolase (Ephx) 2, and polymerase (RNA) II (DNA directed) polypeptide K (Polr2k), and nuclear factor erythroid-2-related factor 2 (Nrf2). In summary, CGA ameliorates the AP-induced liver injury probably by slightly inhibiting CYP2E1 and CYP1A2 enzymatic properties. In addition, cellular important antioxidant signals such as Prx1, 2, 3, 5, 6, Ephx2, Polr2k, and Nrf2 also contributed to the protection of CGA against AP-induced oxidative stress injury.
authors.affiliation: Shanghai Key Laboratory of Complex Prescription, the MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Center for Traditional Chinese Medicine and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Center for Drug Safety Evaluation and Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Pang
authors.forename: Yu-chen
authors.initials: YC
authors.lastname: Sheng
authors.forename: Ping
authors.initials: P
authors.lastname: Jiang
authors.forename: Hai
authors.initials: H
authors.lastname: Wei
authors.forename: Li-li
authors.initials: LL
authors.lastname: Ji
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D018712:Analgesics, Non-Narcotic / Q000506:poisoning; D000975:Antioxidants / Q000378:metabolism; D002460:Cell Line; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D002726:Chlorogenic Acid / Q000008:administration & dosage*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D018712:Analgesics, Non-Narcotic; D000975:Antioxidants; D017382:Reactive Oxygen Species; D002726:Chlorogenic Acid; D000082:Acetaminophen; D003577:Cytochrome P-450 Enzyme System
keywords: Acetaminophen; CYP450; Chlorogenic acid; Oxidative stress injury