title: The therapeutic detoxification of chlorogenic acid against acetaminophen-induced liver injury by ameliorating hepatic inflammation.
abstract: Chlorogenic acid (CGA) has been reported to prevent acetaminophen (AP)-induced hepatotoxicity when mice were pre-administered orally with CGA for consecutive 7days before AP intoxication in our previous study. This study investigated the therapeutic detoxification of CGA against AP-induced hepatotoxicity and the engaged mechanism. The mice were orally administered with CGA (10, 20, 40mg/kg) at 1h after given AP (400mg/kg), and another 3h later the mice were killed for the following experiments. Results of serum transaminases analysis and histological evaluation demonstrated the detoxification of CGA against AP-induced hepatotoxicity. CGA reduced AP-induced the increased myeloperoxidase (MPO) enzymatic activity and its expression. CGA reduced AP-induced the increased liver expression of toll-like receptor (TLR)-3/4 and MyD88, and the increased phosphorylation of inhibitor of kappa B (IκB) and p65 subunit of nuclear factor κB (NFκB). CGA reduced AP-induced the increased NFκBp65 expression in nucleus. In addition, CGA reduced AP-induced the increased serum levels and liver mRNA expression of tumor necrosis factor alpha (TNFα), interleukin (IL)-1β, IL-6, monocyte chemoattractant protein-1 (MCP-1), and keratinocyte chemoattractant (KC). Taken together, our results demonstrate the therapeutic detoxification of CGA against AP-induced liver injury, and TLR3/4 and NFκB signaling pathway are involved in such process.
authors.affiliation: The Shanghai Key Laboratory of Complex Prescription, The MOE Key Laboratory for Standardization of Chinese Medicines, and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Center for Drug Safety Evaluation and Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: The Shanghai Key Laboratory of Complex Prescription, The MOE Key Laboratory for Standardization of Chinese Medicines, and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Lu
authors.affiliation: The Shanghai Key Laboratory of Complex Prescription, The MOE Key Laboratory for Standardization of Chinese Medicines, and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: lichenyue1307@126.com.
authors.forename: Lili
authors.initials: L
authors.lastname: Ji
mesh_terms: D000082:Acetaminophen / Q000633:toxicity; D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000517:prevention & control*; D002726:Chlorogenic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation; D008099:Liver / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D016207:Cytokines; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; C519703:TLR3 protein, mouse; C493487:Tlr4 protein, mouse; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D002726:Chlorogenic Acid; D000082:Acetaminophen; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D051550:I-kappa B Kinase
keywords: Acetaminophen; Chlorogenic acid; Detoxification; Hepatic inflammation; NFκB; TLR3/4