Acanthoic acid, a diterpene in Acanthopanax koreanum, protects acetaminophen-induced hepatic toxicity in mice

作者: Yan-Ling Wu , Ying-Zi Jiang , Xue-Jun Jin , Li-Hua Lian , Juan-Yu Piao

DOI: 10.1016/J.PHYMED.2009.07.011

关键词:

摘要: Abstract The protective effect of a diterpenoid acanthoic acid (AA) isolated from Acanthopanax koreanum Nakai was investigated in acetaminophen (APAP)-induced hepatic toxicity. Drug-induced hepatotoxicity induced by an intraperitoneal (i.p.) injection 300 mg/kg (sub-lethal dose) APAP. Pretreatment with AA (50 and 100 mg/kg) orally 2 h before the APAP administration attenuated APAP-induced acute increase serum aspartate aminotransferase (AST), alanine (ALT) activites, replenished depleted glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), peroxidase (GSH-Px) activities, decreased malondialdehyde (MDA) level considerably reduced histopathological alterations manner similar to silymarin (Sily). Immunohistochemical analyses also demonstrated that could reduce appearance necrosis regions as well caspase-3 hypoxia inducible factor-1α (HIF-1α) expression liver tissue. Our results indicated protected tissue oxidative stress elicites damage suggestes protection mechanism would relate antioxidation factor on hepatotoxicity.

参考文章(10)
J A Hinson, D W Potter, Reactions of N-acetyl-p-benzoquinone imine with reduced glutathione, acetaminophen, and NADPH. Molecular Pharmacology. ,vol. 30, pp. 33- 41 ,(1986)
Yan-Ling Wu, Dong-Ming Piao, Xue-Hua Han, Ji-Xing Nan, Protective effects of salidroside against acetaminophen-induced toxicity in mice. Biological & Pharmaceutical Bulletin. ,vol. 31, pp. 1523- 1529 ,(2008) , 10.1248/BPB.31.1523
Ji-Xing Nan, Xue-Jun Jin, Li-Hua Lian, Xing Fu Cai, Ying-Zi Jiang, Hong Ri Jin, Jung Joon Lee, A Diterpenoid Acanthoic Acid from Acanthopanax koreanum Protects against D-Galactosamine/Lipopolysaccharide-Induced Fulminant Hepatic Failure in Mice Biological & Pharmaceutical Bulletin. ,vol. 31, pp. 738- 742 ,(2008) , 10.1248/BPB.31.738
Gregg L Semenza, Signal transduction to hypoxia-inducible factor 1. Biochemical Pharmacology. ,vol. 64, pp. 993- 998 ,(2002) , 10.1016/S0006-2952(02)01168-1
Young H Kim, Bo S Chung, Ushio Sankawa, None, Pimaradiene diterpenes from Acanthopanax koreanum. Journal of Natural Products. ,vol. 51, pp. 1080- 1083 ,(1988) , 10.1021/NP50060A005
Hyung-Sik Kang, Young-Ho Kim, Choong-Sik Lee, Jung-Joon Lee, Inpyo Choi, Kwang-Ho Pyun, None, Suppression of Interleukin-1 and Tumor Necrosis Factor-α Production by Acanthoic Acid, (−)-Pimara-9(11),15-dien-19-oic Acid, and Its Antifibrotic Effectsin Vivo Cellular Immunology. ,vol. 170, pp. 212- 221 ,(1996) , 10.1006/CIMM.1996.0154
Ning Gao, Bing-Hua Jiang, Stephen S. Leonard, Linda Corum, Zhuo Zhang, Jenny R. Roberts, Jim Antonini, Jenny Z. Zheng, Daniel C. Flynn, Vince Castranova, Xianglin Shi, p38 Signaling-mediated Hypoxia-inducible Factor 1α and Vascular Endothelial Growth Factor Induction by Cr(VI) in DU145 Human Prostate Carcinoma Cells Journal of Biological Chemistry. ,vol. 277, pp. 45041- 45048 ,(2002) , 10.1074/JBC.M202775200
Harmeet Malhi, Gregory J. Gores, John J. Lemasters, Apoptosis and necrosis in the liver: a tale of two deaths? Hepatology. ,vol. 43, ,(2006) , 10.1002/HEP.21062
Anne M. Larson, Julie Polson, Robert J. Fontana, Timothy J. Davern, Ezmina Lalani, Linda S. Hynan, Joan S. Reisch, Frank V. Schiødt, George Ostapowicz, A. Obaid Shakil, William M. Lee, , Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology. ,vol. 42, pp. 1364- 1372 ,(2005) , 10.1002/HEP.20948