Induction of Nrf2 and Metallothionein as a Common Mechanism of Hepatoprotective Medicinal Herbs

American Journal of Chinese Medicine

Volumn 42, Issue 1, 2014, Pages 207-221

  Wu, Qin ^a   Zhang, Dan ^a   Tao, Na ^a   Zhu, Qiong Ni ^a   Jin, Tao ^a   Shi, Jing Shan ^a   Liu, Jie ^a,b  

^a ZUNYI MEDICAL UNIVERSITY   (China)

^b UNIVERSITY OF KANSAS MEDICAL CENTER   (United States)

Author keywords

CCl4Hepatotoxicity; D galactosamine; Metallothionein; Nrf2 Null Mice; Nrf2 Target Genes; Piper puberulum Extract (PPE)

Indexed keywords

ALANINE AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; CARBON TETRACHLORIDE; GALACTOSAMINE; LIVER PROTECTIVE AGENT; METALLOTHIONEIN; PARACETAMOL; PIPER PUBERULUM EXTRACT; PLANT EXTRACT; TRANSCRIPTION FACTOR NRF2; UNCLASSIFIED DRUG;

ADULT; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; CHINESE MEDICINE; CONTROLLED STUDY; DRUG EFFECT; ENZYME ACTIVITY; ENZYME BLOOD LEVEL; GENE EXPRESSION; GENE INDUCTION; GENE TARGETING; HISTOPATHOLOGY; LIVER; LIVER PROTECTION; LIVER TOXICITY; MALE; MOLECULAR MECHANICS; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; PIPER (PLANT); PIPER PUBERULUM; TOXIC HEPATITIS; TREATMENT DURATION;

ACETAMINOPHEN; ANIMALS; ANTIOXIDANTS; CARBON TETRACHLORIDE POISONING; DRUG-INDUCED LIVER INJURY; GALACTOSAMINE; GLUTAMATE-CYSTEINE LIGASE; HEME OXYGENASE-1; LIVER; MALE; METALLOTHIONEIN; MICE; MICE, INBRED STRAINS; MOLECULAR TARGETED THERAPY; NAD(P)H DEHYDROGENASE (QUINONE); NADP; NF-E2-RELATED FACTOR 2; OXIDATIVE STRESS; PHYTOTHERAPY; PIPER; PLANT EXTRACTS;

EID: 84893439238     PISSN: 0192415X     EISSN: None     Source Type: Journal    
DOI: 10.1142/S0192415X14500141     Document Type: Article

References (46)

1. Abdul-Hussain, S.K. and H.M. Mehendale. Studies on the age-dependent effects of galactosamine in primary rat hepatocyte cultures. Toxicol. Appl. Pharmacol. 107: 504-513, 1991.
2. Al-Dosari, M.S. In vitro and in vivo antioxidant activity of alfalfa (Medicago sativa L.) on carbon tetrachloride intoxicated rats. Am. J. Chin. Med. 40: 779-793, 2012.
3. Cho, B.O., H.W. Ryu, C.H. Jin, D.S. Choi, S.Y. Kang, D.S. Kim, M.W. Byun and I.Y. Jeong. Blackberry extract attenuates oxidative stress through up-regulation of Nrf2-dependent antioxidant enzymes in carbon tetrachloride-treated rats. J. Agric. Food Chem. 59: 11442-11448, 2011.
4. Das, J., J. Ghosh, A. Roy and P.C. Sil. Mangiferin exerts hepatoprotective activity against D-galactosamine induced acute toxicity and oxidative/nitrosative stress via Nrf2-NFB pathways. Toxicol. Appl. Pharmacol. 260: 35-47, 2012.
5. Davis, S.R., D.A. Samuelson and R.J. Cousins. Metallothionein expression protects against carbon tetrachloride-induced hepatotoxicity, but overexpression and dietary zinc supplementation provide no further protection in metallothionein transgenic and knockout mice. J. Nutr. 131: 215-222, 2001.
6. Hussain, K., Z. Ismail, A. Sadikun and P. Ibrahim. Standardization and in vivo antioxidant activity of ethanol extracts of fruit and leaf of Piper sarmentosum. Planta Med. 76: 418-425, 2010.
7. Jaeschke, H., C.D. Williams, M.R. McGill, Y. Xie and A. Ramachandran. Models of drug-induced liver injury for evaluation of phytotherapeutics and other natural products. Food Chem. Toxicol. 55: 279-289, 2013.
8. James, L.P., P.R. Mayeux and J.A. Hinson. Acetaminophen-induced hepatotoxicity. Drug Metab. Dispos. 31: 1499-1506, 2003.
9. Kang, J.W., S.J. Kim, H.Y. Kim, S.H. Cho, K.N. Kim, S.G. Lee and S.M. Lee. Protective effects of HV-P411 complex against D-galactosamine-induced hepatotoxicity in rats. Am. J. Chin. Med. 40: 467-480, 2012.
10. Kang, Y.J. Herbogenomics: from traditional Chinese medicine to novel therapeutics. Exp. Biol. Med. 233: 1059-1065, 2008.
11. Kensler, T.W., N. Wakabayashi and S. Biswal. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Ann. Rev. Pharmacol. Toxicol. 47: 89-116, 2007.
12. Keppler, D.O., J. Pausch and K. Decker. Selective uridine triphosphate deficiency induced by D-galactosamine in liver and reversed by pyrimidine nucleotide precursors. Effect on ribonucleic acid synthesis. J. Biol. Chem. 249: 211-216, 1974.
13. Kimura, T., N. Itoh, M. Takehara, I. Oguro, J.I. Ishizaki, T. Nakanishi and K. Tanaka. Sensitivity of metallothionein-null mice to LPS/D-galactosamine- induced lethality. Biochem. Biophys. Res. Commun. 280: 358-362, 2001.
14. Klaassen, C.D., J. Liu and S. Choudhuri. Metallothionein: an intracellular protein to protect against cadmium toxicity. Ann. Rev. Pharmacol. Toxicol. 39: 26-294, 1999.
15. Klaassen, C.D., and J. Liu. Induction of metallothionein as an adaptive mechanism affecting the magnitude and progression of toxicological injury. Environ. Health Perspect. 106: 297-300, 1998.
16. Klaassen, C.D. and S.A. Reisman. Nrf2 the rescue: effects of the antioxidative/electrophilic response on the liver. Toxicol. Appl. Pharmacol. 244: 57-65, 2010.
17. Kundu, R., S. Dasgupta, A. Biswas, A. Bhattacharya, B.C. Pal, D. Bandyopadhyay, S. Bhattacharya and S. Bhattacharya. Cajanus cajan Linn. (Leguminosae) prevents alcohol-induced rat liver damage and augments cytoprotective function. J. Ethnopharmacol. 118: 440-447, 2008.
18. Kuo, Y.C., N.S. Yang, C.J. Chou, L.C. Lin and W.J. Tsai. Regulation of cell proliferation, gene expression, production of cytokines, and cell cycle progression in primary human T lymphocytes by piperlactam S isolated from Piper kadsura. Mol. Pharmacol. 58: 1057-1066, 2000.
19. Li, M., X. Zhang, L. Cui, R. Yang, L. Wang, L. Liu and W. Du. The neuroprotection of oxymatrine in cerebral ischemia/reperfusion is related to nuclear factor erythroid 2-related factor 2 (Nrf 2)-mediated antioxidant response: role of Nrf2 and hemeoxygenase-1 expression. Biol. Pharm. Bull. 34: 595-601, 2011.
20. Lin, B.R., C.J. Yu, W.C. Chen, H.S. Lee, H.M. Chang, Y.C. Lee, C.T. Chien and C.F. Chen. Green tea extract supplement reduces D-galactosamine-induced acute liver injury by inhibition of apoptotic and proinflammatory signaling. J. Biomed. Sci. 25: 16-35, 2009.
21. Liu, J., Y. Liu and C.D. Klaassen. Protective effect of oleanolic acid against chemical-induced acute necrotic liver injury in mice. Zhong Guo Yao Li Xue Bao 16, 97-102, 1995.
22. Liu, J., Y. Liu, S.S. Habeebu and C.D Klaassen. Metallothionein (MT)-null mice are sensitive to cisplatin-induced hepatotoxicity. Toxicol. Appl. Pharmacol. 49: 24-31, 1988.
23. Liu, J., Y. Liu, D. Hartley, C.D. Klaassen, S.E. Shehin-Johnson, A. Lucas and S.D. Cohen. Metallothionein-I/II knockout mice are sensitive to acetaminophen-induced hepatotoxicity. J. Pharmacol. Exp. Ther. 289: 580-586, 1999.
24. Liu, J., Q. Wu, Y.F. Lu and J. Pi. New insights into generalized hepatoprotective effects of oleanolic acid: key roles of metallothionein and Nrf2 induction. Biochem. Pharmacol. 76: 922-928, 2008.
25. Liu, J., K.C. Wu, Y.F. Lu, E. Ekuase and C.D. Klaassen. NRF2 protection against liver injury produced by various hepatotoxicants. Oxidat. Med. Cell Longev. ID 305861, 2013.
26. Matsuda, H., K. Ninomiya, T. Morikawa, D. Yasuda, I. Yamaguchi and M. Yoshikawa. Hepatoprotective amide constituents from the fruit of Piper chaba: structural requirements, mode of action, and new amides. Bioorg. Med. Chem. 17: 7313-7323, 2009.
27. Oliver, J.R., S. Jiang and M.G. Cherian. Augmented hepatic injury followed by impaired regeneration in metallothionein-I/II knockout mice after treatment with thioacetamide. Toxicol. Appl. Pharmacol. 210: 190-199, 2006.
28. Pushpavalli, G., C. Veeramani and K.V. Pugalendi. Effect of Piper betle on plasma antioxidant status and lipid profile against D-galactosamine-induced hepatitis in rats. Redox. Report 14: 7-12, 2009.
29. Rajeswary, H., R. Vasuki, P. Samudram and A. Geetha. Hepatoprotective action of ethanolic extracts of Melia azedarach Linn. and Piper longum Linn and their combination on CCl4 induced hepatotoxicity in rats. Indian J. Exp. Biol. 49: 276-281, 2011.
30. Randle, L.E., C.E. Goldring, C.A. Benson, P.N. Metcalfe, N.R. Kitteringham, B.K. Park and D.P. Williams. Investigation of the effect of a panel of model hepatotoxins on the Nrf2-Keap1 defence response pathway in CD-1 mice. Toxicology 243: 249-260, 2008.
31. Reisman, S.A., L.M. Aleksunes and C.D. Klaassen. Oleanolic acid activates Nrf2 and protects from acetaminophen hepatotoxicity via Nrf2-dependent and Nrf 2-independent processes. Biochem. Pharmacol. 77: 1273-1282, 2009.
32. Ruttkay-Nedecky, B., L. Nejdl, J. Gumulec, O. Zitka, M. Masarik, T. Eckschlager, M. Stiborova, V. Adam and R. Kizek. The role of metallothionein in oxidative stress. Int. J. Mol. Sci. 14: 6044-6066, 2013.
33. Shi, Y., J. Sun, H. He, H. Guo and S. Zhang. Hepatoprotective effects of Ganoderma lucidum peptides against D-galactosamine-induced liver injury in mice. J. Ethnopharmacol. 117: 415-419, 2008.
34. Sun, S.M., N. Yu, J. Liu, Y.M. Song, S.P. Wang and Y.X. Feng. Comparative study of pharmacological effects of Piper family plants. Zhong Cao Yao 29: 677-679, 1998.
35. Suresh, V. and V.V. Asha. Preventive effect of ethanol extract of Phyllanthus rheedii Wight. on D-galactosamine induced hepatic damage in Wistar rats. J. Ethnopharmacol. 116: 447-453, 2008.
36. Wang, Q. and E.J. Zhang. Overview of pharmacologic research of Piper. J. Pharm. Pract. 24: 139-145, 2006.
37. Wang, X., C.X. Hai, X. Liang, S.X. Yu, W. Zhang and Y.L. Li. The protective effects of Acanthopanax senticosus Harms aqueous extracts against oxidative stress: role of Nrf2 and antioxidant enzymes. J. Ethnopharmacol. 127: 424-432, 2010.
38. Weber, L.W., M. Boll and A. Stampfl. Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit. Rev. Toxicol. 33: 105-136, 2003.
39. Wen, Z., Z. Wang, S. Wang, R. Ravula, L. Yang, J. Xu, C. Wang, Z. Zuo, M.S. Chow, L. Shi and Y. Huang. Discovery of molecular mechanisms of traditional Chinese medicinal formula Si-Wu-Tang using gene expression microarray and connectivity map. PLoS One 6: e18278, 2011.
40. Wills, P.J. and V.V. Asha. Protective effect of Lygodium flexuosum (L.) Sw. (Lygodiaceae) against D-galactosamine induced liver injury in rats. J. Ethnopharmacol. 108: 116-123, 2006.
41. Wu, K.C., J.J. Liu and C.D. Klaassen. Nrf2 activation prevents cadmium-induced acute liver injury. Toxicol. Appl. Pharmacol. 263: 14-20, 2012.
42. Wu, S., Y. Yue, H. Tian, Z. Li, X. Li, W. He and H. Ding. Carthamus red from Carthamus tinctorius L. exerts antioxidant and hepatoprotective effect against CCl4-induced liver damage in rats via the Nrf2 pathway. J. Ethnopharmacol. 148: 570-578, 2013.
43. Xie, Q., F.F. Guo and W. Zhou. Protective effects of cassia seed ethanol extract against carbon tetrachloride-induced liver injury in mice. Acta Biochim. Pol. 59, 265-270, 2012.
44. Zhang, S.X., K. Chen, X.J. Liu, D.C. Zhang, T.W. Tao-Wiedmann, S.L. Leu, A.T. McPhail and K.H. Lee. The isolation and structural elucidation of three new neolignans, piperulins A, B, and C, as platelet activating factor receptor antagonists from Piper puberulum. J. Nat. Prod. 58: 540-547, 1995.
45. Zhang, Y.K., R.L. Yeager, Y. Tanaka and C.D. Klaassen. Enhanced expression of Nrf2 in mice attenuates the fatty liver produced by a methionine-and choline-deficient diet. Toxicol. Appl. Pharmacol. 245: 326-334, 2010.
46. Zhou, L., S.D. Xu and JS. Yang. Research progress on alkaloids and lignans from Piper plants. Chin. Pharm. J. 37: 161-163, 2002.