DOI QR코드

DOI QR Code

Isorhamnetin-3-O-galactoside Protects against CCl4-Induced Hepatic Injury in Mice

  • Kim, Dong-Wook (School of Pharmacy, Sungkyunkwan University) ;
  • Cho, Hong-Ik (School of Pharmacy, Sungkyunkwan University) ;
  • Kim, Kang-Min (School of Pharmacy, Sungkyunkwan University) ;
  • Kim, So-Jin (School of Pharmacy, Sungkyunkwan University) ;
  • Choi, Jae-Sue (Faculty of Food Science and Biotechnology, Pukyoung National University) ;
  • Kim, Yeong-Shik (College of Pharmacy, Seoul National University) ;
  • Lee, Sun-Mee (School of Pharmacy, Sungkyunkwan University)
  • Received : 2012.07.04
  • Accepted : 2012.07.16
  • Published : 2012.07.31

Abstract

This study was performed to examine the hepatoprotective effect of isorhamnetin-3-O-galactoside, a flavonoid glycoside isolated from Artemisia capillaris Thunberg (Compositae), against carbon tetrachloride ($CCl_4$)-induced hepatic injury. Mice were treated intraperitoneally with vehicle or isorhamnetin-3-O-galactoside (50, 100, and 200 mg/kg) 30 min before and 2 h after $CCl_4$ (20 ${\mu}l/kg$) injection. Serum aminotransferase activities and hepatic level of malondialdehyde were significantly higher after $CCl_4$ treatment, and these increases were attenuated by isorhamnetin-3-O-galactoside. $CCl_4$ markedly increased serum tumor necrosis factor-${\alpha}$ level, which was reduced by isorhamnetin-3-O-galactoside. The levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and heme oxygenase-1 (HO-1) protein and their mRNA expression levels were significantly increased after $CCl_4$ injection. The levels of HO-1 protein and mRNA expression levels were augmented by isorhamnetin-3-O-galactoside, while isorhamnetin-3-O-galactoside attenuated the increases in iNOS and COX-2 protein and mRNA expression levels. $CCl_4$ increased the level of phosphorylated c-Jun N-terminal kinase, extracellular signal-regulated kinase and p38, and isorhamnetin-3-O-galactoside reduced these increases. The nuclear translocation of nuclear factor kappa B (NF-${\kappa}B$), activating protein-1, and nuclear factor erythroid 2-related factor 2 (Nrf2) were significantly increased after $CCl_4$ administration. Isorhamnetin-3-O-galactoside attenuated the increases of NF-${\kappa}B$ and c-Jun nuclear translocation, while it augmented the nuclear level of Nrf2. These results suggest that isorhamnetin-3-O-galactoside ameliorates $CCl_4$-induced hepatic damage by enhancing the anti-oxidative defense system and reducing the inflammatory signaling pathways.

Keywords

Carbon tetrachloride;Heme oxygenase-1;Hepatotoxicity;Inflammation;Isorhamnetin-3-O-galactoside;Oxidative stress

Acknowledgement

Grant : Studies on the Identifi cation of Efficacy of Biologically Active Components from Oriental Herbal Medicines

Supported by : Korea Food and Drug Administration

References

  1. Badger, D. A., Sauer, J. M., Hoglen, N. C., Jolley, C. S. and Sipes, I. G. (1996) The role of infl ammatory cells and cytochrome P450 in the potentiation of CCl4-induced liver injury by a single dose of retinol. Toxicol. Appl. Pharmacol. 141, 507-519. https://doi.org/10.1006/taap.1996.0316
  2. Basu, S. (1999) Oxidative injury induced cyclooxygenase activation in experimental hepatotoxicity. Biochem. Biophys. Res. Commun. 254, 764-767. https://doi.org/10.1006/bbrc.1998.9956
  3. Brouckaert, P. and Fiers, W. (1996) Tumor necrosis factor and the systemic infl ammatory response syndrome. Curr. Top. Microbiol. Immunol. 216, 167-187. https://doi.org/10.1007/978-3-642-80186-0_8
  4. Buege, J. A. and Aust, S. D. (1978) Microsomal lipid peroxidation. Methods Enzymol. 52, 302-310. https://doi.org/10.1016/S0076-6879(78)52032-6
  5. Chang, H. M. and But, P. P. H. (1987) Pharmacology and applications of chinese materia medica. World Scientific, Singapore.
  6. Choi, J. H., Kim, D. W., Yun, N., Choi, J. S., Islam, M. N., Kim, Y. S. and Lee, S. M. (2011) Protective effects of hyperoside against carbon tetrachloride-induced liver damage in mice. J. Nat. Prod. 74, 1055-1060. https://doi.org/10.1021/np200001x
  7. Czaja, M. J. (2003) The future of GI and liver research: editorial perspectives. III. JNK/AP-1 regulation of hepatocyte death. Am. J. Physiol. Gastrointest. Liver Physiol. 284, G875-879. https://doi.org/10.1152/ajpgi.00549.2002
  8. DeCicco, L. A., Rikans, L. E., Tutor, C. G. and Hornbrook. K. R. (1998) Serum and liver concentrations of tumor necrosis factor alpha and interleukin-1beta following administration of carbon tetrachloride to male rats. Toxicol. Lett. 98, 115-121. https://doi.org/10.1016/S0378-4274(98)00110-6
  9. Han, K. H., Jeon, Y. J., Athukorala, Y., Choi, K. D., Kim, C. J., Cho, J. K., Sekikawa, M., Fukushima, M. and Lee, C. H. (2006) A water extract of Artemisia capillaris prevents 2,2'-azobis(2-amidinopropane) dihydrochloride-induced liver damage in rats. J. Med. Food 9, 342- 347. https://doi.org/10.1089/jmf.2006.9.342
  10. Hong, S. H., Seo, S. H., Lee, J. H. and Choi, B. T. (2004) The aqueous extract from Artemisia capillaris Thunb. inhibits lipopolysaccharideinduced infl ammatory response through preventing NF-kappaB activation in human hepatoma cell line and rat liver. Int. J. Mol. Med. 13, 717-720.
  11. Iida, C., Fujii, K., Kishioka, T., Nagae, R., Onishi, Y., Ichi, I. and Kojo, S. (2007) Activation of mitogen activated protein kinase (MAPK) during carbon tetrachloride intoxication in the rat liver. Arch. Toxicol. 81, 489-493. https://doi.org/10.1007/s00204-007-0181-x
  12. Kim, H. Y., Kim, J. K., Choi, J. H., Jung, J. Y., Oh, W. Y., Kim, D. C., Lee, H. S., Kim, Y. S., Kang, S. S., Lee, S. H. and Lee, S. M. (2010) Hepatoprotective effect of pinoresinol on carbon tetrachloride-induced hepatic damage in mice. J. Pharmacol. Sci. 112, 105-112. https://doi.org/10.1254/jphs.09234FP
  13. Kobayashi, M. and Yamamoto, M. (2006) Nrf2-Keap1 regulation of cellular defense mechanisms against electrophiles and reactive oxygen species. Adv. Enzyme. Regul. 46, 113-140. https://doi.org/10.1016/j.advenzreg.2006.01.007
  14. Koo, H. N., Hong, S. H., Jeong, H. J., Lee, E. H., Kim, N. G., Choi, S. D., Ra, K. W., Kim, K. S., Kang, B. K., Kim, J. J., Oh, J. G. and Kim, H. M. (2002) Inhibitory effect of Artemisia capillaris on ethanol-induced cytokines (TNF-alpha, IL-1alpha) secretion in Hep G2 cells. Immunopharmacol. Immunotoxicol. 24, 441-453. https://doi.org/10.1081/IPH-120014728
  15. Kwon, O. S., Choi, J. S., Islam, M. N., Kim, Y. S. and Kim, H. P. (2011) Inhibition of 5-lipoxygenase and skin infl ammation by the aerial parts of Artemisia capillaris and its constituents. Arch. Pharm. Res. 34, 1561-1569. https://doi.org/10.1007/s12272-011-0919-0
  16. Lee, C. H., Park, S. W., Kim, Y. S., Kang, S. S., Kim, J. A., Lee, S. H. and Lee, S. M. (2007) Protective mechanism of glycyrrhizin on acute liver injury induced by carbon tetrachloride in mice. Biol. Pharm. Bull. 30, 1898-1904. https://doi.org/10.1248/bpb.30.1898
  17. Manibusan, M. K., Odin, M. and Eastmond, D. A. (2007) Postulated carbon tetrachloride mode of action: a review. J. Environ. Sci. Health C Environ. Carcinog. Ecotoxicol. Rev. 25, 185-209. https://doi.org/10.1080/10590500701569398
  18. Morio, L. A., Chiu, H., Sprowles, K. A., Zhou, P., Heck, D. E., Gordon, M. K. and Laskin, D. L. (2001) Distinct roles of tumor necrosis factor-alpha and nitric oxide in acute liver injury induced by carbon tetrachloride in mice. Toxicol. Appl. Pharmacol. 172, 44-51. https://doi.org/10.1006/taap.2000.9133
  19. Otterbein, L. E. and Choi, A. M. (2000) Heme oxygenase: colors of defense against cellular stress. Am. J. Physiol. Lung Cell Mol. Physiol. 279, L1029-1037. https://doi.org/10.1152/ajplung.2000.279.6.L1029
  20. Planaguma, A., Claria, J., Miquel, R., Lopez-Parra, M., Titos, E., Masferrer, J. L., Arroyo, V. and Rodes, J. (2005) The selective cyclooxygenase- 2 inhibitor SC-236 reduces liver fi brosis by mechanisms involving non-parenchymal cell apoptosis and PPARgamma activation. FASEB J. 19, 1120-1122. https://doi.org/10.1096/fj.04-2753fje
  21. Rodenas, J., Mitjavila, M. T. and Carbonell, T. (1995) Simultaneous generation of nitric oxide and superoxide by infl ammatory cells in rats. Free Radic. Biol. Med. 18, 869-875. https://doi.org/10.1016/0891-5849(94)00215-6
  22. Ryter, S. W., Morse, D. and Choi, A. M. (2007) Carbon monoxide and bilirubin: potential therapies for pulmonary/vascular injury and disease. Am. J. Respir. Cell Mol. Biol. 36, 175-182. https://doi.org/10.1165/rcmb.2006-0333TR
  23. Seeff, L. B., Lindsay, K. L., Bacon, B. R., Kresina, T. F. and Hoofnagle, J. H. (2001) Complementary and alternative medicine in chronic liver disease. Hepatology 34, 595-603. https://doi.org/10.1053/jhep.2001.27445
  24. Taieb, D., Malicet, C., Garcia, S., Rocchi, P., Arnaud, C., Dagorn, J. C., Iovanna. J. L. and Vasseur, S. (2005) Inactivation of stress protein p8 increases murine carbon tetrachloride hepatotoxicity via preserved CYP2E1 activity. Hepatology 42, 176-182.
  25. Taniguchi, M., Takeuchi, T., Nakatsuka, R., Watanabe, T. and Sato, K. (2004) Molecular process in acute liver injury and regeneration induced by carbon tetrachloride. Life Sci. 75, 1539-1549. https://doi.org/10.1016/j.lfs.2004.02.030

Cited by

  1. NLRP3 inflammasome activation in d- galactosamine and lipopolysaccharide-induced acute liver failure: Role of heme oxygenase-1 vol.65, 2013, https://doi.org/10.1016/j.freeradbiomed.2013.08.178
  2. Molecular mechanism and therapeutic modulation of high mobility group box 1 release and action: an updated review vol.10, pp.6, 2014, https://doi.org/10.1586/1744666X.2014.909730
  3. Recent Studies and Progression of Yin Chen Hao (茵陳蒿 Yīn Chén Hāo), a Long-term Used Traditional Chinese Medicine vol.3, pp.1, 2013, https://doi.org/10.4103/2225-4110.106533
  4. Protective Mechanisms of Acacetin againstd-Galactosamine and Lipopolysaccharide-Induced Fulminant Hepatic Failure in Mice vol.77, pp.11, 2014, https://doi.org/10.1021/np500537x
  5. Impaired autophagy contributes to hepatocellular damage during ischemia/reperfusion: Heme oxygenase-1 as a possible regulator vol.68, 2014, https://doi.org/10.1016/j.freeradbiomed.2013.12.014
  6. Effects of C-Glycosides from Apios americana Leaves against Oxidative Stress during Hyperglycemia through Regulating Mitogen-Activated Protein Kinases and Nuclear Factor Erythroid 2-Related Factor 2 vol.65, pp.34, 2017, https://doi.org/10.1021/acs.jafc.7b03163
  7. β-Caryophyllene alleviates d-galactosamine and lipopolysaccharide-induced hepatic injury through suppression of the TLR4 and RAGE signaling pathways vol.764, 2015, https://doi.org/10.1016/j.ejphar.2015.08.001
  8. Activation of protein kinase C delta reduces hepatocellular damage in ischemic preconditioned rat liver vol.185, pp.2, 2013, https://doi.org/10.1016/j.jss.2013.07.005
  9. Novel Mechanisms of Herbal Therapies for Inhibiting HMGB1 Secretion or Action vol.2015, 2015, https://doi.org/10.1155/2015/456305
  10. Protective Mechanism of Anethole on Hepatic Ischemia/Reperfusion Injury in Mice vol.76, pp.9, 2013, https://doi.org/10.1021/np4004323
  11. The Potential and Action Mechanism of Polyphenols in the Treatment of Liver Diseases vol.2018, pp.1942-0994, 2018, https://doi.org/10.1155/2018/8394818
  12. Protective effects of dietary kaempferol glycoside components from unripe soybean (Edamame, Glycine max L. Merrill. ‘Jindai’) leaves and their serous metabolite on carbon tetrachloride-induced liver injury mice vol.55, pp.11, 2018, https://doi.org/10.1007/s13197-018-3385-6