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http://dx.doi.org/10.4062/biomolther.2013.005

Protective Effects of Geniposide and Genipin against Hepatic Ischemia/Reperfusion Injury in Mice  

Kim, Joonki (Natural Medicine Center, Korea Institute of Science & Technology)
Kim, Hyo-Yeon (School of Pharmacy, Sungkyunkwan University)
Lee, Sun-Mee (School of Pharmacy, Sungkyunkwan University)
Publication Information
Biomolecules & Therapeutics / v.21, no.2, 2013 , pp. 132-137 More about this Journal
Abstract
Geniposide is an active product extracted from the gardenia fruit, and is one of the most widely used herbal preparations for liver disorders. This study examined the cytoprotective properties of geniposide and its metabolite, genipin, against hepatic ischemia/reperfusion (I/R) injury. C57BL/6 mice were subjected to 60 min of ischemia followed by 6 h of reperfusion. Geniposide (100 mg/kg) and genipin (50 mg/kg) were administered orally 30 min before ischemia. In the I/R mice, the levels of serum alanine aminotransferase and hepatic lipid peroxidation were elevated, whereas hepatic glutathione/glutathione disulfide ratio was decreased. These changes were attenuated by geniposide and genipin administration. On the other hand, increased hepatic heme oxygenase-1 protein expression was potentiated by geniposide and genipin administration. The increased levels of tBid, cytochrome c protein expression and caspase-3 activity were attenuated by geniposide and genipin. Increased apoptotic cells in the I/R mice were also significantly reduced by geniposide and genipin treatment. Our results suggest that geniposide and genipin offer significant hepatoprotection against I/R injury by reducing oxidative stress and apoptosis.
Keywords
Geniposide; Genipin; Ischemia; Reperfusion; Liver; Apoptosis;
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1 Yu, H. C., Qin, H. Y., He, F., Wang, L., Fu, W., Liu, D., Guo, F. C., Liang, L., Dou, K. F. and Han, H. (2011) Canonical Notch pathway protects hepatocytes from ischemia/reperfusion injury in mice by repressing reactive oxygen species production through JAK2/STAT3 signaling. Hepatology 54, 979-988.   DOI   ScienceOn
2 Yun, N., Eum, H. A. and Lee, S. M. (2010) Protective role of heme oxygenase-1 against liver damage caused by hepatic ischemia and reperfusion in rats. Antioxid. Redox Signal. 13, 1503-1512.   DOI   ScienceOn
3 Liu, J., Yin, F., Zheng, X., Jing, J. and Hu, Y. (2007) Geniposide, a novel agonist for GLP-1 receptor, prevents PC12 cells from oxidative damage via MAP kinase pathway. Neurochem. Int. 51, 361-369.   DOI   ScienceOn
4 Liu, J. H., Yin, F., Guo, L. X., Deng, X. H. and Hu, Y. H. (2009) Neuroprotection of geniposide against hydrogen peroxide induced PC12 cells injury: involvement of PI3 kinase signal pathway. Acta Pharmacol. Sin. 30, 159-165.   DOI   ScienceOn
5 Ma, T., Huang, C., Zong, G., Zha, D., Meng, X., Li, J. and Tang, W. (2011) Hepatoprotective effects of geniposide in a rat model of nonalcoholic steatohepatitis. J. Pharm. Pharmacol. 63, 587-593.   DOI   ScienceOn
6 Marubayashi, S., Dohi, K., Ochi, K. and Kawasaki, T. (1987) Protective effects of free radical scavenger and antioxidant administration on ischemic liver cell injury. Transplant. Proc. 19, 1327-1328.
7 Morin, D., Pires, F., Plin, C. and Tillement, J. P. (2004) Role of the permeability transition pore in cytochrome C release from mitochondria during ischemia-reperfusion in rat liver. Biochem. Pharmacol. 68, 2065-2073.   DOI   ScienceOn
8 Peng, C. H., Huang, C. N. and Wang, C. J. (2005) The anti-tumor effect and mechanisms of action of penta-acetyl geniposide. Curr. Cancer Drug Targets 5, 299-305.   DOI   ScienceOn
9 Sasaki, H., Matsuno, T., Ishikawa, T., Ishine, N., Sadamori, H., Yagi, T. and Tanaka, N. (1997) Activation of apoptosis during early phase of reperfusion after liver transplantation. Transplant. Proc. 29, 406-407.   DOI   ScienceOn
10 Shang, Y., Liu, Y., Du, L., Wang, Y., Cheng, X., Xiao, W., Wang, X., Jin, H., Yang, X., Liu, S. and Chen, Q. (2009) Targeted expression of uncoupling protein 2 to mouse liver increases the susceptibility to lipopolysaccharide/galactosamine-induced acute liver injury. Hepatology 50, 1204-1216.   DOI   ScienceOn
11 Suzuki, Y., Kondo, K., Ikeda, Y. and Umemura, K. (2001) Antithrombotic effect of geniposide and genipin in the mouse thrombosis model. Planta Med. 67, 807-810.   DOI   ScienceOn
12 Tietze, F. (1969) Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal. Biochem. 27, 502-522.   DOI   ScienceOn
13 Wei, M. C., Zong, W. X., Cheng, E. H., Lindsten, T., Panoutsakopoulou, V., Ross, A. J., Roth, K. A., MacGregor, G. R., Thompson, C. B. and Korsmeyer, S. J. (2001) Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292, 727-730.   DOI   ScienceOn
14 Xu, M., Sun, Q., Su, J., Wang, J., Xu, C., Zhang, T. and Sun, Q. (2008) Microbial transformation of geniposide in Gardenia jasminoides Ellis into genipin by Penicillium nigricans. Enzyme Microb. Technol. 42, 440-444.   DOI   ScienceOn
15 Yin, F., Liu, J., Zheng, X., Guo, L. and Xiao, H. (2010) Geniposide induces the expression of heme oxygenase-1 via PI3K/Nrf2-signaling to enhance the antioxidant capacity in primary hippocampal neurons. Biol. Pharm. Bull. 33, 1841-1846.   DOI   ScienceOn
16 Cursio, R., Gugenheim, J., Ricci, J. E., Crenesse, D., Rostagno, P., Maulon, L., Saint-Paul, M. C., Ferrua, B. and Auberger, A. P. (1999) A caspase inhibitor fully protects rats against lethal normothermic liver ischemia by inhibition of liver apoptosis. FASEB J. 13, 253-261.   DOI
17 Jaeschke, H. (2006) Mechanisms of liver injury. II. Mechanisms of neutrophil-induced liver cell injury during hepatic ischemia-reperfusion and other acute inflammatory conditions. Am. J. Physiol. Gastrointest. Liver Physiol. 290, G1083-1088.   DOI   ScienceOn
18 Eum, H. A., Cha, Y. N. and Lee, S. M. (2007) Necrosis and apoptosis: sequence of liver damage following reperfusion after 60 min ischemia in rats. Biochem. Biophys. Res. Commun. 358, 500-505.   DOI   ScienceOn
19 Green, D. R. and Reed, J. C. (1998) Mitochondria and apoptosis. Science 281, 1309-1312.   DOI   ScienceOn
20 Hong, H. Y. and Kim, B. C. (2007) Mixed lineage kinase 3 connects reactive oxygen species to c-Jun NH2-terminal kinase-induced mitochondrial apoptosis in genipin-treated PC3 human prostate cancer cells. Biochem. Biophys. Res. Commun. 362, 307-312.   DOI   ScienceOn
21 Kang, J. J., Wang, H. W., Liu, T. Y., Chen, Y. C. and Ueng, T. H. (1997) Modulation of cytochrome P-450-dependent monooxygenases, glutathione and glutathione S-transferase in rat liver by geniposide from Gardenia jasminoides. Food Chem. Toxicol. 35, 957-965.   DOI   ScienceOn
22 Khanal, T., Kim, H. G., Choi, J. H., Do, M. T., Kong, M. J., Kang, M. J., Noh, K., Yeo, H. K., Ahn, Y. T., Kang, W., Kim, D. H., Jeong, T. C. and Jeong, H. G. (2012) Biotransformation of geniposide by human intestinal microflora on cytotoxicity against HepG2 cells. Toxicol. Lett. 209, 246-254.   DOI   ScienceOn
23 Koo, H. J., Lee, S., Shin, K. H., Kim, B. C., Lim, C. J. and Park, E. H. (2004a) Geniposide, an anti-angiogenic compound from the fruits of Gardenia jasminoides. Planta Med. 70, 467-469.   DOI   ScienceOn
24 Koo, H. J., Lim, K. H., Jung, H. J. and Park, E. H. (2006) Anti-inflammatory evaluation of gardenia extract, geniposide and genipin. J. Ethnopharmacol. 103, 496-500.   DOI   ScienceOn
25 Liaw, J. and Chao, Y. C. (2001) Effect of in vitro and in vivo aerosolized treatment with geniposide on tracheal permeability in ovalbumin-induced guinea pigs. Eur. J. Pharmacol. 433, 115-121.   DOI   ScienceOn
26 Koo, H. J., Song, Y. S., Kim, H. J., Lee, Y. H., Hong, S. M., Kim, S. J., Kim, B. C., Jin, C., Lim, C. J. and Park, E. H. (2004b) Antiinflammatory effects of genipin, an active principle of gardenia. Eur. J. Pharmacol. 495, 201-208.   DOI   ScienceOn
27 Kuo, W. H., Wang, C. J., Young, S. C., Sun, Y. C., Chen, Y. J. and Chou, F. P. (2004) Differential induction of the expression of GST subunits by geniposide in rat hepatocytes. Pharmacology 70, 15-22.   DOI   ScienceOn
28 Lee, P., Lee, J., Choi, S. Y., Lee, S. E., Lee, S. and Son, D. (2006) Geniposide from Gardenia jasminoides attenuates neuronal cell death in oxygen and glucose deprivation-exposed rat hippocampal slice culture. Biol. Pharm. Bull. 29, 174-176.   DOI   ScienceOn
29 Akao, T., Kobashi, K. and Aburada, M. (1994) Enzymic studies on the animal and intestinal bacterial metabolism of geniposide. Biol. Pharm. Bull. 17, 1573-1576.   DOI   ScienceOn
30 Buege, J. A. and Aust, S. D. (1978) Microsomal lipid peroxidation. Methods Enzymol. 52, 302-310.   DOI