Publisher : The Korean Society of Food Science and Nutrition
DOI : 10.3746/jkfn.2016.45.3.307
Title & Authors
Effects of Oleanolic Acid and Hederagenin on Acute Alcohol-Induced Hepatotoxicity in Mice Jung, Suhan; Lee, Sanghoon; Ko, Kwang Suk;
We studied the effects of oleanolic acid and hederagenin on acute alcohol-induced hepatotoxicity in mice. Oleanolic acid [10 and 20 mg/kg body weight (BW)/d] or hederagenin (10 and 20 mg/kg BW/d) was orally administered to the study group for 1 week. On the last day of treatment, ethanol (5 g/kg BW) was orally administered to induce acute liver injury. The oleanolic acid-treated group showed lower levels of alanine aminotransferase compared to the ethanol-treated group (EtOH). The mRNA expression level of alcohol dehydrogenase was significantly increased in the high dosage oleanolic acid-treated group compared with the control and EtOH groups. The glutathione levels of the oleanolic acid or hederagenin-treated groups were elevated significantly compared with those of the control and EtOH groups. The mRNA expression levels of glutathione synthetic enzymes were also elevated in the oleanolic acid-treated groups. The oleanolic acid or hederagenin-treated groups also showed lower levels of mRNA expression of tumor necrosis factor alpha. Thus, these results show that oleanolic acid and hederagenin could reduce oxidative stress and hepatotoxicity in ethanol-treated mouse liver.
Ramchandani VA, Bosron WF, Li TK. 2001. Research advances in ethanol metabolism. Pathol Biol 49: 676-682.
Rouach H, Clement M, Orfanelli MT, Janvier B, Nordmann J, Nordmann R. 1983. Hepatic lipid peroxidation and mitochondrial susceptibility to peroxidative attacks during ethanol inhalation and withdrawal. Biochim Biophys Acta 753: 439-444.
Ohshima H, Tazawa H, Sylla BS, Sawa T. 2005. Prevention of human cancer by modulation of chronic inflammatory processes. Mutat Res 591: 110-122.
Choi J, Jung HJ, Lee KT, Park HJ. 2005. Antinociceptive and anti-inflammatory effects of the saponin and sapogenins obtained from the stem of Akebia quinata. J Med Food 8: 78-85.
Jung HJ, Lee CO, Lee KT, Choi J, Park HJ. 2004. Structure- activity relationship of oleanane disaccharides isolated from Akebia quinata versus cytotoxicity against cancer cells and NO inhibition. Biol Pharm Bull 27: 744-747.
Ikuta A. 1995. Saponins and triterpenes from callus tissues of Akebia trifoliate and comparison with the constituents of other lardizabalaceous callus tissues. J Nat Prod 58: 1378-1383.
Higuchi R, Kawasaki T. 1976. Pericarp saponins of Akebia quinata DECNE. I. Glycosides of hederagenin and oleanolic acid. Chem Pharm Bull 24: 1021-1032.
Ikuta A, Itokawa H. 1988. A triterpene from Akebia quinata callus tissue. Phytochemistry 27: 3809-3810.
Liu J. 1995. Pharmacology of oleanolic acid and ursolic acid. J Ethnopharmacol 49: 57-68.
Hung CY, Yen GC. 2001. Extraction and identification of antioxidative components of Hsian-tsao (Mesona procumbens Hemsl.). LWT-Food Sci Technol 34: 306-311.
Kinjo J, Okawa M, Udayama M, Sohno Y, Hirakawa T, Shii Y, Nohara T. 1999. Hepatoprotective and hepatotoxic actions of oleanolic acid-type triterpenoidal glucuronides on rat primary hepatocyte cultures. Chem Pharm Bull 47: 290-292.
Lee SH, Song YS, Lee SY, Kim SY, Ko KS. 2014. Protective effects of Akebia quinata fruit extract on acute alcohol-induced hepatotoxicity in mice. Korean J Food Sci Technol 46: 622-629.
Chai J, Du X, Chen S, Feng X, Cheng Y, Zhang L, Gao Y, Li S, He X, Wang R, Zhou X, Yang Y, Luo W, Chen W. 2015. Oral administration of oleanolic acid, isolated from Swertia mussotii Franch, attenuates liver injury, inflammation, and cholestasis in bile duct-ligated rats. Int J Clin Exp Med 8: 1691-1702.
Lu SH, Guan JH, Huang YL, Pan YW, Yang W, Lan H, Huang S, Hu J, Zhao GP. 2015. Experimental study of antiatherosclerosis effects with hederagenin in rats. J Evidence- Based Complementary Altern Med 504: 456354.
Letteron P, Fromenty B, Terris B, Degott C, Pessayre D. 1996. Acute and chronic hepatic steatosis lead to in vivo lipid peroxidation in mice. J Hepatol 24: 200-208.
Balanehru S, Nagarajan B. 1991. Protective effect of oleanolic acid and ursolic acid against lipid peroxidation. Biochem Int 24: 981-990.
Hoog JO, Ostberg LJ. 2011. Mammalian alcohol dehydrogenases- A comparative investigation at gene and protein levels. Chem Biol Interact 191: 2-7.
Mansouri A, Demeilliers C, Amsellem S, Pessayre D, Fromenty B. 2001. Acute ethanol administration oxidatively damages and depletes mitochondrial DNA in mouse liver, brain, heart, and skeletal muscles: protective effects of antioxidants. J Pharmacol Exp Ther 298: 737-743.
Ko K, Yang H, Noureddin M, Iglesia-Ara A, Xia M, Wagner C, Luka Z, Mato JM, Lu SC. 2008. Changes in S-adenosylmethionine and GSH homeostasis during endotoxemia in mice. Lab Invest 88: 1121-1129.
Liu H, Wang H, Shenvi S, Hagen TM, Liu RM. 2004. Glutathione metabolism during aging and in Alzheimer disease. Ann N Y Acad Sci 1019: 346-349.
Adachi Y, Moore LE, Bradford BU, Gao W, Thurman RG. 1995. Antibiotics prevent liver injury in rats following longterm exposure to ethanol. Gastroenterology 108: 218-224.
Ji C, Deng Q, Kaplowitz N. 2004. Role of TNF-$\alpha$ in ethanol- induced hyperhomocysteinemia and murine alcoholic liver injury. Hepatology 40: 442-451.
Zhao XJ, Dong Q, Bindas J, Piganelli JD, Magill A, Reiser J, Kolls JK. 2008. TRIF and IRF-3 binding to the TNF promoter results in macrophage TNF dysregulation and steatosis induced by chronic ethanol. J Immunol 181: 3049- 3056.