Protective Effects of Persimmon Leaf and Fruit Extracts against Acute Ethanol-Induced Hepatotoxicity

  • Ma, Jie ;
  • Liu, Xiao-Yu ;
  • Noh, Kyung-Hee ;
  • Kim, Myo-Jeong ;
  • Song, Young-Sun
  • Published : 2007.12.31


Persimmon is well-known as a Korean traditional medicine for alleviating coughs and enhancing blood circulation; it is also used for treatment of hypertension, cancer, diabetes and atherosclerosis. To evaluate the protective properties of persimmon leaf methanol extract (PLME) and persimmon fruit methanol extract (PFME) administration on acute ethanol-induced hepatotoxicity, C57BL/6 male mice were gavaged with or without persimmon extracts for 1 week. Hepatotoxicity was then induced by gavage of 5 g/kg BW ethanol. After 12 hr of ethanol administration, blood and liver were collected and analyzed for biochemical markers of hepatotoxicity. The results showed PLME and PFME treatments decreased the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared with ethanol control. Both PLME and PFME reduced serum lactate dehydrogenase (LDH) activity, but elevated alcohol dehydrogenase (ADH) activity. Serum triglyceride (TG) and hepatic cholesterol levels were significantly decreased when treated with PLME and PFME. Liver malondialdehyde (MDA) levels were significantly decreased in PLME and PFME groups compared with ethanol control. Furthermore, the administration of PLME and PFME significantly increased the activities of catalase, glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-red). In summary, PLME and PFME appeared to prevent hepatic injury by accelerating alcohol metabolism by increasing alcohol-metabolizing enzyme activities, by activating the antioxidative enzyme system against oxidative stress, and by decreasing fat accumulation, which is evidenced by decreased hepatotoxic indices in serum.


persimmon (Diospyros kaki);ethanol;hepatoprotective effect;C57BL/6 mice


  1. Nordmann R, Ribiere C, Rouch H. 1992. Implication of free radical mechanisms in ethanol-induced cellular injury. Free Radic Biol Med 12: 219-240
  2. Lieber CS. 1997. Ethanol metabolism, cirrhosis and alcoholism. Clin Chim Acta 257: 59-84
  3. Mira L, Maia L, Barreira L, Manso CF. 1995. Evidence for radical generation due to NADH oxidation by aldehyde oxidase during ethanol metabolism. Arch Biochem Biophys 318: 53-58
  4. Arteel GE. 2003. Oxidants and antioxidants in alcohol-induced liver disease. Gastroenterology 124: 778-790
  5. Tsukamoto H, Horne W, Kamimura S, Niemela O, Parkkila S, YlaHerttuala S, Bittenham GM. 1995. Experimental liver cirrhosis induced by alcohol and iron. J Clin Invest 96: 620-630
  6. Meagher EA, Barry OP, Burke A, Lucey MR, Lawson JA, Rokach J, FitzGerald GA. 1999. Alcohol-induced generation of lipid peroxidation products in humans. J Glin Invest 104: 805-813
  7. Zhou Z, Sun X, Lambert JC, Saari JT, Kang YJ. 2002. Metallothionein-independent zinc protection from alcoholic liver injury. Am J Pathol 160: 2267-2274
  8. Appel AL. 1978. Glutathione peroxidase and hydroperoxides. Methods Enzymol 52: 506-513
  9. Deleve L, Kaplowitz N. 1991. Glutathione metabolism and its role in hepatotoxicity. Pharmacol Ther 52: 287- 305
  10. Fernandez-Cheaca J, Lu Sc, Ockhtens M. 1992. The regulation of hepatic glutathione. In Hepatic Anion Transport and Bile Secretion. Physiology and Pathophysiology, Tavloni N, Berk PD, eds. Marcel Dekker, New York. p 363-395
  11. Fernandez-Checa J, Kaplowitz N, Garcia-Ruitz C, Colell A, Miranda M, Mari M, Ardite E, Morales A. 1997. GSH transport in mitochondria: defense against TNF-induced oxidative stress and alcohol-induced effect. Am J Physiol 273: G7-G17
  12. Li JL, Stantman FW, Lardy HA. 1988. Antioxidant enzymes in rat liver and skeletal muscle. Arch Biochem Biophys 263: 150-160
  13. Halliwell B. 1994. Free radicals, antioxidants and human diseases, curiosity, causes or consequence?. Lancet 344: 721-724
  14. Avagaro P, Cazzlolatu G, 1975. Changes in the composition and physiochemical characteristics of serum lipoproteins during ethanol induced lipidemia in alcohol subjects. Metabolism 241: 1231-1242
  15. Rukkumani R, Sri Balasubhashini M, Viswanathan P, Menon VP. 2002. Comparative effects of curcumin and photo-irradiated curcumin on alcohol and polyunsaturated fatty acid-induced hyperlipidemia. Pharmacol Res 46: 257-264
  16. Jung KM, Kang GH, Kwon MK, Song IK, Cho DH, Chou YD. 2004. Chemical components and antioxidant activity of persimmon leaves. Kor J Food Preservation 11: 175- 181
  17. Kim SK, Lee HY, Kim MK. 2001. Effect of water and ethanol extracts of persimmon leaf and green tea different conditions on lipid metabolis and antioxidant capacity in 12-month old rats. Kor J Nutr 34: 499-512
  18. Folch J, Lees M, Sloane Stanley GH. 1957. A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226: 497-509
  19. Fraga CG, Leibovita RM, Roeder RG. 1988. Lipid peroxidation measured as thiobar bituric-reactive substances in tissue slices: characterization and comparision with homogenates and microsomes. Free Radic Biol Med 4: 155-161
  20. Gornal AG, Bardawill CJ, David MM. 1949. Determination of serum protein by means of Biuret reaction. J Biol Chem 177: 751-766
  21. Abei H. 1984. Catalase in vitro. In Method in Enzymology. William BJ, ed. Academic Press, New York. Vol 105, p 121-126
  22. Paglia DE, Valentine WN. 1967. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70: 158-169
  23. Richterich R. 1971. Glutathione reductase. Clin Chem 2: 366-367
  24. Katerina V, Jitka U, Ladislav C, Vilm S. 2007. Cytoprotective effect of a blueberry extract against oxidative damage of rat hepatocytes. Food Chemistry 101: 912-917
  25. Choi JS, Yoon JJ, Kang KR, Lee KH, Kim WH, Suh YH, Song J, Jung MH. 2006. Glycoprotein isolated from Acanthopanax senticosus protects against hepatotoxicity induced by acute and chronic alcohol treatment. Biol Pharm Bull 29: 306-314
  26. Niemela O. 1999. Aldehyde-protein adducts in the liver as a result of ethanol-induced oxidative stress. Front Biosci 4: 506-513
  27. Apple FS, Murakami M, Panteghini M, Christenson RH, Dati F, Mair J, Wu AH; IFCC Committee on standardization of markers of cardiac damage. 2001. International survey on the use of cardiac markers. Clin Chem 47: 587-588
  28. Wu AH, Apple FS, Gibler WB, Jesse RL, Warshaw MM, Valdes R Jr. 1999. National academy of clinical biochemistry standards of laboratory practice: recommendations for the use of cardiac markers in coronary artery diseases. Clin Chem 45: 1104-1121
  29. Bakker J, Gris P, Coffernils M, Kahn RJ, Vincent JL. 1996. Serial blood lactate levels can predict the development of multiple organ failure following septic shock. Am J Surg 171: 221-226
  30. Song Z, Deaciuc I, Song M, Lee DY-W, Ji X, McClain C. 2006. Silymarin protects against cute ethanol-induced hepatotoxicity in mice. Alcohol J Clin Exp Res 30: 407-413
  31. Srivastava A, Shivanandappa T. 2006. Hepatoprotective effect of the aqueous extract of the roots of Decalepishamiltonii against ethanol-induced oxidative stress in rats. Hepatol Res 35: 267-275
  32. Lieber CS. 2000. Alcohol and the liver: metabolism of alcohol and its role in hepatic and extrahepatic diseases. Mt Sinai J Med 67: 84-94
  33. Skursk L, Kov J, Tachov M. 1979. A sensitive photometric assay for alcohol dehydrogenase activity in blood serum. Anal Biochem 99: 65-71
  34. Sugimoto T, Yamashita S, Ishigami M. 2002. Decreased microsomal triglyceride transfer protein activity contributes to initiation of alcoholic liver steatosis in rats. J Hepatol 36: 157-162
  35. Parthasarathy R, Ragupathi SG, Janardhanem S. 1999. The functions and tests of the liver. In Drug and Alcohol Abuse. Zimmerman HJ, Seef LB, eds. Pergamon Press, Philadelphia. p 1-4
  36. Koch OR, Pani G, Borrello S. 2004. Oxidative stress and antioxidant defenses in ethanol-induced cell injury. Mol Aspects Med 20: 191-198
  37. You M, Fischer M, Deeg MA. 2002. Ethanol induces fatty acid synthesis pathways by activation of sterol regulatory element-binding protein (SREBP). J Biol Chem 277: 29342-29347
  38. Purohit V, Russo D, Coates PM. 2004. Role of fatty liver, dietary fatty acid supplements, and obesity in the progression of alcoholic liver disease: introduction and summary of the symposium. Alcohol 34: 3-8
  39. Day CP, James OF. 1998. Steatohepatitis: a tale of two 'hits'? Gastroenterology 114: 842-845
  40. Yang SQ, Lin HZ, Lane MD, Clemens M, Diehl AM. 1997. Obesity increases sensitivity to endotoxin liver injury: implications for the pathogenesis of steatohepatitis. Proc Natl Acad Sci USA 94: 2557-2562
  41. Letteron P, Fromenty R, Terris B, Deqott C, Pessayre D. 1996. Acute and chronic hepatic steatosis lead to in vivo lipid peroxidation in mice. J Hepatol 24: 200-208
  42. Masalkar PD, Abhang SA. 2005. Oxidative stress and antioxidant status in patients with alcoholic liver disease. Clin Chim Acta 355: 61-65
  43. Kurose I, Higuchi H, Kato S, Miura S, Watanabe N, Kamegaya Y, Tomita K, Takaishi M, Horie Y, Fukuda M, Mizukami K, Ishii H. 1997. Oxidative stress on mitochondria and cell membrane of cultured rat hepatocytes and perfused liver exposed to ethanol. Gastroenterology 112: 1331-1343
  44. Wieland P, Lauterburg B. 1995. Oxidation of mitochondrial proteins and DNA following administration of ethanol. Biochem Biophys Res Commum 24: 815-819
  45. Nordmann R, Ribiere C, Rouach H. 1992. Implication of free radical mechanisms in ethanol-induced cellular injury. Free Radic Biol Med 12: 219-240
  46. Weng D, Lu Y, Wei YN, Liu Y, She PP. 2007. The role of ROS in microcystin-LR-induced hepatocyte apoptosis and liver injury in mice. Toxicology 232: 15-23
  47. Navasumrit P, Ward TH, Dodd NJ, O'Connor PJ. 2000. Ethanol-induced free radicals and hepatic DNA strand breaks are prevented in vivo by antioxidants: effect of acute and chronic ethanol exposure. Carcinogenesis 21: 93-99
  48. Rouach H, Fataccioli V, Gentil M, French S, Morimoto M, Nordman R. 1997. Effect of chronic ethanol feeding on lipid peroxidation and protein oxidation in relation to liver pathology. Hepatology 25: 351-355
  49. Zhou Z, Sun X, Kang Y. 2002. Metallothionein protection against alcoholic liver injury through inhibition of oxidative stress. Exp Biol Med 227: 214-222
  50. An BJ, Choi HJ, Son JH, Woo HS, Han HS, Park JH, Son GM, Choi C. 2003. Identification of biological effect and chemical structure of polyphenol compounds fro the leaves of Korea persimmon (Diospyrus kaki L. Folium). Kor J Food Culture 18: 443-456
  51. Choi JH, Lee EY, Kim CJ, Park IH, Kim JS, Choi GB, Jung SG, Ham YS. 2006. Physiocochemical properties and physiological activities of Ulsan sweet persimmon peel.flesh according to cultivars. J Korean Soc Appl Biol Chem 49: 309-314

Cited by

  1. Antioxidative and Antidiarrheal Effects of Persimmon Extracts vol.26, pp.4, 2010,
  2. Natural Products for the Prevention and Treatment of Hangover and Alcohol Use Disorder vol.21, pp.1, 2016,
  3. Effects of a Preparation of Combined Glutathione-Enriched Yeast and Rice Embryo/Soybean Extracts on Ethanol Hangover vol.12, pp.6, 2009,
  4. Antioxidative and Antiallergic Effect of Persimmon Leaf Extracts vol.38, pp.12, 2009,