DOI QR코드

DOI QR Code

Eliminatory Effect of Mixture including Hot Water Extract of Dendropanax morbifera Lev. on Alcohol-induced Blood Alcohol Concentration and Hangover in Rat

흰쥐에서 황칠나무 열수 추출물을 포함한 혼합물의 혈중 알코올 농도와 숙취 해소 효과

  • 나주련 ((주)비엔텍 중앙연구원) ;
  • 김은 ((주)제이웰바이오팜 중앙연구소) ;
  • 박소이 ((주)비엔텍 중앙연구원) ;
  • 이기훈 ((주)비엔텍 중앙연구원) ;
  • 정의선 ((주)비엔텍 중앙연구원) ;
  • 김진석 ((주)비엔텍 중앙연구원) ;
  • 김용재 ((주)제이웰바이오팜 중앙연구소) ;
  • 김선오 ((주)비엔텍 중앙연구원)
  • Received : 2018.12.04
  • Accepted : 2018.12.19
  • Published : 2018.12.30

Abstract

This study was performed to investigate the ameliorating effect of a hangover beverage mixture (SBJ) that contains Dendropanax morbifera Lev. and several medicinal plant extracts, on hepatoprotection and alcohol-metabolizing enzymes in alcohol-induced hangover in both in vitro and in vivo models. In human hepatoma cell line, HepG2, 300 mM of ethanol-induced hepatotoxicity was significantly improved by pretreatment of SBJ by dose-dependent manner. In the in vivo study, administration of alcohol to rats raised to the concentration of blood alcohol and lactate dehydrogenase (LDH). Blood alcohol and LDH levels in SBJ-treated rats significantly decreased at 0.5 h and 8 h after acute ethanol administration (40%, 4.6 g/kg body weight) as compared to alcohol-treated rats. Hepatic alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity were significantly higher in SBJ-treated rats than in alcohol-treated rats. SBJ supplementation reduced formation of malondialdehyde (MDA), and inhibited reductions of hepatic superoxide dismutase (SOD), hepatic glutathione (GSH), glutathione-S-transferase (GST), glutathione reductase (GR) and glutathione peroxidase (GPx) levels, compared with rats administered alcohol. Plasma catalase (CAT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels showed unaltered resulted in all experimental groups compared with the control group. These results suggest that SBJ exhibit hepatoprotective properties by enhancing ADH, ALDH activity and stimulating the antioxidant defense system in alcohol-induced hangover.

본 연구에서는 숙취해소에 좋은 것으로 알려진 식품 소재와 황칠나무 추출물을 복합하여 in vitro 및 in vivo에서 알코올 유도된 간 손상에 대한 보호효과를 검토하였다. HepG2세포에서 300 mM 알코올과 SBJ 혼합물을 처리하였을 때 농도 의존적으로 LDH 수치가 감소하였으나 황칠나무 추출물을 제외한 복합물인 SBJ-복합물에서는 그 효과가 유의적으로 낮아지는 것을 관찰하였다. In vivo에서 SBJ 혼합물의 보호효과를 확인하고자 흰쥐에 알코올과 SBJ 혼합물을 투여한 결과, 알코올 투여 후 1시간까지 급격하게 혈중 알코올 수치가 EtOH군에서 증가하는 것이 관찰되었으며, SBJ 혼합물 투여군은 유의적인 차이로 감소되었음이 관찰되었으며 또한 농도의존적인 경향을 확인하였다. ADH 및 ALDH 활성의 증가는 SBJ 혼합물의 알코올 분해 및 대사산물의 제거 활성에 기여할 것으로 예상된다. 뿐만 아니라, 알코올에 의하여 증가한 LDH의 농도가 대조군과 유사한 수준으로 유지하는 것을 확인하였으며, GST, SOD, GPx 및 reduced glutathione와 같은 항산화 인자 및 효소의 활성은 대조군보다 EtOH군이 유의적으로 감소했으며, SBJ 혼합물에 의해 개선되는 경향을 관찰하였다. 이를 통해 SBJ 혼합물은 ADH, ALDH 활성 증가 및 항산화 방어계를 향상시킴으로써 산화적 스트레스 감소를 통한 간보호 효과가 있는 것으로 생각되며, 이러한 간보호에 미치는 주요한 추출물은 황칠나무 추출물임을 알 수 있었다. 이러한 결과를 토대로 향후 숙취해소 작용을 갖는 신규 식품소재로 활용될 수 있을 것으로 기대된다.

Keywords

Acknowledgement

Supported by : 농림식품기술기획평가원

References

  1. Swift, R. and Davidson, D.: Alcohol hangover, mechanisms and mediators. Alcohol Health Res. World 1998, 22, 54-60.
  2. Kee, J. Y., Kim, M. O., You, I. Y., Chai, J. Y., Hong, E. S., An, S. C., Kim, H., Park, S. M., Youn, S. J., and Chae, H. B.: Effects of genetic polymorphisms of ethanol-metabolizing enzymes on alcohol drinking behaviors. Korean J. Hepatology 2003, 9, 89-97.
  3. Lieber, C. S.: Liver adaptation and injury in alcoholism. New Eng. J. Med. 1973, 288, 356-362. https://doi.org/10.1056/NEJM197302152880710
  4. Paek, S. C.: Ethanol oxidation is accelerated by augmentation of malate-aspartate shuttle with aspartate. Korean J. Biochem. 1993, 25, 137-143.
  5. Kim, C. I.: Cause and effect of hangover. Food Ind. Nutr. 1999, 4, 26-30.
  6. Jeong, B. S., Jo, J. S., Pyo, B. S., and Hwang, B.: Studies on the distribution of Dendropanax morbifera and component analysis of the golden lacquer. Korean J. Biotechnol. Bioeng. 1995, 10, 393-400.
  7. Hyun, T. K., Kim, M. O., Lee, H., Kim, Y., Kim, E., and Kim, J. S.: Evaluation of anti-oxidant and anti-cancer properties of Dendropanax morbifera Leveille. Food Chem. 2013, 141, 1947-1955. https://doi.org/10.1016/j.foodchem.2013.05.021
  8. Halstead, B. W. and Hood, L. L.: An introduction to adaptogenic medicine. In Eleutherococcus senticosus: Siberian ginseng. In Oriental Healing Arts Institute Processing, pp. 1-94. Bristol, CT, 1984.
  9. Hirata, F., Fujita, K., Ishikura, Y., Hosoda, K., Ishikawa, H., and Nakamura, H.: Hypocholesterolemic effect of sesame lignan in humans. Atherosclerosis 1996, 122, 135-136. https://doi.org/10.1016/0021-9150(95)05769-2
  10. Kim, I. D., Kang, K. S., Kwon, R. H., and Ha, B. J.: Antioxidative effect of Rubus coreanum Miquel extract on hepatic injury induced by lipopolysaccharide. J. Toxicol. Pub. Health 2007, 23, 347-352.
  11. Arao, T., Udayama, M., Kinjo, J., and Nohara, T.: Preventive effects of saponins from the Pueraria lobata root on in vitro immunological liver injury of rat primary hepatocyte cultures. Planta Med. 1998, 64, 413-416. https://doi.org/10.1055/s-2006-957471
  12. Keung, W. M. and Vallee, B. L.: Daidzin and its antidipsotropic analogs inhibit serotonin and dopamine metabolism in isolated mitochondria. Proc. Natl. Acad. Sci. USA 1998, 95, 2198-2203. https://doi.org/10.1073/pnas.95.5.2198
  13. Inoue, M., Wu, C. Z., Dou, D. Q., Chen, Y. J., and Ogihara, Y.: Lipoprotein lipase activation by red ginseng saponins in hyperlipidemia model animals. Phytomedicine 1999, 6, 257-265. https://doi.org/10.1016/S0944-7113(99)80018-X
  14. Kim, H. J., Nam, S. H., Kim, H. S., and Lee, S. K.: Studies on the components of Korean Panax ginseng, C. A. Meyer. Korean J. Food Sci. Technol. 1997, 9, 109-123.
  15. Park, S. J., Kang, J. H., Kong, H. J., Hwang, S. J., Jang, J. H., and Yang, K. M.: Effects of Gastrodiae rhizoma on the liver function and alcohol metabolism in alcohol treated rats. Korean J. Food Cook Sci. 2016, 32, 818-827. https://doi.org/10.9724/kfcs.2016.32.6.818
  16. Yoon, J., Ham, H., Sung, J., Kim, Y., Choi, Y., Lee, J. S., Jeong, H. S., Lee, J., and Kim, D.: Black rice extract protected HepG2 cells from oxidative stress-induced cell death via ERK 1/2 and Akt activation. Nutr. Res. Pract. 2014, 8, 125-131. https://doi.org/10.4162/nrp.2014.8.2.125
  17. Bae, D., Kim, J., Lee, S. Y., Choi, E. J., Jung, M. A., Jeong, C. S., Na, J. R., Kim, J. J., and Kim, S.: Hepatoprotective effects of aqueous extracts from leaves of Dendropanax morbifera Leveille against alcohol-induced hepatotoxicity in rats and in vitro anti-oxidant effects. Food Sci. Biotechnol. 2015, 24, 1495-1503. https://doi.org/10.1007/s10068-015-0193-x
  18. Rajendram, R. and Preedy, V. R.: Effect of alcohol consumption on the gut. Dig. Dis. 2005, 23, 214-221. https://doi.org/10.1159/000090168
  19. Tolstrup, J. S., Gronbaek, M., Tybjaerg-Hansen, A., and Nordestgaard, B. G.: Alcohol intake, alcohol dehydrogenase genotypes, and liver damage and disease in the Danish general population. Am. J. Gastroenterol. 2009, 104, 2182-2188. https://doi.org/10.1038/ajg.2009.370
  20. Saygi, S., Konuklugil, B., Kutsal, O., Uzbay, I. T., Deniz, G., and Goren, Z.: Assessment of therapeutic effect of inula heterolepsis boiss in alcoholic rats. Phytother. Res. 2003, 17, 683-687. https://doi.org/10.1002/ptr.1221
  21. Park, E. M., Ye, E. J., Kim, S. J., Choi, H. I., and Bae, M. J.: Eliminatory effect of health drink containing Hovenia dulcis Thunb extract on ethanol-induced hangover in rats. Korean J. Food Culture 2006, 21, 71-75.
  22. Van Waes, L. and Lieber, C.S.: Glutamate dehydrogenase, a reliable marker of liver cell necrosis in the alcoholic. Br. J. Med. 1977, 2, 1508-1510. https://doi.org/10.1136/bmj.2.6101.1508
  23. Yoon, Y. S. and Lee, K. J.: The effect of extract powder of fruits and vegetables on hangover. Korean J. Water 2011, 2, 36-42.
  24. Cha, J. Y., Jung, H. J., Jeong, J. J., Yang, H. J., Kim, Y. T., and Lee, Y.S.: Effect of amino acids on the activities of alcohol metabolizing enzyme alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH). J. Life Sci. 2009, 19, 1321-1327. https://doi.org/10.5352/JLS.2009.19.9.1321
  25. You, Y., Lee, H., Chung, C., Lee, M. J., and Jun, W.: Effect of mixture including hot water extract of Houttuynia cordata Thunb on ethanol-induced hangover in rats. J. Korean Soc. Food Sci. Nutr. 2016, 45, 1508-1512. https://doi.org/10.3746/jkfn.2016.45.10.1508
  26. Yu, K. H., Lee, S. Y., Yang, H. M., Ham, Y. A., Lee, S. U., Chae, S. W., and Lee, Y. J.: Effect of fermented water extracts from Ligularia fischeri on hepatotoxicity induced by D-galactosamine in rats. J. Korean Soc. Food Sci. Nutr. 2015, 44, 1422-1430. https://doi.org/10.3746/jkfn.2015.44.10.1422
  27. Choi, K., Kim, B. I., Cho, Y. K., Park, C. Y., Sohn, J. I., Jeon, W. K., Kim, H., Chung, E. S., Keum, D. G., Lee, H. Y., and Lee, S. J.: Diagnostic usefulness of serum $\gamma$-glutamyl transferase (GGT) activity in fatty liver and relationship with other factors. Korean J. Med. 1999, 57, 1006-1013.
  28. Meister, A.: Glutathione deficiency produced by inhibition of its synthesis, and its reversal; applications in research and therapy. Pharmacol. Ther. 1991, 51, 155-194. https://doi.org/10.1016/0163-7258(91)90076-X
  29. Halliwell, B. and Chirico, S.: Lipid peroxidation: Its mechanism, measurement, and significance. Am. J. Clin. Nutr. 1993, 57, 715S-724S. https://doi.org/10.1093/ajcn/57.5.715S
  30. Kurose, I., Higuchi, H., Miura, S., Saito, H., Watanabe, N., Hokari, R., Hirokawa, M., Takaishi, M., Zeki, S., Nakamura, T., Ebinuma, H., Kato, S., and Ishii, H.: Oxidative stress-mediated apoptosis of hepatocytes exposed to acute ethanol intoxication. Hepatology 1997, 25, 358-378.
  31. Wu, D. and Cederbaum, A. l.: Ethanol cytotoxicity to a transfected HepG2 cell line expressing human cytochrome P4502 E1. J. Biol. Chem. 1996, 271, 23914-23919. https://doi.org/10.1074/jbc.271.39.23914
  32. Kim, C. W. and Lee, H. Y.: Studies on the constituents of seeds of Acanthopanax senticosus for inermis harms. Korean J. Pharmacogn. 1990, 21, 235-238.
  33. Choi, Y. J. and Jung, K. I.: Anti-diabetic, alcohol-metabolizing, and hepatoprotective activities of moringa (Moringa oleifera Lam.) leaf extract. J. Korean Soc. Food Sci. Nutr. 2016, 45, 819-827. https://doi.org/10.3746/jkfn.2016.45.6.819