Lipase Inhibitory Mode of Dieckol Isolated from Eisenia bicyclis Ethanol Extract

Eisenia bicyclis 에탄올 추출물로부터 분리한 Dieckol의 Lipase 저해 Mode

  • Jung, Seul-A (Department of Food Science and Technology / Institute of Food Science, Pukyong National University) ;
  • Kim, Koth-Bong-Woo-Ri (Institute of Fisheries Sciences, Pukyong National University) ;
  • Kim, Dong-Hyun (Department of Food Science and Technology / Institute of Food Science, Pukyong National University) ;
  • Cho, Ji-Young (Department of marine biotechnology, Soonchunhyang University) ;
  • Kim, Tae-Wan (Department of Food Science and Biotechnology, Andong National University) ;
  • Ahn, Dong-Hyun (Department of Food Science and Technology / Institute of Food Science, Pukyong National University)
  • 정슬아 (부경대학교 식품공학과/식품연구소) ;
  • 김꽃봉우리 (부경대학교 수산과학 연구소) ;
  • 김동현 (부경대학교 식품공학과/식품연구소) ;
  • 조지영 (순천향대학교 해양생명공학과) ;
  • 김태완 (안동대학교 식품생명공학과) ;
  • 안동현 (부경대학교 식품공학과/식품연구소)
  • Received : 2012.10.11
  • Accepted : 2012.12.01
  • Published : 2013.03.28


This study was performed to investigate the possible use of Eisenia bicyclis (EB) ethanol extract to inhibit activity against lipase. In tests, the lipase inhibitory activity of EB ethanol extract was noted as being 43, 27, and 24% at concentrations of 5, 2.5, and 1 mg/ml, respectively. Isolation was carried out by liquid and liquid extraction, silica-gel column chromatography, and HPLC. The results showed that the lipase inhibitory activity of the ethyl acetate (EA) fraction from EB ethanol extract exhibited the strongest lipase inhibitory activity with an $IC_{50}$ value of 1.31 mg/ml. The EA fraction was separated using silica-gel column chromatography and we obtained 22 sub-fractions. Amongst them, the EA1 fraction showed the highest lipase inhibitory activity with an $IC_{50}$ value of 0.54 mg/ml. Eight peaks were obtained from the EA1 fraction by HPLC. Fraction 5 also showed a strong lipase inhibitory activity with an $IC_{50}$ value of 0.37 mg/ml. The fraction 5 was identified as dieckol and the inhibition pattern analyzed from Lineweaver-Burk plots revealed a non-competitive inhibitor. These results suggest that EB has potential as a natural anti-obesity agent.


Eisenia bicyclis;lipase inhibotory;dieckol;anti-obesity agent


  1. Ahn, M. J., K. D. Yoon, S. Y. Min, J. S. Lee, J. H. Kim, T. G.Kim, S. H. Kim, N. K. Kim, H. Huh, and J. W. Kim. 2004. Inhibition of HIV-1 reverse transcriptase and protease by phlorotannins from the brown alga Ecklonia cava. Biol. Pharm. Bull. 27: 544-547.
  2. Barwell, C. J., G. Blunden, and P. D. Manandhar. 1989. Isolation and characterization of brown algal polyphenols as inhibitors of α-amylase, lipase and trypsin. J. Appl. Phycol. 1: 319-323.
  3. Birari, R. B. and K. K. Bhutani. 2007. Pancreactic lipase inhibitors from natural sources: unexplored potential. Drug Discov. Today 12: 879-889.
  4. Bitou, N., M. Ninomiya, T. Tsujita, and H. Okuda. 1999. Screening of inhibitors from marine algae. Lipids 34: 441-445.
  5. Bray, G. A. and B. M. Popkin. 1998. Dietary fat intake dose affect obesity. Am. J. Clin. Nutr. 68: 1157-1173.
  6. Cahyana, A. H., Y. Shuto, and Y. Kinoshita. 1992. Pyropheophytin a as an antioxidative substance from the marine alga, Arame (Eisenia bicyclis). Biosci. Biotech. Bioch. 56: 1533- 1535.
  7. Chu, M. A. and B. H. Choe. 2010. Obesity and metabolic syndrome among children and adolescents in Korea. J. Korean Med. Assoc. 53: 142-152.
  8. Cleland, W. W. 1967. Enzyme Kinetics. Annu. Rev. Biochem. 36: 77-112.
  9. Deavile, E. R., R. J. Green, I. Muller-Harvey, I. Willoughby, and R. A. Frazier. 2007. Hydrolyzable tannin structures influence relative globular and random coil protein binding strengths. J. Agr. Food Chem. 55: 4554-4561.
  10. Drent, M. L., I. Larsson, T. William-Olsson, F. Quaade, F. Czubayko, K. Von Bergmann, W. Strobel, L. Sjotro, and E. A. Van der Veen. 1995. Orlistat (RO 18-0647), a lipase inhibitor, in the treatment of human obesity: a multiple dose study. Int. J. Obesity. 19: 221-226.
  11. Eom, S. H., M. S. Lee, E. W. Lee, Y. M. Kim, and T. H. Kim. 2012. Pancreatic lipase inhibitory activity of phlorotannins isolated from Eisenia bicyclis. Phytother. Res. DOI: 10.1002/ptr. 4696.
  12. Gibbons, G. F. and D. Wiggins. 1995. Intracellular triacylglycerol lipase: Its role in the assembly of hepatic very low density lipoprotein (VLDL). Adv. Enzyme Regul. 35: 179-198.
  13. Hadvay, P., H. Lengsfeld, and H. Wolter. 1988. Inhibition of pancreatic lipase in vitro by covalent inhibitor tetrahydrolipstatin. Biochem. J. 256: 357-361.
  14. Joo, D. S., J. K. Lee, Y. S. Choi, S.Y. Cho, Y. K. Je, and J. W. Choi. 2003. Effect of sea tangle oligosaccharide drink on serum and hepatic lipids in rats fed a hyperlipidemic diet. J. Korean Soc. Food Sci. Nutr. 32: 1364-1369.
  15. Kang, K., Y. Park, H. J. Hwang, S. H. Kim, J. G. Lee, and H. C. Shin. 2003. Antioxidative properties of brown algae polyphenolics and their perspectives as chemopreventive agents against vascular risk factors. Arch. Pharm. Res. 26: 286-293.
  16. Kang, M. C., Y. J. Lee, R. K. Ko, H. B. Kim, S. H. Hong, and G. O. Kim. 2008. Melanin inhibitory effect and anti-inflammatory effects of Dietyota coriacea extracts derived from adjacent sea of the Jeju island. Korean J. Biotechnol. Bioeng. 23: 311-316.
  17. Kang, S. M., S. J. Heo, K. N. Kim, S. H. Lee, H. M. Yang, A. D. Kim, and Y. J. Jeon. 2012. Molecular docking studies of a phlorotannin, dieckol isolated from Ecklonia cava with tyrosinase inhibitory activity. Bioorgan. Med. Chem. 20: 311-316.
  18. Kim, D. H., E. H. Lee, J. C. Hwang, J. H. Jeung, D. H. Kim, J. Y. Cheong, S. W. Cho, and Y. B. Kim. 2002. A case of acute cholestatic hepatitis associated with orlistat. Korean J. Hepatol. 8: 317-320.
  19. Kim, J. A., J. M. Lee, D. B. Shin, and N. H. Lee. 2004. The antioxidant activity and tyrosinase inhibitory of phlorotannin in Ecklonia cava. Food Sci. Biotechnol. 13: 476-480.
  20. Kim, J. H., H. J. Kim, C. Y. Kim, H. Y. Jung, Y. O. Kim, J. Y. Ju, and C. S. Shin. 2007. Development of lipase inhibitors from various derivatives of monascus pigment produced by Monascus fermentation. Food Chem. 101: 357-364.
  21. Kim, K. B. W. R., J. Y. Jung, J. Y. Cho, and D. H. Ahn. 2012. Lipase inhibitory activity of ethyl acetate fraction from Ecklonia cava extracts. Biotechnol. Bioprocess Eng. 17: 739-745.
  22. Kim, K. Y., K. A. Nama, H. Kurihara, and S. M. Kim. 2008. Potent $\alpha$-glucosidase inhibitors purified from the red alga Grateloupia elliptica. Phytochemistry 69: 2820-2825.
  23. Kim, S. A., J. Kim, M. K. Woo, C. S. Kwak, and M. S. Lee. 2005. Antimutagenic and cytotoxic effects of ethanol extracts from five kinds of seaweeds. J. Korean Soc. Food Sci. Nutr. 34: 451-459.
  24. Kim, Y. M., C. K. Han, S. J. Bang, and J. H. Park. 2006. Effect of laminaran from Eisenia bicyclis on serum lipids in rats fed high choelsterol diet. J. Korean Soc. Food Sci. Nutr. 36: 841-846.
  25. Kobayashi, A., T. Osaka, Y. Namba, S. Inoue, T. H. Lee, and S. Kimura. 1998. Capsaicin activates heat loss and heat production simultaneously and independently in rats. Am. J. Physiol. 275: 92-98.
  26. Kong, C. S., Y. R. Um, J. I. Lee, Y. A. Kim, J. S. Lee, and Y. W. Seo. 2008. Inhibition effects of extracts and its solvent fractions isolated from Limonium tetragonum on growth of human cancer cells. Korean J. Biotechnol. Bioeng. 23: 177-182.
  27. Lee, H. O., D. S. Kim, J. R. Do, and Y. S. Ko. 1999. Angiotensin- I converting enzyme inhibitory activity of algae. J. Korean Fish Soc. 32: 427-431.
  28. Lee, S. H., Y. Li, F. Karadeniz, M. M. Kim, and S. K. Kim. 2009. $\alpha$-Glucosidase and α-amylase inhibitory activities of phloroglucinal derivatives from edible marine brown alge, Ecklonia cava. J. Sci. Food Agric. 89: 1552-1558.
  29. Mattes, R. D. and L. Bormann. 2000. Effects of hydroxycitric acid on appetitive variables. Physiol. Behav. 71: 87-94.
  30. Moon, H. E., M. N. Islam, B. R. Ahn, S. S. Chowdhury, H. S. Sohn, H. A. Jung, and J. S. Choi. 2011. Protein tyrosine phosphatase 1B and α-glucosidase inhibitory phlorotannins from edible brown algae, Ecklonia stolonifera and Eisenia bicyclis.Biosci. Biotech. Bioch. 75: 1472-1480.
  31. Nakamura, T., K. Nagayama, K. Uchida, and R. Tanaka. 1996. Antioxidant activity of phlorotannins isolated from the brown alge Eisenia bicylis. Fisheries Sci. 62: 923-926.
  32. Pi-Sunyer, F. X. 1991. Health implications of obesity. Am. J. Clin. Nutr. 5: 15955-16035.
  33. Prpkins, B. M. and C. M. Doak. 1998. The obesity prevalence is a worldwide phenomenon. Nutr. Rev. 56: 104-114.
  34. Sugiura, Y., K. Matsuda, Y. Yamada, M. Nishikawa, K. Shioya, H. Katsuzaki, K. lmai, and H. Amano. 2006. Isolation of a new anti-allergic phlorotannin, phlorofucofuroeckol-B, from and edible brown alge, Eisenia arborea. Biosci. Biotech. Biochem. 70: 2807-2811.
  35. Westerterp-Plantenga, M. S., A. Smeets, and M. P. G. Lejeune. 2005. Sensory and gastrointestinal satiety effects of capsaicin on food intake. Int. J. Obesity. 29: 682-688.
  36. Witvrouw, M. and E. De Clercq. 1997. Sulfated polysaccharides extracted from sea algae as potential antiviral drugs. Gen. Pharmacol. 29: 497-511.