Skip to main content
Log in

Anti-hyperlipidemic effect of an edible brown algae, Ecklonia stolonifera, and its constituents on poloxamer 407-induced hyperlipidemic and cholesterol-fed rats

  • Research Article
  • Drug Efficacy and Safety
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

We conducted this study to isolate novel anti-hyperlipidemic agents derived from natural marine products. To accomplish this, we investigated the effects of ethanolic (EtOH) extracts of Ecklonia stolonifera and its phlorotannin constituents, eckol and dieckol, on serum lipid levels in rats with hyperlipidemia that was induced by a high-cholesterol diet or poloxamer 407. Treatment with the EtOH extracts of E. stolonifera and its phlorotannin-rich ethyl acetate (EtOAc) and n-butanol (n-BuOH) fractions induced a significant reduction in triglycerides (TG), total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C) levels, as well as a significant increase in the high-density lipoprotein-cholesterol (HDLC) level in hyperlipidemic rats. However, treatment with the water (H2O) fraction did not exert any significant effects on the serum levels of hyperlipidemic rats. In addition, eckol and dieckol isolated from the active EtOAc fraction induced a significant reduction in serum TG, TC, and LDL-C levels, as well as in the atherogenic index (A.I.). Furthermore, treatment with dieckol induced a greater decrease in the serum TG, TC, and LDL-C levels of hyperlipidemic rats than eckol or lovastatin, as well as an increase in the serum HDL-C levels. Taken together, these results suggest that phlorotannins such as eckol and dieckol have the potential for use for the prevention of hyperlipidemic atherosclerosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Ahn, M. J., Yoon, K. D., Kim, C. Y., Min, S. Y., Kim, Y. U., Kim, H. J., Kim, J. H., Shin, C. G., Lee, C. K., Kim. T. G., Kim, S. H., Huh, H., and Kim, J. W., Inhibition of HIV-1 reverse transcriptase and HIV-1 integrase and antiviral activity of Korean seaweed extracts. J. Appl. Phycol., 14, 325–329 (2002).

    Article  CAS  Google Scholar 

  • Ara, J., Sultana, V., Qasim, R., and Ahmad, V. U., Hypolipidemic activity of seaweed from Karachi Coast. Phytother. Res., 16, 479–483 (2002).

    Article  PubMed  Google Scholar 

  • Berliner, J. A. and Heinecks, J. W., The role of oxidized lipoproteins in atherogenesis. Free Radical Biol. Med., 20, 707 (1996).

    Article  CAS  Google Scholar 

  • Choi, J. S., Yokozawa, T., and Oura, H., Antihyperlipidemic effect of flavonoids from Prunus davidiana. J. Nat. Prod., 54, 218–224 (1991).

    Article  PubMed  CAS  Google Scholar 

  • Cogger, V. C., Warren, A., Fraser, R., Nqu, M., McLean, A. J., and Le Couteur, D. G., Hepatic sinusoidal pseudocapillarization with aging in the non-human primate. Exp. Gerontol., 38, 1101–1107 (2003).

    Article  PubMed  Google Scholar 

  • Dallinga-Thie, G. M., Berk-Planken, II, Bootsma, A. H., and Jansen, H., Diabetes atorvastatin lipid intervention (DALI) Study Group, Atorvastatin decreases apolipoprotein C-III in apolipoprotein B-containing lipoprotein and HDL in type 2 diabetes: a potential mechanism to lower plasma triglycerides. Diabetes Care, 27, 1358–1364 (2004).

    Article  PubMed  CAS  Google Scholar 

  • De Bono, D. P. and Boon, N. A., Diseases of the cardiovascular system. In: Edwards, C. R. W., and Bouchier, I. A. D. (Eds.). Davidson’s principles and practice of medicine. ELBS Churchill Livingstone, Edinburgh, pp. 249–340 (1992).

  • Elwood, J. C., Nash, D. T., and Streeten, D. H., Effect of highchromium brewer’s yeast on human serum lipids. J. Am. Coll. Nutr., 1, 263–274 (1982).

    PubMed  CAS  Google Scholar 

  • Feussner, G., HMG-CoA reductase inhibitors. Curr. Opin. Lipidiol., 5, 59–60 (1994).

    Article  CAS  Google Scholar 

  • Fki, I., Bouaziz, M., Sahnoun, Z., and Sayadi, S., Hypocholesterolemic effects of phenolic-rich extracts of Chemlali olive cultivar in rats fed a cholesterol-rich diet. Bioorg. Med. Chem., 13, 5362–5370 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Grundy, S. M., Summary of the second report of the National Cholesterol Education Program (NCEP) export panel on detection, evaluation and treatment of high blood cholesterol in adults. JAMA., 269, 3015–3023 (1993).

    Article  Google Scholar 

  • Isley, W. L., Miles, J. M., Parrerson, B. W., and Harris, W. S., The effect of high-dose simvastatin on triglyceride-rich lipoprotein metabolism in patients with type 2 diabetes mellitus. J. Lipid Res., 47, 193–200 (2006).

    Article  PubMed  CAS  Google Scholar 

  • John K. S., Kathiravan, M. K., Somani, R. S., and Shishoo, C. J., The biology and chemistry of hyperlipidemia. Bioorg. Med. Chem., 15, 4674–4699 (2005).

    Google Scholar 

  • Johnston, T. P. and Palmer, W. K., Effect of poloxamer 407 on the activity of microsomal 3-hydroxy-3-methylglutaryl CoA reductase in rats. J. Cardiovasc. Pharmacol., 29, 580–585 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Jung, H. A., Hyun, S. K., Kim, H. R., and Choi, J. S., Angiotensin-converting enzyme I inhibitory activity of phlorotannins from Ecklonia stolonifera. Fisheries Sci., 72, 1292–1299 (2006).

    Article  CAS  Google Scholar 

  • Kang, H. S., Chung, H. Y., Jung, J. H., Son, B. W., and Choi, J. S., A new phlorotannin from the brown alga Ecklonia stolonifera. Chem. Pharm. Bull., 51, 1012–1014 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Kang, H. S., Chung, H. Y., Kim, J. Y., Son, B. W., Jung, H. A., and Choi, J. S., Inhibitory phlorotannins from the edible brown alga Ecklonia stolonifera on total reactive oxygen species (ROS) generation. Arch. Pharm. Res., 27, 194–198 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Kim, J. M., Seong, N. S., and Lee, Y. J., The effects of jwa kum-wham and soo ryeon-whan on the hyperlipidemia in rats. Korean J. Herbology, 20, 91–102 (2001).

    Google Scholar 

  • Kim, Y. C., An, R. B., Yoon, N. Y., Nam, T. J., and Choi, J. S., Hepatoprotective constituents of the edible brown alga Ecklonia stolonifera on tacrine-induced cytotoxicity in Hep G2 cell. Arch. Pharm. Res., 28, 1376–1380 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Kim, Y. M., Han, C. K., Bang, S. J., and Park, J. H., Effect of laminaran from Eisenia bicyclis on serum lipid in rats fed high cholesterol diet. J. Kor. Soc. Food Sci. Nutr., 35, 841–846 (2006).

    CAS  Google Scholar 

  • Kimura, Y., Watanabe, K., and Okuda, H., Effects of soluble sodium alginate on cholesterol excretion and glucose tolerance in rats. J. Ethnopharmacol., 54, 47–54 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Libby, P., Aikawa, M., and Schinbeck, U., Cholesterol and atherosclerosis. Biochim. Biophys. Acta., 1529, 299–309 (2000).

    PubMed  CAS  Google Scholar 

  • McKenney, J. M., Pharmacotherapy of dyslipidemia. Cardiovasc. Drugs Ther., 15, 413–422 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Megalli, S., Aktan, F., Davies, N. M., and Roufogalis, B. D., Phytopreventative anti-hyperlipidemic effects of Gynostemma pentaphyllum in rats. J. Pharm. Pharm. Sci., 8, 507–515 (2005).

    PubMed  CAS  Google Scholar 

  • Michanek, G., Seaweed resources for pharmaceutical uses. In: Hoppe, H. A., Levring, T., and Tanaka, Y. (Eds.). Marine Algae in Pharmaceutical Science. Walter de Gruyter, Berlin, New York, pp. 303–342 (1979).

    Google Scholar 

  • Moral, D. W., Hessler, J. R., and Chisolm, G. M., Low density lipoprotein cytotoxicity induced by free radical peroxydation of lipid. J. Lipid Research, 24, 1070–1076 (1983).

    Google Scholar 

  • Navab, M., Berliner, J. A., Watson A. D., Hama, S. Y., Territo, M. C., Lusis, A. J., Shih, D. M., Van Lenten, B. J., Frank, J. S., Demer, L. L., Edwards, P. A., and Fogelman, A. M., The yin and yang of oxidation in the development of the fatty streak: a review based on the 1994 george lyman duff memorial lecture. Arterioscler. Thromb. Vasc. Biol., 16, 839–842 (1996).

    Google Scholar 

  • Nigon, F., Serfaty-Lacrosniere, C., Beucler, I., Beucler, I., Chauvois, D., Neveu, C., Giral, P., Chapman, M. J., and Bruckert, E., Plant sterol-enriched margarine lowers plasma LDL in hyperlipidemic subjects with low cholesterol intake: effect of fibrate treatment. Clin. Chem. Lab. Med., 39, 634–640 (2001).

    Article  PubMed  CAS  Google Scholar 

  • O’Keefe Jr. J. M., Lavie Jr. C. J., and McCallister, B. D., Insight into the pathogenesis and prevention of coronary artery disease. May. Clinic Proceeding, 70, 69–79 (1995).

    Article  Google Scholar 

  • Oliveros, L. B., Videla, A. M., Ramirez, D. C., and Gimenez, M. S., Dietary fat saturation produces lipid modifications in peritoneal macrophage of mouse. J. Nutr. Biochem., 14, 370–377 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Park, C. S., Hwang, E. K., Lee, S. J., Roh, K. W., and Sohn, C. H., Age of growth of Ecklonia stolonifera Okamura in Pusan bay, Korea. Bull. Korean Fish. Soc., 27, 390–396 (1994).

    Google Scholar 

  • Pengzhan, Y., Ning, L., Xiguang, L., Gefei, Z., Quanbin, Z., and Pengcheng, L., Antihyperlipidemic effects of different molecular weight sulfated polysaccharides from Ulva pertusa (Chlorophyta). Pharmacol. Res., 48, 543–549 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Raymond, J., Metcalfe, A., Salazkin, I., and Schwarz, A., Temporary vascular occlusion with poloxamer 407. Biomaterials, 25, 3983–3989 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Ricci, E. J., Lunardi, L. D., Nauclares, D. M., and Marchetti, J. M., Sustained release of lidocaine from poloxamer 407 gels. Int. J. Pharm., 288, 235–244 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Ro, H. S., Kim, O. J., Park, K. K., Cho, T. H., and Park, H. S., Studies on diet regimens for the development of hyperlipidemic animal model. J. Kor. Pharm. Sci., 24, 297–321 (1994).

    CAS  Google Scholar 

  • Ross, R., The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature, 362, 801–809 (1993).

    Article  PubMed  CAS  Google Scholar 

  • Rota, S., McWilliam, N. A., Baglin, T. P., and Byrne, C. D., Atherogenic lipoproteins support assembly of the prothrombinase complex and thrombin generation modulation by oxidation and vitamin E. Blood, 91, 509–515 (1998).

    Google Scholar 

  • Sanna, V., Kirschvink, N., Gustin, P., Garini, E., Roland, I., Delattre, L., and Evrard, B., Preparation and in vivo toxicity study of solid lipid microparticles as carrier for pulmonary administration. AAPS. Pharm. Sci. Tech., 5, e27 (2004).

    Article  Google Scholar 

  • Schaefer, E. J., Lichtenstein, A. H., Lamom-Fava, S., McNamara, J. R., and Ordovas, J. M., Lipoproteins, nutrition, aging, and atherosclerosis. Am. J. Clin. Nutr., 61, 726S–740S (1995).

    PubMed  CAS  Google Scholar 

  • Schmolka, I. R., Poloxamers in the pharmaceutical industry. In: Tarch, P. J. (Ed.). Polymers for controlled drug delivery. CSC Press, Boca Raton, pp. 189–215 (1991).

    Google Scholar 

  • Sliskovic, D. R., and White, A. D., Therapeutic potential of ACAT inhibitors as lipid lowering and anti-atherosclerotic agents. Trends Pharmacol. Sci., 12, 194–199 (1991).

    Article  PubMed  CAS  Google Scholar 

  • Szilvassy, Z., Csont, T., Pali, T., Droy-lefaix, M. T., and Ferdinandy, P., Nitric oxide, peroxinitrite and cGMP in atheroscleosis-induced hypertention in rabbits: beneficial effects of cicleranine. J. Vasc. Res., 38, 39–46 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Talbert, R., Hyperlipidemia, DePiro Textbook of Threrapeytics. Appleton and Lange, Connecticut, pp. 357–386 (1997).

    Google Scholar 

  • Taniguchi, K., Kurata, K., and Suzuki, M., Feeding-deterrent effect of phlorotannins from the brown alga Ecklonia stolonifera against the abalone Haliotis discushannai. Nippon Suisan Gakkaishi, 57, 2065–2071 (1991).

    CAS  Google Scholar 

  • Wald, N. J. and Law, M. R., Serum cholesterol and ischemic heart disease. Atherosclerosis, 118, S1–S5 (1995).

    Article  PubMed  CAS  Google Scholar 

  • White, C. R., Brock, T. A., Chang, L. Y., Crapo, J., Briscoe, P., Ku, D., Bardley, W. A., Gianturco, S. H., Gore, J., Freeman, B. A., and Tarpey, M. M., Superoxide and peroxinitrite in atherosclerosis. Proc. Natl. Acad. Sci. USA, 91, 1044–1048 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Wout, Z. G., Pec E. A., and Maggiore, J. A., Poloxamer 407-mediated changes in plasma cholesterol and triglycerides following intraperitoneal injection to rats. J. Parenter. Sci. Technol., 46, 192–200 (1992).

    PubMed  CAS  Google Scholar 

  • Yamada, K., Tokunaga, Y., Ikeda, A., Ohkura, K., Kaku-Ohkura, S., Mamiya, S., Lim, B. O., and Tachibana, H., Effect of dietary fiber on the lipid metabolism and immune function of aged Sprague-Dawley rats. Biosci. Biotechnol. Biochem., 67, 429–433 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Yasuda, S., Townsend, D., Michele, D. E., Favre, E. G., Day, S. M., and Metzger, J. M., Dystrophic heart failure blocked by membrane sealant poloxamer. Nature, 436, 1025–1029 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Yokozawa, T., Cho, E. J., Sasaki, S., Satoh, A., Okamato, T., and Sei, Y., The protective role of Chinese prescription kangen-karyu extract on diet-induced hypercholesterolemia in rats. Biol. Pharm. Bull., 29, 760–765 (2006).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jae Sue Choi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yoon, N.Y., Kim, H.R., Chung, H.Y. et al. Anti-hyperlipidemic effect of an edible brown algae, Ecklonia stolonifera, and its constituents on poloxamer 407-induced hyperlipidemic and cholesterol-fed rats. Arch. Pharm. Res. 31, 1564–1571 (2008). https://doi.org/10.1007/s12272-001-2152-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-001-2152-8

Key words

Navigation