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Acetyl- and butyrylcholinesterase inhibitory activities of sterols and phlorotannins from Ecklonia stolonifera

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Abstract

As part of this study on the isolation of cholinesterase inhibitors from natural marine products, the bioactivity of the ethanolic extracts from 27 Korean seaweeds were screened using acetylcholinesterase (AChE) and butyrylcholine sterase (BChE) inhibitory assays. Ecklonia stolonifera exhibited promising inhibitory properties against both AChE and BChE. Bioassay-guided fractionation of the active n-hexane and ethyl acetate (EtOAc) soluble fractions, obtained from the ethanolic extract of E. stolonifera, resulted in the isolation of the sterols; fucosterol (1) and 24-hydroperoxy 24-vinylcholesterol (2), from the n-hexane fraction and the phlorotannins; phloroglucinol (3), ecks-tolonol (4), eckol (5), phlorofucofuroeckol-A (6), dieckol (7), triphlorethol-A (8), 2-phloroeckol (9) and 7-phloroeckol (10), from the EtOAc fraction. Of these, compounds 2, 9 and 10 were isolated from E. stolonifera for the first time. Compounds 4–7, 9 and 10 exhibited inhibitory potential against AChE, with 50% inhibition concentration (IC50) values of 42.66±8.48, 20.56±5,61, 4.89±2.28, 17.11±3.24, 38.13±4.95 and 21.11±4.16 μM, respectively; whereas, compounds 1, 2, 4 and 6 were found to be active against BChE, with IC50 values of 421.72±1.43, 176.46±2.51, 230.27±3.52 and 136.71±3.33 μM, respectively. It has been suggested that the inhibition of these enzymes by the sterols and phlorotannins derived from marine brown algae could be a useful approach for the treatment of Alzheimer’s disease.

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References

  1. Alzheimer A. Über eine eijenartige Erkrankung der Hirnride. Allg. Z. Psychiatr. 1907; 64: 146–148.

    Google Scholar 

  2. Davies P, Maloney AJF. Selective loss of central cholinergic neurons in Alzheimer’s disease. Lancet 1976; 2: 1403.

    Article  PubMed  CAS  Google Scholar 

  3. Whitehouse PJ, Price DL, Struble GR, Clarke AW, Coyle JT, DeLong MR. Alzheimer’s disease and senile dementia: loss of neurons in the basal forebrain. Science 1982; 15: 1237–1239.

    Article  Google Scholar 

  4. Schulz V. Ginkgo extract or, cholinesterase inhibitors in patients with dementia: what clinical trials and guidelines fail to consider. Phytomedicine 2003; 10: 74–79.

    Article  PubMed  CAS  Google Scholar 

  5. Small GW, Robins RV, Barry PP, Buckholts NS, Dekosky ST, Ferris SH, Finkel SI, Gwyther LP, Khachaturian ZS, Lebowitz BD, McRae TD, Morris JO, Oakley F, Schneider LS, Streim JE, Sunderland T, Teri LA, Tune LE. Diagnosis and treatment of Alzheimer’s disease and related disorder. JAMA 1997; 278: 1363–1371

    Article  PubMed  CAS  Google Scholar 

  6. Melzer D. New drug treatment for Alzheimer’s disease: lesson for healthcare policy. BMJ 1998; 316: 762–764.

    PubMed  CAS  Google Scholar 

  7. Rahman AU, Parveen S, Khalid A, Farooq A, Choudhary MI. Acetyl and butyrylcholinesterase-inhibiting triterpenoid alkaloids from Buxus papillosa. Phytochemistry 2001; 58: 963–968.

    Article  Google Scholar 

  8. Cláudia V Jr, Bolzani VS, Pimentel LSB, Castro NG, Cabral RR, Costa RS, Floyd C, Rocha MS, Young MCM, Barreiro EJ, Fraga CAM. New selective acetylcholinesterase inhibitors designed from natural piperidine alkaloids. Bioorg. Med. Chem. 2005; 13: 4184–4190.

    Article  CAS  Google Scholar 

  9. Cho KM, Yoo ID, Kim WG. 8-Hydroxydihydrochelerythrine and 8-hydroxydihytrosanguinarine with a potent acetylcholinesterase inhibitory activity from Chelidonium majus L. Biol. Pharm. Bull. 2006; 29: 2317–2320.

    Article  PubMed  CAS  Google Scholar 

  10. Kim DK, Lee KT, Baek NI, Kim SH, Park HW, Lim JP, Shin TY, Eom DO, Yang JH, Eun JS. Acetylcholinesterase inhibitors from the aerial parts of Corydalis speciosa. Arch. Pharm. Res. 2004; 27: 1127–1131.

    Article  PubMed  CAS  Google Scholar 

  11. Rahman AU, Wahab AT, Nawaz SA, Choudhary MI. New cholinesterase inhibiting bisbenzylisoquinoline alkaloids from Cocculus pendulus. Chem. Pharm. Bull. 2004; 52: 802–806.

    Article  Google Scholar 

  12. Decker M. Novel inhibitors of acetyl- and butyrylcholinesterase derived from the alkaloids dehydroevodiamine and rutaecarpine. Eur. J. Med. Chem. 2005; 40: 305–313.

    Article  PubMed  CAS  Google Scholar 

  13. Rahman AU, Akhtar MN, Choudhary MI, Tsuda Y, Sener B, Khalid A, Parvez M. New steroidal alkaloids from Fritillaria imperialis and their cholinesterase inhibiting activities. Chem. Pharm. Bull. 2002; 50: 1013–1016.

    Article  Google Scholar 

  14. Ryu GS, Park SH, Kim ES, Choi BW, Ryu SY, Lee BH. Cholinesterase inhibitory activity of two farnesylacetone derivatives from the brown alga Sargassum sagamianum. Arch. Pharm. Res. 2003; 26: 796–799.

    Article  PubMed  CAS  Google Scholar 

  15. Ucar G, Gokhan N, Yesilada A, Bilgin AA. 1-N-substituted thiocarbomoyl-3-phenyl-5-thienyl-2-prozolines: a novel cholinesterase and selected monoamine oxidase B inhibitors for the treatment of Parkinson’s and Alzheimer’s diseases. Neurosci. Lett. 2005; 382: 327–331.

    Article  PubMed  CAS  Google Scholar 

  16. Chounhary MI, Yousuf S, Nawaz SA, Ahmed S, Rahman AU. Cholinesterase inhibiting withanolides from Withania somnifera. Chem. Pharm. Bull. 2004; 52: 1358–1361.

    Article  Google Scholar 

  17. Perry NS, Houghton PJ, Theobald A, Jennar P, Perry EK. In vitro inhibition of human erythrocyte acetylcholinesterase by Salvia lavandulaefolia essential oil and constituent terpenes. J. Pharm. Parmacol. 2000; 52: 895–902.

    Article  CAS  Google Scholar 

  18. Savelev S, Okello E, Perry NSL, Wilkins RM, Perry EK. Synergistic and antagonistic interactions of anticholinesterase terpenoids in Salvia lavandulaefolia essential oil. Pharmacol. Biochem. Behav. 2003; 75: 661–668.

    Article  PubMed  CAS  Google Scholar 

  19. Lee JH, Lee KT, Yang JH, Baek NL, Kim DK. Acetylcholinesterase inhibitors from the twigs of Vaccinium oldhami Miquel. Arch. Pharm. Res. 2004; 27: 53–56.

    Article  PubMed  CAS  Google Scholar 

  20. Orhan I, Terzioglu S, Sener B. Alpha-onocerin: an acetylcholinesterase inhibitor from Lycopodium clavatum. Planta Med. 2003; 69: 265–267.

    Article  PubMed  CAS  Google Scholar 

  21. Yoo ID, Cho KM, Lee CK, Kim WG. Isoterreulactone A, a novel meroterpenoid with anti-acetylcholinesterase activity produced by Aspergillus terreus Bioorg. Med. Chem. Lett. 2005; 15: 353–356.

    Article  PubMed  CAS  Google Scholar 

  22. Cho KM, Kim WG, Lee CK, Yoo ID. Terreulactones A, B, C, and D: novel acetylcholinesterase inhibitors produced by Aspergillus terreus. I. Taxonomy, fermentation, isolation and biological activities. J. Antibiot. 2003; 56: 344–350.

    PubMed  CAS  Google Scholar 

  23. Mizayawa M, Tsukamoto T, Anzai J, Ishikawa Y. Insecticidal effect of phthalides and furanocoumarins from Angelica acutiloba against Drosophila melanogaster. J. Agric. Food Chem. 2004; 52: 4401–4405.

    Article  CAS  Google Scholar 

  24. Kang SY, Lee KY, Sung SH, Park MJ, Kim YC. Coumarins isolated from Angelica gigas inhibit acetylcholinesterase: structure-activity relationships. J. Nat. Prod. 2001; 64: 583–685.

    Article  CAS  Google Scholar 

  25. Urbain A, Marston A, Queriroz EF, Ndjoko K, Hostettmann K. A new coumarin from Murraya paniculata. Planta Med. 2004; 70: 1011–1014.

    Article  PubMed  CAS  Google Scholar 

  26. Ahmad I, Anis I, Malik A, Nawaz SA, Choudhary MI. A new coumarin from Murraya paniculata. Chem. Pharm. Bull. 2003; 51: 412–414.

    Article  PubMed  CAS  Google Scholar 

  27. Bruehlmann C, Marston A, Hostettmann K, Carrupt PA, Testa B. Screening of non-alkaloidal natural compounds as acetylcholinesterase inhibitors. Chem. Biodiversity 2004; 1: 819–829.

    Article  CAS  Google Scholar 

  28. Ahmed E, Nawaz SA, Malik A, Choudhary I. Isolation and cholinesterase-inhibition studies of sterol from Haloxylon recuvum. Bioorg. Med. Chem. Lett. 2006; 16: 573–580.

    Article  PubMed  CAS  Google Scholar 

  29. Chapman VJ, Champman DJ. Seaweeds and Their Uses. Champman and Hall, New York, 1980; 62–97.

    Google Scholar 

  30. Hoppe HA, Lerving T. Marine Algae in Pharmaceutical Science, Vol. 2. Walter de Gruyter, Berlin, 1982; 3–48.

    Google Scholar 

  31. Srivastava R, Kulshreshtha DK. Bioactive polysaccharide from plants. Phytochemistry 1989; 28: 2877–2883.

    Article  CAS  Google Scholar 

  32. Okada Y, Ishimaru A, Suzuki R, Okuyama T. A new phloro-glucinol derivative from the brown alga Eisenia bicylis: potential for the effective treatment of diabetic complications. J. Nat. Prod. 2004; 67: 103–105.

    Article  PubMed  CAS  Google Scholar 

  33. Noda H, Amano H, Arashima K, Hashimoto S, Nisizawa K. Studies on the antitumor activity of marine algae. Nippon Suisan Gakkaishi 1989; 55: 1259–1264.

    Google Scholar 

  34. Kim YC, An RB, Yoon NY, Nam TJ, Choi JS. Hepatoprotective constituents of the edible brown alga Ecklonia stolonifera on tacrine-induced cytotoxicity in Hep G2 cells. Arch. Pharm. Res. 2005; 28: 1376–1380.

    Article  PubMed  CAS  Google Scholar 

  35. Ahn MJ, Yoon KD, Kim CY, Min SY, Kim YU, Kim HJ, Kim JH, Shin CG, Lee CK, Kim TG, Kim SH Huh H, Kim JW. Inhibition of HIV-1 reverse transcriptase and HIV-1 integrase and antiviral activity of Korean seaweed extracts. J. Appl. Phycol. 2002; 14: 325–329.

    Article  CAS  Google Scholar 

  36. Fukuyama Y, Kodama M, Miura J, Kinzyo Z, Mori H, Nakayama Y, Takahashi M. Structure of an anti-plasmin inhibitor, eckol, isolated from the brown alga Ecklonia kurome Okamura and inhibitory activities of its derivatives on plasma plasmin inhibitors. Chem. Pharm. Bull. 1989; 37: 349–353.

    PubMed  CAS  Google Scholar 

  37. Fukuyama Y, Kodama M, Miura I, Kinzyo Z, Mori H, Nakayama Y, Takahashi M. Anti-plasmin inhibitor. VI. Structure of phlorofucofuroeckol A, a novel phlorotannin with both dibenzo-1,4-dioxin and dibenzofuran elements, from Ecklonia kurome Okamura. Chem. Pharm. Bull. 1990; 38: 133–135.

    PubMed  CAS  Google Scholar 

  38. Nagayama K, Shibata T, Fujimoto K, Honjo H, Nakamura T. Algicidal effect of phlorotannins from the brown alga Ecklonia kurome on red tide microalgae. Aquaculture 2003; 218: 601–611.

    Article  CAS  Google Scholar 

  39. Kang HS, Kim HR, Byun DS, Son BW, Nam TJ, Choi JS. Tyrosinase inhibitors isolated from the edible brown alga Ecklonia stolonifera. Arch. Pharm. Res. 2004; 27: 1226–1232.

    Article  PubMed  CAS  Google Scholar 

  40. Shin HC, Hwang HJ, Kang KJ, Lee BH. An antioxidative and anti-inflammatory agent for potential treatment of osteoarthritis from Ecklonia cava. Arch. Pharm. Res. 2006; 29: 165–171.

    Article  PubMed  CAS  Google Scholar 

  41. Choi JS, Lee JH, Jung JH. The screening of nitrite scavenging effect of marine algae and active principles of Ecklonia stolonifea. J. Kor. Fish. Soc. 1997; 30: 909–915.

    CAS  Google Scholar 

  42. Kim MM, Ta QV, Mendis E, Rajapakse N, Jung WK, Byun HK, Jeon YJ, Kim SK. Phlorotannins in Ecklonia cava extract inhibit matrix metalloproteinase activity. Life Sci. 2006; 79: 1436–1443.

    Article  PubMed  CAS  Google Scholar 

  43. Joe MJ, Kim SN, Choi HY, Shin WS, Park GM, Kang DW, Kim YK. The inhibitory effects of eckol and dieckol from Ecklonia stolonifera on the expression of matrix metalloproteinase-I in human dermal fibroblasts. Biol. Pharm. Bull. 2006; 29: 1735–1739.

    Article  PubMed  CAS  Google Scholar 

  44. Athukorala Y, Jung WK, Vasanthan T, Jeon YJ. An anticoagulative polysaccharide from an enzymatic hydrolysate of Ecklonia cava. Carbohydr. Polym. 2006; 66: 184–191.

    Article  CAS  Google Scholar 

  45. Yuan YV, Walsh NA. Antioxidant and antiproliferative activities of extracts from a variety of edible seaweeds. J Food Chem. Toxicol. 2006; 44: 1144–1150.

    Article  CAS  Google Scholar 

  46. Kang HS, Chung HY, Kim JY, Son BW, Jung HA, Choi JS. Inhibitory phlorotannins from the edible brown alga Ecklonia stolonifera on total reactive oxygen species (ROS) generation. Arch. Pharm. Res. 2004; 27: 194–198.

    Article  PubMed  CAS  Google Scholar 

  47. Kang HS, Chung HY, Jung JH, Son BW, Choi JS. A new phlorotannin from the brown alga Ecklonia stolonifera. Chem. Pharm. Bull. 2003; 51: 1012–1014.

    Article  PubMed  CAS  Google Scholar 

  48. Sugiura Y, Matsuda K, Yamada Y, Nishikawa M, Shioya K, Katsuzaki H, Imai K, Amano H. Isolation of a new antiallergic phlorotannin, phlorofucofuroeckol-B, from an edible brown alga, Eisenia arborea. Biosci. Biotechnol. Biochem. 2006; 70: 2807–2811.

    Article  PubMed  CAS  Google Scholar 

  49. Park CS, Hwang EK, Lee SJ, Roh KW, Sohn CH. Age of growth of Ecklonia stolonifera Okamura in Pusan bay, Korea. Bull. Kor. Fish. Soc. 1994; 27: 390–396.

    Google Scholar 

  50. Taniguchi K, Kurata K, Suzuki M. Feeding-detergent effect of phlorotannins from the brown alga Ecklonia stolonifera against the abalone Haliotis discus hannai. Nippon Suisan Gakkaishi 1991; 57: 2065–2071.

    CAS  Google Scholar 

  51. Park DC, Ji CI, Jung KJ, Lee TG, Kim IS, Park YH, Kim SB. Characteristics of tyrosinase inhibitory extract from Ecklonia stolonifera. J. Kor. Fish. Soc. 2000; 3: 195–199.

    Google Scholar 

  52. Jung HA, Hyun SK, Kim HR, Choi JS. Angiotensin-converting enzyme I inhibitory activity of phlorotannins from Ecklonia stolonifera. Fish. Sci. 2006; 72: 1292–1299.

    Article  CAS  Google Scholar 

  53. Ellman GL, Courtney D, Andres KDV, Featherstone RM. A new and rapid colorimetric determination of acetylcholineserase activity. Biochem. Pharmacol. 1961; 7: 88–95.

    Article  PubMed  CAS  Google Scholar 

  54. Govindan M, Hodge JD, Brown KA, Nunez-Smith M. Distribution of cholesterol in Caribbean marine algae. Steroids 1993; 58: 178–180.

    Article  PubMed  CAS  Google Scholar 

  55. Sheu JH, Wang GH, Sung PJ, Chiu YH, Duh CY. Chtotoxic sterols from the Formosan brown alga Turbinaria ornate. Planta Med. 1997; 63: 571–572.

    Article  PubMed  CAS  Google Scholar 

  56. Fukuyama Y, Miura I, Kinzyo Z, Mori H, Kido M, Nakayama Y, Takahashi M, Ochi M. Eckols, novel phlorotannins with a dibenzo-p-dioxin skeleton possessing inhibitory effects on α2-macroglobulin from the brown alga Ecklonia kurome Okamura. Chem. Lett. 1985, 739–742.

  57. Houghton PJ, Ren Y, Howes MJ. Acetylcholinesterase inhibitors from plants and fungi. Nat. Prod. Rep. 2006; 23: 181–199.

    Article  PubMed  CAS  Google Scholar 

  58. Silman I, Sussman JL. Acetylcholinesterase: ‘classical’ and ‘non-classical’ functions and pharmacology. Curr. Opin. Pharmacol. 2005; 5: 293–302.

    Article  PubMed  CAS  Google Scholar 

  59. Soreq H, Seidman S. Acetylcholinesterase-new roles for an old actor. Nat. Rev. Neurosci. 2001; 2: 294–302.

    Article  PubMed  CAS  Google Scholar 

  60. Mack A, Robitzki A. The key, role of butyrylcholinesterase during neurogenesis and neural disorders: an antisense-5′-butyrylcholinesterase-DNA study. Prog. Neurobiol 2000; 60: 607–628.

    Article  PubMed  CAS  Google Scholar 

  61. Rakinczay Z, Brimijoin S. Biochemistry and pathophysiology of the molecular forms of cholinesterase. Subcell. Biochem. 1988; 12: 335–378.

    Google Scholar 

  62. Giacobini E. Drugs that target cholinesterase. In: Buccafusco JJ (ed.). Cognitive Enhancing Drugs. Birkhäuser-Verlag. Basel. 2004: 11–36.

    Google Scholar 

  63. Yu SQ, Utsuki HW, Brossi T, Greig ANH. Synthesis of novel phenserine-based-selective inhibitors of butyrylcholinesterase for Alzheimer’s disease. J. Med. Chem. 1999; 42: 1855–1861.

    Article  PubMed  CAS  Google Scholar 

  64. Myung CS, Shin HC, Bao HY, Yeo SJ, Lee BH, Kang JS. Improvement of memory by dieckol and phlorofucofuroeckol in ethanol-treated mice: possible involvement of the inhibition of acetylcholinesterase. Arch. Pharm. Res. 2005; 28: 691–698.

    Article  PubMed  CAS  Google Scholar 

  65. Lee SH, Lee YS, Jung SH, Kang SS, Shin KH. Anti-oxidant activities of fucosterol from the marine algae Pelvetia siliquosa. Arch. Pharm. Res. 2003; 26: 719–722.

    Article  PubMed  CAS  Google Scholar 

  66. Lee YS, Shin KH, Kim BK, Lee SH. Anti-diabetic activities of fucosterol from Pelvetia siliquosa. Arch. Pharm. Res. 2004; 27: 1120–1122.

    Article  PubMed  CAS  Google Scholar 

  67. Brenner GM. Pharmacology. W.B. Saunders Company, Philadelphia, PA. 2000.

    Google Scholar 

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Authors and Affiliations

  1. Division of Food Science and Biotechnology, Pukyong National University, 608-737, Busan, Japan

    Na Y Yoon, Hyeung R Kim & Jae E Choi

  2. College of Pharmacy, Pusan National University, 609-735, Busan, Republic of Korea

    Hae Y Chung

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Yoon, N.Y., Chung, H.Y., Kim, H.R. et al. Acetyl- and butyrylcholinesterase inhibitory activities of sterols and phlorotannins from Ecklonia stolonifera . Fish Sci 74, 200–207 (2008). https://doi.org/10.1111/j.1444-2906.2007.01511.x

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