Food Science and Biotechnology

Korean Society of Food Science and Technology (한국식품과학회)
권호 표지

Isolation of Acetylcholinesterase Inhibitors from the Flowers of Chrysanthemum indicum Linne

  • Lim, Soon-Sung (Regional Innovation Center, Hallym University) ;
  • Han, Sag-Myung (Department of Food Science and Nutrition, The Korean Institute of Nutrition, Hallym University) ;
  • Kim, Sun-Young (Department of Food Science and Nutrition, The Korean Institute of Nutrition, Hallym University) ;
  • Bae, Young-Soo (Department of Wood Science and Engineering, Kangwon National University) ;
  • Kang, Il-Jun (Department of Food Science and Nutrition, The Korean Institute of Nutrition, Hallym University)
  • Published : 2007.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

There is significant interest in finding new sources of acetylcholinesterase (AChE) inhibitors for use in treating Alzheimer's disease, since only a few AChE inhibitors are available for clinical use, such as galanthamine, physostigmine, and tacrine. The ethanol extract of Chrysanthemum indicum Linne flowers was analyzed and found to markedly decrease AChE activity. Acaciin and $acacetin-7-O-{\beta}-D-galactopyranoside$ were identified as the active compounds responsible for the AChE inhibition by using an activity-guided fractionation strategy. The relationship between structure and activity for five flavonoids (acaciin, $acacetin-7-O-{\beta}-D-galactopyranoside$, luteolin, and two other commercially available flavonoids, i.e., apigenin and acacetin) was also investigated, revealing that the presence of methoxy groups at C-4' in the B ring and a sugar at O-7 in ring A appear to be essential for the inhibition of AChE.

Keywords

References

  1. Quinn DM. Acetylcholinesterase - enzyme structure, reaction dynamics, and virtual transition states. Chem. Rev. 87: 955-979 (1987) https://doi.org/10.1021/cr00081a005
  2. Lleo A, Greenberg SM, Growdon JH. Current pharmacotherapy for Alzheimer's disease. Annu. Rev. Med. 57: 513-533 (2006) https://doi.org/10.1146/annurev.med.57.121304.131442
  3. Lane RM, Potkin SG, Enz A. Targeting acetylcholinesterase and butyrylcholinesterase in dementia. Int. J. Neuropsychoph. 9: 101-124 (2006)
  4. Bores GM, Huger FP, Petko W, Mutlib AE, Camacho F, Rush DK, Selk DE, Wolf V, Kosley RW Jr, Davis L, Vargas HM. Pharmacological evaluation of novel Alzheimer's disease therapeutics: acetylcholinesterase inhibitors related to galanthamine. J. Pharmacol. Exp. Ther. 277: 728-738 (1996)
  5. Wang ZG, Ren AN, Xu L, Sun XJ, Hua XB. The experimental study on the immunological and anti-inflammatory activities of Chrysanthemum indicum. Chinese J. Trad. Med. Sci. Technol. 2: 92-93 (2000)
  6. Yoshikawa M, Morikawa T, Murakami T, Toguchida I, Harima S, Matsuda H. Medicinal flowers. I. Aldose reductase inhibitors and three new eudesmane-type sesquiterpenes, kikkanols A, B, and C, from the flowers of Chrysanthemum indicum L. Chem. Pharm. Bull. 47: 340-345 (1999) https://doi.org/10.1248/cpb.47.340
  7. Yoshikawa M, Morikawa T, Toguchida I, Harima S, Matsuda H. Medicinal flowers. II. Inhibitors of nitric oxide production and absolute stereostructures of five new germacrane-type sesquiterpenes, kikkanols D, D monoacetate, E, F, and F monoacetate from the flowers of Chrysanthemum indicum L. Chem. Pharm. Bull. 48: 651-656 (2000) https://doi.org/10.1248/cpb.48.651
  8. Matsuda H, Morikawa T, Toguchida I, Harima S, Yoshikawa M. Medicinal flowers. VI. Absolute stereostructures of two new flavanone glycosides and a phenylbutanoid glycoside from the flowers of Chrysanthemum indicum L.: their inhibitory activities for rat lens aldose reductase. Chem. Pharm. Bull. 50: 972-975 (2002) https://doi.org/10.1248/cpb.50.972
  9. Zhu S, Yang Y, Yu H, Ying Y, Zou G. Chemical composition and antimicrobial activity of the essential oils of Chrysanthemum indicum. J. Ethnopharmacol. 96: 151-158 (2005) https://doi.org/10.1016/j.jep.2004.08.031
  10. Michael WW, Huang KC. The dried flower and petal of Chrysanthemum indicum L., C boreale Mak., and C.lavandulaefolium (Fisch.) Mak. p. 83. In: The Pharmacology of Chinese Herbs: 2nded. CRC Press, lnc., Boca Raton, FL, USA (1997)
  11. Ingkaninan K, Temkitthawon P, Chuenchom K, Yuyaem T, Thongnoi W. Screening for acetylcholinesterase inhibitory activity in plants used in Thai traditional rejuvenating and neurotonic remedies. J. Ethnopharmacol. 89: 261-264 (2003) https://doi.org/10.1016/j.jep.2003.08.008
  12. Ellman GL, Lourtney DK, Andres V, Gmelin G A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 7: 88-95 (1961) https://doi.org/10.1016/0006-2952(61)90145-9
  13. Tabarrini O, Cecchetti V, Temperini A, Filipponi E, Lamperti MG, Fravolini A. Velnacrine thia-analogues as potential agents for treating Alzheimer's disease. Bioorgan. Med. Chem. 9: 2921-2928 (2001) https://doi.org/10.1016/S0968-0896(01)00171-7
  14. Sugimoto H, Tsuchiya Y, Sugumi H, Higurashi K, Karibe N, Iimura Y, Sasaki A, Kawakami Y, Nakamura T, Araki S. Novel piperidine derivatives. Synthesis and anti-acetylcholinesterase activity of 1benzyl-4-[2-(N-benzoylamino)ethyl]piperidine derivatives. J. Med. Chem. 33: 1880-1887 (1990) https://doi.org/10.1021/jm00169a008
  15. Jann MW. Rivastigmine, a new-generation cholinesterase inhibitor for the treatment of Alzheimer's disease. Pharmacotherapy 20: 1-12 (2000) https://doi.org/10.1592/phco.20.1.1.34664
  16. Hana SY, Sweeneyb JE, Bachmanb ES, Schweigera EJ, Forlonic G, Coyleb JT, Davis BM, Joullie MM. Chemical and pharmacological characterization of galanthamine, an acetylcholinesterase inhibitor, and its derivatives. A potential application in Alzheimer's disease. Eur. J. Med. Chem. 27: 673-687 (1992) https://doi.org/10.1016/0223-5234(92)90087-H
  17. Winkler J, Thai LJ, Gage FH, Fisher LJ. Cholinergic strategies for Alzheimer's disease. J. Mol. Med. 76: 555-567 (1998) https://doi.org/10.1007/s001090050250
  18. Fredj G, Dietlin F, Barbier G, Jasmin C, Bonhomme L, Esctein S, Misset JL, Meyer P, Kalifa D, Beugre T. Comparison oftacrine hepatotoxicity in patients with Alzheimer disease or AIDS. Therapie 47: 245-247 (1992)
  19. Wagner H, Aurnhammer G, Horammer L, Farkas L. Investigations on the glycosides of acacetin. II. Note on the identity of acaciin from Robinia pseudoacacia L. with Iinarin from Linaria vulgaris P. Mill. Chem. Ber. 102: 1445-1446 (1969) https://doi.org/10.1002/cber.19691020443
  20. Chatterjee A, Sarkar S, Saha SK. Acacetin 7-O-$\beta$-D-galactopyranoside from Chrysanthemum indicum. Phytochemistry 20: 1760-1761 (1981) https://doi.org/10.1016/S0031-9422(00)98580-7
  21. Loy C, Schneider L. Galantamine for Alzheimer's disease. Cochrane DB. Syst. Rev. 18: CD001747 (2004)
  22. Nunomura A, Perry G, Aliev G, Hirai K, Takeda A, Balraj EK, Jones PK, Ghanbari H, Wataya T, Shimohama S, Chiba S, Atwood CS, Petersen RB, Smith MA. Oxidative damage is the earliest event in Alzheimer disease. J. Neuropath. Exp. Neur. 60: 759-767 (2001) https://doi.org/10.1093/jnen/60.8.759
  23. Duh P. Antioxidant activity of water extract of four Harng Jyur (Chrysanthemum morifolium Rarnat) varieties in soybean oil emulsion. Food Chem. 66: 471-476 (1999) https://doi.org/10.1016/S0308-8146(99)00081-3
  24. Duh P, Tu Y, Yen G. Antioxidant activity of water extract of Harng Jyur (Chrysanthemum morifolium Ramat) Lebensm. -Wiss. Technol. 32: 269-277 (1999) https://doi.org/10.1006/fstl.1999.0548
  25. Cha JD, Jeong MR, Lee YE. Induction of apoptosis in human oral epidermoid carcinoma cells by essential oil of Chrysanthemum boreale Makino. Food Sci. BioTechnol. 14: 350-354 (2005)
  26. Jeon JR, Park JR. Effects of Chrysanthemum boreale M. water extract on serum liver enzyme activities and Kupffer cells of carbon tetrachloride-induced rats. Food Sci. Biotechnol. 14: 290-296 (2005)
  27. Woo ER, Piao MS. Antioxidative constituents from Lycopus lucidus. Arch. Pharm. Res. 27: 173-176 (2004) https://doi.org/10.1007/BF02980102
  28. Kim S, Cho J, Wee J, Jang M, Kim C, Rim Y, Shin S, Ma S, Moon J, Park K. Isolation and characterization of antioxidative compounds from the aerial parts of Angelica keiskei. Food Sci. Biotechnol. 14: 58-63 (2005)