Improvement of Learning Behavior of Mice by an Antiacetylcholinesterase and Neuroprotective Agent NX42, a Laminariales-Alga Extract

Acetylcholinesterase 억제 및 신경세포 보호 활성을 갖는 다시마목 해조 추출물 NX42의 마우스 학습능력 향상 효과

  • Published : 2004.12.31

Abstract

Brown-alga-derived natural agent NX42, mainly composed of algal polysaccharides and phlorotannins, showed mild but dose-dependent inhibition of acetylcholinesterase with $IC_{50}=600-700\;{\mu}g/mL$. Phlorotannin-rich fraction of NX42 showed substantial increase of the activity by more than one order of magnitude ($IC_{50}=54\;{\mu}g/mL$) and significant protection of SK-N-SH cells from oxidative stress by $H_2O_2$. Learning trials of mice for 5 consecutive days revealed electric-shock treatment during learning period significantly retarded learning process, whereas NX42-treated mice showed significant resistance against leaning deficiency possibly mainly due to anticholinesterase and neuroprotective activities of phlorotannin.

Keywords

learning behavior;anticholinesterase;neuroprotective;alga extract

References

  1. Roman GC, Rogers SJ. Donepezil: a clinical review of current and emerging indications. Expert Opin. Pharmacother. 5: 161-180 (2004) https://doi.org/10.1517/14656566.5.1.161
  2. Tracy HM. Disorders of memory: mild cognitive impairment. Neuro Invest. 102: 4-18 (2003)
  3. Sanford LD, Yang L, Tang X. Influence of contextual fear on sleep in mice: a strain comparison. Sleep 26: 527-540 (2003) https://doi.org/10.1093/sleep/26.5.527
  4. Jang CG, Lee SY, Yoo JH, Yan JJ, Song DK, Loh HH, Ho IK. Impaired water maze learning performance in m-opioid receptor knockout mice. Mol. Brain Res. 117: 68-72 (2003) https://doi.org/10.1016/S0169-328X(03)00291-2
  5. Ba F, Pang PK, Benishin CG. The establishment of a reliable cytotoxic system with SK-N-SH neuroblastoma cell culture. J. Neurosci. Meth. 123: 11-22 (2003) https://doi.org/10.1016/S0165-0270(02)00324-2
  6. Shibata T, Fujimoto K, Nagayama K, Yamaguchi K, Nakamura T. Inhibitory activity of brown algal phlorotannins against hyaluronidase. Int. J. Food Sci. Technol. 37: 703-709 (2002) https://doi.org/10.1046/j.1365-2621.2002.00603.x
  7. Fukuyama Y, Kodama M, Miura I, Kinzyo Z, Kido M, 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 plasmin inhibitors. Chem. Pharm. Bull. 37: 349-353 (1989) https://doi.org/10.1248/cpb.37.349
  8. Nakamura T, Nagayama K, Uchida K, Tanaka R. Antioxidant activity of phlorotannins isolated from the brown alga Eisenia bicyclis. Fish. Sci. 62: 923-926 (1996) https://doi.org/10.2331/fishsci.62.923
  9. Morita K, Nakano T. Seaweed accelerates the excretion of dioxin stored in rats. J. Agric. Food Chem. 50: 910-917 (2002) https://doi.org/10.1021/jf0111920
  10. Ellmans GL, Courtney KD, Andress VJ, Featherstone RM. 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
  11. Wenk GL. The nucleus basalis magnocellularis cholinergic system: one hundred years of progress. Neurobiol. Learn. Mem. 67: 85-95 (1997) https://doi.org/10.1006/nlme.1996.3757
  12. Power AE, Vazdarjanova A, McGaugh JL. Muscarinic cholinergic influences in memory consolidation. Neurobiol. Learn. Mem. 80: 178-193 (2003) https://doi.org/10.1016/S1074-7427(03)00086-8
  13. Fagen ZM, Mansvelder HD, Keath JR, McGehee DS. Short- and long-term modulation of synaptic inputs to brain reward areas by nicotine. Ann. N.Y. Acad. Sci. 1003: 185-195 (2003) https://doi.org/10.1196/annals.1300.011
  14. Mori K, Muto Y, Kokuzawa J, Yoshioka T, Yoshimura S, Iwama T, Okano Y, Sakai N. Neuronal protein NP25 interacts with Factin. Neurosci. Res. 48: 439-446 (2004) https://doi.org/10.1016/j.neures.2003.12.012
  15. Dubois B, Albert ML. MCI or prodromal Alzheimer's disease? Lancet Neurol. 3: 246-248 (2004) https://doi.org/10.1016/S1474-4422(04)00710-0
  16. Ruehl ML, Orozco JA, Stoker MB, McDonagh PF, Coull BM, Ritter LS. Protective effects of inhibiting both blood and vascular selectins after stroke and reperfusion. Neurol. Res. 24: 226-232 (2002) https://doi.org/10.1179/016164102101199738
  17. Delagarza VW. New drugs for Alzheimer's disease. Am. Fam. Phys. 58: 1175-1182 (1998)
  18. Rasmusson DD. The role of acetylcholine in cortical synaptic plasticity. Behav. Brain Res. 115: 205-218 (2000) https://doi.org/10.1016/S0166-4328(00)00259-X
  19. Kwon EK, Oh SW, Lee CH, Han D. Screening of HMG-CoA reductase inhibitoryactivity in several natural products (abstract no P7-32). In: 70th Nutrigenomics Symposium: Recent trends in food science and technology. June 26-28, Gyeongju TEMF Hotel,Gyeongju, Korea. The Korean Society of Food Science and Technology (2003)
  20. Kang JW. Illustrated Encyclopedia of Fauna and Flora of Korea. Vol. 8. Sam Hwa Publishing Co., Seoul, Korea (1968)
  21. Shibata T, Nagayama K, Tanaka R, Yamaguchi K, Nakamura T. Inhibitory effects of brown algal phlorotannins on secretory phospholipase $A_2s$ , lipoxygenases, and cycloxygenases. J. Appl. Phy-col.15:61-66(2003) https://doi.org/10.1023/A:1022972221002
  22. Disterhoft JF, Matthew OM. Modulation of cholinergic transmission enhances excitability of hippocampal pyramidal neurons and ameliorates learning impairments in aging animals. Neurobiol. Learn. Mem. 80: 223-233 (2003) https://doi.org/10.1016/j.nlm.2003.08.004
  23. Power AE. Slow-wave sleep, acetylcholine, and memory consolidation. Proc. Natl. Acad. Sci. USA. 101: 1795-1796 (2004) https://doi.org/10.1073/pnas.0400237101
  24. Tsukada H, Nishiyama S, Fukumoto D, Ohba H, Sato K, Kakiuchi T. Effects of acute acetylcholinesterase inhibition on the cerebral cholinergic neuronal system and cognitive function: functional imaging of the conscious monkey brain using animal PET in combination with microdialysis. Synapse 52: 1-10 (2004) https://doi.org/10.1002/syn.10310
  25. Taira K, Tanaka H, Arakawa M, Nagahama N, Uza M, Shirakawa S. Sleep health and lifestyle of elderly people in Ogimi, a village of longevity. Psych. Clinic. Neurosci. 56: 243-244 (2002) https://doi.org/10.1046/j.1440-1819.2002.01014.x
  26. Sharma SK, Carlson EC. Ebadi, neuroprotective actions of selegiline in inhibiting 1-methyl-4-phenylpyridinium ion (MPP+)- induced apoptosis in SK-N-SH neurons. J. Neurocytol. 32: 329- 343 (2003) https://doi.org/10.1023/B:NEUR.0000011327.23739.1b
  27. Uhm CS, Kim KB, Lim JH, Pee DH, Kim YH, Kim H, Eun BL, Tockgo YC. Effective treatment with fucoidan for perinatal hypoxic-ischemic encephalopathy in rats. Neurosci. Lett. 353: 21- 24 (2003) https://doi.org/10.1016/j.neulet.2003.09.013
  28. Glombitza KW, Gerstberger G. Phlorotannins with dibenzodioxin structural elements from the brown alga Eisenia arborea. Phytochemistry 24: 543-551 (1985) https://doi.org/10.1016/S0031-9422(00)80764-5
  29. Yasuji K, Takatoshi H, Dai W, Ira P, Shigetada N. Impairment of reward-related learning by cholinergic cell ablation in the striatum. Proc. Natl. Acad. Sci. USA. 100: 7965-7970 (2003) https://doi.org/10.1073/pnas.1032899100
  30. Ba F, Pang PK, Davidge ST, Benishin CG. The neuroprotective effects of estrogen in SK-N-SH neuroblastoma cell cultures. Neurochem. Intl. 44: 401-411 (2004) https://doi.org/10.1016/j.neuint.2003.08.004