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Research article

Clinical Microbiology and Biomedical Sciences

Memory-Enhancing Effects of Silk Fibroin-Derived Peptides in Scopolamine-Treated Mice

Yong Koo Kang 1*, Woojoo Lee 2, Byunghoon Kang 1 and Hannah Kang 1

1BrainOn Inc., Seoul 150-037, Republic of Korea, 2Department of Statistics, Inha University, Incheon 402-751, Republic of Korea

Received: August 20, 2013; Accepted: September 16, 2013

J. Microbiol. Biotechnol. 2013; 23(12): 1779-1784

Published December 28, 2013 https://doi.org/10.4014/jmb.1308.08059

Copyright © The Korean Society for Microbiology and Biotechnology.

Abstract

Although enzyme-hydrolyzed silk fibroin has been reported to enhance cognitive function before, it has been still unknown which peptides can improve memory. Here we report that amino acid sequences of three novel peptides were identified from fibroin hydrolysate. Fibroin hydrolysate was obtained by hydrolysis with protease after partial hydrolysis with 5M CaCl2. Synthesized peptides derived from these sequences improved scopolamine-induced memory impairments in mice. We confirmed this hydrolysate had effects that improved learning and memory abilities by performing the Rey-Kim test. From this hydrolysate of silk fibroin, amino acid sequences of eight peptides were identified by LC-MS/MS. Three peptides (GAGAGTGSSGFGPY, GAGAGSGAGSGAGAGSGAGAGY, and SGAGSGAGAGSGAGAGSGA) were synthesized to investigate whether they could improve memory. Passive avoidance test and Morris water maze test were performed, and all peptides showed memory-enhancing abilities on scopolamine-induced memory impairments in mice. In this study, we identified three novel peptides that could improve memory, and that silk fibroin hydrolysate was a mixture of various active peptides that could enhance memory.

Keywords

peptide, memory, fibroin, silk, scopolamine

References

  1. Akai H. 1999. New physiological functions of silk material. Shokuhin to Kaihatsu 34: 45-47.
  2. Chen K, Umeda Y, Hirabayashi K. 1996. Enzymatic hydrolysis of silk fibroin. J. Seric. Sci. Jpn. 65: 131-133.
  3. Gill I , L opez-F andino R , J orba X , V ulfson E N. 1 996. Biologically active peptides and enzymatic approaches to their production. Enzyme Microb. Technol. 18: 162-183.
    CrossRef
  4. Gotoh K, Izumi H, Kanamoto T, Tamada Y, Nakashima H. 2000. Sulfated fibroin, a nove1 sulfated peptide derived from silk, inhibits human immunodeficiency virus replication in vitro. Biosci. Biotechnol. Biochem. 64: 1664-1670.
    Pubmed CrossRef
  5. Hanawa T, Watanabe A, Tsuchiya T, Ikoma R, Hidaka M, Sugihara M. 1995. New oral dosage form for elderly patients: preparation and characterization of silk fibroin gel. Chem. Pharm. Bull. 42: 282-288.
    CrossRef
  6. Igarashi K, Yoshioka K, Mizutani K, Miyakoshi M, Murakami T, Akizawa T. 2006. Blood pressure-depressing activity of a peptide derived from silkworm fibroin in spontaneously hypertensive rats. Biosci. Biotechnol. Biochem. 70: 517-520.
    Pubmed CrossRef
  7. Ikegawa Y, Sato S, Lim G, Hur W, Tanaka K, Komori M, et al. 2012. Amelioration of the progression of an atopic dermatitis-like skin lesion by silk peptide and identification of functional peptides. Biosci. Biotechnol. Biochem. 76: 473477.
    Pubmed CrossRef
  8. Kim DK, Kang YK, Lee MY, Lee KG, Yeo JH, Lee WB, et al. 2005. Neuroprotection and enhancement of learning and memory by BF-7. J. Health Sci. 51: 317-324.
    CrossRef
  9. Kim DK, Kim YH, Kim KB, Chin YG. 2001. The changes of molecular weight and structure in the preparation process of silk fibroin powder. J. Kor. Fiber Soc. 38: 105-110.
  10. Kim DK, Lee JY, Sung JJ, Kim ET, Kim YS, Kwon OS, et al. 2004. The role of BF-7 on enhancement of memory and cognitive function. Kor. J. Anat. 37: 519-527.
  11. Kim ED, Bayaraa T, Shin EJ, Hyun CK. 2009. Fibroinderived peptides stimulate glucose transport in normal and insulin-resistant 3T3-L1 adipocytes. Biol. Pharm. Bull. 32:427-433.
    Pubmed CrossRef
  12. Kim H. 1999. Rey-Kim Memory Test. Korea Neuropsychology Press, Seoul.
  13. Kim MK, Lee KH, Lim HJ, Lee SJ, Lee SH, Min KS. 1996. Preparation protocols for the functional polypeptide materials from cocoon. Kor. Patent 98712.
  14. Lee SH, Kim YS, Kang YK, Kwon OS, Shin YK, Song JH, et al. 2004. The improvement of learning and memory ability of normal persons by BF-7. Kor. J. Physiol. Pharmacol. 8: 307312.
  15. Lezak MD. 1983. Neuropsychological Assessment, Oxford University Press, New York.
  16. Luo J, Chen K, Xu Q, Hirabayashi K. 1993. Study on foodization of fibroin and its functionality. In: Collection of Papers for the Second International Silk Conference, China, pp. 73-87.
  17. Meisel H. 1997. Biochemical properties of bioactive peptides derived from milk proteins: potential nutraceuticals for food and pharmaceutical applications. Livestock Prod. Sci. 50: 125138.
    CrossRef
  18. Minoura N, Aiba SI, Higuchi M, Gotoh Y, Tsukada M, Imai Y. 1995. Attachment and growth of fibroblast cells on silk fibroin. Biochem. Biophys. Res. Commun. 208: 511-516.
    Pubmed CrossRef
  19. Minoura N, Tsukada M, Nagura M. 1990. Physico-chemical properties of silk fibroin membrane as a biomaterial. Biomaterials 11: 430-434.
    CrossRef
  20. Myhrer T. 2003. Neurotransmitter systems involved in learning and memory in the rat: a meta-analysis based on studies of four behavioral tasks. Brain Res. Brain Res. Rev. 41: 268-287.
    CrossRef
  21. Nahm JH, Oh YS. 1995. A study of pharmacological effect of silk fibroin. RDA J. Agric. Sci. 37: 145-157.
  22. Oh SR, Kim SJ, Kim DH, Ryu JH, Ahn EM, Jung JW. 2013 Angelica keiskei ameliorates scopolamine-induced memory impairments in mice. Biol. Pharm. Bull. 36: 82-88
    Pubmed CrossRef
  23. Qian J, Liu Y, Liu H, Yu T, Deng J. 1997. Immobilization of horseradish peroxidase with a regenerated silk fibroin membrane and its application to a tetrathiafulvalene-mediating H2O2 sensor. Biosens. Bioelectron. 12: 1213-1218.
    CrossRef
  24. Rey A. 1964. L’examen clinique en psychologie. Paris Press Universitaire de France, Paris.
  25. Rey A. 1941. L’examen psychologique dans lescas d’encphalopathie traumatique. Arch. Psychol. 28: 286-340.
  26. Takano R, Hirabayashi K, Chen K. 1991. Preparation of soluble silk fibroin powder by hydrochloric acid hydrolysis. Sov. Phys. Crystallogr. 60: 358-362.
  27. Yeo JH, Lee KG, Kweon HY, Woo SO, Han SM, Lee YW, et al. 2004. Cognitive ability enhancement effects in rats by B. mori fibroin by enzymatic hydrolysate. Korean J. Seric. Sci. 46: 23-27.

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Article

Research article

J. Microbiol. Biotechnol. 2013; 23(12): 1779-1784

Published online December 28, 2013 https://doi.org/10.4014/jmb.1308.08059

Copyright © The Korean Society for Microbiology and Biotechnology.

Memory-Enhancing Effects of Silk Fibroin-Derived Peptides in Scopolamine-Treated Mice

Yong Koo Kang 1*, Woojoo Lee 2, Byunghoon Kang 1 and Hannah Kang 1

1BrainOn Inc., Seoul 150-037, Republic of Korea, 2Department of Statistics, Inha University, Incheon 402-751, Republic of Korea

Received: August 20, 2013; Accepted: September 16, 2013

Abstract

Although enzyme-hydrolyzed silk fibroin has been reported to enhance cognitive function
before, it has been still unknown which peptides can improve memory. Here we report that
amino acid sequences of three novel peptides were identified from fibroin hydrolysate. Fibroin
hydrolysate was obtained by hydrolysis with protease after partial hydrolysis with 5M CaCl2.
Synthesized peptides derived from these sequences improved scopolamine-induced memory
impairments in mice. We confirmed this hydrolysate had effects that improved learning and
memory abilities by performing the Rey-Kim test. From this hydrolysate of silk fibroin, amino
acid sequences of eight peptides were identified by LC-MS/MS. Three peptides
(GAGAGTGSSGFGPY, GAGAGSGAGSGAGAGSGAGAGY, and SGAGSGAGAGSGAGAGSGA)
were synthesized to investigate whether they could improve memory. Passive avoidance test
and Morris water maze test were performed, and all peptides showed memory-enhancing
abilities on scopolamine-induced memory impairments in mice. In this study, we identified
three novel peptides that could improve memory, and that silk fibroin hydrolysate was a
mixture of various active peptides that could enhance memory.

Keywords: peptide, memory, fibroin, silk, scopolamine

References

  1. Akai H. 1999. New physiological functions of silk material. Shokuhin to Kaihatsu 34: 45-47.
  2. Chen K, Umeda Y, Hirabayashi K. 1996. Enzymatic hydrolysis of silk fibroin. J. Seric. Sci. Jpn. 65: 131-133.
  3. Gill I , L opez-F andino R , J orba X , V ulfson E N. 1 996. Biologically active peptides and enzymatic approaches to their production. Enzyme Microb. Technol. 18: 162-183.
    CrossRef
  4. Gotoh K, Izumi H, Kanamoto T, Tamada Y, Nakashima H. 2000. Sulfated fibroin, a nove1 sulfated peptide derived from silk, inhibits human immunodeficiency virus replication in vitro. Biosci. Biotechnol. Biochem. 64: 1664-1670.
    Pubmed CrossRef
  5. Hanawa T, Watanabe A, Tsuchiya T, Ikoma R, Hidaka M, Sugihara M. 1995. New oral dosage form for elderly patients: preparation and characterization of silk fibroin gel. Chem. Pharm. Bull. 42: 282-288.
    CrossRef
  6. Igarashi K, Yoshioka K, Mizutani K, Miyakoshi M, Murakami T, Akizawa T. 2006. Blood pressure-depressing activity of a peptide derived from silkworm fibroin in spontaneously hypertensive rats. Biosci. Biotechnol. Biochem. 70: 517-520.
    Pubmed CrossRef
  7. Ikegawa Y, Sato S, Lim G, Hur W, Tanaka K, Komori M, et al. 2012. Amelioration of the progression of an atopic dermatitis-like skin lesion by silk peptide and identification of functional peptides. Biosci. Biotechnol. Biochem. 76: 473477.
    Pubmed CrossRef
  8. Kim DK, Kang YK, Lee MY, Lee KG, Yeo JH, Lee WB, et al. 2005. Neuroprotection and enhancement of learning and memory by BF-7. J. Health Sci. 51: 317-324.
    CrossRef
  9. Kim DK, Kim YH, Kim KB, Chin YG. 2001. The changes of molecular weight and structure in the preparation process of silk fibroin powder. J. Kor. Fiber Soc. 38: 105-110.
  10. Kim DK, Lee JY, Sung JJ, Kim ET, Kim YS, Kwon OS, et al. 2004. The role of BF-7 on enhancement of memory and cognitive function. Kor. J. Anat. 37: 519-527.
  11. Kim ED, Bayaraa T, Shin EJ, Hyun CK. 2009. Fibroinderived peptides stimulate glucose transport in normal and insulin-resistant 3T3-L1 adipocytes. Biol. Pharm. Bull. 32:427-433.
    Pubmed CrossRef
  12. Kim H. 1999. Rey-Kim Memory Test. Korea Neuropsychology Press, Seoul.
  13. Kim MK, Lee KH, Lim HJ, Lee SJ, Lee SH, Min KS. 1996. Preparation protocols for the functional polypeptide materials from cocoon. Kor. Patent 98712.
  14. Lee SH, Kim YS, Kang YK, Kwon OS, Shin YK, Song JH, et al. 2004. The improvement of learning and memory ability of normal persons by BF-7. Kor. J. Physiol. Pharmacol. 8: 307312.
  15. Lezak MD. 1983. Neuropsychological Assessment, Oxford University Press, New York.
  16. Luo J, Chen K, Xu Q, Hirabayashi K. 1993. Study on foodization of fibroin and its functionality. In: Collection of Papers for the Second International Silk Conference, China, pp. 73-87.
  17. Meisel H. 1997. Biochemical properties of bioactive peptides derived from milk proteins: potential nutraceuticals for food and pharmaceutical applications. Livestock Prod. Sci. 50: 125138.
    CrossRef
  18. Minoura N, Aiba SI, Higuchi M, Gotoh Y, Tsukada M, Imai Y. 1995. Attachment and growth of fibroblast cells on silk fibroin. Biochem. Biophys. Res. Commun. 208: 511-516.
    Pubmed CrossRef
  19. Minoura N, Tsukada M, Nagura M. 1990. Physico-chemical properties of silk fibroin membrane as a biomaterial. Biomaterials 11: 430-434.
    CrossRef
  20. Myhrer T. 2003. Neurotransmitter systems involved in learning and memory in the rat: a meta-analysis based on studies of four behavioral tasks. Brain Res. Brain Res. Rev. 41: 268-287.
    CrossRef
  21. Nahm JH, Oh YS. 1995. A study of pharmacological effect of silk fibroin. RDA J. Agric. Sci. 37: 145-157.
  22. Oh SR, Kim SJ, Kim DH, Ryu JH, Ahn EM, Jung JW. 2013 Angelica keiskei ameliorates scopolamine-induced memory impairments in mice. Biol. Pharm. Bull. 36: 82-88
    Pubmed CrossRef
  23. Qian J, Liu Y, Liu H, Yu T, Deng J. 1997. Immobilization of horseradish peroxidase with a regenerated silk fibroin membrane and its application to a tetrathiafulvalene-mediating H2O2 sensor. Biosens. Bioelectron. 12: 1213-1218.
    CrossRef
  24. Rey A. 1964. L’examen clinique en psychologie. Paris Press Universitaire de France, Paris.
  25. Rey A. 1941. L’examen psychologique dans lescas d’encphalopathie traumatique. Arch. Psychol. 28: 286-340.
  26. Takano R, Hirabayashi K, Chen K. 1991. Preparation of soluble silk fibroin powder by hydrochloric acid hydrolysis. Sov. Phys. Crystallogr. 60: 358-362.
  27. Yeo JH, Lee KG, Kweon HY, Woo SO, Han SM, Lee YW, et al. 2004. Cognitive ability enhancement effects in rats by B. mori fibroin by enzymatic hydrolysate. Korean J. Seric. Sci. 46: 23-27.