Korean Journal of Medicinal Crop Science (한국약용작물학회지)

The Korean Society of Medicinal Crop Science (한국약용작물학회)
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Inhibitory Activity of Plant Extracts against Prolyl Endopeptidase

식물자원의 Prolyl Endopeptidase 저해활성 탐색

  • Kim, Geum-Soog (Ginseng & Medicinal Crops Division, National Institute of Crop Science, RDA) ;
  • Lee, Seung-Eun (Ginseng & Medicinal Crops Division, National Institute of Crop Science, RDA) ;
  • Lee, Hee-Ju (Dept. of Agricultural Chemistry, Kyungpook National University) ;
  • Kim, Yi-Min (Ginseng & Medicinal Crops Division, National Institute of Crop Science, RDA) ;
  • Jeon, So-Young (Dept. of Agricultural Chemistry, Kyungpook National University) ;
  • Park, Chun-Geon (Ginseng & Medicinal Crops Division, National Institute of Crop Science, RDA) ;
  • Seong, Nak-Sul (Ginseng & Medicinal Crops Division, National Institute of Crop Science, RDA) ;
  • Song, Kyung-Sik (Dept. of Agricultural Chemistry, Kyungpook National University)
  • Published : 2004.03.31
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Abstract

Prolyl endopeptidase (PEP) is proline-specific serine protease, cleaving peptide bonds on the biologically active neuropeptides such as substance P, vassopressin, and thyrotropin-releasing hormone and is, therefore, suggested to play important roles in learning and memory process. In this work, the inhibitory effect of plant extracts on PEP was investigated. Out of 200 plant extracts, Prunus mume, Pyrola. japonica, Hypericum ascyron, Astilbe chinensis var. typica, and Elaeagnus umbellata inhibited more than 90% of PEP activity at the concentration of 5 ppm.

200종의 식물추출물을 대상으로 PEP 저해활성을 측정한 결과, 81종의 식물추출물은 $10{\sim}30%$ 범위의 저해율을, 28종의 식물추출물은 10%이하의 저해율을 나타내어 총 200종의 식물추출물 중 약 55% 정도의 식물추출물이 30%이하의 낮은 PEP 저해활성을 나타내었다. 반면에, Prunus mume (매화나무) 잎 (95.3%), 노루발과 (Pyrolaceae)의 Pyrola japonica (노루발) 잎과 줄기 (93.2%), 물레나물과 (Hypericaseae)의 Hypericum ascyron (물레나물) 지상부 (90.2%), 범의귀과(Saxifragaceae)의 Astilbe chinensis var. typica (노루오줌) 지상부 (90.1%), 보리수나무과 (Elaeagnaceae)의 Elaeagnus umbellata (보리수나무) 잎과 줄기 (90.1%)등 5종의 추출물들이 5 ppm에서 PEP에 대하여 90% 이상의 강한 저해활성을 나타내었다.

Keywords

References

  1. Aoyagi T， Nagai M， Ogawa K， Kojima F. Okada M， Ikeda T， Hmada M， Takeuchi (1991) Postatin, a new inhibitor of prolyl endopeptidase， produced by Streptomyces viridochromogenes MH534-30F3. 1. Taxonomy， production， isolation， physico-chemical properties and biological activities. J. Antibiotics 44:949-955 https://doi.org/10.7164/antibiotics.44.949
  2. Auld DS， Kar S， Quirion R (1998) $\beta$-amyloid peptides as direct cholinergic neuromodulators missing link? Trends Neurosci 21:43-49 https://doi.org/10.1016/S0166-2236(97)01144-2
  3. Butterweck V， Bockers T， Korte B， Wittkowski W， Winterhoff H (2002) Long-term effects of St. John's wort and hypericin on monoamine levels in rat hypothalamus and hippocampus. Brain Res. 930:21-29 https://doi.org/10.1016/S0006-8993(01)03394-7
  4. Copani A， Sortino MA， Nicoletti F， Giuffrida Stella AM (2002) Alzheimer's disease research enters a 'new cycle' How singificant? Neurochem. Res. 27(1/2):173-176 https://doi.org/10.1023/A:1014879311761
  5. Han JS， Lee JY， Baek NI， Back IW， Shin DH (2002) Isolation of growth inhibition substance on food borne microorganisms from Hypericum ascyron L. an application to food preservation Korean J. Food. Sci. Technol. 34(2):274-282
  6. Han JT， Lee SY， Kim KN， Baek NI (200l) Rutin， antioxidant compound isolation from the fruit of Prunus mume. J. Korean Soc. Agric. Chem. Biotechnol. 44(1):35-37
  7. Ichai C， Chevalier N， Delaere P， Dournaud P， Epelbaum J， Hauw JJ， Vicent JP， Cheder F (1994) Influence of regionspecific alterations of neuropeptidase content on the catabolic rates of neuropeptides in Alzheimer's disease. J. Neurochem. 62:645-655 https://doi.org/10.1046/j.1471-4159.1994.62020645.x
  8. Irazusta J， Larrinaga G， Gonzalez-Maeso J， Gil J， Meana J， Casis L (2002) Distribution of prolyl endopeptidase activities in rat and human brain. Neurochem. Int. 40:337-345 https://doi.org/10.1016/S0197-0186(01)00078-X
  9. Jung SE， Bae JH (2002) The effect of Prunus mume extracts on the growth of HepG2 and HeLa cell lines. Korean J. Nutrition 35(4):439-445
  10. Kamei H， Ueki T， Obi Y， Fukagawa Y， Oki T (1992) Protective effect of eurystatin A and B， new prolyl endopeptidase inhibitors， on scopolamine-induced amnesia in rats. Japan]. Pharmacol. 60:377-380 https://doi.org/10.1254/jjp.60.377
  11. Kato A， Fukunari A， Tabira T， Shimizu T， Arahata K， Sugita HD (1997) Prevention of amyolid-like deosition by a selective prolyl endopeptidase inhibitor， Y-29794， in senescenceaccelerated mouse. J. Phamacol. Exp. Therap. 283:328-335
  12. Kim BJ， Kim JH (1997) Biological screening of 100 plant extracts for cosmetic use (II) : anti-oxidative activity and tree radical scavenging activity. Intl. J. Cosmet Sci. 19:299-307 https://doi.org/10.1046/j.1467-2494.1997.171726.x
  13. Kim KB， Kim SI， Kim JS， Song KS (1999) Prolyl endopeptidase inhibiting isoflavonoids from Puerariae Flos and some revision of their 13C-NMR assignment. J. Korean Soc. Agric. Chern. Biotechnol. 42(4):351-355
  14. Kim SI， Song KS (2000) 1，2，3，4，6-pentagalloyl-，$\beta$-D glucopyranose， a prolyl endopeptidase inhibitor from moutan cortex. J. Korean Soc. Agric,. Chem. Biotechnol. 43(2):158-161
  15. Lee KH， Kwak JH， Lee KB， Song KS (1998) Prolyl endopeptidase inhibitors from Caryophylli Flos. Arch. Pharm. Res. 21(2):207-211 https://doi.org/10.1007/BF02974029
  16. Masters CL， Simms G， Weinman NA， Multhaup G， McDonald BL，Beyreuther K (1985) Amyloid plaque core protein in Alzheimer disease and down syndrome. Pro. Natl. Acad Sci. USA. 82:4245-4249 https://doi.org/10.1073/pnas.82.12.4245
  17. Nagai M， Ogawa K， Muraoka Y， Naganawa H， Aoyagi T， Takeuchi T (1991) Poststatin， a new inhibitor of prolyl endopeptidase， produced by Streptomyces MH534-30F3. II Structure determination and inhibitory activities. J. Antibiotics 44:956-961 https://doi.org/10.7164/antibiotics.44.956
  18. Nakajima T， Ono Y， Kato A， Maeda]， Ohe T (1992) Y-29794-a non-peptide prolyl endopeptidase inhibitor that can penetrate into brain. Neurosci. Lett. 141:156-160 https://doi.org/10.1016/0304-3940(92)90884-A
  19. Schneider JS， Giardiniere M， Morain P (2002) Effects of the prolyl endopeptidase inhibitor S 17092 on cognitive deficits in chronic low dose MPTP-treated monkeys. Neuropsychopharmacol. 26(2):176-182 https://doi.org/10.1016/S0893-133X(01)00307-4
  20. Seo MH， Bae JH (2002) Effect of butanol extracts from Prunus mume on the growth of Salmonella typhunrium. Korean J. Nutrition 35(9):926-931
  21. Shishido Y, Furushiro M, Tanabe S, Nishiyama S, Hashimoto S, Ohno M, Yamamoto T, Watanabe S(1996) ZTTA, a post proline cleaving enzyme inhibitor, improves cerebral ischemia-induced deficits in a three-panel runway task in rats. Pharmacol. Biochem. Behav. 55:333-338 https://doi.org/10.1016/S0091-3057(96)00102-5
  22. hishido Y, Furushiro M, Tanabe S, Shibata S,Hashimoto S, Yokokura T (1999) Effects of prolyl endopeptidase inhibitors and neuropeptides on delayed neuronal death in rats. Eur. J. Pharmacol. 372:135-142 https://doi.org/10.1016/S0014-2999(99)00185-5
  23. Suh YH (1992) Molecular biology of Alzheimer' s disease. Saengwhahak Nyusu 12:283-241
  24. Toda S， Obi Y， Numata K， Hamagishi Y， Tomita K， Komiyama N， Kotake C， Furumai T， Oki T (1992) Eurystatins A and B， new prolyl endopeptidase inhibitors. I. Taxonomy， production， isolation and biological activities. J. Antibiotics 45:1573-1579 https://doi.org/10.7164/antibiotics.45.1573
  25. Toide K， Iwamoto Y， Fujiwara T， Abe H (1995) JTP-4819: a novel pr이yl endopeptidase inhibitor with potential as cognitive enhancerι J. Pharmacol. ，Exp. Therapeutics 274:1370-1378
  26. Toide K， Shinoda M， Iwamoto Y， Fujiwara T， Okamiya K， Uemura A (1997) A novel prolyl endopeptidase inhibitor， JTP-4819， with potential for treating Alzheimer's disease. ，Behav. Brain Res. 83:147-151 https://doi.org/10.1016/S0166-4328(97)86059-7
  27. Tsuru D， Yoshmoto T (1987) 抗健忘症藥の開發-プロリルエンドペプチダ-ゼ沮害劑の開發 Bio Industry 4:778-796
  28. Turner AJ (1986) Processing and metabolism of neuropeptides. Essays Biochem 22:69-119
  29. Vendeville S， Goossens F， Debreu-Fontaine MA， Landry V，Davioud-Charvet ED， Grellier P， Scharpe S， Sergheraert C (2002) Comparison of the inhibition of human and Trypanosoma cruzi prolyl endopeptidases, Bioorgan. Med. Chem. 10:1719-1729 https://doi.org/10.1016/S0968-0896(02)00035-4
  30. Walter R， Shlank H， Glass JD， Schwartz IL， Kerenyi TD (1971) Leucyl-glycinamide released from oxytocin by human uterine enzyme. Science 173:827-829 https://doi.org/10.1126/science.173.3999.827
  31. Welches WR， Brosniham KB， Ferrari CM (1993) A comparison of the properties and enzymatic activities of three angiotinsin processing enzymes angiotensin converting enzyme， prolyl endopeptidase and neutral endopeptidase 24. 11. Life Sci. 52:1461-1480 https://doi.org/10.1016/0024-3205(93)90108-F
  32. Yoshimoto T， Kado K， Matsubara F， Koriyama N， Kaneto H， Tsuru D (1987) Specific inhibitors for prolyl endopeptidase and their anti-amnesic effect. J. Pharmacobio-Dyn. 10:730-735 https://doi.org/10.1248/bpb1978.10.730
  33. 김창민， 신민교， 안덕균， 이청순(완역) 1998. 중약대사전 도서출판 정담. p. 3952-3954