Archives of Pharmacal Research

, Volume 30, Issue 7, pp 827–833 | Cite as

Plant phenolics as prolyl endopeptidase inhibitors

  • Seung -Ho Lee
  • Mira Jun
  • Ji -Young Choi
  • Eun -Ju Yang
  • Jong -Moon Hur
  • KiHwan Bae
  • Yeon -Hee Seong
  • Tae -Lin Huh
  • Kyung -Sik Song
Article Drug discovery

Abstract

Prolyl endopeptidase (PEP, EC 3.4.21.26), a serine protease, is widely distributed in various organs, particularly in the brains of Alzheimer’s disease patients. The expression of PEP in Alzheimer’s patients has been found to be significantly higher than that of the normal person, suggesting that a specific PEP inhibitor can be a good candidate for an anti-amnestic drug. In the current study, thirty-nine plant phenolics were investigated to determine their roles as prolyl endopeptidase (PEP) inhibitors. Nineteen compounds such as 1,2,3-trigalloyl glucopyranoside, 1,2,6-trigalloyl glucopyranoside, 1,2,3,4,6-pentagalloyl gluco-pyranoside, 1,2,6-trigalloyl alloside, 1,3,6-trigalloyl alloside, 1,2,3,6-tetragalloyl alloside, acetonyl geraniin, corilagin, elaeocarpusin, euphorscopin, geraniin, helioscopin B, helioscopinin A, helioscopinin B, jolkinin, macranganin, rugosin E, supinanin, and teracatain exhibited strong inhibition against PEP (IC50 26.7 - 443.7x10-9 M). Rugosin E (IC50 26.7x10-9 M) showed the most effective inhibition followed by 1,2,6-trigalloyl glucopyranoside (IC5031.4x10-9 M) and macranganin (IC50 42.6x10-9 M). No significant structure-activity relationship was found; however, at least, three pyrogallol groups seem to be a minimal requirement for stronger activity against PEP. All 19 active compounds inhibited PEP in a non-competitive mode with a substrate in Dixon plots. They did not show significant effects against other serine proteases such as trypsin, chymotrypsin and elastase, indicating that they were relatively specific PEP inhibitors.

Key words

Prolyl endopeptidase (PEP) Inhibitor Plant phenolics Alzheimer’s disease Antiamnesia 

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Copyright information

© The Pharmaceutical Society of Korea 2007

Authors and Affiliations

  • Seung -Ho Lee
    • 2
  • Mira Jun
    • 3
  • Ji -Young Choi
    • 2
  • Eun -Ju Yang
    • 1
  • Jong -Moon Hur
    • 2
  • KiHwan Bae
    • 4
  • Yeon -Hee Seong
    • 5
  • Tae -Lin Huh
    • 3
  • Kyung -Sik Song
    • 1
  1. 1.College of Agriculture & Life SciencesKyungpook National UniversityDaeguKorea
  2. 2.College of PharmacyYeungnam UniversityGyeongbukKorea
  3. 3.Department of Genetic EngineeringKyungpook National UniversityKorea
  4. 4.College of PharmacyChungnam National UniversityDaejonKorea
  5. 5.College of VeterinaryChungbuk National UniversityChungbukKorea

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