Plant phenolics as prolyl endopeptidase inhibitors
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Prolyl endopeptidase (PEP, EC 126.96.36.199), 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.
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- Plant phenolics as prolyl endopeptidase inhibitors
Archives of Pharmacal Research
Volume 30, Issue 7 , pp 827-833
- Cover Date
- Print ISSN
- Online ISSN
- Pharmaceutical Society of Korea
- Additional Links
- Prolyl endopeptidase (PEP)
- Plant phenolics
- Alzheimer’s disease
- Industry Sectors
- Author Affiliations
- 1. College of Pharmacy, Yeungnam University, 712-749, Gyeongbuk, Korea
- 2. Department of Genetic Engineering, Kyungpook National University, Korea
- 3. College of Agriculture & Life Sciences, Kyungpook National University, 702-701, Daegu, Korea
- 4. College of Pharmacy, Chungnam National University, 305-764, Daejon, Korea
- 5. College of Veterinary, Chungbuk National University, 361-763, Chungbuk, Korea