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KMID : 0043320070300070827
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Archives of Pharmacal Research
2007 Volume.30 No. 7 p.827 ~ p.833
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Plant Phenolics as Prolyl Endopeptidase Inhibitors
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Lee Seung-Ho
Jun Mi-Ra
Choi Ji-Young
Yang Eun-Ju
Hur Jong-Moon
Bae Ki-Hwan
Seong Yeon-Hee
Huh Tae-Lin
Song Kyung-Sik
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Abstract
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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 Alzheimer뭩 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 ?443.7?0? M). Rugosin E (IC50 26.7?0? M) showed the most effective inhibition followed by 1,2,6-trigalloyl glucopyranoside (IC50 31.4?0? M) and macranganin (IC50 42.6?0? 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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KEYWORD
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Prolyl endopeptidase (PEP), Inhibitor, Plant phenolics, Alzheimer’s disease, Antiamnesia
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