Abstract
Prolyl endopeptidase (PEP, EC 3.4.21.26) hydrolyzes proline-containing neuropeptides,
such as vasopressin, substance P, and thyrotropin-releasing hormone (TRH), and is
suggested to participate in learning and memory processes. Ginkgo biloba leaves, upon examination for anti-amnestic constituents as new types of PEP inhibitors,
showed significant PEP inhibition. PEP activity-guided fractionation and column chromatography
of the MeOH extracts of G. biloba leaves resulted in the isolation of 6-(8′Z-pentadecenyl)salicylic acid (1) and 6-(10′Z-heptadecenyl)salicylic acid (2). The kinetic study indicated that compounds 1 and 2 are non-competitive inhibitors of prolyl endopeptidase with Ki values of 0.87 and 0.80 μM, respectively.
References
- 1
Cunningham D F, O’Connor B.
Proline specific peptidase.
Biochem Biophys Acta.
1997;
1343
160-86
- 2
Walter R, Shlank H, Glass J D, Schwartz I L, Kerenyi T D.
Leucylglycinamide released from oxytocin by human uterine enzyme.
Science.
1971;
173
827-9
- 3
Kalwant S, Porter A G.
Purification and characterization of human brain prolyl endopeptidase.
Biochem J.
1991;
276
237-44
- 4
Okada C, Mizuochi T, Shirasawa T, Morain P, Checler F.
Murine T cells expressing high activity of prolyl endopeptidase are susceptible to
activation-induced cell death.
FEBS Lett.
2002;
512
163-7
- 5
Maes M, Goossens F, Scharpe S, Calabrese J, Desnyder R, Meltzer H Y.
Alterations in plasma prolyl endopeptidase activity in depression, mania and schizophrenia:
effects of antidepressants, mood stabilizers and antipsychotic drugs.
Psych Res.
1995;
58
217-25
- 6
Aoyagi T, Wada T, Nagai M, Kojima F, Harada S, Takeuchi T, Takahashi H, Hirokawa K,
Tsumita T.
Deficiency of kallikrein-like enzyme activities in cerebral tissue of patients with
Alzheimer’s disease.
Experientia.
1990;
46
94-7
- 7
Maidment I.
The use of Ginkgo biloba in the treatment of dementia.
Psychiatric Bull.
2001;
25
353-6
- 8
Lichtblau D, Berger J M, Nakanishi K.
Efficient extraction of ginkgolides and bilobalide form Ginkgo biloba leaves.
J Nat Prod.
2002;
65
1501-4
- 9
Lee J S, Cho Y S, Park E J, Kim J W, Oh W K, Lee H S, Ahn J S.
Phospholipase Cγ1 inhibitory principles from the sarcotestas of Ginkgo biloba
.
J Nat Prod.
1998;
61
867-71
- 10
Jaggy H, Koch E.
Chemistry and biology of alkylphenols from Ginkgo biloba L.
Pharmazie.
1997;
52
735-8
- 11
Itokawa H, Totsuka N, Nakahara K, Takeya K, Lepoittevin J -P, Asakawa Y.
Antitumor principles from Ginkgo biloba L.
Chem Pharm Bull.
1987;
35
3016-20
- 12
Fan W, Tezuka Y, Komatsu K, Namba T, Kadota S.
Prolyl endopeptidase inhibitors from the underground part of Rhodiola sacra S. H. Fu.
Biol Pharm Bull.
1999;
22
157-61
- 13
Kimura K, Kawaguchi N, Yoshihama M, Kawanishi G.
Staurosporine, a prolyl endopeptidase inhibitor.
Agric Biol Chem.
1990;
54
3021-2
- 14
Sultanova N, Makhmoor T, Yasin A, Abilov Z A, Omurkamzinova V B, Atta-ur-Rahman ,
Choudhary M I.
Isotamarixen - a new antioxidant and prolyl endopeptidase-inhibiting triterpenoid
from Tamarix hispida
.
Planta Medica.
2004;
70
65-7
- 15
Kimura K, Kanou F, Takahashi H, Esumi Y, Uramoto M, Yoshihama M.
Propeptin, a new inhibitor of prolyl endopeptidase produced by microbispora. I. fermentation,
isolation and biological properties.
J Antibiot.
1997;
50
373-8
- 16
Song K S, Raskin I.
A prolyl endopeptidase-inhibiting benzofuran dimer from Polyozellus multiflex
.
J Nat Prod.
2002;
65
76-8
- 17
Yoshimoto T, Walter R, Tsuru D.
Proline-specific endopeptidase from Flavobacterium
.
J Biol Chem.
1980;
255
4786-92
Young-Sook Paik
College of Environment and Applied Chemistry
Kyung Hee University
Suwon, 449-701
South Korea
Fax: +82-31-202-7337
Email: paikys@khu.ac.kr