Prolyl endopeptidase inhibitors from the leaves of Ginkgo biloba.
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 microM, respectively.
Lee
Jung-Han
JH
College of Environment and Applied Chemistry, Kyung Hee University, Suwon, Korea.
Lee
Si-Young
SY
Lee
Kyung-Seok
KS
Jang
Hyun-Jung
HJ
Lee
Kyung-Ho
KH
Hahn
Tae-Ryong
TR
Paik
Young-Sook
YS
D004305:Dose-Response Relationship, Drug; D020441:Ginkgo biloba; D006801:Humans; D020128:Inhibitory Concentration 50; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018515:Plant Leaves; D000085822:Prolyl Oligopeptidases; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D012697:Serine Endopeptidases / Q000187:drug effects*
D010936:Plant Extracts; D011480:Protease Inhibitors; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases