Prolyl endopeptidase inhibitors from the underground part of Rhodiola sachalinensis

Chem Pharm Bull (Tokyo). 2001 Apr;49(4):396-401. doi: 10.1248/cpb.49.396.

Abstract

The methanolic extract of the underground part of Rhodiola sachalinensis was found to show inhibitory activity on prolyl endopeptidase (PEP, EC. 3.4.21.26), an enzyme that plays a role in the metabolism of proline-containing neuropeptidase which is recognized to be involved in learning and memory. From the MeOH extract, five new monoterpenoids named sachalinols A (24), B (25) and C (26) and sachalinosides A (23) and B (27) were isolated, together with twenty-two known compounds, gallic acid (1), trans-p-hydroxycinnamic acid (2), p-tyrosol (3), salidroside (4), 6n-O-galloylsalidroside (5), benzyl beta-D-glucopyranoside (6), 2-phenylethyl beta-D-glucopyranoside (7), trans-cinnamyl beta-D-glucopyranoside (8), rosarin (9), rhodiocyanoside A (10), lotaustralin (11), octyl beta-D-glucopyranoside (12), 1,2,3,6-tetra-O-galloyl-beta-D-glucose (13), 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (14), kaempferol (15), kaempferol 3-O-beta-D-xylofuranosyl(1-->2)-beta-D-glucopyranoside (16), kaempferol 3-O-beta-D-glucopyranosyl(1-->2)-beta-D-glucopyranoside (17), rhodionin (18), rhodiosin (19), (-)-epigallocatechin (20), 3-O-galloylepigallocatechin-(4-->8)-epigallocatechin 3-O-gallate (21) and rosiridin (22). Among these, nineteen compounds other than 3, 4 and 9 have been isolated for the first time from R. sachalinensis, and six (6, 8, 13, 16, 17, 20) are isolated from Rhodiola plants for the first time. Among them, six compounds (13, 14, 18, 19, 21, 22) showed noncompetitive inhibition against Flavobacterium PEP, with an IC50 of 0.025, 0.17, 22, 41, 0.44 and 84 microM, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding, Competitive / drug effects
  • Flavobacterium / enzymology
  • Hydrolysis
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Methanol
  • Plant Roots / chemistry
  • Plants, Medicinal / chemistry*
  • Prolyl Oligopeptidases
  • Protease Inhibitors / isolation & purification*
  • Protease Inhibitors / pharmacology*
  • Serine Endopeptidases / metabolism*
  • Spectrometry, Mass, Fast Atom Bombardment
  • Spectrophotometry, Ultraviolet
  • Tibet

Substances

  • Protease Inhibitors
  • Serine Endopeptidases
  • Prolyl Oligopeptidases
  • Methanol