Prolyl endopeptidase inhibitors from the underground part of Rhodiola sachalinensis

The methanolic extract of the underground part of Rhodiola sachalinensis wa s found to show inhibitory activity on prolyl endopeptidase (PEP, EC. 3.4.2 1.26), an enzyme that plays a role in the metabolism of proline-containing neuropeptidase which is recognized to be involved in learning and memory Fr om the MeOH extract, five new monoterpenoids named sachalinols A (24), B (2 5) and C (26) and sachalinosides A (23) and B (27) were isolated, together with twenty-two known compounds, gallic acid (1), trans-p-hydroxycinnamic a cid (2), p-tyrosol (3), salidroside (4), 6"-O-galloylsalidroside (5), benzy l beta -D-glutopyranoside (6), 2-phenylethyl beta -D-glucopyranoside (7), t rails-cinnamyl beta -D-glucopyranoside (8), rosarin (9), rhodiocyanoside A (10), lotaustralin (II), 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 (2 1) 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. Am ong them, six compounds (13, 14, 18, 19, 21, 22) showed noncompetitive inhi bition against Flavobacterium PEP, with an IC50 of 0.025, 0.17, 22, 41, 0.4 4 and 83 muM, respectively.