Prolyl Endopeptidase Inhibitory Activity of Fourteen Kampo Formulas and Inhibitory Constituents of Tokaku-joki-to ( ?? ?? ?? ?? ?? )

抄録

Prolyl endopeptidase (PEP, EC 3.4.21.26) is an enzyme playing a role in the metabolism of proline-containing neuropeptides which have been suggested to be involved in learning and memory processes. In screening for PEP inhibitors from fourteen traditional Kampo formulas, we found that Tokaku-joki-to( ?? ?? ?? ?? ?? ) shows a significant inhibitory activity. Examination of the constitutents of the Kampo formula resulted in the isolation of two new compounds, cis-3, 5, 4'-trihydroxystilbene 4'-O-β-D-(6-O-galloyl)glucopyranoside (10) and 4-(4-hydroxyphenyl)-2-butanone 4'-O-β-D-(6-O-galloyl-2-O-cinnamoyl)glucopyranoside (16), along with twenty-five known compounds, cinnamic acid (1), protocatechuic acid (2), gallic acid (3), torachrysone 8-O-β-D-glucoside (4), emodin (5), emodin 8-O-β-D-glucoside (6), 3, 5, 4'-trihydroxystilbene 4'-O-β-D-glucopyranoside (7), 3, 5, 4'-trihydroxystilbene 4'-O-β-D-(2-O-galloyl)glucopyranoside (8), 3, 5, 4'-trihydroxystilbene 4'-O-β-D-(6-O-galloyl)glucopyranoside (9), 4-(4-hydroxyphenyl)-2-butanone 4'-O-β-D-glucopyranoside (11), isolindleyin (12), lindleyin (13), 4-(4-hydroxyphenyl)-2-butanone 4'-O-β-D-(2, 6-di-O-galloyl)glucopyranoside (14), 4-(4-hydroxyphenyl)-2-butanone 4'-O-β-D-(2-O-galloyl-6-O-cinnamoyl)glucopyranoside (15), 1-O-galloylglucose (17), 1, 2, 6-tri-O-galloylglucose (18), gallic acid 4-O-β-D-(6-O-galloyl)glucopyranoside (19), liquiritigenin (20), liquiritigenin 4'-O-β-D-glucoside (21), liquiritigenin 7, 4'-diglucoside (22), liquiritigenin 4'-O-β-D-apiofuranosyl-(1→2)-β-D-glucopyranoside (23), licuroside (24), (-)-epicatechin (25), (-)-epicatechin 3-O-gallate (26) and (+)-catechin (27). Among these compounds, twelve (7-10, 14-16, 18, 19, 24-26) showed noncompetitive inhibtion with an IC₅₀ of 22.9, 3.0, 14.9, 2.8, 10.5, 0.69, 8.2, 0.44, 9.39, 26.5, 28.1 and 0.052μM, respectively.