Iridoids from Fraxinus excelsior with adipocyte differentiation-inhibitory and PPARα activation activity

Article abstract of DOI:10.1021/np9003118

Two new secoiridoid glucosides, excelsides A (1) and B (2), were isolated from the seeds of Fraxinus excelsior. Their structures were elucidated as (2S,4S,3E)-methyl 3-ethylidene-4-(2-methoxy-2-oxoethyl)-2-[(6-O-β-D- glucopyranosyl-β-D-glucopyranosyl)oxy]-3,4-dihydro-2H-pyran-5-carboxylate and (2S,4S,3E)-methyl 3-ethylidene-4-{2-[2-(4-hydroxyphenyl)ethyl]oxy-2- oxoethyl}-2-[(6-O-β-D-glucopyranosyl-β-D-glucopyranosyl)oxy]-3, 4-dihydro-2H-pyran-5-carboxylate, respectively, on the basis of NMR and MS data. Eight known compounds were identified as nuzhenide (3), GI3 (4), GI5 (5), ligstroside (6), oleoside 11-methyl ester (7), oleoside dimethyl ester (8), 1?-O-β-D-glucosylformoside (9), and salidroside (10). Compounds 1-9 inhibited adipocyte differentiation in 3T3-L1 cells. Dilutions of the aqueous extract of F. excelsior (1:10 000) as well as compounds 2, 3, 4, 5, and 8 activated the peroxisome proliferator-mediated receptor-α (PPARα) reporter cell system in the range of 10^-4 M, compared to 10 ^-7-10^-8 M for the synthetic PPARα activiator, WY14,643. Both biological activity profiles support the hypothesis that inhibition of adipocyte differentiation and PPARα-mediated mechanisms might be relevant pathways for the antidiabetic activity of F. excelsior extract.