Iridoids from Fraxinus excelsior with Adipocyte Differentiation-Inhibitory and PPARα Activation Activity

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2010-01, Vol.73 (1), p.2-6
• Main Authors: Bai, Naisheng, He, Kan, Ibarra, Alvin, Bily, Antoine, Roller, Marc, Chen, Xiaozhuo, Rühl, Ralph
• Format: Article
• Language: English
• ISSN: 0163-3864; 1520-6025
• 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.