Iridoids from Fraxinus excelsior with adipocyte differentiation-inhibitory and PPARalpha activation activity.
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-beta-D-glucopyranosyl-beta-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-beta-d-glucopyranosyl-beta-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-beta-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-alpha (PPARalpha) reporter cell system in the range of 10(-4) M, compared to 10(-7)-10(-8) M for the synthetic PPARalpha activator, WY14,643. Both biological activity profiles support the hypothesis that inhibition of adipocyte differentiation and PPARalpha-mediated mechanisms might be relevant pathways for the antidiabetic activity of F. excelsior extract.
Bai
Naisheng
N
Naturex, Inc., 375 Huyler Street, South Hackensack, New Jersey 07606, USA.
He
Kan
K
Ibarra
Alvin
A
Bily
Antoine
A
Roller
Marc
M
Chen
Xiaozhuo
X
Rühl
Ralph
R
D017667:Adipocytes / Q000187:drug effects; D000818:Animals; D031661:Fraxinus / Q000737:chemistry*; D057888:Iridoid Glucosides; D057889:Iridoid Glycosides; D039823:Iridoids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D047493:PPAR alpha / Q000187:drug effects*; D010946:Plants, Medicinal / Q000737:chemistry*; D012639:Seeds / Q000737:chemistry; D013237:Stereoisomerism
D057888:Iridoid Glucosides; D057889:Iridoid Glycosides; D039823:Iridoids; D047493:PPAR alpha; C546761:excelside A; C546763:excelside B