In the present study, the bioactivity-monitored isolation of flavonoid glucopyranosides from the saltmarsh plant Salicornia herbacea was performed, and their effects on adipogenic differentiation were evaluated in 3T3-L1 adipocytes. Among the solvent-partitioned fractions from S. herbacea, the 85% aq. MeOH and n-BuOH fractions effectively reduced the levels of triglyceride accumulation, glucose consumption and adipogenic transcription factor peroxisome proliferator-activated receptor-gamma (PPAR gamma) expression. Further purification of the n-BuOH fraction led to the isolation of two flavonoid glucopyranosides. isorhamnetin 3-O-beta-D-glucopyranoside (A) and quercetin 3-O-beta-D-glucopyranoside (B), as the active principles. The presence of glucopyranosides A and B in adipocyte cells effectively suppressed adipogenic differentiation. Comparative analysis indicated that adipogenic differentiation was dramatically attenuated in the presence of glucopyranoside B rather than glucopyranoside A. The anti-adipogenic activity of glucopyranosides B was confirmed by down-regulation of sterol regulatory element-binding protein 1 (SREBP1), CCAAT/enhancer-binding proteins (C/EBP alpha), PPAR gamma and the adipocyte-specific proteins. Moreover, the specific mechanism mediating the effects of glucopyranosides B was confirmed by activation of AMP-activated protein kinase (AMPK). Findings from this study should underscore the nutraceutical value of S. herbacea-derived glucopyranosides as potent anti-obesity agents via alleviation of lipid accumulation. (c) 2012 Elsevier Ltd. All rights reserved.