Abstract
Rhus verniciflua Stokes (RVS) has been used as a traditional herbal medicine for its various biological activities including anti-adipogenic effects. Activity-guided separation led to the identification of the anti-adipogenic functions of butein. Butein, a novel anti-adipogenic compound, robustly suppressed lipid accumulation and inhibited expression of adipogenic markers. Molecular studies showed that activated transforming growth factor-β (TGF-β) and suppressed signal transducer and activator of transcription 3 (STAT3) signaling pathways were mediated by butein. Analysis of the temporal expression profiles suggests that TGF-β signaling precedes the STAT3 in the butein-mediated anti-adipogenic cascade. Small interfering RNA-mediated silencing of STAT3 or SMAD2/3 blunted the inhibitory effects of butein on adipogenesis indicating that an interaction between two signaling pathways is required for the action of butein. Upon butein treatments, stimulation of TGF-β signaling was still preserved in STAT3 silenced cells, whereas regulation of STAT3 signaling by butein was significantly impaired in SMAD2/3 silenced cells, further showing that TGF-β acts upstream of STAT3 in the butein-mediated anti-adipogenesis. Taken together, the present study shows that butein, a novel anti-adipogenic compound from RVS, inhibits adipocyte differentiation through the TGF-β pathway followed by STAT3 and peroxisome proliferator-activated receptor γ signaling, further implicating potential roles of butein in TGF-β- and STAT3-dysregulated diseases.
Highlights
Rhus verniciflua Stokes (RVS) has been used as a traditional herbal medicine for its various biological activities including anti-adipogenic effects
To identify the bioactive compounds responsible for anti-adipogenic effects, C3H10T1/2 cells were differentiated into adipocytes and treated with 10, 25, and 50 g/ml of the extracts
The extracts were further separated successively into ethanol, hexane, DCM, ethyl acetate, n-butanol, and water fractions to enrich the bioactive compounds potentially mediating the anti-adipogenic effects of RVS
Summary
Rhus verniciflua Stokes (RVS) has been used as a traditional herbal medicine for its various biological activities including anti-adipogenic effects. A novel anti-adipogenic compound, robustly suppressed lipid accumulation and inhibited expression of adipogenic markers. Molecular studies showed that activated transforming growth factor- (TGF-) and suppressed signal transducer and activator of transcription 3 (STAT3) signaling pathways were mediated by butein. Analysis of the temporal expression profiles suggests that TGF- signaling precedes the STAT3 in the butein-mediated anti-adipogenic cascade. The present study shows that butein, a novel anti-adipogenic compound from RVS, inhibits adipocyte differentiation through the TGF- pathway followed by STAT3 and peroxisome proliferatoractivated receptor ␥ signaling, further implicating potential roles of butein in TGF-- and STAT3-dysregulated diseases.—Song, N-J., H-J. Bioactive compounds identified from natural products have been extensively studied for their effects on obesity and its underlying molecular mechanisms [6].
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