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Butein is a novel anti-adipogenic compound.

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-? (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. 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-? 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-? 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-? pathway followed by STAT3 and peroxisome proliferator-activated receptor ? signaling, further implicating potential roles of butein in TGF-?- and STAT3-dysregulated diseases.

SUBMITTER: Song NJ

PROVIDER: S-EPMC3622332 | biostudies-other | 2013 May

REPOSITORIES: biostudies-other

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Butein is a novel anti-adipogenic compound.

Song No-Joon NJ Yoon Hyang-Jin HJ Kim Ki Hyun KH Jung So-Ra SR Jang Woo-Seok WS Seo Cho-Rong CR Lee Young Min YM Kweon Dae-Hyuk DH Hong Joung-Woo JW Lee Jeong-Soo JS Park Ki-Moon KM Lee Kang Ro KR Park Kye Won KW

Journal of lipid research 20130306 5

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 ...[more]

PMID: 23468131

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Project description:BackgroundRoyal jelly (RJ) has been used traditionally for dietary, cosmetic and health purposes for a long time in different parts of the world. Scientific studies have also shown its numerous health-promoting properties including hypoglycemic and anti-hypercholesterolemic action. In this study, we investigated the anti-adipogenic activity of RJ in 3 T3-L1 cells and isolated the major responsible root component for the activity.MethodsAn active anti-adipogenic compound was isolated through bioassay-guided isolation process by successive treatment of RJ and its active fractions on 3 T3-L1 cell line. (E)-10-Hydroxy-2-decenoic Acid (10-HDA) was identified using NMR spectroscopy and ultra-performance liquid chromatography (UPLC). As 10-HDA showed significant anti-adipogenic activity with Oil Red O staining and TG content assay on 3 T3-L1 adipocytes, further study was carried out in molecular level for the expression of adipogenic transcription factors such as PPARγ, FABP4, C/EBPα, SREBP-1c, and Leptin. The effect of 10-HDA on preliminary molecules such as pAkt, pERK, C/EBPβ, and pCREB were studied in the early stage of adipogenesis. The effect of 10-HDA on reactive oxygen species (ROS) production in fully differentiating adipocytes was measured by nitro blue tetrazolium (NBT) assay.ResultResults showed that triacylglycerol accumulation and ROS production was markedly suppressed by 10-HDA. Preliminary molecules such as pAkt, pERK, pCERB, and C/EBPβ were found to be down-regulated by 10-HDA, which led to down-regulation of key adipogenic transcription factors such as PPARγ, FABP4, CEBPα, SREBP-1c, and Leptin on 3 T3-L1 adipocytes.ConclusionOur results suggest that anti-adipogenesis of 10-HDA on 3 T3-L1 adipocyte takes place via two mechanisms: inhibition of cAMP/PKA pathway and inhibition of p-Akt and MAPK dependent insulin signaling pathway. So it is considered that 10-HDA, a major component of RJ, can be a potential therapeutic medicine for obesity.

Project description:Glutaredoxin (Grx1) is a ubiquitously expressed thiol-disulfide oxidoreductase that specifically catalyzes reduction of S-glutathionylated substrates. Grx1 is known to be a key regulator of pro-inflammatory signaling, and Grx1 silencing inhibits inflammation in inflammatory disease models. Therefore, we anticipate that inhibition of Grx1 could be an anti-inflammatory therapeutic strategy. We used a rapid screening approach to test 504 novel electrophilic compounds for inhibition of Grx1, which has a highly reactive active-site cysteine residue (pKa 3.5). From this chemical library a chloroacetamido compound, CWR-J02, was identified as a potential lead compound to be characterized. CWR-J02 inhibited isolated Grx1 with an IC50 value of 32 μM in the presence of 1 mM glutathione. Mass spectrometric analysis documented preferential adduction of CWR-J02 to the active site Cys-22 of Grx1, and molecular dynamics simulation identified a potential non-covalent binding site. Treatment of the BV2 microglial cell line with CWR-J02 led to inhibition of intracellular Grx1 activity with an IC50 value (37 μM). CWR-J02 treatment decreased lipopolysaccharide-induced inflammatory gene transcription in the microglial cells in a parallel concentration-dependent manner, documenting the anti-inflammatory potential of CWR-J02. Exploiting the alkyne moiety of CWR-J02, we used click chemistry to link biotin azide to CWR-J02-adducted proteins, isolating them with streptavidin beads. Tandem mass spectrometric analysis identified many CWR-J02-reactive proteins, including Grx1 and several mediators of inflammatory activation. Taken together, these data identify CWR-J02 as an intracellularly effective Grx1 inhibitor that may elicit its anti-inflammatory action in a synergistic manner by also disabling other pro-inflammatory mediators. The CWR-J02 molecule provides a starting point for developing more selective Grx1 inhibitors and anti-inflammatory agents for therapeutic development.

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Butein is a novel anti-adipogenic compound.

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Butein is a novel anti-adipogenic compound.

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