Decursin and Decursinol Angelate Suppress Adipogenesis through Activation of β-catenin Signaling Pathway in Human Visceral Adipose-Derived Stem Cells

Abstract

Visceral adiposity is closely associated with metabolic disorders and cardiovascular diseases. Angelica gigas Nakai (AGN) has been reported to possess anti-obesity effects and higher amounts of coumarin compounds are present in AGN. However, the active compounds suppressing adipogenesis in AGN and mechanisms of action have not been investigated in adipose-derived stem cells (ASCs) isolated from visceral adipose tissue (VAT). Among four coumarin compounds of AGN, decursin (D) and decursinol angelate (DA) significantly inhibited adipocyte differentiation from ASCs. D and DA downregulated CCAAT/enhancer binding protein α (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), adipocyte fatty acid binding protein (aP2), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) at both mRNA and protein levels. Next, treatment with adipogenic differentiation medium (ADM) on ASCs downregulated β-catenin expression at protein level, while addition of D and DA could restore protein expression and nuclear translocation of β-catenin suppressed by ADM. D and DA treatment on ADM treated ASCs increased inhibitory phosphorylation of Glycogen synthase kinase (GSK)-3β, thereby preventing β-catenin from degradation. Additionally, si-β-catenin transfection significantly upregulated protein expression of C/EBPα and PPARγ, alleviating the anti-adipogenic effect of D and DA on ADM treated ASCs. Overall, D and DA, active compounds from AGN, suppressed adipogenesis through activation of β-catenin signaling pathway in ASCs derived from human VAT, possibly using as natural anti-visceral adiposity agents.

Piceatannol Is Superior to Resveratrol at Suppressing Adipogenesis in Human Visceral Adipose-Derived Stem Cells

“…Therefore, the anti-adipogenic effect of Res and Pic in vASCs may regulate the SIRT1, AMPK, and AKT signaling pathways, and the expression levels of SIRT1, AMPK, and AKT may show different levels between Res and Pic treatment. Increasing evidence suggests that nutraceuticals from natural products attenuate adipogenesis in mesenchymal stem cells by activating the wingless-type mouse mammary tumor virus (MMTV) integration site (WNT)/β-catenin signaling pathways [ 37 , 38 ]. Therefore, it would be interesting to study the underlying molecular mechanisms involved in regulating the adipogenesis of vASCs by Res and Pic.…”

Pharmacological Properties of a Traditional Korean Formula Bojungchiseup‐tang on 3T3‐L1 Preadipocytes and High‐Fat Diet‐Induced Obesity Mouse Model

“…In this study, mice were fed HFD to induce weight gain through an increase in energy intake. BJT has long been used to treat edema and dampness-phlegm [11], and its components have been shown to have antiobesity activities [12][13][14][15][16][17][18][19][20], but the pharmacological activity of BJT has not yet been investigated. In the present study, we found that BJT suppressed HFDinduced weight gain in an obese mouse model.…”

“…The compound MDG-1 from Ophiopogon japonicas shows potent hypoglycemic and weight control effects in mice [17]. Decursin, present in Angelica gigas Nakai, has an antiadipogenic effect in adipose-derived stem cells isolated from human visceral adipose tissue [18]. Akebia quinata extract also has antiobesity and hypolipidemic effects in HFD-fed mice [19].…”

Decursin alleviates LPS-induced lung epithelial cell injury by inhibiting NF-κB pathway activation

“…In fact, the biological activities of decursin have been revealed widely. 18 Decursin has antioxidative and anti-inflammation effects in several diseases. 19 Decursin inhibits osteoclast formation and bone loss both in vitro and in vivo.…”