Dibenzoylmethane, a Component of Licorice, Suppresses Monocyte-to-Macrophage Differentiation and Inflammatory Responses in Human Monocytes and Mouse Macrophages.

The objective of this study was to investigate the effect of dibenzoylmethane (DBM) on monocyte-to-macrophage differentiation, the inflammatory response, and the resulting signaling in human monocytes and murine macrophage. DBM effectively inhibited the monocyte-to-macrophage differentiation induced by phorbol 12-myristate 13-acetate (PMA) through a reduction in adhesion of THP-1 cells. Cluster of differentiation molecule ß (CD11ß) and CD36, which are surface markers of macrophage differentiation, were downregulated by 80 and 74%, respectively. DBM also significantly inhibited lipopolysaccharide (LPS)-induced nitrite (NO) production through the downregulation of inducible oxide synthase (iNOS) in RAW264.7 cells. The abundance of cyclooxygenase-2 (COX-2), a pro-inflammatory protein, was also effectively decreased by DBM in a dose-dependent manner. DBM (50 µM) reduced the levels of COX-2 and iNOS by 81 and 78%, respectively. DBM significantly inhibited the translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), an inflammatory transcription factor, into the nucleus. DBM-mediated increase of NF-κB translocation resulted from the DBM-induced suppression of the phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα). In contrast, DBM effectively increased the expression of nuclear factor E2-related factor 2 (Nrf2) and its target protein, hemeoxygenase-1 (HO-1). Nrf2 translocation into the nucleus was also significantly enhanced by DBM. Furthermore, DBM effectively inhibited the expression of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), IL-6, and monocyte chemoattractant protein-1 (MCP-1). These results indicated that the DBM-mediated differential regulation of NF-κB and Nrf2, which are major transcription factors involved in inflammation, inhibited the expression of inflammatory cytokines.

Dibenzoylmethane Suppresses Lipid Accumulation and Reactive Oxygen Species Production through Regulation of Nuclear Factor (Erythroid-Derived 2)-Like 2 and Insulin Signaling in Adipocytes.

The aim of this study was to investigate the effects of dibenzoylmethane (1,3-diphenyl-1,3-propanedione, DBM) from licorice roots on lipid accumulation and reactive oxygen species (ROS) production in 3T3-L1 cells. DBM effectively inhibited lipid accumulation during adipogenesis, and its inhibitory effect was shown to be due to the down-regulation of adipogenic factors such as CCAAT-enhancer-binding protein-α (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), and fatty acid-binding protein 4 (FABP4). DBM was observed to exert its inhibitory effect on lipid accumulation in the early adipogenic stage (days 0-2) by regulating early adipogenic factors including CCAAT-enhancer-binding protein-ß (C/EBPß) and Krueppel-like factor (KLF) 2. DBM significantly increased the translocation of nuclear factor (erythroid-derived 2)-like 2(Nrf2) into the nucleus, promoting the protein expression of its target gene, heme oxygenase-1 (HO-1). DBM significantly suppressed the insulin-mediated activation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt), which are components of insulin signaling. In addition, intracellular ROS production was effectively reduced by DBM treatment, which upregulated antioxidant genes such as glutathione peroxidase (Gpx), catalase (CAT), and superoxide dismutase 1 (SOD1). Furthermore, DBM significantly regulated the expression of the adipokines, resistin and adiponectin. This DBM-mediated regulation of lipid accumulation, ROS production, and adipokine production was shown to be involved in the regulation of the Nrf2 and insulin signaling.

Cholecalciferol inhibits lipid accumulation by regulating early adipogenesis in cultured adipocytes and zebrafish.

Cholecalciferol (CCF) is a common dietary supplement as a precursor of active vitamin D. In the present study, the effect of CCF on lipid accumulation was investigated in adipocyte cells and zebrafish models. CCF effectively inhibited lipid accumulation in both experimental models; this effect was attributed to the CCF-mediated regulation of early adipogenic factors. CCF down-regulated the expressions of CCAAT-enhancer-binding protein-ß (C/EBPß), C/EBPδ, Krueppel-like factor (KLF) 4, and KLF5, while KLF2, a negative adipogenic regulator, was increased by CCF treatment. CCF inhibited cell cycle progression of adipocytes through down-regulation of cyclin A and cyclinD; p-Rb was suppressed by CCF, but p27 was up-regulated with CCF treatment. This CCF-mediated inhibition of cell cycle progression is highly correlated to the inhibitions of extracellular signal-regulated kinase (ERK), serine threonine-specific kinase (AKT), and mammalian target of rapamycin (mTOR). Furthermore, CCF-induced inactivation of acetyl-CoA carboxylase (ACC), a fatty acid synthetic enzyme, with the activation of AMP-activated protein kinase α (AMPKα) was also observed. Consistent with the observations in adipocytes, CCF effectively inhibited lipid accumulation with the down-regulation of adipogenic factors in zebrafish. The present study indicates that CCF showed anti-adipogenic effect in adipocytes and zebrafish, and its inhibitory effect was involved in the regulation of early adipogenic events including cell cycle arrest and activation of AMPKα signaling.

Changes in the chemical properties and anti-oxidant activities of curcumin by microwave radiation.

Curcumin is a dietary phenolic compound that has numerous beneficial health effects. In the present study, changes in the chemical properties and anti-oxidant activities of curcumin by microwave radiation were investigated. Degradation of curcumin dissolved in distilled water was accelerated according to the increase in radiation time or radiation intensity. Residual levels of curcumin after 5 min radiation at 500 W were 24-29%. Scavenging activities of curcumin against DPPH radical decreased by microwave radiation; those of curcumin against ABTS and AAPH radicals and nitrite were rather significantly enhanced. Conventional heating at 95°C also increased scavenging activities of ABTS, AAPH, and nitrite of curcumin but to a lesser extent. Fluorescence intensity of curcumin increased by regular heating but decreased by microwave heating. Among curcuminoids, bisdemethoxycurcumin was most resistant under microwave radiation as compared to curcumin or demethoxycurcumin.