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

Abstract

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 β (CD11β) 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-1β), 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.

Punicalagin, a Pomegranate‐Derived Ellagitannin, Suppresses Obesity and Obesity‐Induced Inflammatory Responses Via the Nrf2/Keap1 Signaling Pathway

“…RAW264.7 cells (5.0 × 10 5 cells per well) were seeded into six‐well plates. They were treated with PCG for 2 h, after which the medium was replaced with ACM and the cells were cultured for a further 24 h. Nitric oxide (NO) was examined as previously described …”

Red ginseng extract regulates differentiation of monocytes to macrophage and inflammatory signalings in human monocytes

“…RGE-mediated activation and suppression of Nrf2 and NF-jB, respectively, on the translocation into nucleus was shown to be interplayed for anti-inflammation (Wardyn et al, 2015). A recent study showed that the interaction of NF-jB and its target genes for inflammatory responses was interrupted by the Nrf2 activation (Kang et al, 2018). In reality, p-65, a NF-jB subunit, and Nrf2 were shown to compete for binding to transcriptional co-activator CREB-binding protein (CBP)-p300 complex (Sun et al, 2009).…”

“…It moves into the nucleus, binds to promoter regions of inflammatory genes, and stimulates their expression, promoting inflammatory responses (Lee et al, 2008;Sung et al, 2012). In recent years, nuclear factor E2-related factor 2 (Nrf2) signaling, an antioxidant machinery, has also been implicated to inflammation (Kang et al, 2018;Kobayashi et al, 2016). The up-regulation of Nrf2 and its target gene, hemeoxygenase-1 (HO-1), a ratelimiting enzyme in heme catabolism, has been known to have cytoprotective effect, and suppress the inflammatory responses (Kobayashi et al, 2016).…”