PMID- 30068872 OWN - NLM STAT- MEDLINE DCOM- 20181016 LR - 20181016 IS - 1347-5215 (Electronic) IS - 0918-6158 (Linking) VI - 41 IP - 8 DP - 2018 TI - Dibenzoylmethane, a Component of Licorice, Suppresses Monocyte-to-Macrophage Differentiation and Inflammatory Responses in Human Monocytes and Mouse Macrophages. PG - 1228-1236 LID - 10.1248/bpb.b18-00064 [doi] AB - 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 beta (CD11beta) 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 microM) 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-kappaB), an inflammatory transcription factor, into the nucleus. DBM-mediated increase of NF-kappaB translocation resulted from the DBM-induced suppression of the phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IkappaBalpha). 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-alpha), interleukin-1 beta (IL-1beta), IL-6, and monocyte chemoattractant protein-1 (MCP-1). These results indicated that the DBM-mediated differential regulation of NF-kappaB and Nrf2, which are major transcription factors involved in inflammation, inhibited the expression of inflammatory cytokines. FAU - Kang, Bobin AU - Kang B AD - Department of Public Health Sciences, Korea University. FAU - Kim, Joo Hyoun AU - Kim JH AD - Department of Food Science and Technology, College of Natural Science, Seoul Women's University. FAU - Kim, Chae Young AU - Kim CY AD - Department of Public Health Sciences, Korea University. FAU - Hong, Jungil AU - Hong J AD - Department of Food Science and Technology, College of Natural Science, Seoul Women's University. FAU - Choi, Hyeon-Son AU - Choi HS AD - Department of Food Science and Technology, College of Natural Science, Seoul Women's University. LA - eng PT - Journal Article PL - Japan TA - Biol Pharm Bull JT - Biological & pharmaceutical bulletin JID - 9311984 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Chalcones) RN - 0 (Cytokines) RN - 0 (NF-E2-Related Factor 2) RN - 0 (NF-kappa B) RN - ANS7ME8OKC (dibenzoylmethane) SB - IM MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Cell Adhesion/drug effects MH - Cell Differentiation/drug effects MH - Cell Line MH - Cell Survival/drug effects MH - Chalcones/*pharmacology MH - Cytokines/genetics MH - Glycyrrhiza MH - Humans MH - Macrophages/cytology/*drug effects/metabolism MH - Mice MH - Monocytes/cytology/*drug effects MH - NF-E2-Related Factor 2/metabolism MH - NF-kappa B/metabolism MH - RAW 264.7 Cells MH - Signal Transduction/drug effects OTO - NOTNLM OT - RAW264.7 OT - THP-1 OT - cytokine OT - dibenzoylmethane OT - inflammatory response OT - monocyte-to-macrophage differentiation EDAT- 2018/08/03 06:00 MHDA- 2018/10/17 06:00 CRDT- 2018/08/03 06:00 PHST- 2018/08/03 06:00 [entrez] PHST- 2018/08/03 06:00 [pubmed] PHST- 2018/10/17 06:00 [medline] AID - 10.1248/bpb.b18-00064 [doi] PST - ppublish SO - Biol Pharm Bull. 2018;41(8):1228-1236. doi: 10.1248/bpb.b18-00064.