Citreorosein Inhibits Production of Proinflammatory Cytokines by Blocking Mitogen Activated Protein Kinases, Nuclear Factor-κB and Activator Protein-1 Activation in Mouse Bone Marrow-Derived Mast Cells

• Published in: Biological & pharmaceutical bulletin 2012/06/01, Vol.35(6), pp.938-945
• Main Authors: Lu, Yue, Suh, Seok-Jong, Li, Xian, Liang, Jing Lu, Chi, Meijuan, Hwangbo, Kyoung, Kwon, Okyun, Chung, Tae-Wook, Kwak, Choong-Hwan, Kwon, Kyung-Min, Murakami, Makoto, Jahng, Yurndong, Kim, Cheorl-Ho, Son, Jong-Keun, Chang, Hyeun Wook
• Format: Article
• Language: English
• Subjects: activator protein-1; Animals; Anthraquinones - pharmacology; Anti-Inflammatory Agents - pharmacology; Bone Marrow Cells - cytology; Cells, Cultured; Citreorosein; Cytokines - antagonists & inhibitors; Cytokines - metabolism; Male; Mast Cells - drug effects; Mast Cells - metabolism; Mice; Mice, Inbred BALB C; mitogen activated protein kinase; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; mouse bone marrow-derived mast cell; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; nuclear factor-κB; proinflammatory cytokine; Protein Kinase Inhibitors - pharmacology; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-jun - metabolism; Transcription Factor AP-1 - antagonists & inhibitors; Transcription Factor AP-1 - metabolism
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.35.938

Citreorosein (CIT), an anthraquinone component of Polygoni cuspidati (P. cuspidati) radix, suppressed gene expression of proinflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in mouse bone marrow-derived mast cells (BMMCs) stimulated with phorbol 12-myristate 13-acetate (PMA) plus the calcium ionophore A23187. To investigate the molecular mechanisms underlying CIT inhibition of the pro-inflammatory cytokine production, its effects on the activation of both nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) were assessed. CIT attenuated phosphorylation of the MAPKs including extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAP kinase and c-Jun NH2-terminal kinase (JNK). Furthermore, CIT strongly inhibited DNA binding activity of NF-κB through the inhibition of phosphorylation and degradation of inhibitor of kappaB (IκB) as well as activator protein-1 (AP)-1 through the reduction of phosphorylation of c-Jun. These results demonstrate that CIT inhibits proinflammatory cytokines production through the inhibition of both MAPKs and AKT-mediated IκB kinase (IKK) phosphorylation and subsequent inhibition of transcription factor NF-κB activation, thereby attenuating the production of proinflammatory cytokines.