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.
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 NH(2)-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.
College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.
Yue
Y
Lu
Seok-Jong
SJ
Suh
Xian
X
Li
Jing Lu
JL
Liang
Meijuan
M
Chi
Kyoung
K
Hwangbo
Okyun
O
Kwon
Tae-Wook
TW
Chung
Choong-Hwan
CH
Kwak
Kyung-Min
KM
Kwon
Makoto
M
Murakami
Yurndong
Y
Jahng
Cheorl-Ho
CH
Kim
Jong-Keun
JK
Son
Hyeun Wook
HW
Chang
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism
D000880:Anthraquinones; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; C540595:citreorosein