title: Citreorosein, a naturally occurring anthraquinone derivative isolated from Polygoni cuspidati radix, attenuates cyclooxygenase-2-dependent prostaglandin D2 generation by blocking Akt and JNK pathways in mouse bone marrow-derived mast cells.
abstract: In this study, we examined the effects of citreorosein (CIT), an anthraquinone component of Polygoni cuspidati radix (P. cuspidati, Polygonaceae), on cyclooxygenase (COX)-2 dependent prostaglandin (PG)D2 generation in mast cells, central effector cells of allergy and other inflammatory diseases. CIT strongly inhibited COX-2-dependent PGD2 generation in a concentration-dependent manner in mouse bone marrow-derived mast cells (BMMCs) stimulated with stem cell factor (SCF)/IL-10/LPS. In an effort to identify the mechanisms underlying the inhibition of COX-2-dependent PGD2 generation by CIT, we examined the effects of this compound on MAP kinases, Akt and NF-κB signaling pathways, which are essential for COX-2 induction. CIT inhibited nuclear translocation of the nuclear factor (NF)-κB p65 subunit and its cognate DNA-binding activity, which correlated with its inhibitory effects on the phosphorylation of Akt and IKK and subsequent phosphorylation and degradation of IκB. Furthermore, CIT significantly attenuated the DNA binding of activator protein (AP)-1 that regulates COX-2 expression through the reduction of the phosphorylation of c-Jun. Moreover, inhibition of PGD2 generation by CIT was accompanied by a decrease in phosphorylation of cytosolic phospholipase A2α. Taken together, the present study suggests that CIT represents a potential therapeutic approach for the treatment of inflammatory diseases.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Yue
authors.initials: Y
authors.lastname: Lu
authors.forename: Seok-Jong
authors.initials: SJ
authors.lastname: Suh
authors.forename: Xian
authors.initials: X
authors.lastname: Li
authors.forename: Seung-Lark
authors.initials: SL
authors.lastname: Hwang
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Kyoung
authors.initials: K
authors.lastname: Hwangbo
authors.forename: Soon Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Makoto
authors.initials: M
authors.lastname: Murakami
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Yurndong
authors.initials: Y
authors.lastname: Jahng
authors.forename: Jong-Keun
authors.initials: JK
authors.lastname: Son
authors.forename: Cheorl-Ho
authors.initials: CH
authors.lastname: Kim
authors.forename: Hyeun Wook
authors.initials: HW
authors.lastname: Chang
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000302:isolation & purification / Q000494:pharmacology*; D001483:Base Sequence; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000201:enzymology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D004790:Enzyme Induction; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors*; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D009841:Oligonucleotides; D010766:Phosphorylation; D028502:Polygonum / Q000737:chemistry*; D015230:Prostaglandin D2 / Q000096:biosynthesis*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000880:Anthraquinones; D016328:NF-kappa B; D009841:Oligonucleotides; D051546:Cyclooxygenase 2; D051057:Proto-Oncogene Proteins c-akt; D048670:MAP Kinase Kinase 4; C540595:citreorosein; D015230:Prostaglandin D2