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

In this study, we examined the effects of citreorosein (CIT), an anthraquinone component of Polygonui cuspidati radix (P. cuspidati, Polygonaceae), on cyclooxygenase (COX)-2 dependent prostaglandin (PG)D-2 generation in mast cells, central effector cells of allergy and other inflammatory diseases. CIT strongly inhibited COX-2-dependent PGD(2) 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 PGD(2) generation by CIT, we examined the effects of this compound on MAP kinases, Akt and NF-kappa B signaling pathways, which are essential for COX-2 induction. CIT inhibited nuclear translocation of the nuclear factor (NF)-kappa B p65 sub-unit 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 I kappa B. 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 PGD(2) generation by CIT was accompanied by a decrease in phosphorylation of cytosolic phospholipase A(2)alpha. Taken together, the present study suggests that CIT represents a potential therapeutic approach for the treatment of inflammatory diseases. 0 2011 Elsevier Ltd. All rights reserved.