期刊
FOOD AND CHEMICAL TOXICOLOGY
卷 50, 期 3-4, 页码 913-919出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2011.11.046
关键词
Citreorosein; Mast cells; Cyclooxygenase-2; Akt; NF-kappa B; JNK
资金
- Yeunganm University [211-A-380-076]
- Grants-in-Aid for Scientific Research [22116001] Funding Source: KAKEN
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.
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