Effect of wogonin, a plant flavone from Scutellaria radix, on the suppression of cyclooxygenase-2 and the induction of inducible nitric oxide synthase in lipopolysaccharide-treated RAW 264.7 cells

Plant flavonoids show anti-inflammatory activity both in vitro and in vivo. Some flavonoids, such as flavone derivatives, have been reported previousl y to inhibit nitric oxide (NO) production by suppressing inducible nitric o xide synthase (iNOS) expression. In this investigation. the effects of wogo nin, a potent inhibitor of NO production among the flavonoids tested, on cy clooxygenase-2 (COX-2) induction and activity were elucidated further in co nnection with iNOS, using a mouse macrophage cell line, RAW 264.7. Wogonin inhibited NO and prostaglandin E-2 (PGE(2)) production from lipopolysacchar ide-induced RAW cells with IC50 values of 31 and 0.3 muM, respectively. Whe n added after the induction of iNOS and COX-2. wogonin inhibited the format ion of PGE(2) (IC50 = 0.8 muM), but not the production of NO. Wogonin inhib ited COX-2 activity directly (IC50 = 46 muM) from the homogenate of aspirin -pretreated RAW cells, as determined by measuring [C-14]PGE(2) formation fr om [C-14]arachidonic acid. However, it did not inhibit iNOS or phospholipas e A(2) activity. Western blotting showed that wogonin suppressed the induct ion of both iNOS and COX-2. Prednisolone also suppressed the induction of i NOS and COX-2. Whereas RU-486 (a steroid receptor antagonist) reversed the suppressive activity of prednisolone, it did not affect the suppressive act ivity of wogonin, suggesting that the suppressive activity of wogonin is no t mediated by binding to a steroid receptor. Results from the present study demonstrated that wogonin is a direct COX-2 inhibitor, as well as an inhib itor of iNOS and COX-2 induction. Wogonin may be a potential agent for use in the treatment of inflammatory diseases. (C) 2001 Elsevier Science Inc. A ll rights reserved.