Polyphenols are major components of many traditional herbal remedies, which exhibit
several beneficial effects including anti-inflammation. The exact mechanism of the
anti-inflammatory action of polyphenols, however, has not been determined. In the
present study, we examined the effects of eight different polyphenols isolated from
Chinese herbs, including two flavonoids (myricitrin and oroxylin A), four ellagitannins
(penta-O-galloyl-beta-glucopyranose, woodfordin C, oenothein B, and cuphiin D1), and
two anthraquinones (emodin and physcion), on lipopolysaccharide (LPS)-induced nitric
oxide (NO) production, and inducible nitric oxide synthase (iNOS) and cyclooxygenase-2
(COX-2) gene expression in RAW264.7 macrophages. The results indicated that only oroxylin
A and emodin concentration-dependently inhibited LPS-induced NO production. The remaining
compounds slightly inhibited LPS-induced NO production only at the highest concentration
examined. Furthermore, oroxylin A inhibited the expression of LPS-induced iNOS and
COX-2 proteins and mRNAs without an appreciable cytotoxic effect on RAW264.7 cells.
Emodin also inhibited LPS-induced iNOS protein as potently as oroxylin A, but it inhibited
LPS-induced iNOS mRNA expression only slightly and did not affect COX-2 mRNA and proteins.
This was consistent with the findings that oroxylin A but not emodin or physcion inhibited
prostaglandin E(2) synthesis induced by LPS. The inhibitory effects of oroxylin A
on LPS-induced iNOS and COX-2 gene expression were also demonstrated in Bcl-2-overexpressing
RAW264.7 macrophages, suggesting that oroxylin A inhibition of iNOS and COX-2 expression
was not due to its antioxidant effect. Furthermore, oroxylin A but not emodin blocked
nuclear factor-kappaB (NF-kappaB) binding and transcriptional activation associated
with decreased p65 proteins in the nucleus induced by LPS. These results indicated
that oroxylin A, an active component in Huang Qin, inhibited LPS-induced iNOS and
COX-2 gene expression by blocking NF-kappaB activation, whereas emodin inhibition
of LPS-induced iNOS expression may be mediated by a different transcription factor.