I. Brouet et H. Ohshima, CURCUMIN, AN ANTITUMOR PROMOTER AND ANTIINFLAMMATORY AGENT, INHIBITS INDUCTION OF NITRIC-OXIDE SYNTHASE IN ACTIVATED MACROPHAGES, Biochemical and biophysical research communications, 206(2), 1995, pp. 533-540
L-Arginine-derived nitric oxide (NO) and its derivatives, such as pero
xynitrite and nitrogen dioxide, play a role in inflammation and also p
ossibly in the multistage process of carcinogenesis. We investigated t
he effect of various non-steroidal anti-inflammatory agents and relate
d compounds on the induction of NO synthase (NOS) in RAW 264.7 macroph
ages activated with lipopolysaccharide (LPS) and interferon-gamma (IFN
-gamma). Low concentrations of curcumin, a potent anti-tumour agent ha
ving anti-inflammatory and anti-oxidant properties, inhibited NO produ
ction, as measured by the amount of nitrite released into the culture
medium in 24 h (IC50 = 6 mu M). NOS activity in soluble extracts of ma
crophages activated for 6 - 24 h in the presence of curcumin (10 mu M)
was significantly lower than that of macrophages activated without cu
rcumin. Northern-blot and immunoblotting analyses demonstrated that si
gnificantly reduced levels of the mRNA and 130-kDa protein of inducibl
e NOS were expressed in macrophages activated with curcumin, compared
to those without curcumin. Inhibition of NOS induction was maximal whe
n curcumin was added together with LPS and IFN-gamma, and decreased pr
ogressively as the interval between curcumin and LPS/IFN-gamma was inc
reased to 18 h. (C) 1995 Academic Press, Inc.