Polygonum tinctorium extract suppresses nitric oxide production by activated macrophages through inhibiting inducible nitric oxide synthase expression

Despite its beneficial role in host defense mechanisms, excessive nitric ox ide (NO) production by activated macrophages has been implicated in several inflammatory diseases. To clarify the mechanisms of anti-inflammatory acti vities of Polygonum tinctorium, we evaluated whether extracts of P. tinctor ium could modulate the production of NO by activated macrophages. An AcOEt extract of P. tinctorium markedly inhibited NO synthesis by interferon-gamm a (IFN-gamma)/lipopolysaccharide (LPS)-stimulated murine peritoneal macroph ages and the macrophage-like cell line RAW 264.7 in a dose-dependent manner . Inhibition of NO synthesis was achieved by reducing inducible NO synthase (iNOS) expression at protein and mRNA levels. However, the AcOEt extract o f P. tinctorium failed to inhibit NO synthesis when iNOS was already expres sed following stimulation with IFN-gamma and LPS. The AcOEt extract also ex hibited inhibitory activity on iNOS expression in human lung epithelial A54 9 cells stimulated with a combination of IFN-gamma, TNF-alpha and IL-1 beta without affecting the expression of constitutive isoforms of NOS. Furtherm ore, in vivo injection of the AcOEt extract of P. tinctorium into LPS-treat ed mice significantly reduced NO synthesis by peritoneal exudate cells unde r ex vivo conditions. These results suggest that P. tinctorium extract may be a potential therapeutic modulator of NO synthesis in various pathologica l conditions. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.