The water extract of Samultang protects the Lipopolysaccharide (LPS)Phorbol 12-myristate 13-acetate (PMA)-induced damage and nitric oxide production of C6 glial cells via down-regulation of NF-kappa B

Samultang has been traditionally used for treatment of ischemic heart and b rain diseases in oriental medicine. However, little is known about the mech anism by which Samultang rescues the myocardial and neuronal cells from isc hemic damage. This study was designed to evaluate whether the water extract of Samultang may modulate the production of nitric oxide (NO) in LPS and P MA treated-C6 glial cells to protect the cells from NO-induced cytotoxicity . C6 glial cells heated with both LPS and PMA significantly produced a larg e amount of NO compared to untreated, PMA, or LPS-treated cells. In paralle l with NO production, cotreatment of LPS and PMA induced the severe apoptot ic death of C6 glial cells. However, Samultang significantly reduced both c ell death and NO production by LPS/PMA in a dose-dependent manner. In addit ion, the modulatory effects of Samultang on LPS/PMA-induced cytotoxicity an d NO production could be mimicked by exogenous treatments of N(G)MMA, a nit ric oxide synthase (NOS) inhibitor, and pyrrolidine dithiocarbamate (PDTC), a strong NF-kappaB inhibitor. Treatment of C6-glial cells with LPS/PMA ind uced the transcriptional activation of NF-kappaB, which was markedly inhibi ted by Samultang. Taken together, we suggest that the protective effects of Samultang against LPS/PMA-induced cytotoxicity may be mediated by the supp ression of NO synthesis via down-regulation of NF-kappaB activation. (C) 20 01 Elsevier Science Inc. All rights reserved.