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-κB

Abstract

Samultang has been traditionally used for treatment of ischemic heart and brain diseases in oriental medicine. However, little is known about the mechanism by which Samultang rescues the myocardial and neuronal cells from ischemic damage. This study was designed to evaluate whether the water extract of Samultang may modulate the production of nitric oxide (NO) in LPS and PMA treated-C6 glial cells to protect the cells from NO-induced cytotoxicity. C6 glial cells treated with both LPS and PMA significantly produced a large amount of NO compared to untreated, PMA, or LPS-treated cells. In parallel with NO production, cotreatment of LPS and PMA induced the severe apoptotic death of C6 glial cells. However, Samultang significantly reduced both cell death and NO production by LPS/PMA in a dose-dependent manner. In addition, the modulatory effects of Samultang on LPS/PMA-induced cytotoxicity and NO production could be mimicked by exogenous treatments of N^GMMA, a nitric oxide synthase (NOS) inhibitor, and pyrrolidine dithiocarbamate (PDTC), a strong NF-κB inhibitor. Treatment of C6-glial cells with LPS/PMA induced the transcriptional activation of NF-κB, which was markedly inhibited by Samultang. Taken together, we suggest that the protective effects of Samultang against LPS/PMA-induced cytotoxicity may be mediated by the suppression of NO synthesis via down-regulation of NF-κB activation.