ABSTRACT
Oxymatrine, a potent monosomic alkaloid extracted from Chinese herb Sophora japonica [Sophora flavescens Ait.]. Possesses anti-inflammatory activittyes. This study was designed to investigate the effects of oxymatrine on nuclear factor-kappa B [NF-[kappa]B] and mitogen-activated protein kinase [MAPK]-dependent inflammatory responses in lipopolysaccharide [LPS]-activated microglia. In this paper, BV2 microglia were pretreated with different concentrations of oxymatrine [1, 10 and 20 Microg/mL] for 30 min as followed by stimulation with LPS [1 Microg/mL] for different times [30 min, 1 h, 3 h, and 6 h]. Concentrations of nitric oxide [NO], prostaglandin E[2] [PGE[2]], tumor necrosis factor-alpha [TNF-alpha], interleukin-1beta [IL-1beta] and interleukin-6 [IL-6] in supernatant, mRNA levels of inducible nitric oxide synthase [iNOS] and cyclooxygenase-2 [COX-2], cytosolic inhibitor of kappa B-alpha [I-[kappa]B alpha] and phospho- I-[kappa]B[alpha] and nuclear p65 protein levels, and the phosphorylations of MAPK molecules such as extracellular-signal-regulated kinase [ERK] 1/2, p38 MAPK and c-Jun N-terminal kinase [JNK] were determined. It was shown that oxymatrine inhibited the productions of NO, PGE2, TNF-alpha, IL-1beta and IL-6, attenuated the mRNA levels of iNOS and COX-2, suppressed the phosphorylation of I-[kappa]B[alpha] in cytosol, decreased the nuclear levels of p65, and also blocked ERK, p38 and JNK pathway in LPS-stimulated BV2 microglial cells in a dose-dependent manner. According to the results; it is suggested that oxymatrine may attenuate inflammatory responses of microglia and could be potentially useful in modulation of inflammatory status in the brain disorders