Anti-inflammatory Effects of Oxymatrine Through Inhibition of Nuclear Factor–kappa B and Mitogen-activated Protein Kinase Activation in Lipopolysaccharide-induced BV2 Microglia Cells

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-κB) 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 μg/mL) for 30 min as followed by stimulation with LPS (1 µg/mL) for different times (30 min, 1 h, 3 h, and 6 h). Concentrations of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) 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-κBα) and phospho-I-κBα 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-α, IL-1β and IL-6, attenuated the mRNA levels of iNOS and COX-2, suppressed the phosphorylation of I-κBα 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.