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

作者：Dong, Xiao-Qiao; Du, Quan; Yu, Wen-Hua; Zhang, Zu-Yong; Zhu, Qiang; Che, Zhi-Hao^*; Chen, Feng; Wang, Hao; Chen, Jun

来源：Iranian Journal of Pharmaceutical Research, 2013, 12(1): 165-174.

• Microglia
• Oxymatrine
• Nuclear factor kappa-B
• Mitogen-activated protein kinase
• Inflammation

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 mu g/mL) for 30 min as followed by stimulation with LPS (1 mu g/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-1 beta) 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, PGE(2), TNF-alpha, IL-1 beta 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.

• 出版日期2013-WIN
• 单位南京医科大学