Lavandulyl flavonoids from sophora flavescens suppress lipopolysaccharide-induced activation of nuclear factor-κB and mitogen-activated protein kinases in RAW264.7 cells

Abstract

Oxidized low-density lipoprotein (oxLDL) and reactive oxygen species (ROS) play key roles in the early stage of atherosclerosis. Nitric oxide (NO) and ROS are responsible for regulation of the transcriptional pathways of nuclear Factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK), key regulators of cellular inflammatory and immune responses. Previously, we examined LDL-antioxidant activities of the nine flavonoids isolated from Sophora flavescens. Among these, two lavandulyl flavonoids, kurarinone (1) and kuraridin (2) inhibited inducible nitric oxide synthase (iNOS)-dependent NO production and ROS generation, and suppressed remarkably the expression of inflammatory cytokines, CCL2, tumor necrosis factor (TNF)-α, interleukin (IL)-1 ß,and iNOS in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Moreover, compounds 1 and 2 attenuated NF-κB activation by inhibition of IkBa proteolysis and p65 nuclear translocation, as well as phosphorylation of extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK), and p38 MAP kinases. © 2010 Pharmaceutical Society of Japan.