Angelicae gigantis radix regulates LPS-induced neuroinflammation in BV2 microglia by inhibiting NF-κB and MAPK activity and inducing NrF-2 activity

Abstract

Angelicae Gigantis Radix (AGR) has been widely used as a traditional medicine in East Asia. The effects of AGR on neuroinflammation have not previously been studied in detail. In the study presented here, we investigated the antineuroinflammatory properties of this herb and its mechanism of operation. The effects of AGR on neuroinflammation were studied by measuring the production of inflammatory factors and related enzymes, and analyzing the expression levels of proteins and genes involved its activity, in lipopolysaccharide (LPS)-stimulated BV2 microglia. We found that AGR pretreatment strongly inhibits the production of nitric oxide (NO), cytokines, and the enzymes inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2, and effectively induces the activation of heme oxygenase (HO)-1 and its regulator, nuclear factor erythroid 2-related factor 2 (Nrf-2). We also found that AGR effectively regulates the activation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK). We confirmed the antineuroinflammatory effects of the main constituents of the plant as identified by high-performance liquid chromatography (HPLC). Our results indicate that the neuroinflammation inhibitory activity of AGR occurs through inhibition of NF-κB and MAPK and activation of Nrf-2.