Saussureae Radix Attenuates Neuroinflammation in LPS-Stimulated Mouse BV2 Microglia via HO-1/Nrf-2 Induction and Inflammatory Pathway Inhibition

Abstract

The activation of microglial cells and their subsequent neuroinflammatory reactions are related to various degenerative brain diseases. Therefore, the regulation of microglial cell activation is an important point for the research of therapeutic agents for treating or preventing neurodegenerative disorders. Saussureae Radix (SR) is the root of Saussurea lappa Clarke, and it has been used for a long time as an herbal medicine in East Asia to treat indigestion and inflammation of the digestive system. In previous studies, however, the effect of SR ethanolic extract on microglial cell-mediated neuroinflammation was not fully explained. In this study, we explored the antineuroinflammatory activities and molecular mechanisms of SR in microglial cells stimulated with LPS (lipopolysaccharide). Our results illustrated that SR does not cause cytotoxicity and significantly weakens the production of nitric oxide (NO) and inflammatory cytokines. SR treatment also inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase- (COX-) 2, induced heme oxygenase- (HO-) 1, and activated the nuclear factor erythroid 2-related factor 2 (Nrf-2) pathway. In addition, SR significantly repressed the transcriptional activities of the nuclear factor- (NF-) κB and activator protein- (AP-) 1. Furthermore, SR effectively inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT). Isolation and high-performance liquid chromatography (HPLC) analysis indicated two major sesquiterpenoids (costunolide and dehydrocostuslactone). These compounds significantly inhibited the production of neuroinflammatory mediators and induced HO-1 expression. These findings show that SR could be a potential candidate for the treatment of inflammation-related degenerative brain diseases.