Nardosinone-Type Sesquiterpenes from the Hexane Fraction of Nardostachys jatamansi Attenuate NF- κB and MAPK Signaling Pathways in Lipopolysaccharide-Stimulated BV2 Microglial Cells

In this study, we investigated their anti-neuroinflammatory effects in lipopolysaccharide (LPS)-induced BV2 microglial cells. The results showed that nardosinone-type sesquiterpenes inhibited the production of pro-inflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-induced BV2 microglial cells. These inhibitory effects were correlated with the downregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, these sesquiterpenes also attenuated the mRNA expression of pro-inflammatory cytokines including interleukin-1 β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) in LPS-induced BV2 microglial cells. During the evaluation of the signaling pathways involved in these anti-neuroinflammatory effects, western blot analysis and DNA-binding activity assay revealed that the suppression of inflammatory reaction by these sesquiterpenes was mediated by the inactivation of nuclear factor-kappa B (NF-κB) pathway. These sesquiterpenes also suppressed the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) signaling pathw ays in LPS-stimulated BV2 microglial cells. Taken together, these four nardosinone-type sesquiterpenes inhibited NF-κB- and MAPK-mediated inflammatory pathways, demonstrating their potential role in the treatment of neuroinflammation conditions.
Source: Inflammation - Category: Allergy & Immunology Source Type: research