Nardochinoid B Inhibited the Activation of RAW264.7 Macrophages Stimulated by Lipopolysaccharide through Activating the Nrf2/HO-1 Pathway

Molecules. 2019 Jul 6;24(13):2482. doi: 10.3390/molecules24132482.

Abstract

Nardochinoid B (NAB) is a new compound isolated from Nardostachys chinensis. Although our previous study reported that the NAB suppressed the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated RAW264.7 cells, the specific mechanisms of anti-inflammatory action of NAB remains unknown. Thus, we examined the effects of NAB against LPS-induced inflammation. In this study, we found that NAB suppressed the LPS-induced inflammatory responses by restraining the expression of inducible nitric oxide synthase (iNOS) proteins and mRNA instead of cyclooxygenase-2 (COX-2) protein and mRNA in RAW264.7 cells, implying that NAB may have lower side effects compared with nonsteroidal anti-inflammatory drugs (NSAIDs). Besides, NAB upregulated the protein and mRNA expressions of heme oxygenase (HO)-1 when it exerted its anti-inflammatory effects. Also, NAB restrained the production of NO by increasing HO-1 expression in LPS-stimulated RAW264.7 cells. Thus, it is considered that the anti-inflammatory effect of NAB is associated with an induction of antioxidant protein HO-1, and thus NAB may be a potential HO-1 inducer for treating inflammatory diseases. Moreover, our study found that the inhibitory effect of NAB on NO is similar to that of the positive drug dexamethasone, suggesting that NAB has great potential for developing new drugs in treating inflammatory diseases.

Keywords: Nardostachys chinensis; heme oxygenase-1; inducible nitric oxide synthase; nardochinoid B; nitric oxide.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Cyclooxygenase 2 / metabolism
  • Cytokines / biosynthesis
  • Heme Oxygenase-1 / metabolism*
  • Inflammation Mediators
  • Macrophage Activation / drug effects*
  • Macrophage Activation / immunology*
  • Macrophages / drug effects*
  • Macrophages / physiology*
  • Magnoliopsida / chemistry
  • Mice
  • Models, Biological
  • Molecular Structure
  • NF-E2-Related Factor 2 / metabolism*
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • RAW 264.7 Cells
  • Signal Transduction / drug effects*

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Inflammation Mediators
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Plant Extracts
  • Nitric Oxide Synthase Type II
  • Heme Oxygenase-1
  • Cyclooxygenase 2