Leocarpinolide B attenuates LPS-induced inflammation on RAW264.7 macrophages by mediating NF-κB and Nrf2 pathways

Eur J Pharmacol. 2020 Feb 5:868:172854. doi: 10.1016/j.ejphar.2019.172854. Epub 2019 Dec 16.

Abstract

Macrophages-mediated inflammation is involved in the regulation of rheumatoid arthritis (RA). Sigesbeckiae Herba (SH) has been traditionally used for rheumatism. However, the bioactive ingredients of SH are still unclear. Recently, we isolated a compound (Leocarpinolide B, LB) from SH and identified its potent anti-inflammatory and antioxidant effects on RAW264.7 macrophages for the first time. LB effectively inhibited excessive production of nitric oxide (NO), prostaglandin E2 (PGE2), cytokines (IL-6, TNF-α and MCP-1), and the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthases (iNOS) in lipopolysaccharide (LPS)-induced RAW264.7 cells. LB blocked the degradation of inhibitor of kappa B (IκBα) and translocation of nuclear factor kappa B (NF-κB) p65. Additionally, LB reduced the intracellular reactive oxygen species, and increased the expression of heme oxygenase-1 (HO-1) and the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) in the presence or absence of LPS. The results suggested that LB might be one of the bioactive components of SH, and be potential for the treatment of RA and valuable to be further investigated.

Keywords: Leocarpinolide B; Nuclear factor erythroid 2-related factor 2 (Nrf2); Nuclear transcription factor-kappa B (NF-κB); Rheumatoid arthritis (RA); Sigesbeckiae herba (SH).

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy
  • Disease Models, Animal
  • Drugs, Chinese Herbal / isolation & purification
  • Drugs, Chinese Herbal / pharmacology*
  • Drugs, Chinese Herbal / therapeutic use
  • Humans
  • Lipopolysaccharides / immunology
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Mice
  • NF-E2-Related Factor 2 / metabolism
  • NF-kappa B / metabolism
  • RAW 264.7 Cells
  • Signal Transduction / drug effects*
  • Signal Transduction / immunology

Substances

  • Anti-Inflammatory Agents
  • Drugs, Chinese Herbal
  • Lipopolysaccharides
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Nfe2l2 protein, mouse