Macluraxanthone B inhibits LPS-induced inflammatory responses in RAW264.7 and BV2 cells by regulating the NF-κB and MAPK signaling pathways

Immunopharmacol Immunotoxicol. 2022 Feb;44(1):67-75. doi: 10.1080/08923973.2021.2006215. Epub 2021 Nov 25.

Abstract

Objective: The prenylated xanthones compounds, macluraxanthone B (MCXB) was isolated from the MeOH extracts of Cudrania tricuspidata. In this study, we investigated the effect of MCXB on inflammatory response.

Materials and methods: Anti-inflammatory effects of MCXB were examined in lipopolysaccharide (LPS)-stimulated RAW264.7 and BV2 cells. We observed their anti-inflammatory effects by ELISA, western blot analysis, and immunofluorescence.

Results: MCXB significantly inhibited the LPS-stimulated production of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-6 (IL-6), and tumor necrosis factor (TNF)-α in RAW264.7 and BV2 cells. MCXB also reduced the LPS-induced expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 proteins. Incubating cells with MCXB prevented subsequent activation of the nuclear factor kappa B (NF-κB) signaling pathway by inhibiting the nuclear localization and DNA-binding activity of the p65 subunit induced by LPS. MCXB inhibited the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 mitogen-activated protein kinases (MAPKs) in RAW264.7 and BV2 cells. MCXB induced the expression of heme oxygenase (HO)-1 protein, and the inhibitory effect of MCXB on nitric oxide production was partially reversed by a selective HO-1 inhibitor.

Discussion and conclusions: Our results suggested that the anti-inflammatory effect of MCXB is partly regulated by HO-1 induction. In conclusion, MCXB could be a useful candidate for the development of therapeutic and preventive agents to treat inflammatory diseases.

Keywords: Macluraxanthone B; anti-inflammation; heme oxygenase-1; mitogen-activated protein kinase; nuclear factor kappa B.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Cyclooxygenase 2 / metabolism
  • Lipopolysaccharides* / toxicity
  • MAP Kinase Signaling System
  • Mice
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • RAW 264.7 Cells
  • Signal Transduction
  • Xanthones* / pharmacology

Substances

  • Anti-Inflammatory Agents
  • Lipopolysaccharides
  • NF-kappa B
  • Xanthones
  • macluraxanthone B
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2