Anti-inflammatory and antioxidant effects of Chaetoglobosin Vb in LPS-induced RAW264.7 cells: Achieved via the MAPK and NF-κB signaling pathways

Food Chem Toxicol. 2021 Jan:147:111915. doi: 10.1016/j.fct.2020.111915. Epub 2020 Dec 5.

Abstract

There are few reports on the biological activities of chaetoglobosin Vb (Cha Vb) (a cytochalasin alkaloid). In this study, we investigated the molecular mechanisms underlying the anti-inflammatory and antioxidant effects of Cha Vb in the RAW264.7 cells stimulated lipopolysaccharide (LPS). LPS stimulation-induced oxidative stress (i.e. increase production of reactive oxygen species (ROS) and decreased expression of antioxidant superoxide dismutase (SOD)) was suppressed after a Cha Vb treatment. Cha Vb could significantly inhibit the upregulated expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) gene and protein induced by LPS whilst attenuating the production of pro-inflammatory cytokines TNF-α, IL-6 and IL-1β. Such antioxidant and anti-inflammatory effects were achieved through the TLR4-mediated MyD88-dependent signaling pathways (via suppressing the phosphorylation of p38, ERK, JNK MAPK and translocation of the NF-κB p65 subunit into nucleus), and the TRIF-dependent signaling pathways (via reducing IFN-β release without inhibiting interferon-regulated factor 3 (IRF3) and IRF7). At 25-100 μM (a concentration range with no cytotoxicity), Cha Vb dose-dependently influenced SOD enzyme activity and phosphorylation of p38, ERK1/2 and JNK, and at 100 μM, likely exerted the greatest inhibition towards LPS-induced oxidative stress and inflammatory response via the MAPK and NF-κB signaling pathway.

Keywords: Anti-inflammation; Antioxidant; Chaetoglobosin V(b); RAW264.7 cells; Signaling pathway.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Cell Survival / drug effects
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation / drug effects
  • Indole Alkaloids / chemistry
  • Indole Alkaloids / pharmacology*
  • Lipopolysaccharides / toxicity*
  • Macrophages / drug effects
  • Mice
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mitogen-Activated Protein Kinase Kinases / metabolism*
  • Molecular Structure
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Nitric Oxide / metabolism
  • RAW 264.7 Cells
  • Signal Transduction / drug effects

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Indole Alkaloids
  • Lipopolysaccharides
  • NF-kappa B
  • Nitric Oxide
  • chaetoglobosins
  • Mitogen-Activated Protein Kinase Kinases