Berbamine Exerts Anti-Inflammatory Effects via Inhibition of NF-κB and MAPK Signaling Pathways

Cell Physiol Biochem. 2017;41(6):2307-2318. doi: 10.1159/000475650. Epub 2017 Apr 26.

Abstract

Background/aims: This study aimed to investigate the anti-inflammatory activity of Berbamine (BER), a bisbenzylisoquinoline alkaloid extracted from Berberis amurensis (Xiao Bo An), and the underlying mechanisms.

Methods: Macrophages and neutrophils were treated with BER in vitro and stimulated with LPS and fMLP. The effects of BER on the expression of pro-inflammatory mediators in macrophages were evaluated with quantitative RT-PCR and ELISA. The effects of BER on the activation and superoxide release of neutrophils were determined with flow cytometry and WST-1 reduction test. The inhibitory effects of BER on the activation of signaling pathways related to inflammatory response in macrophages were evaluated by western blot analysis. In addition, a mouse peritonitis model was made by peritoneal injection of thioglycollate medium and anti-inflammatory effects of BER were investigated in vivo by quantitative analysis of pro-inflammatory factor production and leukocyte exudation.

Results: BER significantly inhibited inflammatory factor expression by LPS-stimulated macrophages and suppressed activation and superoxide release of fMLP-stimulated neutrophils. In the mouse peritonitis model, BER significantly inhibited the activation of macrophages and exudation of neutrophils. According to analysis, BER significantly suppressed phosphorylation of NF-κB and MAPK (JNK and ERK1/2) signaling pathways in LPS-stimulated macrophages.

Conclusions: Collectively, data from this study suggest that BER has anti-inflammatory potential, which is effected via inhibition of NF-κB and MAPK signaling pathways, and thus holds promise for treatment of inflammatory disease.

Keywords: Berbamine; MAPK; Macrophages; NF-κB; Neutrophils; Peritonitis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Apoptosis / drug effects
  • Benzylisoquinolines / pharmacology*
  • Benzylisoquinolines / therapeutic use
  • Berberis / chemistry
  • Berberis / metabolism
  • Bone Marrow Cells / cytology
  • Cell Survival / drug effects
  • Cyclooxygenase 2 / metabolism
  • Cytokines / analysis
  • Dinoprostone / metabolism
  • Lipopolysaccharides / toxicity
  • MAP Kinase Signaling System / drug effects*
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / metabolism*
  • Neutrophils / cytology
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Peritonitis / drug therapy
  • RAW 264.7 Cells

Substances

  • Anti-Inflammatory Agents
  • Benzylisoquinolines
  • Cytokines
  • Lipopolysaccharides
  • NF-kappa B
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Dinoprostone
  • berbamine