Andrographolide interferes with binding of nuclear factor-κB to DNA in HL-60-derived neutrophilic cells

Marí A. Hidalgo, Alex Romero, Jaime Figueroa, Patricia Cortés, Ilona I. Concha, Juan L. Hancke, Rafael A. Burgos

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159 Scopus citations

Abstract

Andrographolide, the major active component from Andrographis paniculata, has shown to possess anti-inflammatory activity. Andrographolide inhibits the expression of several proinflammatory proteins that exhibit a nuclear factor kappa B (NF-κB) binding site in their gene. In the present study, we analyzed the effect of andrographolide on the activation of NF-κB induced by platelet-activating factor (PAF) and N-formyl-methionyl-leucyl-phenylalanine (fMLP) in HL-60 cells differentiated to neutrophils. PAF (100nM) and fMLP (100nM) induced activation of NF-κB as determined by degradation of inhibitory factor B α (IκBα) using Western blotting in cytosolic extracts and by binding to DNA using electrophoretic mobility shift assay (EMSA) in nuclear extracts. Andrographolide (5 and 50 μM) inhibited the NF-κB-luciferase activity induced by PAF. However, andrographolide did not reduce phosphorylation of p38 MAPK or ERK1/2 and did not change IκBα degradation induced by PAF and fMLP. Andrographolide reduced the DNA binding of NF-κB in whole cells and in nuclear extracts induced by PAF and fMLP. Andrographolide reduced cyclooxygenase-2 (COX-2) expression induced by PAF and fMLP in HL-60/neutrophils. It is concluded that andrographolide exerts its anti-inflammatory effects by inhibiting NF-κB binding to DNA, and thus reducing the expression of proinflammatory proteins, such as COX-2.

Original languageEnglish
Pages (from-to)680-686
Number of pages7
JournalBritish Journal of Pharmacology
Volume144
Issue number5
DOIs
StatePublished - Mar 2005

Keywords

  • Andrographolide
  • COX-2
  • HL-60 cells
  • NF-κB
  • Neutrophils
  • PAF
  • fMLP

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