Andrographolide acts as an anti-inflammatory agent in LPS-stimulated RAW264.7 macrophages by inhibiting STAT3-mediated suppression of the NF-κB pathway

J Ethnopharmacol. 2011 Jun 1;135(3):678-84. doi: 10.1016/j.jep.2011.03.068. Epub 2011 Apr 8.

Abstract

Ethnopharmacological significance: Inflammation is involved in numerous diseases, such as chronic inflammatory disease and cancer. Many plant products exhibit useful biological activities, including antifungal, antibacterial, and anti-inflammatory actions.

Aim of study: However, our understanding of the anti-inflammatory effects of andrographolide is limited.

Materials and methods: We use lipopolysaccharide (LPS)-stimulated macrophages as a model of inflammation to investigate the anti-inflammatory effects of andrographolide, which contains polyphenolic structures.

Results: We found that andrographolide exhibited a potent anti-inflammatory effect. In this study, we investigated the inhibitory effects of andrographolide on the induction of nitric oxide synthase (NOS) and cyclooxygenase-2 (COX-2) as well as their respective downstream products, NO and PGE2, in RAW264.7 cells treated with LPS. Treatment with andrographolide also reduced nuclear factor-κB (NF-κB) and activation protein-1 (AP-1) DNA-binding activity. Western blot analysis showed that andrographolide significantly inhibited the phosphorylation of signal transducer and activator of transcription-3 (STAT3) and the protein expression of CCAAT/enhancer-binding protein δ (C/EBPδ). We also found that andrographolide suppressed LPS-induced suppressor of cytokine signalling 1 and 3 (SOCS1 and 3) mRNA expression, which, in turn, inhibited apoptosis signalling and mitochondria membrane potential activation. Our results demonstrate that andrographolide downregulates inflammatory iNOS and COX-2 gene expression by inhibiting the activation of NF-κB and STAT3 by interfering with the expression of SOCS1 and SOCS3 signalling.

Conclusion: Therefore, andrographolide exerts a potent anti-inflammatory effect and could potentially be developed as a useful agent for the chemoprevention of cancer or inflammatory diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Andrographis / chemistry*
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Apoptosis / drug effects
  • CCAAT-Enhancer-Binding Protein-delta / metabolism
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Disease Models, Animal
  • Diterpenes / pharmacology
  • Diterpenes / therapeutic use*
  • Down-Regulation
  • Gene Expression Regulation / drug effects
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • NF-kappa B / metabolism*
  • Phosphorylation
  • Phytotherapy*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • RNA, Messenger / metabolism
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects
  • Suppressor of Cytokine Signaling Proteins / metabolism
  • Transcription Factor AP-1 / metabolism

Substances

  • Anti-Inflammatory Agents
  • Diterpenes
  • Inflammation Mediators
  • Lipopolysaccharides
  • NF-kappa B
  • Plant Extracts
  • RNA, Messenger
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Suppressor of Cytokine Signaling Proteins
  • Transcription Factor AP-1
  • CCAAT-Enhancer-Binding Protein-delta
  • andrographolide
  • Cyclooxygenase 2