title: Andrographolide acts as an anti-inflammatory agent in LPS-stimulated RAW264.7 macrophages by inhibiting STAT3-mediated suppression of the NF-κB pathway.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  However, our understanding of the anti-inflammatory effects of andrographolide is limited.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Graduate Institute of Clinical Medicine Science, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Ko-Chen
authors.initials: KC
authors.lastname: Lee
authors.forename: Hen-Hong
authors.initials: HH
authors.lastname: Chang
authors.forename: Ying-Hui
authors.initials: YH
authors.lastname: Chung
authors.forename: Tzung-Yan
authors.initials: TY
authors.lastname: Lee
mesh_terms: D035685:Andrographis / Q000737:chemistry*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D004224:Diterpenes; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins; D018808:Transcription Factor AP-1; D051743:CCAAT-Enhancer-Binding Protein-delta; C030419:andrographolide; D051546:Cyclooxygenase 2