Andrographolide exerted its antimicrobial effects by upregulation of human β-defensin-2 induced through p38 MAPK and NF-κB pathway in human lung epithelial cells

Can J Physiol Pharmacol. 2012 May;90(5):647-53. doi: 10.1139/y2012-050. Epub 2012 Apr 27.


Andrographis paniculata (Burm. f) Nees is a traditional herbal medicine for the treatment of infection and inflammation in China. Andrographolide (andro) is one of the major components. Human β-defensin-2 (hBD-2) is an inducible antimicrobial peptide that plays an important role in innate immunity. The present study aimed to investigate the effect of andro on upregulation of hBD-2 and the key signaling pathways involved in andro-induced hBD-2 expression. Real-time reverse transcription - PCR and Western blot assays showed that andro (1.0-10 µmol/L) can upregulate the expression of hBD-2 in a dose-dependent manner. Further studies suggested that hBD-2 mRNA and protein expression in responsive to andro were attenuated by pretreatment with SB203580 (an inhibitor of p38 mitogen-activated protein kinase (p38 MAPK)), MG-132 (an inhibitor of nuclear factor κB (NF-κB)), and an NF-κB activator inhibitor, but not by an inhibitor of ERK (PD98059) or by an inhibitor of JNK(SP600125). Moreover, we found that a second p38 MAPK inhibitor (SB202190) significantly blocked andro-mediated hBD-2 induction in SPC-A-1 lung epithelial cells. Finally, the p-c-Jun transcription factor activity assay also showed that AP-1 activity was induced by andro compared with the untreated group. We conclude that andro may exert its antimicrobial effects by upregulating the expression of hBD-2 through the p38 MAPK and NF-κB pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / pharmacology*
  • Cells, Cultured
  • Diterpenes / pharmacology*
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression / drug effects
  • Humans
  • Lung / drug effects
  • Lung / metabolism
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / genetics
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • RNA, Messenger / genetics
  • Signal Transduction / drug effects
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Up-Regulation / drug effects
  • beta-Defensins / biosynthesis*
  • beta-Defensins / genetics*
  • beta-Defensins / metabolism
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • Anti-Infective Agents
  • DEFB4A protein, human
  • Diterpenes
  • NF-kappa B
  • RNA, Messenger
  • Transcription Factor AP-1
  • Transcription Factors
  • beta-Defensins
  • andrographolide
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases