Astragalus polysaccharides exerts anti-infective activity by inducing human cathelicidin antimicrobial peptide LL-37 in respiratory epithelial cells

Phytother Res. 2018 Aug;32(8):1521-1529. doi: 10.1002/ptr.6080. Epub 2018 Apr 19.

Abstract

Astragalus polysaccharides (APS), one of the major active components in Astragalus membranaceus, is an effective immunomodulator used in the treatment of immunological diseases in China. However, the anti-infective action and mechanism of APS is not fully known. In the present study, we found that APS induced the expression of human cathelicidin antimicrobial peptide LL-37, a key host anti-infective molecule, in both mRNA and protein levels in respiratory epithelial cells HBE16 and A549. Furthermore, the lysate and supernatant from APS-treated HBE16 cells both exhibited an obvious antibacterial action, which was partially neutralizated by LL-37 monoclonal antibody. In addition, APS also significantly elevated the phosphorylation of p38 MAPK and JNK and caused the degradation of IκBα. Specific inhibitors of p38 MAPK, JNK, or NF-κB obviously abolished APS-induced LL-37 synthesis and antibacterial activity, respectively. Taken together, our results confirmed the enhancement of APS on LL-37 induction and antibacterial action in respiratory epithelial cells, which may be attributed to activation of p38 MAPK/JNK and NF-κB pathways. Furthermore, these results also supported the clinical application of APS in the treatment of infectious diseases.

Keywords: NF-κB signaling; anti-infective activity; astragalus polysaccharides; human cathelicidin antimicrobial peptide LL-37; p38 MAPK and JNK signaling.

MeSH terms

  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides
  • Astragalus propinquus / chemistry*
  • Cathelicidins / biosynthesis*
  • Cell Line
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Humans
  • I-kappa B Proteins / metabolism
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism
  • Phosphorylation / drug effects
  • Polysaccharides / pharmacology
  • Transcription Factor RelA
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides
  • Cathelicidins
  • I-kappa B Proteins
  • NF-kappa B
  • NFKBIA protein, human
  • Polysaccharides
  • RELA protein, human
  • Transcription Factor RelA
  • NF-KappaB Inhibitor alpha
  • p38 Mitogen-Activated Protein Kinases