Crataegus laevigata Suppresses LPS-Induced Oxidative Stress during Inflammatory Response in Human Keratinocytes by Regulating the MAPKs/AP-1, NFκB, and NFAT Signaling Pathways

Molecules. 2021 Feb 6;26(4):869. doi: 10.3390/molecules26040869.

Abstract

Crataegus laevigata belongs to the family Rosaceae, which has been widely investigated for pharmacological effects on the circulatory and digestive systems. However, there is limited understanding about its anti-oxidative stress and anti-inflammatory effects on skin. In this study, 70% ethanol C. laevigata berry extract (CLE) was investigated on lipopolysaccharide (LPS)-stimulated keratinocytes. The LPS-induced overproduction of reactive oxygen species (ROS) was suppressed by the treatment with CLE. In response to ROS induction, the overexpression of inflammatory regulating signaling molecules including mitogen-activated protein kinases (MAPK)/activator protein-1 (AP-1), nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB), and nuclear factor of activated T-cells (NFAT) were reduced in CLE-treated human keratinocytes. Consequently, CLE significantly suppressed the mRNA levels of pro-inflammatory chemokines and interleukins in LPS-stimulated cells. Our results indicated that CLE has protective effects against LPS-induced injury in an in vitro model and is a potential alternative agent for inflammatory treatment.

Keywords: Crataegus laevigata; LPS; MAPK/AP-1; NF-κB; NFAT; inflammation; keratinocytes; oxidative stress.

MeSH terms

  • Cell Survival / drug effects
  • Chemokines / genetics
  • Crataegus / chemistry*
  • Gene Expression Regulation / drug effects
  • Humans
  • Inflammation / metabolism
  • Inflammation / pathology
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • Keratinocytes / pathology*
  • Lipopolysaccharides / pharmacology*
  • MAP Kinase Signaling System / drug effects*
  • NF-kappa B / metabolism
  • NFATC Transcription Factors / metabolism
  • Oxidative Stress / drug effects*
  • Plant Extracts / pharmacology*
  • RNA, Messenger / genetics
  • Transcription Factor AP-1 / metabolism

Substances

  • Chemokines
  • Lipopolysaccharides
  • NF-kappa B
  • NFATC Transcription Factors
  • Plant Extracts
  • RNA, Messenger
  • Transcription Factor AP-1