Anti-inflammatory effects of Capparis ecuadorica extract in phthalic-anhydride-induced atopic dermatitis of IL-4/Luc/CNS-1 transgenic mice

Pharm Biol. 2020 Dec;58(1):1263-1276. doi: 10.1080/13880209.2020.1856146.

Abstract

Context: The natural products derived from Capparis ecuadorica H.H. Iltis (Capparaceae) could have great potential for anti-inflammation since they inhibited the inflammatory response in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells.

Object: This study investigated the anti-inflammatory effects and related mechanism of methanol extract of C. ecuadorica leaves (MCE) during atopic dermatitis (AD) responses.

Materials and methods: Alterations in the phenotypical markers for AD, luciferase signal, iNOS-mediated COX-2 induction pathway, and inflammasome activation were analysed in non-Tg (n = 5) and 15% phthalic anhydride (PA) treated IL-4/Luc/CNS-1 transgenic (Tg) HR1 mice (n = 5 per group), subsequent to treatment with acetone-olive oil (AOO), vehicle (DMSO) and two dose MCE (20 and 40 mg/kg) three times a week for 4 weeks.

Results: MCE treatment reduced the intracellular ROS level (48.2%), NO concentration (7.1 mmol/L) and inflammatory cytokine expressions (39.1%) in the LPS-stimulated RAW264.7 cells. A significant decrease was detected for ear thickness (16.9%), weight of lymph node (0.7 mg), IgE concentration (1.9 µg/mL), and epidermal thickness (31.8%) of the PA + MCE treated Tg mice. MCE treatment induced the decrease of luciferase signal derived from the IL-4 promoter and the recovery of the IL-4 downstream regulator cytokines. PA + MCE treated Tg mice showed decreasing infiltration of mast cells (42.5%), iNOS-mediated COX-2 induction pathway, MAPK signalling pathway and inflammasome activation in the ear tissue.

Conclusions: These findings provide the first evidence that MCE may have great potential to suppress chemical-induced skin inflammation through the suppression of IL-4 cytokine and the iNOS-mediated COX-2 induction pathway, and activation of inflammasome.

Keywords: COX-2; IgE; Inflammation; iNOS; luciferase signal.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Capparis*
  • Cyclooxygenase 2 / physiology
  • Dermatitis, Atopic / chemically induced
  • Dermatitis, Atopic / drug therapy*
  • Inflammasomes / physiology
  • Interleukin-4 / genetics*
  • Luciferases, Firefly / genetics*
  • Mast Cells / physiology
  • Mice
  • Mice, Transgenic
  • Nitric Oxide Synthase Type II / physiology
  • Phthalic Anhydrides / toxicity*
  • Plant Extracts / pharmacology*
  • RAW 264.7 Cells

Substances

  • Anti-Inflammatory Agents
  • Inflammasomes
  • Phthalic Anhydrides
  • Plant Extracts
  • Interleukin-4
  • Luciferases, Firefly
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • phthalic anhydride

Grants and funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) [No. 2019R1A2C108414011 and 2019R1A2C108414012].