Inhibition of neutrophil migration and reduction of oxidative stress by ethyl p-coumarate in acute and chronic inflammatory models

Phytomedicine. 2019 Apr:57:9-17. doi: 10.1016/j.phymed.2018.09.034. Epub 2018 Sep 27.

Abstract

Background: It is well known that medicinal plants and their products are relevant candidates for the treatment of inflammatory conditions. Ethyl p-coumarate is a phenylpropanoid that has similar structure to others anti-inflammatory and antioxidant substances. However, these activities have never been tested.

Purpose: The aim of this study was to investigate the effect of ethyl p-coumarate on inflammatory and oxidative stress parameters.

Study design: This is an experimental study to evaluate the anti-inflammatory and antioxidant activities of ethyl p-coumarate in acute and chronic models of inflammation.

Methods: The anti-inflammatory effect of ethyl p-coumarate was evaluated in Swiss mice by carrageenan-induced paw edema model (1%, 50 μl), followed by histological analysis, and edema induced by compound 48/80 (12 µg/paw), histamine (100 µg/paw), serotonin (100 µg/paw) and prostaglandin E2 (3 nmol/paw) in comparison to indomethacin treatment (10 mg/kg, p.o.). In addition, peritonitis was induced by carrageenan (500 μg/cavity) to neutrophil and total leukocytes counting, myeloperoxidase (MPO), interleukin 6 (IL-6) and 8 (IL-8), nitrite (NO2-), glutathione (GSH) and malondialdehyde (MDA) measurements. The arthritis model was induced with Freund's complete adjuvant (id. 0.1 ml) in female Wistar rats, with measurement of joint diameter and X-ray. Changes in gastric tissue of Swiss mice were analyzed in comparison to indomethacin (20 mg/kg, p.o.).

Results: After treatment with ethyl p-coumarate, the animals had no apparent toxic effects, and significantly inhibited paw edema induced by edematogenic agents, neutrophil (p < 0.001) and total leukocyte (p < 0.001) migration, MPO (p < 0.01), IL-6 (p < 0.05) and IL-8 (p < 0.5), MDA (p < 0.5), GSH (p < 0.5), NO2- (p < 0.001), joint thickness and bones changes. Furthermore, were not observed significant formation of gastric lesions.

Conclusion: Taken together, these results suggest that ethyl p-coumarate exhibits anti-inflammatory activity through the inhibition of inflammatory mediators and leukocyte migration without causing gastric lesions.

Keywords: Arthritis; Cytokines; Inflammation; Neutrophils; Phenylpropanoid.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Antioxidants / pharmacology
  • Arthritis, Experimental / drug therapy
  • Arthritis, Experimental / pathology
  • Carrageenan / toxicity
  • Cell Movement / drug effects
  • Chronic Disease
  • Coumaric Acids / pharmacology*
  • Edema / chemically induced
  • Edema / drug therapy
  • Female
  • Freund's Adjuvant / toxicity
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Male
  • Mice
  • Neutrophils / drug effects*
  • Neutrophils / metabolism
  • Neutrophils / pathology
  • Oxidative Stress / drug effects*
  • Peritonitis / chemically induced
  • Peritonitis / drug therapy
  • Rats, Wistar

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antioxidants
  • Coumaric Acids
  • Carrageenan
  • Freund's Adjuvant