Epiisopiloturine, an imidazole alkaloid, reverses inflammation and lipid peroxidation parameters in the Crohn disease model induced by trinitrobenzenosulfonic acid in Wistar rats

Biomed Pharmacother. 2018 Jun:102:278-285. doi: 10.1016/j.biopha.2018.03.090. Epub 2018 Mar 22.

Abstract

Epiisopiloturine (EPI) is an important imidazole alkaloid because of its pharmacological properties. The aim of this study was to investigate the effects of epiisopiloturine on inflammatory parameters of the colonic mucosa in a rat model of Crohn's disease (CD). For this, we induced colitis using trinitrobenzenosulfonic acid and determined myeloperoxidase (MPO), interleukin 1 β (IL-1β), glutathione (GSH), and malondialdehyde (MDA) levels in the intestinal mucosa. The location and expression of the inflammatory markers in the colon were investigated by immunohistochemistry for NO synthase induced (iNOS), interleukin 1 beta (IL-1β), and cyclooxygenase-2 (COX-2) and western blotting (iNOS and COX-2), respectively. Compared with TNBS alone, epiisopiloturine at 1 mg/kg reduced the macroscopic and microscopic scores, wet weight of the colon, and neutrophilic infiltration and expression of the pro-inflammatory cytokine IL-1β. Epiisopiloturine at 1 mg/kg maintained or restored GSH levels and simultaneously decreased MDA levels. Animals treated with epiisopiloturine exhibited reduced immunostaining for IL-1β, iNOS, and COX-2 and reduced cell count per field. Epiisopiloturine reduced the expression of COX-2 and iNOS in the colon. Based on these findings, we conclude that epiisopiloturine at 1 mg/kg may be an important pharmacological tool against intestinal inflammatory diseases due to its inhibitory action on key enzymes and products involved in inflammation.

Keywords: Anti-inflammatory; Crohn’s disease; Epiisopiloturine; Myeloperoxidase.

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / pharmacology
  • 4-Butyrolactone / therapeutic use
  • Alkaloids / pharmacology
  • Alkaloids / therapeutic use*
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Crohn Disease / drug therapy*
  • Crohn Disease / immunology
  • Disease Models, Animal
  • Female
  • Imidazoles / pharmacology
  • Imidazoles / therapeutic use*
  • Inflammation
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / immunology
  • Lipid Peroxidation / drug effects*
  • Rats, Wistar
  • Trinitrobenzenesulfonic Acid

Substances

  • Alkaloids
  • Anti-Inflammatory Agents
  • Imidazoles
  • epiisopiloturine
  • Trinitrobenzenesulfonic Acid
  • 4-Butyrolactone