Epiisopiloturine hydrochloride, an imidazole alkaloid isolated from Pilocarpus microphyllus leaves, protects against naproxen-induced gastrointestinal damage in rats

Biomed Pharmacother. 2017 Mar:87:188-195. doi: 10.1016/j.biopha.2016.12.101. Epub 2017 Jan 2.

Abstract

Objective: This study aimed to investigate the protective effect of epiisopiloturine hydrochloride (EPI), an imidazole alkaloid, on NAP-induced gastrointestinal damage in rats.

Methods: Initially, rats were pretreated with 0.5% carboxymethylcellulose (vehicle) or EPI (3, 10 and 30mg/kg, p.o. or i.p., groups 3-5, respectively) twice daily, for 2days. After 1h, NAP (80mg/kg, p.o.) was given. The control group received only vehicle (group 1) or vehicle+naproxen (group 2). Rats were euthanized on 2nd day, 4h after NAP treatment. Stomachs lesions were measured. Samples were collected for histological evaluation and glutathione (GSH), malonyldialdehyde (MDA), myeloperoxidase (MPO), and cytokines levels. Moreover, gastric mucosal blood flow (GMBF) was evaluated.

Results: EPI pretreatment prevented NAP-induced macro and microscopic gastric damage with a maximal effect at 10mg/kg. Histological analysis revealed that EPI decreased scores of damage caused by NAP. EPI reduced MPO (3.4±0.3U/mg of gastric tissue) and inhibited changes in MDA (70.4±8.3mg/g of gastric tissue) and GSH (246.2±26.4mg/g of gastric tissue). NAP increased TNF-α levels, and this effect was reduced by EPI pretreatment. Furthermore, EPI increased GMBF by 15% compared with the control group.

Conclusion: Our data show that EPI protects against NAP-induced gastric and intestinal damage by reducing pro-inflammatory cytokines, reducing oxidative stress, and increasing GMBF.

Keywords: Epiisopiloturine; Gastrointestinal; Naproxen; Rat.

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / isolation & purification
  • 4-Butyrolactone / pharmacology
  • 4-Butyrolactone / therapeutic use
  • Alkaloids / isolation & purification
  • Alkaloids / pharmacology
  • Alkaloids / therapeutic use*
  • Animals
  • Dose-Response Relationship, Drug
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / pathology
  • Gastrointestinal Diseases / chemically induced
  • Gastrointestinal Diseases / pathology
  • Gastrointestinal Diseases / prevention & control*
  • Imidazoles / isolation & purification
  • Imidazoles / pharmacology
  • Imidazoles / therapeutic use*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / pathology
  • Male
  • Naproxen / toxicity*
  • Pilocarpus*
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Leaves
  • Protective Agents / isolation & purification
  • Protective Agents / pharmacology
  • Rats
  • Rats, Wistar

Substances

  • Alkaloids
  • Imidazoles
  • Plant Extracts
  • Protective Agents
  • epiisopiloturine
  • Naproxen
  • 4-Butyrolactone