Histopathological and biochemical evaluation of the protective efficacy of Prunus spinosa L. extract in a rat model of indomethacin-induced gastric ulcer

Abstract

Objectives: Some species of Prunus L. are popularly used to treat gastric ulcers. However, the possible healing mechanisms of the anti-ulcer activity of P. spinosa, which has proven antioxidant, anti-inflammatory, and wound-healing properties, are unclear.

Materials and methods: Ethanol extracts of P. spinosa fruits were administered orally at 100 mg/kg and 200 mg/kg to Wistar albino rats, with an indomethacin-induced gastric ulcer model. The ulcerous areas on the stomach surface were examined macroscopically. Tissues were examined histopathologically and biochemically. LC-HRMS revealed the phytochemical content.

Results: TNF-α, IL-6, IL-1β, IL-8, and NF-kB levels were higher in the gastric ulcer group than in the extract groups. The VEGF values did not differ in each group. A significant difference was found between the lansoprazole group and the high-dose P. spinosa group regarding PGE2 levels. A histopathologically significant difference was observed between the healthy group and the indomethacin-applied groups in terms of neutrophilic infiltration of the gastric mucosa. Ascorbic acid (1547.521 µg/g), homoprotocatechuic acid (1268.217 µg/g), and genistein (1014.462 µg/g) were found as the main compounds in the P. spinosa extract by LC-HRMS.

Conclusion: Our results demonstrated that P. spinosa protected the gastric mucosa from inflammation and also modulated the PGE2 pathway. When considered in terms of TNF-α, IL-1β, IL-8, IL-6, PGE2, and NF-kB values, it can be concluded that it has a similar or even more positive effect than the reference substance. P. spinosa showed its effects in a dose-dependent manner.

Keywords: Gastric ulcer; LC-HRMS; PGE2; Prunus spinose; TNF-α.

Figure 1

Photo of Prunus spinosa L. (Rosaceae)

Figure 2

Total ion chromatogram (TIC) profile of Prunus spinosa extract and standard compounds

Figure 3

(a-f). a: Comparison of TNF-α levels of study groups in Wistar albino rats, b: Comparison of IL-6 levels of study groups, c: Comparison of IL-1β levels of study groups, d: Comparison of IL-8 levels of study groups, e: Comparison of NF-κB levels of study groups, f: Comparison of VEGF levels of study groups (*P<0.05, **P<0.002, ***P<0.0002, ****P<0.0001), (g-j). Comparison of PGE2 levels of study groups, h: Comparison of NO levels of study groups, i: Comparison of COX-1 levels of study groups, j: Comparison of COX-2 levels of study groups (*P<0.05, **P<0.002, ***P<0.0002, ****P<0.0001), k. Heat map of the changes in the biochemical parameters

Figure 4

a: Normal gastric mucosa without inflammation (HEX200) in Wistar albino rats, b: Severe neutrophilic infiltration of gastric mucosa in indomethacin group (Circle)(HEX200), c: Mucosal exfoliation and hemosiderin accumulation at mucosa in indomethacin group (Arrows) (HEX200), Fd. Severe exfoliation of gastric mucosa in high-dose extract group (Arrows) (HEX200)