Effectiveness of Opuntia ficus indica L. inermis Seed Oil in the Protection and the Healing of Experimentally Induced Gastric Mucosa Ulcer

Abstract

Gastric ulcer is a painful lesion of the gastric mucosa which can be disabling, or even more very serious in the case of a perforation of the stomach and internal hemorrhage. Traditional pharmacopeias have shown the efficacy of various plant extracts in the treatment of this pathology. Some extracts from Opuntia ficus indica (OFI) have been proven to have medicinal therapeutic benefits. The aim of this study was to investigate the preventive and curative effects of OFI seed oil extracted by cold pressing on an ethanol-induced gastric ulcer model in rats. Gastroprotective activities of the oil were assessed as pretreatments prior to ethanol gavage of Wistar rats compared to reference drugs. Two oil dose effects were tested. Ulcer and gastric parameters were measured (ulcerated areas (mm²), % of ulcer inhibition, gastric juice volume and pH, and mucus weight). Macroscopical and microscopical assessments of the stomachs as well as gastric biopsy histological studies were carried out. OFI oil exhibited a high efficiency in the protection of the cytoarchitecture and function of the gastric mucosa against the severe damages provoked by ethanol intake. Ulcerated areas were very significantly reduced and the % of ulcer inhibition was the highest under OFI oil pretreatment. Mucus production was stimulated, gastric juice volume was reduced, and its pH was increased. Histopathological examination of H&E-stained biopsies collected from gastric mucosae from the different experimental groups confirmed the gastroprotective efficacy of OFI oil against ethanol-induced symptoms such as inflammation and damages like bleeding, erosions, lesions, necrosis, and ulcers. Furthermore, OFI oil treatment speeded-up the reduction of the surface of ethanol-induced ulcerated areas in a dose-dependent manner, leading to a time gain in the healing process. The healing rate reached 91% on day 2 and 99% on day 3, and a complete heal was attained at the fourth day under OFI oil treatment, while ulcer areas were still partially unhealed in all the other groups. The therapeutic effects of OFI oil against gastric ulcer could be mediated by its varied bioactive compounds that we have demonstrated in the analytical study. They could act synergistically or in a delayed manner to optimize the healing process through protective antioxidant properties, as well as an antagonism against histamine H₂-receptors, a stimulation of the signaling pathways necessary for mucus and bicarbonate production, and reduction of inflammatory processes in the gastric mucosa. Additionally, OFI oil fatty acids (especially unsaturated) and triacylglycerols contribute to the reconstruction and the repair of the cell membrane lipid bilayer during the gastric ulcer healing process.

Figure 1

Chemical structures of pheophytin and lutein fractions. Images depict the chemical structures of major chlorophyll pigments in OI oil.

Figure 2

Chromatographic profile spectra of the fatty acids in the OFI oil. Data analysis of the chromatographic profile of free acids in OFI oil indicates the following composition according to their appearance on the graph: 1—C14 : 0; 2—C16 : 0; 3—C16 : 1; 4—C17 : 0; 5—C17 : 1; 6—C18 : 0; 7—C18 : 1; 8—C18 : 2; 9—C18  :  3 n-3; 10—C20 : 0; 11—C22 : 0.

Figure 3

Chromatographic profile spectra of the sterols in the OFI oil obtained by GC-FID. GC-FID chromatographic profile indicates the following OFI oil composition in phytosterols according to their appearance on the graph: 1—cholesterol; 2—brassicasterol; 3—campesterol; 4—stigmasterol; 5—clerosterol; 6—β-sitosterol; 7—Δ-5,24-stigmastadienol; 8—Δ-7-stigmastenol; 9—Δ-7-avenasterol. α-Cholestanol was used as standard.

Figure 4

Effects of the pretreatments on ulcer (a, b) and gastric parameters (c, d, and e) in ethanol-induced gastric ulcers in rats. Graphs represent the impact of absolute ethanol on ulcer and gastric parameters and the effects of the pretreatments in preventing gastric mucosae damages.

Figure 5

Macroscopic assessment of the pretreatment on gastric mucosa ethanol-induced ulcer: negative control (a), positive control (b), sucralfate pretreated (c), ranitidine pretreated (d), dose 1 oil pretreated (e), and dose 2 oil pretreated (f). Scale bars on the photos indicate 10 mm. Images show gross assessment of the stomachs of the different experimental groups. Ulcer degree induced by ethanol was alleviated in a crescent mode by sucralfate, ranitidine, OFI oil dose 1, and OFI oil dose 2.

Figure 6

Microscopic assessment of the upper surface of ethanol-ulcerated gastric mucosae symptoms (10 × 40). Images represent a microscopic assessment of the symptoms observed on the upper surface of ethanol-ulcerated gastric mucosae like bleeding and cellular and vascular necrosis.

Figure 7

Microscopic assessment of H&E staining biopsies from gastric mucosa of the different experimental groups. M.er: mucosal erosion; N: necrosis; U: ulcer; Vc: vascular congestion. Images depict microscopic assessment of H&E staining biopsies collected from gastric mucosa from the experimental groups. Symptoms like mucosal ulcer, necrosis, and vascular congestion are indicated on the photographs.

Figure 8

Healing rate evolution of the ulcerated areas during the five days postulcer induction in the different experimental groups. Image represents the evolution of the healing rate of the ulcerated surface of gastric mucosa over five days postulcer induction. Comparison between the different groups indicates that OFI oil dose 2 is the most efficient treatment to speed-up the healing process compared to OFI oil dose 1, ranitidine, and sucralfate.