Ferulic Acid Treats Gastric Ulcer via Suppressing Oxidative Stress and Inflammation

Abstract

(1) Background: The aim of the present study was to evaluate the gastroprotective potential of ferulic acid (FA) on indomethacin-induced gastric ulcers in rats with macroscopic and microscopic examinations along with biochemical assays. (2) Methods: After 24 h starvation, the ulcer was induced in male Sprague-Dawley rats by subcutaneous indomethacin (25 mg/kg) injection. Fifteen minutes after ulcer induction, rats were treated with either tween 80 or FA. FA was given by oral gavage at 100 mg/kg, 250 mg/kg, and 500 mg/kg. In the fourth hour, rats were euthanized and collected gastric samples were evaluated macroscopically and microscopically. Antioxidant parameters including malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and inflammatory parameters comprising of myeloperoxidase (MPO), Tumor Necrosis Factor (TNF)-α, Interleukin (IL)-1β, IL-6 and Nuclear Factor Kappa-B (NF-κB) p65 levels were also determined. (3) Results: Indomethacin injection significantly increased the macroscopic and microscopic scores. In addition, it increased the gastric MDA, MPO, TNF-α, IL-1β, IL-6, and NF-κB p65 levels but reduced SOD and GSH content. Treatment with FA significantly improved the gastric injury macroscopically and microscopically. Moreover, FA displayed a marked decrease in the gastric levels of MDA, MPO, TNF-α, IL-1β, IL-6, and NF-κB p65 and a significant increase in SOD and GSH compared to the INDO group. Ultimately, 250 mg/kg FA was determined as the most effective dose. (4) Conclusion: Our results revealed that FA has a gastroprotective effect against indomethacin-induced gastric ulcers in rats due to its antioxidant and anti-inflammatory properties. As a result, FA may be a potential treatment choice for gastric ulcers.

Keywords: anti-inflammatory; antioxidant; ferulic acid; gastric ulcer; indomethacin.

Figure 1

Macroscopic (A) and microscopic (B) damage scores of gastric tissue samples. INDO: Indomethacin; FA100: Indomethacin + Ferulic Acid 100 mg/kg; FA250: Indomethacin + Ferulic Acid 250 mg/kg; FA500: Indomethacin + Ferulic Acid 500 mg/kg. ** p < 0.01 and *** p < 0.001 vs. the control group; + p < 0.05, ++ p < 0.01 and +++ p < 0.001 vs. the INDO group.

Figure 2

MPO (A), MDA (B), GSH (C) and, SOD (D) levels of gastric tissue samples. MDA: Malondialdehyde, MPO: Myeloperoxidase, GSH: Glutathione, SOD: Superoxide dismutase. INDO: Indomethacin; FA100: Indomethacin + Ferulic Acid 100 mg/kg; FA250: Indomethacin + Ferulic Acid 250 mg/kg; FA500: Indomethacin + Ferulic Acid 500 mg/kg. * p < 0.05 and ** p < 0.01 vs. control group; + p < 0.05 and ++ p < 0.01 vs. INDO group.).

Figure 3

TNF-α (A), IL-1β (B), IL-6 (C) and, NF-κB (D) p65 levels of gastric tissue samples. TNF-α: Tumor necrosis factor-α, IL-1β: Interleukin-1β, IL-6: Interleukin 6, NF-κB-p65: Nuclear Factor Kappa-B-p65. INDO: Indomethacin; FA100: Indomethacin + Ferulic Acid 100 mg/kg; FA250: Indomethacin + Ferulic Acid 250 mg/kg; FA500: Indomethacin + Ferulic Acid 500 mg/kg. * p < 0.05, ** p < 0.01 and *** p < 0.001 vs. control group; + p < 0.05, ++ p < 0.01 and +++ p < 0.001 vs. INDO group.

Figure 4

Representative light micrographs of gastric tissue samples. Normal morphology in gastric mucosa with surface epithelium and gland structure in the control group (A). Severe damage in the surface epithelium, glandular degeneration, hemorrhage, and inflammatory cell infiltration in the INDO group (B,C). Mild epithelial damage, glandular degeneration, and inflammatory cell infiltration in the FA100 group (D). Slight mucosal damage with mild glandular degeneration in the FA250 group (E). Moderate mucosal and glandular degeneration in the FA500 group (F). INDO: Indomethacin; FA100: Indomethacin+ Ferulic Acid 100 mg/kg; FA250: Indomethacin + Ferulic Acid 250 mg/kg; FA500: Indomethacin + Ferulic Acid 500 mg/kg. epithelial damage (arrow), inflammatory cell infiltration (arrowhead), hemorrhage (h) glandular degeneration (asterisk). H&E staining.

Figure 5

Representative electron micrographs of gastric tissue samples. Surface epithelium with normal topography in the control group (A,B). Damaged surface epithelium in the INDO group (C,D). Mild epithelial damage in the FA100 (E,F) group. Quite regular morphology in the FA250 group (G,H). Mild epithelial degeneration in the FA500 group (I,J). INDO: Indomethacin; FA100: Indomethacin+ Ferulic Acid 100 mg/kg; FA250: Indomethacin + Ferulic Acid 250 mg/kg; FA500: Indomethacin + Ferulic Acid 500 mg/kg epithelial damage (arrow), normal epithelial cells (arrowhead).