The Protective Roles of Butein on Indomethacin Induced Gastric Ulcer in Mice

Abstract

Objective: Butein is a potential agent first isolated from Rhus verniciflua that has medicinal value in East Asia and has been used in the treatment of gastritis, gastric cancer, and atherosclerosis since ancient times. The aim of our study is to show, for the first time, the anti-ulcerative effect of butein in indomethacin induced gastric ulcer in mice.

Materials and methods: A total of 42 mice were fasted 24 hours for the ulcer experiment, and 10, 20, and 40 mg/kg doses of butein were evaluated for their antiulcer activity. Famotidine 40 mg/kg was used as a positive control group. For ulcer induction, 25 mg/kg dose of indomethacin was administered to the mice and after 6 hours all stomachs were dissected out. After macroscopic analyses, tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), COX-1, and COX-2 mRNA levels of stomachs were evaluated by Real Time PCR, and Superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) were determined by ELISA.

Results: Butein administration exerted 50.8%, 65.9%, and 87.1% antiulcer effects at 10, 20, and 40 mg/kg, respectively. Butein administration decreased oxidative stress and inflammatory parameters in stomach tissues dose dependently. Furthermore, butein administration increased stomach PGE2 levels and decreased COX-1 and COX-2 mRNA levels.

Conclusion: Butein has been shown to have a healing effect on ulcers in macroscopic examinations in our study. We observed that butein has antioxidant and anti-cytokine properties in gastric tissue. Butein could be an important alternative in the treatment of indomethacin-induced ulcers. Whether butein is a partial agonist of the COX enzyme should be investigated in future studies.

Keywords: Butein; indomethacin; mice; ulcer.

Figure 1. a–h

ample images; (a) Healthy, (b) BUT40, (c) INDO (ulcer), (d) INDO+FAMO, (e) INDO+BUT10, (f) INDO+BUT20, (g) INDO+BUT40, (h) Numerical densities of ulcerated hematomas from each group. In our study, numerical density of the ulcerated area has been calculated by dividing the total number of ulcer areas by total volume of stomach tissue

Figure 2. a–c

(a) Stomach tissue SOD activity, (b) GSH level, and (c) MDA level. Means with the same letter are not significantly different; means with different letters indicate significant differences between the groups according to the Duncan test (p <0.05). Results are mean±SD. N=6 animals per group

Figure 3. a–c

Stomach tissue PGE2 concentration (a) COX-1 (b) and COX-2 (c) mRNA expression. Means with the same letter are not significantly different; means with different letters indicate significant differences between the groups according to the Duncan test (p <0.05). Results are mean±SD. N=¼ 6 animals per group

Figure 4. a, b

Stomach tissue TNF-α (a) and IL-1β (b) mRNA expression. Means with the same letter are not significantly different; means with different letters indicate significant differences between the groups according to the Duncan test (p <0.05). Results are mean±SD. N=¼ 6 animals per group