Fisetin Attenuates Gastric Mucosal Lesions through Modulating Nuclear Factor‑Kappa B and Peroxisome Proliferator‑Activated Receptor‑γ in Rats

Objective: The objective of this study was to explore the underlying mechanism of action of fisetin on ethanol‑induced gastric ulcer model. Materials and Methods: In this study, gastric mucosal lesions were induced by ethanol in rats. Five groups of rats were formed based on the treatment administered: model group (model), omeprazole (40 mg/kg) group (omeprazole), high‑dose fisetin group (100 mg/kg, H‑fisetin), medium‑dose fisetin group (50 mg/kg, M‑fisetin), and low‑dose fisetin group (25 mg/kg, L‑fisetin). Interleukin (IL)‑1β, IL‑6, and tumor necrosis factor (TNF)‑α levels were assessed in serum. The expression of peroxisome proliferator‑activated receptor (PPAR)‑γ, nuclear factor‑kappa B (NF‑κB), and p38‑mitogen‑activated protein kinase (p38‑MAPK) in the gastric mucosa was also measured. Results: In the case of the high‑dose fisetin group, the level of TNF‑α, IL‑1β, and IL‑6 decreased from 9.57 pg/mL to 5.19 pg/mL, from 0.59 pg/mL to 0.27 pg/mL, and from 37.96 pg/mL to 21.09 pg/mL, respectively. In the case of the omeprazole group, the level of TNF‑α, IL‑1β, and IL‑6 decreased to 4.38 pg/mL, 0.27 pg/mL, and 18.58 pg/mL, respectively. The expression of PPAR‑γ protein in the high‑dose fisetin and omeprazole groups was about 1.5 times higher than that in the model group. Compared with the model group, the expression of NF‑κB protein reduced to 0.34 level and 0.47 level in the omeprazole and high‑dose fisetin groups, respectively. Compared with the model group, the expression of p38‑MAPK protein reduced to 0.55 level and 0.68 level in the omeprazole and high‑dose fisetin groups, respectively. Conclusion: Fisetin might relieve the symptoms of ethanol‑induced gastric ulcer in rats through the regulation of NF‑κB pathway.