Abstract
Gastric ulcer disease is associated with significant morbidity and mortality rates. The most two common causes of the ulcer are Helicobacter pylori infection and non-steroidal anti-inflammatory drugs. In the past few decades, a significant decrease in the morbidity and mortality rate has been observed probably due to the discovery of proton pump inhibitors. However, the medications used to treat gastric ulcers impose several nauseous side effects. Therefore, recent studies focus on the use of natural products to treat gastric ulcers. In the current study, gastric ulcer was effectively induced using indomethacin, and the protective effect of apigenin, a potent antioxidant flavonoid, was assessed in comparison to omeprazole. The administration of a single oral indomethacin (50 mg/kg) induced gastric ulcer as manifested by hemorrhagic lesions in the gastric mucosa, increased ulcer index, and histopathological alterations. Indomethacin also increased lipid peroxidation, decreased the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase, increased the immunoreactivity of the inflammatory markers cyclo-oxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), and nuclear factor-kappa B (NF-κB), increased the transcription of the apoptotic marker, Bax, and decreased that of the antiapoptotic Bcl-2. Indomethacin also decreased the immunoreactivity of transforming growth factor-beta 1 (TGF-β1). On the other hand, pretreatment with apigenin (10 and 20 mg/kg) resulted in a dose-dependent improvement in the macroscopic and microscopic features of the gastric mucosa in a manner comparable to that of omeprazole. The gastroprotective effects of apigenin may be attributed to its anti-inflammatory, anti-antioxidant, and anti-apoptotic activities as well as enhancing the expression of TGF-β1. Further experimental and clinical research is required to confirm activity of apigenin as anti-ulcer agent.
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Acknowledgements
Special thanks and great appreciation to Prof. Ashraf Abdel-Naim and Dr. Gamal Abd El-Aziz, King Abdulaziz University, for their assistance in the animal handling procedures and histopathological studies.
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Zaenah Zuhair Alamri is a single author. The authors declare that all data were generated in-house and that no paper mill was used.
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Highlights
• In this study, indomethacin was used to induce gastric ulcers in rats.
• Apigenin protected against macroscopic and gastric microscopic pathological changes.
• Apigenin showed anti-inflammatory, anti-antioxidant, and anti-apoptotic activities.
• Apigenin enhanced the expression of TGF-β1.
• Apigenin possesses a promising potential as an anti-ulcer agent.
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Alamri, Z.Z. Apigenin attenuates indomethacin-induced gastric ulcer in rats: emphasis on antioxidant, anti-inflammatory, anti-apoptotic, and TGF-β1 enhancing activities. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-024-03200-w
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DOI: https://doi.org/10.1007/s00210-024-03200-w