In Vivo Evidence for the Preventive Role of Vaccinium macrocarpon Aiton in Indomethacin-Induced Gastric Ulcer: Focusing on Antioxidant, Anti-Inflammatory and Anti-Apoptotic Mechanisms

大果越橘对吲哚美辛诱发的胃溃疡具有预防作用的体内证据:重点关注抗氧化、抗炎和抗凋亡机制

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作者:Ismail Cagri Aydin, Irmak Ferah Okkay, Ufuk Okkay, Mustafa Ozkaraca, Fatma Yesilyurt, Aysegul Yilmaz, Betul Cicek, Ozhan Karatas, Hilal Kadioglu Kalkandelen, Bilge Aydin, Ahmet Hacimuftuoglu, Songul Karakaya, Zuhal Güvenalp, A M Abd El-Aty2

Abstract

The present study aimed to unveil the gastroprotective potential of Vaccinium macrocarpon (VM) extract and its mechanism of action against indomethacin (INDO)-induced gastric ulcers in rats. To achieve this goal, rats were pretreated with either omeprazole (20 mg/kg) or VM (100 mg/kg) orally for 14 consecutive days. Gastric tissue samples were collected and various parameters were evaluated to understand the mechanism of VM's action, including the levels of superoxide dismutase, malondialdehyde, glutathione, CAT and transforming growth factor beta (TGF-β), as well as the mRNA expression levels of tumour necrosis factor alpha, interleukin 1 beta, nuclear factor kappa B (NF-κB) and inhibitor kappa B (IκB). Additionally, the immunopositivity of cyclooxygenase (COX)-1, COX-2, PGE2, proliferating cell nuclear antigen (PCNA) and caspase-3 was assessed. The total amount of phenolic compounds present in the VM extract was high (58.08 µg/mL gallic acid equivalent/mg extract). The healing effect of VM was demonstrated by an increase in the expression of PCNA. Furthermore, the level of TGF-β was found to increase upon treatment with VM. Analyses of COX-1, COX-2 and PGE2 expression in gastric tissue confirmed the gastroprotective effect of VM. Notably, the expression of NF-κB was markedly reduced, whereas that of IκB was substantially increased. Overall, the findings of this study demonstrate that VM extract has gastroprotective and curative effects against INDO-induced ulcers through its antioxidant, anti-inflammatory, mucosal regenerative and anti-apoptotic activities. Therefore, VM may serve as a useful adjuvant treatment for nonsteroidal anti-inflammatory drugs-induced gastric ulcer disease.

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