Abstract
Ethanol consumption is one of the common causative agents implicated in gastric ulcer development. Oxidative stress plays a major role in the induction and development of gastric ulceration. NADPH oxidases (NOXs) and Nuclear factor erythroid 2-related factor 2 (Nrf2) are key players in ethanol-induced ulcers. High-mobility group box 1 (HMGB1), a ubiquitous nuclear protein, mediates various inflammation functions. However, the role of HMGB1 in ethanol-induced gastric ulcer is not yet elucidated. Raspberry Ketone (RK) is a natural phenolic compound with antioxidant and anti-inflammatory properties. In the present study, absolute ethanol (7.5 ml/kg) was used to induce gastric ulceration in rats. Raspberry Ketone (RK) (50 mg/kg) was given orally one hour before the administration of absolute ethanol. Interestingly, ethanol-induced gastric ulcer was associated with Nrf2 downregulation, which was correlated with NOX-1, 2 NOX-4, and HMGB1 upregulation, and was significantly reversed by RK pre-treatment. RK pre-treatment provided 80% gastroprotection. Gastroprotective properties of RK were mediated via antioxidant, anti-inflammatory (suppression of NF-kB and tumor necrosis factor-α), and antiapoptotic activities (reduction of Bax/Bcl2 ratio). Gastroprotective properties of RK were confirmed by histopathological examination. In conclusion, this study is the first to provide evidence to the role of HMGB1 in ethanol-induced gastric ulcer, and the crosstalk of Nrf2, NOXs and HMGB1. It also demonstrates that RK represents a promising gastroprotective activity comparable to omeprazole.
Highlights
Gastric ulcer is the most common gastrointestinal disorder; affecting about 10–15% of the world’s population
High-mobility group box 1 (HMGB1) in ethanol-induced gastric ulcer, protection afforded by Raspberry Ketone
Pre-treatment with Raspberry Ketone (RK) at different doses provided a significant gastroprotection, with a dose of 50mg/kg shows a significant difference from dose of 25 mg/kg, and a non-significant difference from higher RK doses, and reduced the total ulcerated area by 80% compared to the ethanol group (Table 1)
Summary
Gastric ulcer is the most common gastrointestinal disorder; affecting about 10–15% of the world’s population. Achievements and new drugs have been introduced that help to cure gastric ulcerations, the mortality is still high, and drugs still not totally effective with high side effects, that limit patients’ compliance [1]. HMGB1 in ethanol-induced gastric ulcer, protection afforded by Raspberry Ketone
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