Pomegranate peel boosts the potential of Manuka honey to protect against ethanol-induced gastric ulcers in rats by enhancing its anti- inflammatory and antioxidant mechanisms

Discovering alternative safe medicine for the management of gastric ulcers (GU) is a vital issue. This study aimed to investigate the possible protective effect of adding pomegranate peel (PP) to the Manuka honey (MH) against ethanol (EtOH)-induced GU in rats, highlighting the anti-oxidative and anti-inflammatory mechanisms. Twenty four rats were randomly divided into 6 groups; C (control), GU (EtOH 0.5 mL/100 g), OM (omeprazol 40 mg/kg), MH (2.5 g/kg), PP (PP 250 mg/kg), and PP+MH (PP 250 mg/kg and MH 2.5 g/kg). Stomach sections were stained with H&E, PAS, and tumor necrosis factor alpha (TNF alpha) (immunohistochemical staining). Gastric contents of malondialdehyde (MDA), interleukin 2 (IL-2), IL-6, and nitric oxide (NO) were estimated. In comparison with the C group, EtOH caused marked damage of stomach surface mucous epithelium with degenerative changes, and hemorrhage of glandular elements, gastric MDA, TNF alpha, IL-2, and IL-6 were elevated while reduced gastric contents of mucus and NO. Immunohistochemical staining of stomach mucosa showed marked increased TNF alpha expression. Oral administration of OM, MH, and PP+MH improved all biochemical, histological, and immunohistochemical alterations. The best effect owes to the PP+MH combination. The combination of PP+MH had a protective effect on EtOH-induced GU, as it boosted the potential of MH to act as an anti-inflammatory and antioxidant.