It is a dark darling and offers attracted a lot of attention, especially in respect to its antimicrobial agent, antioxidant efficacy, and potential role in wound recovery [11, 12]. darling likely exerted its antiulcer, effect by keeping enzymatic (GPx and SOD) and nonenzymatic (GSH and NO) antioxidants as well as inflammatory cytokines (TNF-, IL-1, and IL-6) in a reduced contact form, inhibited lipid peroxidation (MDA), and preserved mucous glycoproteins levels. == 1 . Launch == Itgb7 Gastric ulcers have long been rated as one of the most common diseases affecting humans in general and young people particularly [1]. There are several drug categories that have been used in the treatment of gastric ulcers, including proton pump inhibitors, M1-receptor blockers, and H2-receptor antagonists [2]. There are numerous side effects associated with the drugs utilized in the treatment of ulcers, including arrhythmia, impotence, gynaecomastia, and hematopoietic changes. Moreover, O4I2 there is a very high relapse price (80% at 1st yr and totally in the 2nd year of treatment). Other issues include the long-term duration of the treatment period (therapy with H2-receptor antagonists for 1 year) and the incomplete eradication of ulcers. Therefore , new treatments have been sought to enhance the efficacy of current drugs or to discover potential new providers that are more effective and less expensive and have fewer health-associated side effects than those currently used [3]. Ethanol is a recognized damaging agent to the gastric mucosa, utilized in animals and clinical studies [4]. The model of an ethanol-induced gastric ulcer is used to get the evaluation of the gastroprotective activity of many new therapeutics and natural products [5]. Ethanol leads to a hurry in neutrophil infiltration into the site of injury, which is essentially an acute inflammatory reaction. This is followed by a surge in the formation of reactive oxygen species (ROS), which cause oxidative bursts in the essential cellular parts, including nucleic acids, lipids, and protein [6]. Ethanol also induces alterations in the cytokine balance responsible for inflammation in the gastric mucosa [7]. The proinflammatory cytokine tumour necrosis factor-(TNF-) was discovered to play an essential role in ethanol-induced apoptosis during gastric ulcer formation [8]. Manuka darling is rich with flavonoids. Flavonoids-polyphenolic compounds are a number of secondary metabolites naturally occurring in the plant kingdom, possess several pharmacological activities (antiinflammatory, antimicrobial and gastroprotective), and prevent gastric ulcer formation through a number of mechanisms, including antisecretory and antioxidant mechanisms [9]. Manuka darling is a unifloral honey derived from the manuka tree, Leptospermum scoparium, belonging to the family Myrtaceae in New Zealand and the Eastern region of Sydney [10]. It is a dark honey and has drawn a lot of attention, especially in regard to its antimicrobial agent, antioxidant efficacy, and potential role in wound healing [11, 12]. Compared to other honey types, manuka darling contains the greatest amount of phenolic and flavonoid compounds (pinobanksin, pinocembrin, and chrysin) that have been determined with potent ROS scavenging activity [1315]. This study aimed at investigating the gastroprotective effects of manuka darling against ethanol-induced gastric ulcers in rats using omeprazole as a control drug. In addition , the mechanism by which darling exerts its efficacy is usually elucidated in terms of oxidative stress measures and O4I2 inflammatory cytokine production response. == 2 . Materials and Methods == == 2 . 1 . Animals == Twenty-four, 6-week-old male albino rats weighing between 220 and 250 g were used in this study. The animals were housed in the animal facility at King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia, under a 12 h light/dark routine at a temperature of 25C and relative humidity ranging from sixty to 70% throughout the experiment. The animals had totally free access to diet and water adlibitum. Prior to the induction of gastric ulcer, animals were fasted to get 36 h to ensure an empty stomach (water was allowed). The animals were separately housed in wire mesh cages to avoid coprophagy. The use of experimental animals was conducted in rigid compliance with all the rules and regulations established by the Research Ethics Committee at King Abdulaziz University after obtaining their ethical authorization to pursue this research. == 2 . 2 . Darling and Omeprazole == Royal Bee 20 + energetic manuka darling 100% (Royal Bee, New Zealand) was used in this research. Omeprazole was obtained from Sigma, USA. Powdered omeprazole and O4I2 liquid darling were separately reconstituted in a 3% v/v tween 80 to prepare a 10% stock solution [16]. Stock solutions were freshly prepared daily and used for feeding. == 2 . 3. Induction of Ulcer == The induction of ulcer was achieved by oral administration (p. o. ) of total ethanol at a dose of 1 mL/200 g.