Molecular Docking and Anti-Ulcerative potential of Cucumis (L. Inodorous) on Ibuprofen induced Gastric Ulceration in male Wistar animals
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Background: The use of NSAIDs have caused stomach injury by inhibiting endogenous mucosal prostaglandin production. Cucumis melo is reported to possess antiulcer potential. This study investigates the mechanism underlying the antiulcer potentials of Cucumis Melo (CUM). Methods: Thirty-five male Wistar rat were randomly assigned to each of seven groups; A(control given water and rat pellets), B(gastric ulcer induced with ibuprofen 400mg/kg), C (Misoprotol 200μg/kg), D to G (pretreated with different variation of CUM extract; 25%,50%,75% and 100% at a dose of 1ml/kg for 3 weeks prior to gastric ulcer induction). Ulcer score, ulcer index and percentage inhibition, total gastric acidity was measured. Antioxidant activities, Malondialdehyde, H+/K+ ATPase, PGE2, TNF-α was done by spectrophotometry. Molecular docking investigation of Cucumis melo compounds against Prostaglandin E2 was carried out. Level of significance was tested at P≤0.05 using Tukey post hoc. Result: Total gastric acidity, ulcer score, ulcer index, MDA, TNF-α significantly decreased after CUM treatment when compared to group B. The percentage inhibition, antioxidant activities, PGE2 concentration was significantly increased in all treatment groups compared to group B. Interactions of selected compounds of CUM with Prostaglandin E2 at various docking pockets showed folic acid has highest binding affinity followed by delta7-avenasterol and codisterol to PGE2 receptor. this study shows that one of the mechanisms by which CUM exhibits its antiulcer potential by enhancing Prostaglandin synthesis and antioxidant capacity. Therefore, cucumis melo can therefore be explored as novel antiulcer agents. Keywords: Cucumis melo, ibuprofen, gastric ulcer, Prostaglandin E2 receptor, Folic acid, delta7-avenasterol
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Thirty-five male Wistar rats (weighing 130-150g) were collected from the Department of Human Physiology, Faculty of Basic Medical Sciences, College of Medical Sciences, Ahmadu Bello University, Zaria LGA, Kaduna State, Nigeria. The animals were housed in the Department of Human Physiology, Faculty of Basic Medical Science at Baze University Abuja, allowed to adapt for two weeks, and given unlimited access to food and water. They were cared for in accordance with the National Institutes of Health guide for laboratory animal care ( (NIH Publications No. 8023, revised 1978). Department of Human Physiology ,Baze University's Research Ethics Review Committee approved the procedures and animal use and ethical committee with certificate No: UAECAU/2022/009 2.2.1. Animal grouping Group A: control Group B: Ibuprofen induced gastric ulceration(400 mg/kg .P.O) Group C:Ibuprofen induced gastric ulceration(400mg/kg, P.O) +200μg/kg Misoprostol Group D: Ibuprofen induced gastric ulceration (400mg/kg, P.O) + 1ml/kg of 25 % Aqueous extract of CUM Group E: Ibuprofen induced gastric ulceration (400mg/kg, P.O) + 1ml/kg of 50 % Aqueous extract of CUM Group F: Ibuprofen induced gastric ulceration (400mg/kg, P.O) + 1ml/kg of 75 % Aqueous extract of CUM Group G: Ibuprofen induced gastric ulceration(400mg/kg, P.O) + 1ml/kg of 100 % Aqueous extract of CUM. All animal received 1ml/kg of the different formulates. 2.3. Preparation of Aqueous Extract of Cucumis melo Fruit The entire fruit was cleaned to remove dirt, the seeds were removed from the almost-white fleshy mesocarp and the thin, yellow pericarp on the exterior. A clean sifter was used to blend and filter the pericarp and mesocarp in order to separate the juice from the solid particles. With the addition of distilled water, concentrated juice was diluted to produce 75%, 50%, and 25% v/v solutions and 1ml/kg of each formulate was administered to the different treatment groups. Every day, new preparations were made. 2.3.1. Phytochemical assessment of cucumis melo CUM pulp was prepared as described above and the total Phenolic was evaluated according to the method of Singletonand Rossi[73] using Folin_coicalteau Reagent mix. Flavonoids component, sterols, tannins, alkaloids , saponins,, glycosides were evaluated by method described by Olubunmi et al[74]. 2.4. Induction of gastric ulceration The aqueous extract formulates of Cucumis Melo were administered to the animals for three weeks prior gastric ulcer induction. The animals were fasted for 24 hours before ibuprofen 400 mg/kg body weight was given via oral gavage in order to induced gastric ulceration. Using the technique outlined by Biwas[19], the animals were sacrificed after 4 hours, and gastric lesions in the fundic stomach were scored and expressed as ulcer index. The mean ulcer index is calculated as the sum of all scores divided by the number of animals.