Abstract
Stress is a typical body's natural defense to a generic physical or psychic change. A specific linking mechanism between ulcer onset and psycho-physical stress prolonged exposure has been reported. We decided to investigate the possible effects of Borago officinalis L. (Borago) in preventing physical (stress)-induced gastric ulcers in a rat model. Eighty male Sprague-Dawley rats were randomly divided into 16 groups, pretreated with a control solution, omeprazole (20 mg/kg), Borago methanolic extract (25, 50, 100, 250, and 500 mg/kg), Borago organic extract (50, 100, 250, and 500 mg/kg), Borago aqueous extract (5, 10, 20, 30, and 40 mg/kg), and D(-)-2-Amino-5-phosphonovaleric acid (AP5) (25 mg/kg) and kept in stressful conditions such as water immersion and restraint-induced stress ulcers. The animals were sacrificed and their stomach scored for the severity and the number of gastric ulcers. Methanolic extract (500 mg/kg) significantly reduced both ulcer parameters (***p < 0.001 and **p < 0.01, respectively). Aqueous and organic extract significantly decreased severity score at 5 and 10 mg/kg (**p < 0.01 and ***p < 0.001, respectively), and at 250 and 500 mg/kg (***p < 0.001), respectively, while gastric ulcers' resulted number significantly reduced only at 10 mg/kg (*p < 0.05) and at 500 mg/kg (**p < 0.01), respectively. On the other hand, aqueous extract significantly increased the mucosal gastric content of cAMP (*p < 0.05) and NR2A and NR2B subunits (*p < 0.05 and **p < 0.01, respectively) at 5 mg/kg. Organic extract showed also a significant cytotoxic effect at 500 and 1,000 mg/kg with a 3T3 cell viability reduction of 43.6% (**p < 0.01) and 92.1% (***p < 0.001), respectively. Borago aqueous extract at 10 mg/kg could be considered as a potential protective agent against stress-induced ulcers, and it is reasonable to possibly ascribe such protective activity to a modulation of the NR2A and NR2B subunit expression.
Highlights
Stress is a typical body’s natural defense to a generic physical or psychic change, which involves a temporary alteration of organism homeostasis [1]
The stress-induced gastric ulcer model showed a high severity score and gastric ulcer number, 3.7 ± 0.4 and 8.0 ± 2.2, respectively, while an opposite significant trend was observed for omeprazole, 0.6 ± 0.1 (∗∗∗p < 0.001) and 1.0 ± 0.3 (∗∗∗p < 0.001), respectively (Figure 1) as shown (Figures 2A,B)
In order to verify any possible molecular modulation of the glutamatergic NMDA receptor, we evaluated mRNA expression of its different subunits by means of real-time reverse transcription-polymerase chain reaction (RT-PCR) on stomach tissue samples from a stress-induced ulcer rat model treated with omeprazole and Borago extracts
Summary
Stress is a typical body’s natural defense to a generic physical or psychic change, which involves a temporary alteration of organism homeostasis [1]. Besides an increased adrenocorticotropic hormone (ACTH) and corticosteroid release, is characterized by an increase in catecholamine release, which, per se, has a protective effect at the gastric level Neurotransmitters such as noradrenaline (NE), dopamine (DA), and γ-aminobutyric acid (GABA) exert a protective effect on the gastric mucosa through an inhibitory control on acid secretion and motility. Further studies highlighted the presence of N-methyl-D-aspartate (NMDA) receptor subunits NR1, NR2A, and NR2B mRNAs at myenteric and submucosal ganglia level [8, 9] This evidence, along with the ability of such receptors to increase intracellular calcium concentration, led to formulate several hypotheses concerning the involvement of the receptors in gastric ulcer onset [10]. Some studies suggested that the cAMP/cGMP ratio might be linked to the onset of ulcerative conditions [15, 16]
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