Protective Effects of Borago officinalis (Borago) on Cold Restraint Stress-Induced Gastric Ulcers in Rats: A Pilot Study

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.

Investigating the L-Glu-NMDA receptor-H2S-NMDA receptor pathway that regulates gastric function in rats’ nucleus ambiguus

“…The expression of NMDA receptor subunits is not altered in stress-induced ulcer models. This indicates, that NMDA receptors are not directly involved in ulcer formation, but rather in protecting the gastric mucosa Di Cerbo et al (2020) . The current study also revealed that pre-injecting the NMDA receptor blocker, D-AP5, eliminated modulation of gastric function by L-Glu and NaHS.…”

Borago Officinalis L.: A Review Oon Extraction, Phytochemical, and Pharmacological Activities

“…Di Cerbo et al., (2020) [62] examined the toxicity of crude methanolic extract, organic (obtained by ethyl acetate) fraction, and aqueous fraction on A31‐1‐1 cells (type of cells derived from mice embryos) at various concentrations (250, 500, and 1000 mg/kg). The organic fraction induced cytotoxic effects at 500 and 1000 mg/kg, reducing cell viability by 43.6 % and 92.1 %, respectively.…”

“…Different concentrations of methanolic extract and its organic (ethyl acetate) and aqueous fractions from B. officinalis leaves were administrated on stress‐induced gastric ulcers in rats [62] . The methanolic extract significantly reduced the severity and number of gastric ulcers in a dose‐dependent manner, particularly at 500 mg/kg.…”

Acute Cold Water-Immersion Restraint Stress Induces Intestinal Injury and Reduces the Diversity of Gut Microbiota in Mice

“…Mice exposed to cold-restraint stress presented gastric ulcer and inflammation ( Di Cerbo et al., 2020 ; Higashimori et al., 2021 ). Further, 15-min cold exposure in mice increased their gastric phasic activity and tone, whereas mice exposed to chronic stress presented with no gastric response ( Gourcerol et al., 2011 ).…”