Ghorbel_2025_Reprod.Fertil.Dev__

BACKGROUND: Estrogen deficiency after menopause is associated with an increased oxidative stress and a cognitive impairment. Given the antioxidant properties of Medicago sativa, this study aimed to evaluate its effects on behavior and oxidative stress parameters in brain and cerebellum of ovariectomized mice. METHODS: The study was carried out on female Swiss mice divided into 2 sham-operated groups: the negative control mice (C) and Medicago sativa treated mice (MS), and 3 ovariectomized groups: ovariectomized mice (OVX) and ovariectomized mice treated either with 17beta-estradiol (OVX-E) or with Medicago sativa (OVX-MS). Open Field and Radial 8-Arm Maze were conducted to evaluate a general locomotor activity and memory of mice. Biochemical analyses were performed to measure oxidative stress markers and acetylcholinesterase activity in cerebrum and cerebellum. RESULTS: In the OVX group, we observed a decrease in locomotor performance during the open field test and a progressive deterioration in spatial memory during the RAM test. An increase in lipid peroxidation, protein carbonyl and advanced oxidation protein product levels as well as a marked inhibition in the activities of antioxidant enzymes in cerebrum and cerebellum indicated the occurrence of oxidative stress after ovariectomy. Elevated acetylcholinesterase activity and histopathological changes in cerebrum and cerebellum were also observed in these mice. However, co-treatment of OVX mice with Medicago sativa resulted in an appreciable improvement of these parameters, emphasizing the therapeutic effects of this plant. CONCLUSION: Our results suggest that Medicago sativa may be a suitable choice for alleviating postmenopausal perturbations caused by estradiol deficiency.