Coumestrol alleviates oxidative stress, apoptosis and cognitive impairments through hippocampal estrogen receptor-beta in male mouse model of chronic restraint stress

Abstract

Background: Coumestrol is well-known as a natural estrogen receptor-beta modulator. Since the role of estrogen receptors in controlling stressful situations has already been reported and their cognitive functions in hippocampus seem to be independent of sexual tasks, the aim of this study was to investigate the improving effects of this phytoestrogen on negative consequences of exposing male mice to chronic restraint stress. Methods: This study was divided into two separate but consecutive phases. In the first phase, the possible effects of Coumestrol (30, 60, 120 µg.kg-1.day-1, i.p.) and its vehicle (sesame oil) on restraint stress-induced cognitive impairments, oxidative stress and apoptosis were evaluated. During the second phase, a selective estrogen receptor-beta antagonist was used to investigate the possible involvement of beta-type estrogen receptors in these processes. Morris water maze and novel object recognition tests were performed to evaluate memory while elevated plus maze test was used to measure the level of anxiety. Spectroscopy and western blotting methods were also employed to evaluate oxidative and apoptotic status in hippocampal tissue. Furthermore, serum level of corticosterone was measured for each group. Results: Behavioral tests indicated memory enhancing and anxiolytic effects of coumestrol. Biochemical evaluations also proved its antioxidant and anti-apoptotic potential. On the other hand, the mentioned behavioral and biochemical improvements were reversed in the group treated with estrogen receptor-beta antagonist. Conclusion: Coumestrol may ameliorate negative consequences of exposure to chronic stress such as oxidative stress, apoptosis and cognitive impairments, via the modulation of beta-type estrogen receptors in hippocampus.

Protective Effects of Coumestrol on Metabolic Dysfunction and Its Estrogen Receptor-Mediated Action in Ovariectomized Mice

“…These findings indicate that the metabolic action of coumestrol is ERβ-dependent. In addition, Fekri et al [ 32 ] recently reported that the memory enhancing and anxiolytic effects of coumestrol were reversed by treatment with an ERβ-selective antagonist in a male mouse model of chronic restraint stress. In their study, the antioxidant and anti-apoptotic effects of coumestrol in brain tissue were lost following co-administration with an ERβ antagonist.…”