Diosmetin Mitigates Cognitive and Memory Impairment Provoked by Chronic Unpredictable Mild Stress in Mice

Abstract

Background and Aim. Numerous reports have indicated that dealing with stressors in life is a main risk factor for the occurrence and progression of cognitive and memory impairment. Available treatments such as benzodiazepine and antidepressants address only certain aspects of this stress disorder and have numerous side effects. The present study was aimed at investigating the effect of diosmetin, as a flavonoid compound with potent antioxidant and anti-inflammatory effects, on cognitive impairment and chronic stress memory. Materials and Methods. In the present experimental study, male NMRI mice were exposed to chronic unpredictable mild stress (CUMS) paradigm for 35 days. Diosmetin (at doses of 10, 20, and 40 mg/kg. i.p.) or diosmetin solvent (normal saline + DMSO, 1 ml/kg; i.p.) was administered 30 min before stress induction. After 28 days, memory and cognitive performance were assessed by shuttle box and novel object recognition tests. Finally, antioxidant capacity (FRAP) and malondialdehyde (MDA) level of serum and brain, and serum corticosterone level were evaluated. Results. Behavioral tests showed that CUMS significantly reduced the secondary latency in passive avoidance memory test and diagnosis index in novel object recognition test compared to the control group ( $P<0.001$ ), whereas treatment with diosmetin (20 and 40 mg/kg) significantly improved memory performance in the two tests ( $P<0.001$ ). In addition, diosmetin (40 mg/kg) could pronouncedly suppress increase in serum corticosterone levels, reduction in antioxidant capacity, and production of excess MDA caused by CUMS compared to the control group ( $P<0.01$ , $P<0.001$ , and $P<0.001$ , respectively). Conclusion. Chronic stress can impair memory and cognition and treatment with diosmetin can partly improve this disorder in male mice by increasing the antioxidant capacity of brain tissue and serum and improving serum corticosterone levels.