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Diosmetin Mitigates Cognitive and Memory Impairment Provoked by Chronic Unpredictable Mild Stress in Mice
Elham Saghaei1,2, Shakiba Nasiri Boroujeni2, Parvin Safavi3
1Department of Physiology and Pharmacology, Faculty of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran.
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.
Insights
Chronic unpredictable mild stress (CUMS) impairs memory in mice. Diosmetin treatment improved cognitive function and antioxidant capacity, while reducing stress hormones.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Chronic unpredictable mild stress (CUMS) is a validated model for inducing stress-related behavioral and physiological changes in rodents.
- Stress-induced cognitive deficits and memory impairment are significant concerns in both animal models and human health.
Purpose of the Study:
- To investigate the potential of diosmetin, a natural flavonoid, in ameliorating cognitive deficits induced by CUMS in male NMRI mice.
- To evaluate the effects of diosmetin on stress markers, including serum corticosterone, antioxidant capacity, and oxidative stress levels.
Main Methods:
- Male NMRI mice were subjected to a 35-day CUMS paradigm.
- Mice received intraperitoneal injections of diosmetin (10, 20, or 40 mg/kg) or vehicle 30 minutes prior to stress exposure.
- Memory and cognitive performance were assessed using shuttle box and novel object recognition tests.
- Serum and brain levels of antioxidant capacity (FRAP) and malondialdehyde (MDA), along with serum corticosterone, were measured.
Main Results:
- CUMS significantly impaired memory and cognitive performance in behavioral tests.
- Diosmetin treatment (20 and 40 mg/kg) significantly improved memory and cognitive function.
- High-dose diosmetin (40 mg/kg) suppressed CUMS-induced increases in serum corticosterone and MDA levels.
- Diosmetin treatment also counteracted the reduction in antioxidant capacity caused by CUMS.
Conclusions:
- Diosmetin demonstrates significant potential in mitigating memory and cognitive impairments associated with chronic stress in mice.
- The neuroprotective effects of diosmetin appear to be mediated through its antioxidant properties and modulation of the stress response (corticosterone levels).
- These findings suggest diosmetin as a potential therapeutic agent for stress-related cognitive disorders.
