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.

Baicalein Ameliorates Aβ-Induced Memory Deficits and Neuronal Atrophy via Inhibition of PDE2 and PDE4

“…The shuttle box test was another approach to evaluate memory loss in rodents, as described previously ( Saghaei et al, 2020 ). The shuttle box apparatus used in the experiment was a box which was divided equally into two small rooms, one bright room and one dark room.…”

Mechanistic Insight into Diosmin-Induced Neuroprotection and Memory Improvement in Intracerebroventricular-Quinolinic Acid Rat Model: Resurrection of Mitochondrial Functions and Antioxidants

“…In the current experiments, DSM (50 and 100 mg/kg) significantly abrogated QA-ICV-triggered intensification in lipid peroxidation and total nitrites in the mitochondrial portion of the brain. Earlier reports also substantiate the free radical attenuating and anti-inflammatory deeds of DSM in the entire brain of experimental animals [16][17][18][19][20]. e standard drug, DNP, also attenuated the lipid peroxidation (TBARS) and total nitrites in the brain of rats exposed to QA-ICV.…”

“…In this study, QA was administered directly through the ICV route to overcome the BBB constraint in the adult rats. DSM is a bioactive natural flavonoid that has shown therapeutic effects against traumatic brain injury [ 16 ], scopolamine-induced amnesia [ 17 ], apomorphine- and ketamine-induced psychosis [ 18 ], and chronic unpredictable mild stress [ 19 ]. DSM is capable of enhancing glucose metabolism, insulin signaling, and diabetic complications, and it may prevent energy depletion and the ensuing adverse consequences implicated in neurodegenerative disorders [ 14 , 15 ].…”

“…It attenuates dyslipidemia and hepatic gluconeogenesis [16]. In previous studies, DSM improved cognitive functions, attenuated the symptoms of schizophrenia, and showed neuroprotective effects in experimental animals [16][17][18][19]. Sawmiller et al [20], in a study, noted DSM-mediated decrease in amyloid-β and tau hyperphosphorylation by attenuating glycogen synthase kinase 3β in the 3 × Tg-AD mouse model.…”

Diosmetin Ameliorates Vascular Dysfunction and Remodeling by Modulation of Nrf2/HO-1 and p-JNK/p-NF-κB Expression in Hypertensive Rats

“…Over more than three decades, a wide range of therapeutic effects for diosmetin have been demonstrated. Diosmetin exhibits an excellent antioxidant capacity, both in vivo and in vitro [ 25 , 26 ]. The anti-inflammatory effects of diosmetin have been observed in dinitrochlorobenzene-induced atopic dermatitis in mice [ 27 ].…”