Effect of Ajwa Dates Seeds Methanolic Extract on Type-2 Diabetes Mellitus-Induced Memory Deficit in Rats

Abstract

Background and purpose: Diabetes mellitus (DM) is a highly prevalent metabolic disorder that affects children, adults, and the elderly and causes various physiological complications. One of its pathological impacts is brain dysfunction, especially memory and cognitive decline. The present study aimed to explore the impacts of methanol extract of Ajwa dates seeds on type 2 diabetes mellitus-induced memory deficits using a rat model. Methods: A total number of 36 male Sprague Dawley rats (3 months old; 200-250 g body weight) was used and randomly assigned into six groups, and each group comprised six rats. Type 2 diabetes was induced in five groups by nicotinamide (120 mg/kg, i.p.) followed by streptozotocin (60 mg/kg, i.p.), and the non-diabetic group was considered as a control. The animals were treated with vehicle (0.5 % w/v CMC), a standard drug metformin, and three different doses (100, 200, 400 mg/kg) of methanolic Ajwa date seeds extract (MASE) for 30 days. During the last five days (26th to 30th days) of drug treatment, behavioral tests such as elevated plus maze (EPM), Y-Maze and Novel object recognition (NOR) were carried out. On the 30th day of treatment, all animals were sacrificed; blood samples and brain homogenates were collected for further biochemical assessment. The blood glucose and plasma insulin levels were estimated to confirm the anti- diabetes functions of extract. From brain homogenate, the acetylcholine (ACH) and neuroinflammatory parameters [cyclooxygenase 2 (COX 2), tumor necrosis factor alpha (TNF-α), interleukin (IL)- 6 & 10 and transforming growth factor beta 1(TGF-ẞ1)] were analyzed. Results: Diabetic-induced rats showed memory impairment in all the behavior models by increasing transfer latency (TL) in EPM, decreasing number of entries to the novel arms in Y-maze and time spend to explore the novel object in NOR. The results of the EPM test showed that the treatment of MASE (100, 200 and 400 mg/kg, p.o.) significantly enhanced (p<0.01) transfer latency (TL) as compared to diabetic-induced animals. Additionally, the high doses (200 and 400 mg/kg, p.o.) of MASE improved the performance (p<0.05) on number of entries to the novel arms in Y- maze and time spend to explore the novel object in diabetic-induced rats using NOR tasks, respectively. In biochemical estimations, treatment of MASE (100, 200 and 400 mg/kg, p.o.) significantly (p<0.001) reversed the blood glucose levels in the diabetic experiment model. On the other hand, the insulin activity increased (p<0.001) with treatment of MASE (200 and 400 mg/kg, p.o.). The MASE improved cholinergic activity in the CNS through elevating ACh levels in diabetic-induced rats. Regarding neuroinflammation, administration of MASE decreased (p<0.01) proinflammatory cytokines (TNF-a and IL-6) levels at all the doses (100, 200 and 400 mg/kg, p.o.) and increased (p<0.05) anti-inflammatory cytokines (IL-10 and TGF-B1) at selected doses. Conclusion: The overall results supported that MASE could reverse the cognitive impairment induced by type-2 diabetes by inhibiting the neuronal inflammation and increasing the ACh levels. It is concluded that these beneficial effects of the extract may be a potential treatment to handle the cognitive deficits in diabetic patients.