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Sukkari dates seed improves type-2 diabetes mellitus-induced memory impairment by reducing blood glucose levels and enhancing brain cholinergic transmission: In vivo and molecular modeling studies

2022; Elsevier BV; Volume: 30; Issue: 6 Linguagem: Inglês

10.1016/j.jsps.2022.03.016

2213-7475

Vasudevan Mani, Minhajul Arfeen, Hamdoon A. Mohammed, Hossam A. Elsisi, Sultan Sajid, Yasser Almogbel, Maha A. Aldubayan, Muralikrishnan Dhanasekaran, Ahmad Alhowail,

Cholinesterase and Neurodegenerative Diseases

Cognitive decline is one of the serious complications associated with diabetes mellitus (T2DM) of type-2. In this reported work, the effect of aqueous sukkari dates seed extract (ASSE) was evaluated in T2DM-induced rats. T2DM was induced using intraperitoneal injection of nicotinamide and streptozocin (STZ) administration. The diabetic rats were then treated orally with 200 mg/kg and 400 mg/kg of dates seed extract for 30 days and results were compared with metformin-treated groups. The memory functions were assessed using three maze models. Glucose and insulin levels in the blood and acetylcholine, acetylcholinesterase brain homogenates were estimated. The results showed a significant reduction in transfer latency (TL) (p < 0.001) during the elevated plus maze (EPM) test. The novel object recognition (NOR) test revealed a longer exploration time (p > 0.05) with novel objects and a higher discrimination index (p > 0.05). The Y-maze test also showed a significant increase in the number of entries to the novel arm (p > 0.05) and the total number of entries in the trial (p > 0.01) as well as in test (p > 0.05) sessions. Reduction in blood glucose (p > 0.05) and improvement in blood insulin (p > 0.05) levels were also noted. Improvement in ACh levels (p > 0.001) with 400 mg/kg of ASSE and reduction in AChE (p > 0.001) with both doses of ASSE were also observed in the brain homogenates. The results of ASSE were found comparable with the metformin-treated rats. The estimation of phytochemical constituents displayed a significant presence of phenolic content. Further, molecular modeling studies showed ellagic acid, catechin, and epicatechin as the potential molecule interacting with GSK-3β, α-amylase, and AChE and may be responsible for observed bioactivity. In conclusion, ASSE has the ability to alleviate T2DM-related cognitive impairments.