The central nervous system (CNS) undergoes alterations due to persistent hyperglycemia and cholinergic dysfunction, leading to cognitive impairment associated with diabetes (T2DM). Animal studies have shown that acetylcholinesterase (AChE) inhibitors and anti-diabetics are effective. Considering the impressive potential of natural products in treating DM and AD, the present research set out to assess the neuroprotective effects of a methanolic extract of Alternanthera pungens (MEAP) against cognitive impairment in mice caused by hyperglycemia. Hence, we used the mobile workforce management (MWM) and enterprise performance management (EPM) assays to analyze for cognitive impairment in diabetic rats. 30 days after the initiation of T2DM, rats had hyperlipidemia, increased escape latency in EPM tasks, and decreased time spent in the TSTQ during probe trials in the MWM. They also displayed notable and persistent hyperglycemia throughout training trials. Changes in blood glucose, lipid, and liver profiles, as well as performance in MWM and EPM tests, were averted in STZ-induced T2DM rats treated with MEAP (200 and 400 mg/kg). In a separate series of experiments, flavonoids (i.e., quercetin and rutin) were detected by the standardization of the extract using high performance thin layer chromatography (HPTLC). Inhibitory actions against alpha-amylase and alpha-glucosidase demonstrate that both of these flavonoids are potent antidiabetic agents that reduce intestinal glucose absorption. Lastly, the inclusion of these flavonoids in the extract from A. pungens is responsible for its action, suggesting that it may provide a novel strategy for preventing cognitive deterioration in diabetes.
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