BackgroundCoptis chinensis Franch is extensively used in traditional Chinese medicine to treat diabetes and dementia. Alkaloids are the main active ingredients of C. chinensis.PurposeThis study was designed to probe the effects and possible mechanisms of the total alkaloids from C. chinensis (TAC) on cognitive deficits in type 2 diabetic rats.MethodsCognitive deficits were induced in rats by streptozotocin and high glucose/high fat diet. After treatment with TAC (80, 120, and 180 mg/kg) for 24 weeks, the behavioral parameters of each rat were assessed by Morris water maze and Y-maze tests. The indexes of glucose and lipid metabolism, pathological changes of brain tissue, and the phosphorylation levels of insulin signaling related proteins were also evaluated.ResultsThe type 2 diabetic rats showed significantly elevated levels of fasting blood glucose, glycosylated hemoglobin and glycosylated serum protein, as well as apolipoprotein B, free fatty acid, triglyceride and total cholesterol but decreased the content of apolipoprotein A1, and TAC treatment dose-dependently reversed these abnormal changes. Furthermore, the behavioral results showed that TAC alleviated the cognitive deficits in type 2 diabetic rats. Moreover, immunohistochemical and histopathologic examinations indicated that the diabetic rats showed significant Aβ deposition, and neuronal damage and loss, which can be reversed by TAC treatment. The western blot results showed that TAC treatment markedly increased the phosphorylation of IRS, PI3K, and Akt, and inhibited the overactivation of GSK3β in the brain of type 2 diabetic rats.ConclusionThese findings conclude that TAC prevents diabetic cognitive deficits, most likely by ameliorating the disorder of glucose and lipid metabolism, attenuating Aβ deposition, and enhancing insulin signaling.