Beneficial effects of Echinacoside on cognitive impairment and diabetes in type 2 diabetic db/db mice

Cognitive dysfunction is an important comorbidity of diabetes. Insulin resistance may play a critical role in diabetes-related cognitive impairment. Echinacoside(ECH), a natural phenylethanoid glycoside, is the active component of anti-diabetes prescriptions in traditional Chinese medicine. Its effect on modulating insulin resistance has been confirmed but modulating neurodegenerative disease still remains to be clarified. Db/db mice, a spontaneous Type 2 diabetes （T2D）mode, were intragastrically administered various doses of ECH or an equivalent volume of saline. Weight, blood glucose, and insulin resistance index were measured. Morris water maze was used to observe the compound effects on cognition. Hippocampal lesions were observed by histochemical analysis. In db/db mice, ECH alleviates diabetes symptoms, memory loss, and hippocampal neuronal damage.Following the step, we found CD44 and phosphorylated tau expression upregulated in diabetic mice. We also found the insulin receptor substrate-1 (IRS1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway dysregulated in diabetic mice. All these changes could be reversed by ECH. Our study provides theoretical support and experimental evidence for the future application of ECH in diabetic cognition dysfunction treatment, promoting the development of traditional medicines.