Tu-Xian decoction ameliorates diabetic cognitive impairment by inhibiting DAPK-1

Background : Tu-Xian decoction (TXD), as traditional Chinese medicine (TCM), has frequently been used in the treatment of diabetic cognitive impairment (DCI). However, the protective mechanism of TXD on DCI remains unknown. Death-associated protein kinase-1 (DAPK-1) is a key modulator in neuronal disease. This study investigated whether TXD alleviates DCI by inhibiting DAPK-1. Method : The diabetes model was established in SD rats by a high-fat, high-sugar (HFHS) diet, and streptozotocin (STZ). This study included: Control, Diabetic, TC-DAPK6, high-dose TXD, medium-dose TXD, and low-dose TXD 6 groups. After 12 weeks of pharmaceutical intervention, the blood glucose, body weight, Morris water maze (MWM), brain magnetic resonance imaging (MRI), hematoxylin-eosin (H&E), and Nissl staining were examined. Western blotting (WB) was used to detect the protein expression of the hippocampus. Results : Diabetic rat model was successfully established. TXD underlying ameliorated spatial learning and memory ability decline, and hippocampal structural injuries in diabetic rats. Moreover, TXD underlying reduced the expression of a protein associated with neurological damage and DAPK-1 in the hippocampus of diabetic rats. Conclusion : TXD has an underlying mitigating effect on DCI, and this effect might be by inhibition of DAPK-1. Therefore, TXD may serve as a prospective therapeutics for DCI.