Sericin improves diabetic cognitive impairment in rats by inhibiting TXNIP/NLRP3 neuroinflammation through SIRT1

This study aimed to examine the effects of sericin on diabetic cognitive impairment (DCI) in rats based on neuroinflammation. SD rats were first fed with a high sugar and high fat diet for 4 weeks, and then injected with 50 mg/kg streptozotocin intraperitoneally to establish a diabetic model. The diabetic rats were randomly divided into 3 groups and treated with distilled water (n = 10), 500 mg/kg (n = 10) or 1000 mg/kg (n = 20) sericin, respectively, by gavage once a day for 8 weeks. Before the end of the trial, 10 rats in the 1000 mg/kg sericin group were injected with 10 μg EX527, a Sirtuin-1 (SIRT1) inhibitor, into the lateral ventricles once every other day for 5 times. Treated with sericin significantly reduced fasting blood glucose and improved DCI in rats. Sericin significantly inhibited neuroinflammation and microglial activation, reduced the expression of NOD-like receptor protein 3 (NLRP3) and thioredoxin-interacting protein (TXNIP) proteins, and reduced cell apoptosis, while increasing the expression of SIRT1 protein in the hippocampus of diabetic rats. After inhibiting SIRT1 with EX527, the above effect of sericin on DCI rats was weakened. These results indicated that sericin may block DCI progression in rats by inhibiting TXNIP/NLRP3 neuroinflammation and neuronal apoptosis through SIRT1.