Sericin attenuates diabetes-associated cognitive dysfunction by inhibiting apoptosis and inflammation with involvement of the PI3K/AKT pathway

Objective Diabetes-associated cognitive dysfunction (DACD) is now acknowledged as a key complication of diabetes, whereas the precise pathological mechanisms remain unclear. Sericin, a naturally water-soluble protein complex extracted from silkworm cocoons, possesses glycemic-regulating and neuroprotective properties. This study aimed to investigate whether sericin could attenuate DACD via the PI3K/AKT pathway. Methods A high-fat diet/streptozotocin (HFD/STZ)-induced diabetic Sprague-Dawley rat model was established. The PI3K inhibitor LY294002 was used to verify pathway involvement. Effects of HFD/STZ induction and sericin treatment were evaluated by analyzing cognitive function, lipid profiles, and hippocampal apoptosis and inflammation markers via Morris water maze test, ELISA assays, Western blot, HE staining, immunohistochemistry, immunofluorescence, and transmission electron microscopy. Results Diabetic rats exhibited hyperglycemia, hyperlipidemia, and cognitive impairment, along with decreased p-PI3K, p-AKT, and Bcl-2 levels, and elevated levels of caspase-3, Bax, IL-1β, and IL-18 in the hippocampus, while NF-κB showed an increasing trend. Sericin treatment significantly ameliorated metabolic disorders, attenuated cognitive deficits, and reduced hippocampal apoptosis and neuroinflammation. Notably, the neuroprotective effects of sericin were partially reversed by LY294002, supporting the involvement of the PI3K/AKT pathway. Conclusion Sericin intervention attenuates DACD by inhibiting neuronal apoptosis and inflammation with involvement of the PI3K/AKT pathway. Thus, sericin might be a potential neuroprotective intervention for DACD.