Sericin Attenuates Diabetes-Associated Cognitive Dysfunction in Diabetic Rat Model

Treatment with sericin, a protein complex derived from silkworm cocoons, significantly attenuated cognitive deficits and reduced metabolic abnormalities in a rat model of diabetes-associated cognitive dysfunction, according to research published in Frontiers in Pharmacology.

Diabetes-associated cognitive dysfunction is recognized as a key complication of diabetes, although its precise pathological mechanisms remain unclear. Sericin is a naturally water-soluble protein complex possessing glycemic-regulating and neuroprotective properties, prompting investigators to examine whether its administration could mitigate cognitive deficits through the PI3K/AKT pathway.

To evaluate this mechanism, the researchers established an animal model using Sprague-Dawley rats subjected to a high-fat diet combined with streptozotocin induction. The chemical PI3K inhibitor LY294002 was also administered to verify whether the therapeutic response was dependent on the PI3K/AKT signaling cascade.

The study evaluated cognitive performance, circulating lipid profiles, and hippocampal apoptosis and inflammation markers across experimental groups. Analytical techniques included the Morris water maze test, enzyme-linked immunosorbent assays, Western blotting, hematoxylin-eosin staining, immunohistochemistry, immunofluorescence, and transmission electron microscopy.

Untreated diabetic rats exhibited hyperglycemia, hyperlipidemia, and cognitive impairment, accompanied by decreased levels of phosphorylated PI3K, phosphorylated AKT, and Bcl-2 in the hippocampus. Concurrently, hippocampal tissues displayed elevated levels of caspase-3, Bax, interleukin-1 beta, and interleukin-18, alongside an increasing trend in NF-kappa-B expression.

Sericin intervention significantly ameliorated metabolic disorders, attenuated cognitive deficits, and reduced hippocampal apoptosis and neuroinflammation. Because these protective outcomes were partially reversed by the inhibitor LY294002, the authors concluded that sericin attenuates diabetes-associated cognitive dysfunction by suppressing neuronal apoptosis and inflammation via the PI3K/AKT pathway, suggesting its potential as a neuroprotective intervention.

To evaluate cognitive performance following high-fat diet and streptozotocin induction, the investigators implemented the Morris water maze test alongside targeted metabolic and biochemical assays. This behavioral paradigm served to document cognitive impairment in the diabetic model and measure the extent to which sericin administration attenuated these cognitive deficits. Alongside behavioral tracking, circulating lipid profiles were evaluated to characterize hyperlipidemia in the disease state and verify the degree to which sericin ameliorated systemic metabolic disorders.

Structural and cellular assessments within hippocampal tissue incorporated complementary histological and imaging approaches. These physical observations were complemented by immunohistochemistry and immunofluorescence procedures, enabling researchers to assess localized hippocampal apoptosis and neuroinflammation across the experimental rat cohorts.

Molecular analyses using Western blot and ELISA assays identified distinct shifts among key apoptotic regulators in the hippocampus.

In parallel with apoptotic shifts, the experimental evaluations revealed pronounced alterations in hippocampal inflammatory signaling. Diabetic rats exhibited elevated levels of IL-1β and IL-18, while NF-κB showed an increasing trend within hippocampal tissue. Following sericin treatment, neuroinflammation was significantly reduced, indicating that the naturally water-soluble protein complex mitigates both apoptotic cascades and inflammatory responses in this metabolic model.

The investigation specifically interrogated the role of the PI3K/AKT pathway by examining phosphorylation states of its central components and applying the chemical inhibitor LY294002. In diabetic rats, levels of phosphorylated PI3K (p-PI3K) and phosphorylated AKT (p-AKT) were decreased in the hippocampus. This partial reversal provided experimental support that sericin operates with the involvement of the PI3K/AKT pathway to suppress apoptosis and inflammation.

In concluding their evaluation, the study authors noted that sericin might serve as a potential neuroprotective intervention for diabetes-associated cognitive dysfunction. However, because the precise pathological mechanisms of this diabetes complication remain unclear, the reported findings reflect observations in a chemically and dietary induced Sprague-Dawley rat model rather than demonstrated clinical efficacy in humans.

Subject of Research: Sericin intervention for diabetes-associated cognitive dysfunction in a rat model

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

Article References: Lang, X., Yi, D., Diao, L., Lu, S., Jia, X., Qin, G., Wei, F., Wang, Y., & Wen, P. (2026). Sericin attenuates diabetes-associated cognitive dysfunction by inhibiting apoptosis and inflammation with involvement of the PI3K/AKT pathway. Frontiers in Pharmacology, 17, Article 1964313. https://doi.org/10.3389/fphar.2026.1964313

Image Credits: AI Generated

DOI: 10.3389/fphar.2026.1964313

Keywords: sericin, diabetes-associated cognitive dysfunction, PI3K/AKT pathway, Sprague-Dawley rats, LY294002, Morris water maze, hippocampal apoptosis, neuroinflammation, hyperglycemia, hyperlipidemia, caspase-3, Bcl-2, Bax, interleukin-1β, interleukin-18, NF-κB, streptozotocin, silkworm cocoons