Schisandrin B combined with vitamin D inhibits NLRP3 inflammasome to improve cognitive dysfunction and Alzheimer's disease.

PURPOSE: This study investigates the therapeutic effects of Schisandrin B (Sch B) combined with vitamin D (VD) on cognitive dysfunction and Alzheimer's disease (AD)-like pathology in aged rats induced by a high-fat and high-sugar (HFHS) diet, with a focus on the inhibition of NLRP3 inflammasome activation as a potential mechanism.

METHODS

Eighteen-week-old male Sprague-Dawley rats were randomly assigned to five groups: Control, HFHS, HFHS + Sch B, HFHS + VD, and HFHS + Sch B + VD. After 20 weeks of treatment, metabolic parameters (body weight, fasting blood glucose, insulin resistance, lipid profiles), inflammatory markers, and hippocampal protein expression were assessed. Cognitive function was evaluated using the Morris water maze, novel object recognition, open field, and elevated plus maze tests.

RESULTS

Combined Sch B and VD markedly attenuated body weight gain, fasting blood glucose, fasting serum insulin, and homeostatic model assessment of insulin resistance (HOMA-IR), while improving lipid profiles (TG, TC, LDL-C). Behavioral tests revealed significant improvements in spatial learning, memory, and object recognition (p < 0.01), with combined therapy outperforming monotherapy. Additionally, the combination downregulated hippocampal NLRP3 inflammasome components (ASC, cleaved caspase-1, IL-1β, IL-18) and reduced pro-inflammatory cytokines (IL-1β, IL-6, TNF-α).

CONCLUSION

In this HFHS diet-induced aging rat model, Sch B combined with VD improved cognitive performance and reduced AD-like lesions, likely via inhibition of NLRP3 inflammasome-mediated neuroinflammation. These findings provide mechanistic insights and support further preclinical evaluation of this combination as a potential strategy for AD prevention and intervention.