A novel nutritional mixture, MBN, prevents memory impairment via inhibiting NLRP3 inflammasome formation in 5xFAD transgenic mice

Objectives: Amyloid beta (A beta)-induced abnormal neuroinflammation is recognized as a major pathological factor of Alzheimer's disease (AD), which results in memory impairment. Inhibition of excessive neuroinflammation mediated by A beta is considered a promising strategy to ameliorate AD symptoms. To regulate the inflammatory response, nutritional and dietary supplements have been used for centuries. Based on this idea, we investigated whether MBN, a novel nutritional mixture including cassia bark, turmeric root, and ginkgo leaf, can prevent AD progression through neuroinflammatory regulation. Methods: MBN (10, 30, or 100 mu g/ml) and A beta(1-42) monomer were incubated together, and the degree of A beta aggregation was measured using Thioflavin T assay. The effects of MBN on A beta pathology in vivo were evaluated by orally administering MBN (40 mg/kg/day for 16 weeks) to five familial AD (5xFAD) mice. Results: We found that treatment with MBN inhibited A beta aggregation in vitro. Next, MBN treatment significantly inhibited the activation of microglia induced by aggregated A beta in 5xFAD mice. Caspase-1 activation, which plays an important role in the maturation of interleukin-1 beta, was markedly reduced by MBN. We also found that oral administration of MBN in 5xFAD mice alleviated memory decline. Taken together, our findings demonstrate that MBN suppresses neuroinflammation by downregulating the caspase-1 expression, thereby ameliorating memory impairment in 5xFAD mice. Discussion: Based on these results, we suggest that MBN may be a preventive and therapeutic supplement for AD through the regulation of neuroinflammation.