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The incidence of cognitive impairment is rising globally, but there is no effective therapy. Recent studies showed that fucoidan (Fuc), a sulfated polysaccharide enriched in brown algae, is widely used due to its anti-inflammatory, antioxidant, and prebiotic effects. However, the effects and mechanisms of Fuc on lipopolysaccharide (LPS)-induced neuronal cell damage and cognitive impairment in mice need to be explored further. In the present study, we found that Fuc treatment protected HT22 cells from LPS-induced damage by inhibiting the activation of NLRP3 inflammasomes. Fuc exerted neuroprotective effects in mice with LPS-induced cognitive impairment by ameliorating neuroinflammation, promoting neurogenesis, and reducing blood-brain barrier and intestinal barrier permeability. Mechanistically, Fuc supplement significantly restructured the gut microbiota composition, which may be related to glucose and fructose metabolism. In conclusion, Fuc ameliorated LPS-induced neuronal cell damage and cognitive impairment in mice, suggesting that Fuc may be a medicinal and food homologous functional agent to improve cognitive function. The possible mechanism by which Fucoidan ameliorates LPS-induced cognitive impairment in mice, especially by remodeling gut microbiota. [Display omitted] • Fuc protected HT22 cells from LPS-induced damage via the inhibition of NLRP3 inflammasome. • Fuc exerted neuroprotective effects on LPS-induced cognitive impairment by reducing BBB and gut permeability. • Fuc remodeled the gut microbiota, which may be related to glucose and fructose metabolism. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a chronic neurodegenerative disease with high prevalence, long duration and poor prognosis. The blood-brain barrier (BBB) is a physiologic barrier in the central nervous system, which hinders the entry of most drugs into the brain from the blood, thus affecting the efficacy of drugs for AD. Natural products are recognized as one of the promising and unique therapeutic approaches to treat AD. To improve the efficiency and therapeutic effect of the drug across the BBB, a natural polyphenolic compound, procyanidin C-1 (C1) was encapsulated in glucose-functionalized bovine serum albumin (BSA) nanoparticles to construct Glu-BSA/C1 NPs in our study. Glu-BSA/C1 NPs exhibited good stability, slow release, biocompatibility and antioxidant properties. In addition, Glu-BSA/C1 NPs penetrated the BBB, accumulated in the brain by targeting Glut1, and maintained the BBB integrity both in vitro and in vivo. Moreover, Glu-BSA/C1 NPs alleviated memory impairment of 5 × FAD mice by reducing Aβ deposition and Tau phosphorylation and promoting neurogenesis. Mechanistically, Glu-BSA/C1 NPs significantly activated the PI3K/AKT pathway and inhibited the NLRP3/Caspase-1/IL-1β pathway thereby suppressing neuroinflammation. Taken together, Glu-BSA/C1 NPs could penetrate the BBB and mitigate neuroinflammation in AD, which provides a new therapeutic approach targeting AD. Schematic illustration of the synthesis and application of Glu-BSA/C1 NPs in a mouse model of Alzheimer's disease. [Display omitted] [ABSTRACT FROM AUTHOR]