Novel Selenium Peptides Obtained from Selenium-Enriched Cordyceps militaris Alleviate Neuroinflammation and Gut Microbiota Dysbacteriosis in LPS-Injured Mice.

Increasing attention focuses on the relationship between neuroinflammation and Alzheimer's disease (AD). The reports on the microbiota-gut-brain axis reveal that the regulation by gut microbiota is an effective way to intervene in neuroinflammation-related AD. In this study, two novel selenium peptides (Se-Ps), VPRKL( Se )M (Se-P1) and RYNA( Se )MNDYT (Se-P2), with neuroprotection effects were obtained from Se-enriched Cordyceps militaris . Se-P1 and Se-P2 pre-protection led to a 30 and 33% increase in the PC-12 cell viability compared to the damage group, respectively. Moreover, Se-Ps exhibited a significant pre-protection against LPS-induced inflammatory and oxidative stress in the colon and brain by inhibiting the production of pro-inflammatory mediators ( p < 0.05) and malondialdehyde, as well as promoting anti-inflammatory cytokine level and antioxidant enzyme activity ( p < 0.05), which may alleviate the cognitive impairment in LPS-injured mice ( p < 0.05). Se-Ps not only repaired the intestinal mucosa damage of LPS-injured mice but also had a positive effect on gut microbiota dysbacteriosis by increasing the abundance of Lactobacillus and Alistipes and decreasing the abundance of Akkermansia and Bacteroides . Collectively, the antioxidant, anti-inflammatory, and regulating properties on gut microflora of Se-Ps contribute to their neuroprotection, supporting that Se-Ps could be a promising dietary supplement in the prevention and/or treatment of AD.