The growing aging population along with the shifting dietary paradigm to Western-type diet worldwide has been implicated in the increasing prevalence of cognitive impairment. Emerging evidence suggests that a high-fiber diet may help improve cognitive function through the gut-brain axis. Euglena gracilis, a unicellular microalga rich in β-1,3-glucans, has gained attention due to its modulatory effect on gut dysbiosis and inflammatory response. This study aimed to explore the efficacy and mechanism of β-1,3-glucans-rich E. gracilis powder (EG) against high-fat-high-fructose (HFHF) diet-induced cognitive disorders in mice. A middle-aged (52-week-old C57BL/6J) mouse model with the following groups was adopted: HFHF, HFHF + EG, and control. At the end of the dietary intervention (8 weeks), cognitive behaviors, metabolic parameters, endotoxin levels, gut microbiota composition, and colon and brain pathology were examined. The results showed that EG supplementation attenuated HFHF-induced cognitive impairment, promoted synaptogenesis in the hippocampus, and improved synaptic ultrastructure. These beneficial effects were partly mediated through the upregulation of protein tyrosine phosphatase 1B (PTP1B)-recombinant insulin receptor substrate (IRS)-phosphorylated protein kinase B (p-AKT)-phosphorylated recombinant glycogen synthase kinase 3β (p-GSK3β)-microtubule associated protein tau (p-Tau) signaling. Furthermore, it prevented gut dysbiosis as evidenced by an increase in β-diversity and enrichment of Akkermansia relative to the control group. EG supplementation was also able to partly reverse the HFHF-induced disruption of intestinal barrier, which was accompanied by reduced systemic and neuronal inflammation, normalized short-chain fatty acid production, and decreased serum lipopolysaccharide concentration. The findings from the present study support that β-1,3-glucans-rich EG is a promising natural agent for the prevention of HFHF diet-induced deterioration in cognitive function that merits further investigation.

Atherosclerosis, as the most prevalent form of cardiovascular disease, is characterized by oxidized lowdensity lipoprotein (ox-LDL) accumulation in the vascular wall, increased inflammation of the large arteries, dysfunction of the endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), which may eventually lead to the formation of plaques. Xanthophylls, one of the main groups of carotenoids, have been proposed as preventive agents or adjunct therapies to prevent and slow the progression of atherosclerosis due to their cardioprotective properties. However, the underlying preventive mechanism of action of xanthophylls on the pathogenesis of atherosclerosis remains unclear, and clinical evidence of the effect of xanthophylls on atherosclerosis have not yet been summarized and critically reviewed. In this regard, we conducted a comprehensive literature search in four scientific databases (PubMed, Google Scholar, ScienceDirect and Web of Science) and carefully analyzed the existing evidence to provide meaningful insights on the association between xanthophylls and atherosclerosis from various aspects. Based on the evidence from in vitro and in vivo studies, we explored several potential mechanisms, including antioxidant effect, anti-inflammatory effect, regulation of lipid metabolism, and modulation of ECs and VSMCs dysfunction, and we found that a clear picture of regulatory pathways of xanthophylls on atherosclerosis prevention and treatment is still lacking. In addition, epidemiological studies suggested the possible relationship among high dietary intake of xanthophylls, high plasma/serum xanthophylls and a reduced risk of atherosclerosis. Direct evidence from interventional studies investigating the effect of xanthophylls on atherosclerosis is very sparse, whilst indirect clinical evidence was only limited to astaxanthin and lutein. Therefore, well-designed long-term randomized controlled trials (RCTs) are highly recommended for future studies to investigate the effective dose of different xanthophylls on atherosclerosis prevention and their possible ancillary effect in conjunction with drug therapies on different stages of atherosclerosis.