Peanut sprouts have shown promise in protecting against obesity and hyperlipemia, but their potentials in hyperglycemia management remains unknown. The aim of this study was to investigate the effects and possible mechanisms of peanut sprout on experimental hyperglycemia. To do so, C57BL/6 male mice were fed a chow diet or high-fat-diet for 8 weeks to induce obesity, and then were given in addition either vehicle or peanut sprout extracts (PSE, 100, 300 and 1000 mg/kg/day) by oral gavage for an additional 6 weeks. Data showed that PSE treatment effectively protected against weight gain, reduced hepatic steatosis and improved hyperglycemia in mice. Using an LC-MS/MS approach, we discovered that PSE contains substantial amounts of resveratrol (RES), piceatannol (PIC), caffeic acid (CA), indole-3-acetic acid (IAA) and tryptophan (Trp). On the basis of bioassay-guided fractionation, we identified IAA as its major active principle suppressing hepatic gluconeogenesis in primary hepatocytes. When administered chronically to mice with diet-induced obesity, IAA effectively improved experimental hyperglycemia in a dose-dependent manner. Mechanistically, we demonstrated that 3-IAA could directly antagonize the action of glucagon, abrogate the phosphorylation of CREB and nuclear translocation of CRTC2, lower the protein expression of key gluconeogenic enzymes including glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PCK1), and thus normalize glucagon-dependent glucose output. Taken together, peanut sprouts might have implications for novel nutrition-based preventive or adjuvant therapeutic strategies against hyperglycemia.

Glycidol is a common lipid-derived foodborne toxicant mainly presents in refined oils and related foodstuffs. Vascular endothelial cells may be potential targets of the deleterious effects associated with glycidol exposure. In human umbilical vein endothelial cells (HUVECs), we found that glycidol treatment promoted endothelialto-mesenchymal transition (EndMT) at a lower concentration (0.5 mmol/L), while induced apoptosis and inflammation at a higher concentration (1 mmol/L). These harmful effects were achieved by the activation of NF-κB/MAPK signaling pathway and were mediated by reactive oxygen species (ROS). In addition, the protective potential of 6-C-(E-2-fluorostyryl)naringenin (6-CEFN) against glycidol was evaluated and compared with naringenin. HUVECs pre-treated with 6-CEFN, but not naringenin, displayed resistance to endothelial dysfunction caused by glycidol.

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.