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These findings suggest that wheat alkylresorcinols increase glucose tolerance and insulin sensitivity by suppressing hepatic lipid accumulation and intestinal cholesterol absorption, which subsequently suppresses diet-induced obesity in mice.

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Certain naturally occurring flavonoids affect immunoregulatory activities in vitro and in vivo against cytokine production. Since tumor necrosis factor (TNF)-alpha is one of the major inflammatory cytokines, the effects of various dietary flavonoids on TNF-alpha production in lipopolysaccharide (LPS)-stimulated J774.1 cells were evaluated in vitro. Flavones, flavonols, and chalcone are the most potent inhibitors of production of TNF-alpha. Flavanone, naringenin, anthocyanidin, pelargodinin, and cyanidin exhibit moderate inhibitory activity. In contrast, genistein isoflavone displays weak inhibition, while eriodictyol flavanone is inactive. It is clear that the double bond between carbons 2 and 3 and the ketone group at position 4 of flavonoids are necessary for potent inhibitory effect. The difference in inhibitory action appears to depend on the categorized subclass of flavonoids.

The present study investigates the suppressive effect of flavonoids on TNF-alpha-stimulated E-selectin expression on HUVECs by carrying out a comparative examination of the 37 flavonoids. Several flavonoids: fisetin, luteolin and apigenin (subclass of flavone), kaempferol and quercetin (flavonols), eriodictyol (flavanones), genistein (isoflavones) and butein (chalcone) exhibit the inhibitory effects. Considerations to the structure of flavonoids, the C2-C3 double bond of C-ring and 4-oxo functional group are essential for their inhibition activities. These results help to explain the pharmacological efficacy of flavonoids as anti-inflammatory compounds.

LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1) is an endothelial scavenger receptor that is important for the uptake of OxLDL (oxidized low-density lipoprotein) and contributes to the pathogenesis of atherosclerosis. However, the precise structural motifs of OxLDL that are recognized by LOX-1 are unknown. In the present study, we have identified products of lipid peroxidation of OxLDL that serve as ligands for LOX-1. We used CHO (Chinese-hamster ovary) cells that stably express LOX-1 to evaluate the ability of BSA modified by lipid peroxidation to compete with AcLDL (acetylated low-density lipoprotein). We found that HNE (4-hydroxy-2-nonenal)-modified proteins most potently inhibited the uptake of AcLDL. On the basis of the findings that HNE-modified BSA and oxidation of LDL resulted in the formation of HNE-histidine Michael adducts, we examined whether the HNE-histidine adducts could serve as ligands for LOX-1. The authentic HNE-histidine adduct inhibited the uptake of AcLDL in a dose-dependent manner. Furthermore, we found the interaction of LOX-1 with the HNE-histidine adduct to have a dissociation constant of 1.22×10(-8) M using a surface plasmon resonance assay. Finally, we showed that the HNE-histidine adduct stimulated the formation of reactive oxygen species and activated extracellular-signal-regulated kinase 1/2 and NF-κB (nuclear factor κB) in HAECs (human aortic endothelial cells); these signals initiate endothelial dysfunction and lead to atherosclerosis. The present study provides intriguing insights into the molecular details of LOX-1 recognition of OxLDL.