Current status of prenyl flavonoids

Flavonoids are distributed across the plant kingdom and have attracted substantial attention owing to their potential benefits for human health. Several studies have demonstrated that flavonoids prenylation enhances various biological activities, suggesting an attractive tool for developing functional foods. This review provides an overview of the current knowledge on how prenylation influences the biological activity and bioavailability of flavonoids. The enhancement effect of prenylation on the biological activities of dietary flavonoids in mammals was demonstrated by comparing the effect of 8-prenyl naringenin (8PN) with that of parent naringenin in the prevention of disuse muscle atrophy in mice. This enhancement results from higher muscular accumulation of 8PN than naringenin. As to bioavailability, despite the lower absorption of 8-prenyl quercetin (8PQ) compared with quercetin, higher 8PQ accumulation was found in the liver and kidney. These data imply that prenylation interferes with the elimination of flavonoids from tissues

血管内皮細胞における過酸化水素誘導のカベオリン-1リン酸化に対するケルセチンの抑制効果

Caveolin-1 is a major protein of the caveolae structure in vascular endothelial cell membrane. Phosphorylation of caveolin-1 is one of the initial events leading to exacerbation of vascular permeability caused by oxidative stress. Although quercetin is known to be an anti-atherosclerosis factor that acts as a dietary antioxidant, little is known about its role in the regulation of caveolin-1 phosphorylation. In this study, we investigated the inhibitory effect of quercetin on hydrogen peroxide-induced caveolin-1 phosphorylation in human umbilical vein endothelial cells. Quercetin inhibited caveolin-1 phosphorylation in cells pretreated with quercetin for 24 h and then exposed to hydrogen peroxide. However, quercetin 3-O-β-glucuronide, a conjugated metabolite of quercetin, did not exert this inhibitory effect. Exposure to hydrogen peroxide increased vascular permeability and reduced mRNA expression of the intercellular adhesion protein, vascular endothelial cadherin (VE-cadherin). By contrast, pretreatment with quercetin suppressed the increase in vascular permeability and decreased VE-cadherin expression. These results indicate that deconjugated quercetin can play a role in the prevention of altered vascular permeability under oxidative stress by suppressing caveolin-1 phosphorylation. Thus, dietary quercetin may be beneficial for the maintenance of endothelial cell function

3-O-Acyl-epicatechins Increase Glucose Uptake Activity and GLUT4 Translocation through Activation of PI3K Signaling in Skeletal Muscle Cells

Tea catechins promote glucose uptake in skeletal muscle cells. In this study, we investigated whether the addition of an acyl group to the C-3 position of catechins to generate 3-O-acyl-catechins promoted glucose uptake in L6 myotubes. 3-O-Myristoyl-(-)-epicatechin (EC-C14) and 3-O-palmitoyl-(-)-epicatechin (EC-C16) promoted glucose uptake and translocation of glucose transporter (GLUT) 4 in the cells. The effect of 3-O-acyl-(-)-epicatechins was stronger than that of (-)-epicatechin (EC), whereas neither 3-O-myristoyl-(+)-catechin (C-C14) nor 3-O-palmitoyl-(+)catechin (C-C16) promoted glucose uptake or GLUT4 translocation as well as (+)-catechin (C). We further investigated an affinity of catechins and 3-O-acyl-catechins to the lipid bilayer membrane by using surface plasma resonance analysis. Maximum binding amounts of EC-C16 and C-C16 to the lipid bilayer clearly increased compared with that of (-)-EC and (+)-C, respectively. We also examined the mechanism of GLUT4 translocation and found EC-C14 and EC-C16 induced the phosphorylation of PI3K, but did not affect phosphorylation of Akt or IR. In conclusion, the addition of an acyl group to the C-3 position of (-)-EC increases its affinity for the lipid bilayer membrane and promotes GLUT4 translocation through PI3K-dependent pathways in L6 myotubes

Cognition of Ma in Language: A Cognitive Linguistic Approach

13301甲第4542号博士（文学）金沢大学博士論文本文Full 掲載予定あ

Cognition of Ma in Language: A Cognitive Linguistic Approach

13301甲第4542号博士（文学）金沢大学博士論文要旨Abstract 掲載予定あ

Chocolate as a food matrix reduces the bioavailability of galloylated catechins from green tea in healthy women

In this study, we evaluated the food matrix effects of chocolate on absorption of green tea catechins (GTCs), (−)-epicatechin (EC), (−)-epigallocatechin (EGC), (−)-epicatechin gallate (ECg), and (−)-epigallocatechin gallate (EGCg), in five healthy 22-year-old women. In the single-intake experiment, the plasma concentrations of ECg (P < 0.05, at 1.5 h) and EGCg (P < 0.05, at 6 h) but not those of EC and EGC were reduced by the chocolate matrix. Regardless of the chocolate matrix, ECg and EGCg were mainly present as their aglycones in the plasma, whereas EGC and EC were found mostly as conjugated metabolites. After daily intake of GTCs mixed with chocolate for 14 days followed by overnight fasting, ECg but not EGCg was detected in the plasma. To compare the plasma profiles of ECg and EGCg, a mixture containing approximately equal amounts of ECg and EGCg was administered to nine rats for 14 days. Following treatment and overnight food deprivation, the plasma content of ECg was higher than that of EGCg. After a single injection of the same mixture in seven rats, ECg levels were higher than those of EGCg, and a greater amount of conjugated metabolites of ECg than those of EGCg was detected in the plasma 10 h after administration. In conclusion, the chocolate matrix affects the plasma profiles of GTCs, particularly ECg. ECg appears to persist in the plasma for a longer period, regardless of the chocolate matrix

血管内皮細胞における酸化LDLおよびリゾホスファチジルコリン誘導によるカベオリン-1発現に対するケルセチンおよび代謝物の効果

Oxidized low-density lipoprotein contributes to atherosclerotic plaque formation, and quercetin is expected to exert anti-atherosclerotic effects. We previously reported accumulation of conjugated quercetin metabolites in the aorta of rabbits fed high-cholesterol diets with quercetin glucosides, resulting in attenuation of lipid peroxidation and inhibition of lipid accumulation. Caveolin-1, a major structural protein of caveolae in vascular endothelial cells, plays a role in atherosclerosis development. Here we investigated effects of oxidized low-density lipoprotein, quercetin and its metabolite, quercetin 3-O-β-glucuronide, on caveolin-1 expression. Oxidized low-density lipoprotein significantly upregulated caveolin-1 mRNA expression. An oxidized low-density lipoprotein component, lysophosphatidylcholine, also induced expression of both caveolin-1 mRNA and protein. However, lysophosphatidylcholine did not affect the location of caveolin-1 proteins within caveolae structures. Co-treatment with quercetin or quercetin 3-O-β-glucuronide inhibited lysophosphatidylcholine-induced caveolin-1 expression. Quercetin and quercetin 3-O-β-glucuronide also suppressed expression of adhesion molecules induced by oxidized low-density lipoprotein and lysophosphatidylcholine. These results strongly suggest lysophosphatidylcholine derived from oxidized low-density lipoprotein contributes to atherosclerotic events by upregulating caveolin-1 expression, resulting in induction of adhesion molecules. Quercetin metabolites are likely to exert an anti-atherosclerotic effect by attenuating caveolin-1 expression in endothelial cells

Anti‐inflammatory effects and molecular mechanisms of 8‐prenyl quercetin

Scope: 8-prenyl quercetin (PQ) is a typical prenylflavonoid distributed in plant foods and shows higher potential bioactivity than its parent quercetin (Q) although the mechanisms are not fully understood. This study aims to clarify the anti-inflammatory effects and molecular mechanisms of PQ in cell and animal models, compared to Q. Methods and results: RAW264.7 cells were treated with PQ or Q to investigate the influence on the production of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and protein kinases by Western blotting. Nitric oxide (NO) and prostaglandin E2 (PGE2) were measured by the Griess method and ELISA, respectively. Cytokines were assayed by the multiplex technology. Mouse paw edema was induced by lipopolysaccharide (LPS). The results revealed that PQ had stronger inhibition on the productions of iNOS, COX-2, NO, PGE2, and 12 kinds of cytokines, than Q. PQ also showed in vivo anti-inflammatory effect by attenuating mouse paw edema. Molecular data revealed that PQ had no competitive binding to Toll-like receptor 4 (TLR4) with LPS, but directly targeted SEK1-JNK1/2 and MEK1-ERK1/2. Conclusion: PQ as a potential inhibitor revealed anti-inflammatory effect in both cell and animal models at least by targeting SEK1-JNK1/2 and MEK1-ERK1/2

Anti‐inflammatory effects and molecular mechanisms of 8‐prenyl quercetin

Scope: 8-prenyl quercetin (PQ) is a typical prenylflavonoid distributed in plant foods and shows higher potential bioactivity than its parent quercetin (Q) although the mechanisms are not fully understood. This study aims to clarify the anti-inflammatory effects and molecular mechanisms of PQ in cell and animal models, compared to Q. Methods and results: RAW264.7 cells were treated with PQ or Q to investigate the influence on the production of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and protein kinases by Western blotting. Nitric oxide (NO) and prostaglandin E2 (PGE2) were measured by the Griess method and ELISA, respectively. Cytokines were assayed by the multiplex technology. Mouse paw edema was induced by lipopolysaccharide (LPS). The results revealed that PQ had stronger inhibition on the productions of iNOS, COX-2, NO, PGE2, and 12 kinds of cytokines, than Q. PQ also showed in vivo anti-inflammatory effect by attenuating mouse paw edema. Molecular data revealed that PQ had no competitive binding to Toll-like receptor 4 (TLR4) with LPS, but directly targeted SEK1-JNK1/2 and MEK1-ERK1/2. Conclusion: PQ as a potential inhibitor revealed anti-inflammatory effect in both cell and animal models at least by targeting SEK1-JNK1/2 and MEK1-ERK1/2