Hisao Nemoto

Prevention of Disuse Muscle Atrophy by Dietary Ingestion of 8-Prenylnaringenin in Denervated Mice

Flavonoids have attracted considerable attention in relation to their effects upon health. 8-Prenylnaringenin (8-PN) is found in the common hop (Humulus lupulus) and assumed to be responsible for the health impact of beer consumption. We wanted to clarify the effects of prenylation on the physiological functions of dietary flavonoids by comparing the effects of 8-PN with that of intact naringenin in the prevention of disuse muscle atrophy using a model of denervation in mice. Consumption of 8-PN (but not naringenin) prevented loss of weight in the gastrocnemius muscle further supported by the lack of induction of the protein content of a key ubiquitin ligase involved in muscle atrophy, atrogin-1, and by the activation of Akt phosphorylation. 8-PN content in the gastrocnemius muscle was tenfold higher than that of naringenin. These results suggested that, compared with naringenin, 8-PN was effectively concentrated into skeletal muscle to exert its preventive effects upon disuse muscle atrophy. It is likely that prenylation generates novel functions for 8-PN by enhancing its accumulation into muscle tissue through dietary intake.

Evaluation of the Inhibitory Effects of Quercetin-Related Flavonoids and Tea Catechins on the Monoamine Oxidase-A Reaction in Mouse Brain Mitochondria

Quercetin, a typical dietary flavonoid, is thought to exert antidepressant effects by inhibiting the monoamine oxidase-A (MAO-A) reaction, which is responsible for regulation of the metabolism of the neurotransmitter 5-hydroxytryptamine (5-HT) in the brain. This study compared the MAO-A inhibitory activity of quercetin with those of O-methylated quercetin (isorhamnetin, tamarixetin), luteolin, and green tea catechins ((-)-epicatechin, (-)-epicatechin gallate, (-)-epigallocatechin, and (-)-epigallocatechin gallate) by measuring the formation of the oxidative deamination product of 5-HT, 5-hydroxyindole aldehyde (5-HIAL), in mouse brain mitochondria. Quercetin was inferior to luteolin in the inhibition of MAO-A activity, whereas isorhamnetin, tamarixetin, and tea catechins scarcely exerted inhibitory activity. Quercetin did not affect MAO-A activity in mouse intestinal mitochondria, indicating that it does not evoke side effects on the metabolism of dietary monoamines in the gut. These data suggest that quercetin is a weak (but safe) MAO-A inhibitor in the modulation of 5-HT levels in the brain.

Absolute structure of vibsanins B and C, and their chemical correlation

Abstract The absolute structure of vibsanin C, a novel 7-membered vibsane-type diterpene isolated from the leaves of Viburnum awabuki , has been established by X-ray crystallographic analysis of its derivative. Vibsanin C has been proved to be one of Cope rearranged products from vibsanin B, a 11-membered vibsane-type diterpene.

A general synthetic method for 2,6-cyclodecadienone system by intramolecular alkylation of protected cyanohydrins

Abstract 2,6-Dimethyl-( E,E )-2,6-cyclodecadienone ( 12 ), 3,7-dimethyl-( E,E )-2,6-cyclodecadienone ( 15 ), 3,7-dimethyl-( Z,E )-2,6-cyclodecadienone ( 18 ) were synthesized by intramolecular alkylation of unsaturated cyanohydrin ethers.

Boron-10 carriers for NCT. A new synthetic method via condensation with aldehydes having boronic moiety

Abstract Several boron-10 containing nucleoside derivatives for neutron capture therapy were synthesized by using 1,2-addition reaction of the carbanions, generated from nucleoside derivatives, with aromatic aldehydes having boronic moiety.

Macroring contraction methodology : 3. Total syntheses of costunolide and haageanolide using transannular [2,3]-wittig rearrangement of 13-membered diallylic ethers as key reaction

Abstract A new route to construct the carbon skeleton of germacrane sesquiterpenes is described wherein the 13-membered diallylic ethers 12 and 41 , prepared by intramolecular O-alkylation of the bromo alcohol and C-alkylation of the cyanohydrin ether respectively, undergo [2,3]-Wittig rearrangement to give the ten-membered carbocycles. Diastereoselectivity in [2,3]-Wittig rearrangement is discussed based on the MM2 transition structure model using the ab-initio calculations.

A first total synthesis of Germacrone by intramolecular alkylation of protected cyanohydrin

Abstract A total synthesis of Germacrone by the intramolecular alkylation of a carbanion generated from protected cyanohydrin is presented.

Prenylation Enhances Quercetin Uptake and Reduces Efflux in Caco-2 Cells and Enhances Tissue Accumulation in Mice Fed Long Term

Prenyl flavonoids are widely distributed in plant foods and have attracted appreciable attention in relation to their potential benefits for human health. Prenylation may enhance the biological functions of flavonoids by introducing hydrophobic properties in their basic structures. Previously, we found that 8-prenyl naringenin exerted a greater preventive effect on muscle atrophy than nonprenylated naringenin in a mouse model. Here, we aimed to estimate the effect of prenylation on the bioavailability of dietary quercetin (Q). The cellular uptake of 8-prenyl quercetin (PQ) and Q in Caco-2 cells and C2C12 myotube cells was examined. Prenylation significantly enhanced the cellular uptake by increasing the lipophilicity in both cell types. In Caco-2 cells, efflux of PQ to the basolateral side was <15% of that of Q, suggesting that prenylation attenuates transport from the intestine to the circulation. After intragastric administration of PQ or Q to mice or rats, the area under the concentration-time curve for PQ in plasma and lymph was 52.5% and 37.5% lower than that of Q, respectively. PQ and its O-methylated form (MePQ) accumulated at much higher amounts than Q and O-methylated Q in the liver (Q: 3400%; MePQ: 7570%) and kidney (Q: 385%; MePQ: 736%) of mice after 18 d of feeding. These data suggest that prenylation enhances the accumulation of Q in tissues during long-term feeding, even though prenylation per se lowers its intestinal absorption from the diet.

Iron and copper catalyzed reaction of benzylamine with carbon tetrachloride: facile formation of 2,4,5- triphenylimidazoline derivatives

Abstract Iron and copper salts catalyzed the reaction of benzylamine with CCl 4 to give a mixture of 2,4,5-triphenylimidazole (1), 1-benzyl-2,4,5-triphenylimidazole (2), 2,4,5-triphenylimidazoline (3), and 1-benzyl-2,4,5-triphenylimidazoline (4) in high yields. The imidazoline 4 was obtained as the main product. The imidazole and imidazoline derivatives were also formed by the iron-catalyzed reaction of benzylidenebenzylamine (8) or dibenzylamine (5) with CCl 4 . The imidazoline 4 slowly underwent debenzylation and dehydrogenation with the aid of CCl 4 and iron catalyst to give 1 and 2. From these results, a mechanism involving formation of 5 and 8, subsequent oxidative dimerization of 5 and 8 to form 4, and further conversion of 4 to 1, 2, and 3 is proposed.

Synthesis of carboranes containing nucleoside bases. Unexpectedly high cytostatic and cytocidal toxicity towards cancer cells

5-Carboranyluridine 1, 5-carboranyldeoxyuridine 2 and 5-hydroxymethylcarboranyluridine 3 have been prepared; they show unexpectedly high cytotoxicity towards cancer cells, with IC50 values being ca. 10–5 mol dm–3.