Effects of eugenol-reduced clove extract on glycogen phosphorylase b and the development of diabetes in db/db mice.

We found that the 50% aqueous EtOH extract of clove (Syzygium aromaticum) had potent dose-dependent inhibitory activity toward glycogen phosphorylase b and glucagon-stimulated glucose production in primary rat hepatocytes. Among the components, eugeniin inhibited glycogen phosphorylase b and glucagon-stimulated glucose production in primary rat hepatocytes, with IC50 values of 0.14 and 4.7 µM, respectively. In sharp contrast, eugenol showed no significant inhibition toward glycogen phosphorylase b, even at a concentration of 400 µM. Eugenol-reduced clove extracts (erCE) were prepared and when fed to a db/db mouse they clearly suppressed the blood glucose and HbA1c levels. Furthermore, plasma triglyceride and non-esterified fatty acid levels in 5% and 10% erCE-fed db/db mice were significantly lowered, compared with control db/db mice without erCE supplementation. These results suggested that dietary supplementation with the erCE could beneficially modify glucose and lipid metabolism and contribute to the prevention of the progress of hyperglycemia and metabolic syndrome.

Adsorption of bile acid by chitosan salts prepared with cinnamic acid and analogue compounds.

A chitosan (CS) powder treated with cinnamic acid and an analogue compound (CN) was prepared as CS-CN. Using it, bile acid adsorption by CS-CN and the release of CN were investigated in vitro. When CS-CN was soaked in a taurocholate solution, it released CN and simultaneously adsorbed the bile acid. For CS-CN prepared with cinnamic acid, the amount of CN released was 0.286 +/- 0.001 mmol/g CS-CN; the amount of taurocholate adsorbed was 0.284 +/- 0.003 mmol/g CS-CN. These two functions were recognized on alginate or pectin gel beads containing CS-CN. The amount of released CN was altered extensively by the species of CN used for gel-bead preparation. Results suggest that CS-CN is a candidate for complementary medicine to prevent lifestyle-related diseases.

Endothelium-dependent contraction of rat thoracic aorta induced by gallic acid.

The vascular effect of a component of hydrolysable tannins, gallic acid, was examined in isolated rat thoracic aorta. Gallic acid exerted a contractile effect on the phenylephrine- or prostaglandin F(2/alpha)-precontracted endothelium-intact arteries. In endothelium-denuded arteries, the contractile response to-gallic acid was absent. Pretreatment with N(G)-nitro-L-arginine methyl ester (30 microM) abolished the gallic acid-induced contraction. Pretreatment with indomethacin (10 microM) or BQ610 (100 nM) had no observed effect. Pretreatment with gallic acid (1-10 microM) significantly attenuated the relaxation induced by acetylcholine, and that with 10 microM gallic acid also reduced the potency of sodium nitroprusside in the relaxation, without a reduction in efficacy, in endothelium-denuded arteries. These findings indicate that gallic acid induced endothelium-dependent contraction and strongly inhibited the endothelium-dependent relaxation rather than the endothelium-independent relaxation, probably through inhibition of endothelial nitric oxide (NO) production. Since NO plays an important role in vasodilative regulation and inflammatory disorders, these findings may also indicate that gallic acid interferes with the inflammatory responses.

Potentiation of vasoconstrictor response and inhibition of endothelium-dependent vasorelaxation by gallic acid in rat aorta.

In the isolated rat thoracic aorta, gallic acid potentiated the vasoconstrictor response to phenylephrine. The potentiation produced by gallic acid was absent in endothelium-denuded arteries. The potentiation was abolished by N(G)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthesis, and slightly attenuated by an addition of L-arginine, while indomethacin or BQ610 had no effect. The potentiation of response to phenylephrine was not found for structural modifications of gallic acid, except for caffeic acid. Gallic acid also inhibited vasorelaxation induced by acetylcholine, sodium nitroprusside or prostacyclin, especially that by acetylcholine. The effect on vasorelaxation induced by acetylcholine was decreased by esterification of the carboxy group of gallic acid, and in the absence or by the methylation of the o-dihydroxy group. Caffeic acid inhibited the vasorelaxation, though the effect was smaller than that of gallic acid. These findings indicate that gallic acid produces a potentiation of contractile response and inhibition of vasorelaxant responses, probably through inactivation of nitric oxide (NO), in which endothelially produced NO is principally involved, and that the modification of functional groups of the gallic acid molecule abolishes the potentiation of contractile response and attenuates the inhibition of vasorelaxant responses.