Effects of Rikkunshi-to, a Traditional Japanese Medicine, on the Delay of Gastric Emptying Induced by NG-Nitro-<sc>L</sc>-arginine

We evaluated the effects of Rikkunshi-to and several of its ingredients on the delay of gastric emptying induced by a nitric oxide (NO) synthase inhibitor, NG-nitro-<sc>L</sc>-arginine (<sc>L</sc>-NNA). After oral administration of <sc>L</sc>-NNA to rats, the gastric emptying rate at 24 h was decreased from 82.8 ± 2.4% to 53.3 ± 5.7%. The decrease of the gastric emptying rate induced by <sc>L</sc>-NNA treatment was markedly ameliorated by administration of Rikkunshi-to (250 and 500 mg/kg, p.o.) in a dose-dependent manner. To identify the active ingredient of Rikkunshi-to, the components were separated according to polarity, and the effects of the respective fractions on gastric emptying were evaluated. Significant efficacy was found in the water and methanol fractions, but not in the 50% aqueous-methanol fraction. Furthermore, hesperidin (1 - 4.29 mg/kg, p.o.) contained in the methanol fraction and <sc>L</sc>-arginine (4.5 mg/kg, p.o.) contained in the water fraction ameliorated the decrease in the gastric emptying rate induced by <sc>L</sc>-NNA treatment. These results suggest that Rikkunshi-to ameliorated abnormalities of NO-mediated gastric functions such as delayed gastric emptying, and hesperidin and <sc>L</sc>-arginine were identified as two of the active ingredients contributing to the ability of Rikkunshi-to to facilitate gastric emptying.