[Effects of iridoid compounds on bile flow].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M Aburada.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
General pharmacological studies were performed on (6)-gingerol and (6)-shogaol which are the pungent constituents of ginger (Zingiber officinale Roscoe). Intravenous (i.v.) administration of (6)-gingerol (at 1.75-3.5 mg/kg) or (6)-shogaol (at 1.75-3.5 mg/kg) and oral administration of them (at 70-140 mg/kg) produced an inhibition of spontaneous motor activity, an antipyretic and analgesic effects, prolonged hexobarbital-induced sleeping time, and these effects of (6)-shogaol were mostly more intensive than that of (6)-gingerol. (6)-Shogaol showed an intense antitussive effect in comparison with dihydrocodeine phosphate. In the electro-encephalogram of cortex, the low amplitude fast wave pattern was observed for 5 min after i.v. administration of (6)-shogaol, and then changed to the drowsy pattern, which was restored after 60 min. In the gastro-intestinal system, (6)-shogaol intensively inhibited the traverse of charcoal meal through the intestine in contrast with (6)-gingerol after i.v. administration of 3.5 mg/kg, but (6)-shogaol facilitated such an intestinal function after oral administration of 35 mg/kg. Both (6)-shogaol and (6)-gingerol suppressed gastric contraction in situ, and the suppression by the former was more intensive than that by the latter. In the cardiovascular system, both (6)-shogaol and (6)-gingerol produced depressor response at lower doses on the blood pressure. At high doses, both drugs produced three phase pattern.
In view of the reduction of side effects as well as the enhancement of anti-tumor activities of anticancer drugs, we have been interested in the combined use of Chinese medicines with them. In the present study, we attempted to examine the effects of Chinese prescription, juzentaihoto (JTX), combined with mitomycin C (MMC). JTX is consisted of Astragali radix, Chinnamomi cortex, Rehmanniae radix, Paeonia radix, Cnidii rhizoma, Atractylodis lanceae rhizoma, Angelicae radix, Ginseng radix, Hoelen and Glycyrrhizae radix. In BDF1-mice which were implanted with P-388 leukemic cells, JTX prolonged significantly the average survival days of MMC-treated group. In tumor-free BDF1-mice, JTX improved the leukopenia and the body weight loss which were caused by MMC. Additionally, JTX delayed the appearance of deaths by lethal dosis of MMC. These results indicate that JTX enhances the anti-tumor activity of MMC and lessens the adverse effects of it. JTX may be useful for patients undertaking MMC treatment.
Explore the source record for details and available documents.
We made a study on choleretic property and mechanism of action of iridoid compounds as well as dehydrocholate (DHC), cholate (CA), and salicylate (SA), examining their effects on factors such as bile flow, bile acids, electrolytes (Na+, K+, Cl-, and HCO3-), and their metabolites. Each sample showed a characteristic property, respectively. Genipin and patrinoside decreased biliary concentrations of bile acids, Na+, Cl-, and HCO3-, corresponding to their rapid choleretic actions which were due to bile acids independent fraction. The choleretic action of DHC is approximately twice as potent as that of CA. Their actions were due to bile acids-dependent fraction. CA gave a marked increase in Na+ concentration but DHC did not. And both compounds gave a marked diminution in Cl- concentration and weakly decreased HCO3- concentration. SA showed a weak and durable choleretic action and also gave a marked increase in HCO3- concentration. The main metabolite detected from the bile given genipin was genipin-1-O-glucuronic acid (GGA). The periodical pattern of GGA level in bile was in agreement with that of genipin- induced choleretic action, and quantitatively cation, anion gap produced was nearly compensated by biliary concentration of GGA. From out various results, the choleretic mechanism of iridoid compounds is considered to be as follows: The hemiacetal moiety of them undergoes conjugation in the liver to give glucuronide. Glucuronide thus formed is secreted into the biliary tree being coupled mainly with Na+ and water is passively excreted.
In this work, the choleretic properties and mechanism of coumarin compounds and phenolic compounds were studied by examining their effects on parameters such as bile flow, bile acids, electrolytes, and biliary metabolites. Choleretic intensity and property of each sample was far different. The choleretic efficacy of 6, 7-dimethylesculetin (6,7-DME) was far weaker than that of 4 methylumbelliferone (4-MU). 4-hydroxybenzyl alcohol (4-HBA), isoeugenol, vanillin, paeonol, and phenolphthalein accelerated bile secretion, but 4 (B-D-glucopyranosyloxy)-benzyl alcohol, safrol, and arbutin did not. 4-MU and 4-HBA underwent conjugation in the liver to give mainly a glucuronide and their metabolites were rapidly excreted into bile, but 6, 7-DME was converted into some metabolites which were excreted little by little over a long period of time. The biliary gap between cations (NA+, K+) and anions (CL-, HCO3-, bile acids) produced after intravenous administration of 4-MU, 6, 7-DME, and 4-HBA was substantially offset by biliary concentrations of their metabolites. It was suggested that a hydroxyl group which can be mainly converted into a glucuronide is necessary in exerting a strong choleretic action. The choleretic mechanism of coumarin compounds and phenolic compounds is considered to be as follows: Their metabolites (mainly glucuronide) are actively secreted into the biliary tree as an organic anion coupled with Na+ or K+, and water is passively excreted.
Explore the source record for details and available documents.
In the experiment on continuous perfusion of rat stomach in vivo, genipin inhibited only the gastric acid secretion induced by carbachol, but not by tetragastrin, or histamine. In the experiment on isolated organs, genipin showed a weak competitive anti-acetylcholine action on the intestinal contraction. Based on these facts and results reported previously, it is conceivable that anti-cholinergic action at least partly contributes to the genipin-induced inhibitory effect on gastric functions. Erythritol clearance was increased with the increase in bile flow by administration of genipin. Genipin showed a significant choleretic action, and just then the concentration of biliary bile acid was decreased inversely. In the relationship between bile flow and biliary bile acid excretion rate, the slope of regression line obtained from genipin-treated group was not significantly different from that of control, and these lines were approximately parallel to each other. Genipin did not affect the concentration of sodium, potassium, chloride, or bicarbonate in the bile collected during the initial stage, in which bile flow was increased, after administration. It is concluded from these results that genipin-induced choleretic action proceeds by a mechanism wherein water is driven along osmotic gradient which originates in the transport of bile acid-independent fraction from hepatocytes into canaliculi, mainly through active Na+ transport.
The relationship between the structures and the choleretic actions of iridoid compounds was examined. Only patrinoside and villoside accelerated bile secretion among the iridoid glucosides but all of the iridoid aglycones increased it after intravenous administration rats. The choleretic effects of villoside, patrinoside aglycone, and 11-deoxy patrinoside aglycone were far weaker in comparison with those of other active iridoid compounds. When an equimolar amount of patrinoside, its aglycone, or 11-deoxy patrinoside aglycone was administered intravenously, their periodical patterns of choleretic activities nearly paralleled with those of isovaleric acid excreted in the bile. Patrinoside was partly hydrolyzed into its aglycone by the artificial gastric juice or the intestinal content. After intraduodenal administration of patrinoside (1 g/kg), the amount of patrinoside enough to exert a choleretic action was detected in the portal blood. These findings indicate that the hemiacetal moiety of iridoid compounds plays an important role in exerting a strong choleretic action and that patrinoside shows the same action following saponification of isovalerate of C-1 position in the liver.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Effects of the Japanese kampo medicine 'Shosaiko-to-go-keishika-shyakuyaku-to' (TJ-960), which is a mixture of 9 herbal drugs and is practically equivalent to 'Saiko-keishi-to' (SK), on the pentylenetetrazol (PTZ)-induced EEG power spectrum changes were examined. The EEG power spectrum change with 2 PTZ administrations at an 80 min interval was clearly inhibited by oral administration of 1.0 mg/kg of TJ-960. By separate single administrations of the main component herbal drugs, Bupleuri radix, Cinnamomi cortex, Paeoniae radix and Zingiberis rhizoma, only Paeoniae radix showed statistically significant inhibition of PTZ-induced EEG power spectrum changes at a proportional dose of 1.0 mg/kg of TJ-960. The other main component herbal drugs showed no statistically significant inhibitory effect although they had a tendency to inhibit. These findings suggest that the Japanese Kampo medicine, TJ-960 (SK), has an inhibitory effect on PTZ-induced power spectrum changes and one of the component herbal drugs, Paeoniae radix, is the important component drug.
The El mouse is an inbred strain developed from ddY mice and is very susceptible to seizure. In El mice, convulsions could be induced by 18 mg/kg of pentylenetetrazol, which is an inert dose in ddY mice. The features of the convulsions were the same as those induced by the tossing-up procedure, a common method to evoke convulsions in El mice. Phenytoin, phenobarbital, valproate sodium, and ethosuximide clearly inhibited pentylenetetrazol-induced convulsions in El mice. These findings suggest that induction of convulsions by pentylenetetrazol in the El mouse is a simple method as compared with induction of convulsions by the tossing-up procedure, and convulsions evoked by this method are a precise experimental model for the study of hereditary epilepsy and for the evaluation of anticonvulsant drugs.
Although hepatocarcinogensis has been reported to be promoted by exogenous administration of bile acids, the relation of endogenous bile acids to hepatocarcinogenesis is not completely understood. This study investigates the relationship between serum concentration of bile acids, the appearance of preneoplastic change, glutathione S-transferase placental form (GST-P)-positive foci in the liver of male Donryu rats which had been fed 0.06% 3'-methyl-4-dimethylamino-azobenzene (3'-MeDAB), and the effects of gomisin A, previously reported to inhibit the tumor promotion process. During the feeding of 3'-MeDAB for 5 weeks, the concentrations of serum bile acids were found to have increased significantly to several times the levels found at the start of the experiment. The increase of serum bile acids, especially deoxycholic acid (DCA), and the appearance of preneoplastic lesions, the number and area of GST-P-positive foci in the liver, were significantly inhibited by simultaneous oral administration of gomisin A (30 mg/kg). When DCA (100 mg/kg) was orally administered after an initiation by 3'-MeDAB, serum bile acids and preneoplastic changes were significantly increased, these increases were inhibited by combined feeding of 0.03% gomisin A in the diet. There were good correlations between the serum concentration of DCA and the number of GST-P-positive foci in the liver in both experimental protocols. These results confirm that DCA is an endogenous risk factor for hepatocarcinogenesis and suggest that anti-promoter effect of gomisin A is based on improving metabolism of bile acids, including DCA.