Twelve questions concerning tannin selected from questions raised by other workers on the author's research were picked up. The answers of each question are as follows. 1. What is tannin? -the differences between the old concept and the new definition of tannin. 2. Is tannic acid the same as tannin? 3. How could each tannin be analyzed as a pure compound? 4. Which tannin found in recent years is implicated with the change of the concept of tannin in medicinal plants? 5. Is it possible that one to several chemical structures represent tannins contained in each plant species? 6. Which tannin-containing plants met in the human life are rich in tannins? 7. Is tannin produced by all species of plants?-a correlation between the occurence of hydrolyzable tannins and the plant evolution system. 8. When and where are the hydrolyzable tannin oligomers produced, in the plant or after extraction? 9. Are tannins bound to other substances in the plants? 10. Is it appropriate to call tannins "plant polyphenols"? 11. Is it true that tannins are inhibitors of enzymes? 12. What kind of biological activities have been found for tannins.
γ-Aminobutyric acid (GABA) has been established as a major inhibitory neurotransmitter in the brain. The GABA-induced inhibitory transmission is mediated by two distinct types of GABA receptors which are termed as GABAA. and GABAA receptors. The GABAA receptor forms a Cl- channel that consists of several subunits. The recent development of molecular cloning clarified the presence of multiple and heterogeneous molecules in the GABAA receptor subunits. Therefore, it is suggested that multiple GABAA receptors generate various functions in the brain. In contrast, the GABAB receptor exhibits various metabotropic actions for the inhibitory neurotransmission, since it is coupled with GTP-binding proteins. The GABAB receptor of approximately 80kDa protein in its molecular weight was purified from the bovine cerebral cortex and the presence of another molecular species of the GABAB receptor was also suspected. These results indicate that studies on the molecular diversity of the GABA receptors is important for elucidating the functional roles of GABA ergic neurons in the brain.
Ecabapide (DQ-2511) has been demonstrated to be effective in preventing water-immersion restraint stress ulceration of rats. In the present study, we aimed to define the active molecular features of ecabapide. Seven of 9 degraded materials identified as ecabapide metabolites were synthesized and their antiulcer activities were compared with that of the parent compound. Ecabapide was potent to prevent gastric ulcer formation at the doses of 30-300 mg/kg i.p. Three metabolites (V, VIII and IX) were also active to inhibit ulceration induced by the stress. The antiulcer activity of IX was similar to that of ecabapide, whereas V and VIII had less activities. After the oral administration of ecabapide, the plasma levels of IX reached to less than 15% of that of ecabapide and also IX was largely excreted into the feces. Therefore, the potential implication of the metabolite (IX) as the active component in the antiulcer effect of ecabapide could be excluded. Furthermore, it is also unlikely that the high polar metabolites (IV and VII) are implicated in significant contribution for antiulcer action. In conclusion, we have shown that ecabapide prevents water-immersion restraint stress-induced gastric ulcers, and that this activity is probably mediated by the action of the parent compound.
The metabolism of lomerizine was investigated after the oral administration of [methine-14C] or [benzyl-14C] lomerizine hydrochloride in rats. 1. Urinary, fecal and biliary excretions of the unchanged drug were less than 1% of dose, showing that lomerizine was eliminated by the extensive biotransformation after the oral administration. 2. The main metabolites were 1-(2, 3, 4-trimethoxybenzyl)piperazine (M7) and 2, 3-dimethoxy-4-hydroxybenzy1piperazine in the urine, and 1-[bis(4-fuluo-rophenyl)methyl]-4-(2, 3-dimethoxy-4-hydroxybenzyl)piperazine in the feces and bile. 3. The radioactive substances in the plasma, liver and brain mainly existed as unconjugated forms, of which the intact drug showed the highest concentration. 4. The main metabolites in the plasma, and in the liver and brain were 1-[bis(4-fuluorophenyl)methyl]-4-(3, 4-dimethoxy-2-hydroxybenzyl)piperazine and bis(4-fluorophenyl)methylpiperazine (M6), respectively. 5. The plasma level of M7 and the biliary excretion of bis(4-fluorophenyl)-methanol in male rats were higher than those in female rats, suggesting the sex difference in the N-dealkylation at the 4-position of piperazine ring of the drug.
In order to know the appropriate harvest time in the cultivation of the medicinal plant, M chamomilla L., we investigated seasonal variations in the yield of the head (capitula) and the content of two phenylpropanoid glycosides ; cis-(1) and trans-2-β-D-glucopyranosyloxy-4-methoxy cinnamic acid (2) and one flavonoid glycoside ; cosmosiin (3) in the head for three months of the flowering time from May to July in 1993. The maximum head size was observed at the beginning of May, and then the size decreased as the development of ligulate flowers retarded. But tubular flowers did not decrease significantly. The content of 1 was the highest among the three glycosides during the flowering time. The values were about 2.0% and 0.5% for 1 and 2, respectively, from the end of May to the middle of June. Then the content of 1 decreased rapidly but 2 decreased gradually. The decline of these two kinds of glycoside was accompanied with a diminution of the ligulate flowers. The content of 3 became higher in an early time. The results showed that the appropriate time for the harvest of the head for the crude drug were from the beginning of May to the middle June. After this time, though external appearance of the head were unfavorable, the content of 1+2 was at the same level as that in the commercial flowers.
We improved the Limulus amebocyte lysate (LAL) test for endotoxins in parenteral drugs using immobilized histidine and a filtration plate. In order to deal with many samples at the same time and to apply to a routine assay, we used a filtration plate having 96 wells instead of a filter unit with a working volume of 2 ml. LAL test-affecting substances which are contained in a parenteral drug were separated from endotoxins by adsorbing endotoxins on immobilized histidine in the well of a filtration plate. Then the adsorbed endotoxins were allowed to react with LAL reagent in the same well. We defined that this method had the higher precision than conventional methods and was not influenced by the concentrations of endotoxin and parenteral drugs. Hence we examined the recovery of endotoxin spiked to 23 kinds of parenteral drugs by this method, as a result, 100±25% of recovery was obtained from 17 kinds of them.
Seasonal variations on the growth and the content of saikosaponin a, c and d (%DW) in the main root of Bupleurum falcatum were investigated using plants monthly collected from July to December in 1993. Bolting started in September, and then the growth of aerial parts and the main root reached the maxima in October. As the maximum diameter of the main root increased rapidly from August to October, a lignified tissue in the xylem of the main root increased remarkably. The content of each saikosaponin (%DW) in the main root was higher in the early time than in the latter time. The total content of saikosaponins (%DW) decreased rapidly from September to October and did not change in December. As regards the distribution of the saikosaponins in each tissue of the main root during cultivation, each saikosaponin accumulated most in the outer tissues from the phloem layer, especially from the pericycle and its neighbouring tissues. The composition of saikosaponins in each tissue in the main root changed significantly during cultivation ; thus in the outer tissues from cambium the content of saikosaponin d (%DW) relatively high. On the other hand in the xylem tissue, the inner tissues from cambium, the composition was quite different from that of the outer tissues as follows : in August and September the content of saikosaponin c was relatively high. After September saikosaponin c was obviously detectable, while saikosaponins a and d were not detectable.