Alkaloids from aerial parts of Annona senegalensis against Streptococcus mutans.

Antimicrobial potential of medicinal plants have been explored extensively these days. This study was carried out to evaluate the antibacterial potential from aerial parts of plant, called 'Annona senegalensis' and its constituents. Bioassay guided fractionation led to the isolation of four metabolites, (+)-catechin (1), (-)-anonaine (2), (-)-asimilobine (3) and (+)-nornantenine (4). This is the first report on the isolation of compounds 1, 3 and 4 from this plant. Compounds 2 and 4 showed good activity, whereas 1 and 3 displayed weak inhibition against Streptococcus mutans (ATCC 25175). The results showed that compound 2 and 3 showed significant activity with a minimum inhibition concentration (MIC) of 0.12 and 0.25 mg/mL, respectively. The present study reports for the first time the antibacterial activity of the extract of A. senegalensis and its constituents. As S. mutans is a rather resistant bacteria, the MIC obtained during the present study is significant.

New type of febrifugine analogues, bearing a quinolizidine moiety, show potent antimalarial activity against Plasmodium malaria parasite.

Febrifugine (1) and isofebrifugine (2), isolated from the roots of Dichroa febrifuga Lour. (Chinese name: Cháng Shan), are active principles against malaria. Adducts of 1 and 2 with acetone, Df-1 (3) and Df-2 (4), respectively, were obtained using silica gel and acetone. They showed high activity against P. falciparum malaria in vitro. Compound 3 was found to be equally effective against P. berghei in vivo as the clinically used drug chloroquine, whereas 4 showed only 1/24 of the activity of 3. Metabolism studies of these compounds revealed that compound 4 is readily metabolized in mouse liver. Accordingly, the dose of 4 must be higher than that of 3 to attain blood levels sufficient for a favorable therapeutic effect.

Pharmacological properties of pteleprenine, a quinoline alkaloid extracted from Orixa japonica, on guinea-pig ileum and canine left atrium.

We have investigated the pharmacological properties of pteleprenine, a quinoline alkaloid, on contractile responses of the guinea-pig ileum and on inotropic responses of the canine left atrium. Although pteleprenine (0.1-1 microM) had no effect on the contraction of the ileum induced by acetylcholine at 10 microM it significantly inhibited acetylcholine-induced contraction of the ileum. Pteleprenine (0.1-10 microM) reduced nicotine induced-contraction of the ileum in a concentration-dependent manner yet had no maximum relaxant effect even at a concentration of 10 microM. From Schild analysis the pA2 of pteleprenine on the guinea-pig ileum was found to be 6.6. The contraction of the ileum induced by 10 microM 1,1-dimethyl-4-phenylpiperazinium, a specific agonist of nicotinic acetylcholine receptors, was concentration-dependently suppressed by 10 nM-10 microM pteleprenine. In contrast, 0.1-10 microM pteleprenine did not antagonize the acetylcholine- and nicotine-induced negative inotropic contractile responses of the canine left atrium. These results show that pteleprenine has inhibitory action against nicotinic acetylcholine receptors in the guinea-pig ileum but not in the canine left atrium. Our findings also suggest that pteleprenine might be a novel lead compound as a nicotinic receptor antagonist.

Enhancement of NO production in activated macrophages in vivo by an antimalarial crude drug, Dichroa febrifuga.

The effect of an antimalarial crude drug, Dichroafebrifuga Lour. on nitric oxide (NO) production in bacillus Calmette Guérin-induced mouse peritoneal macrophages activated by lipopolysaccharide was investigated. The NO production was significantly enhanced by an oral administration of a MeOH extract of D. febrifuga. Febrifugine (1) was isolated as the main active compound, and the activation was dose-dependent in the dosage range of 0.1-1 mg/kg/day.

[Pharmacological properties of pteleprenine, a quinoline alkaloid from Orixa japonica (Rutaceae), in guinea pig ileum and canine left atrium].

We investigated the pharmacological properties of pteleprenine, a quinoline alkaloid contained in the Rutaceous plant, Orixa japonica, on the contractile responses of the guinea pig ileum and on the inotropic responses of the canine left atrium. Contractile responses of the ileum to acetylcholine and histamine were not inhibited by less than 10(-6) M of pteleprenine. Meanwhile, the nicotine induced-contraction of the ileum was dose-dependently diminished by pteleprenine, but the contractile response to nicotine did not reach the maximum value in the presence of 10(-5) M of pteleprenine. The pA2 value of pteleprenine was 6.6 as determined from the Schild plot, which slope was nearly unity. Furthermore, the contraction of the ileum by 10(-5) M of 1,1-dimethyl-4-phenylpiperazinium (DMPP), a specific agonist of nicotinic acetylcholine receptors, was also dose-dependently suppressed by pteleprenine. On the other hand, 10(-5) M of pteleprenine did not have considerable inhibitory effects on acetylcholine- and nicotine-induced negative inotropic effects in the canine left atrium. From these results, it is suggested that pteleprenine has a specific inhibitory effect on nicotinic acetylcholine receptors in the guinea pig ileum.

A putative membrane protein, Pho88p, involved in inorganic phosphate transport in Saccharomyces cerevisiae.

Transcription of a regulatory gene, PHO81, in the phosphatase regulon of Saccharomyces cerevisiae is repressed by inorganic phosphate (Pi) in the medium via that same regulatory system. The activity of Pho81p, the product of PHO81, is also inhibited by a high concentration of Pi in the medium. Increased dosage of PHO86, a gene encoding a putative membrane protein associated with a Pi transporter complex, activates the Pi-inhibited Pho81p produced under the control of the GAL1 promoter. A new gene, PHO88/ YBR106w, has now been identified as a multicopy suppressor of the rAPase- phenotype of the cells caused by the Pi inhibition of Pho81p. The pho86 disruptant expressed rAPase activity in high-Pi medium, while the pho88 disruptant did not. The delta pho86 delta pho88 double disruption resulted in enhanced synthesis of rAPase under the high-Pi condition and conferred arsenate resistance on the cells than those in single disruptants of these genes. Its hydropathy profile and the results of an analysis of its cellular localization suggested that Pho88p is a membrane protein similar to Pho86p. Both disruption and high dosage of PHO88 or PHO86 resulted in reduced Pi uptake. These findings suggest that Pho88p is also involved in Pi transport and modulates Pho81p function together with Pho86p.

Antidepressant principles of Valeriana fauriei roots.

A methanol extract of the roots of Valeriana fauriei (Valerianaceae), exhibited antidepressant activity in mice. The extract was fractioned, monitored by the activity, to afford alpha-kessyl alcohol as an active principle. The antidepressant activity of some guaiane and valerane types of sesquiterpenoids in the active fraction was also evaluated.

Powerful hepatoprotective and hepatotoxic plant oligostilbenes, isolated from the Oriental medicinal plant Vitis coignetiae (Vitaceae).

The methanol extract of the Oriental medicinal plant Vitis coignetiae (Vitaceae) showed hepatoprotective activity in the in vitro assay method using primary cultured rat hepatocytes. Activity-guided fractionation of the extract afforded epsilon-viniferin as an active principle. The protective effect of epsilon-viniferin against mice carbon tetrachloride-induced hepatic injury in mice was shown by serum enzyme assay as well as by pathological examination. In addition to epsilon-viniferin, plant oligostilbenes, ampelopsins A, C, F and the mixture of vitisin A and cis-vitisin A were also present in the extract. Among them, ampelopsin C and the mixture of vitisin A and cis-vitisin A were found to be powerful hepatotoxins.

Pharmacological properties of beta-amyrin palmitate, a novel centrally acting compound, isolated from Lobelia inflata leaves.

Effects of beta-amyrin palmitate isolated from the leaves of Lobelia inflata were studied on the central nervous system of mice and were compared with those of antidepressant drugs, mianserin and imipramine. In the forced swimming test, beta-amyrin palmitate, like mianserin and imipramine, reduced the duration of immobility of mice significantly in a dose-dependent manner (5, 10 and 20 mg kg-1). beta-Amyrin palmitate (5, 10 and 20 mg kg-1) or mianserin (5, 10 and 20 mg kg-1) elicited a dose-related reduction in locomotor activity of mice and antagonized locomotor stimulation induced by methamphetamine. In contrast, imipramine (5, 10 and 20 mg kg-1) increased locomotor activity and potentiated methamphetamine-induced hyperactivity. beta-Amyrin palmitate showed no effect on reserpine-induced hypothermia, whilst mianserin (10 mg kg-1) and imipramine (10 and 20 mg kg-1) antagonized the reserpine-induced effect. Unlike imipramine, beta-amyrin palmitate and mianserin did not affect haloperidol-induced catalepsy, tetrabenazine-induced ptosis and apomorphine-induced stereotypy. beta-Amyrin palmitate and imipramine had no effects on the head-twitch response induced by 5-hydroxytryptophan, whereas mianserin (5, 10 and 20 mg kg-1) decreased it in a dose-dependent manner. A potentiating effect of beta-amyrin palmitate (5, 10 and 20 mg kg-1) on narcosis induced by sodium pentobarbitone was stronger than that of imipramine (10, 20 and 40 mg kg-1) but weaker than that of mianserin (2.5, 5 and 10 mg kg-1). These results suggest that beta-amyrin palmitate has similar properties in some respects to mianserin and might possess a sedative action.(ABSTRACT TRUNCATED AT 250 WORDS)

A possible mechanism of antidepressant activity of beta-amyrin palmitate isolated from Lobelia inflata leaves in the forced swimming test.

A mechanism of antidepressant activity of beta-amyrin palmitate was studied using the forced swimming method in mice. Beta-amyrin palmitate (10 mg/kg) reduced the increase in the duration of immobility induced by tetrabenazine (100 and 200 mg/kg), but showed no effect on that in mice treated with alpha-methyl-para-tyrosine (500 mg/kg). Beta-amyrin palmitate (5 and 10 mg/kg) decreased the duration of immobility in mice treated with desipramine plus 6-hydroxy-dopamine (50 micrograms/mouse), but did not affect that induced by nomifensine plus 6-hydroxydopamine. The decreased immobility produced by desipramine (15 mg/kg) was not affected by beta-amyrin palmitate. A study of norepinephrine release in mouse brain synaptosomes indicated that beta-amyrin palmitate caused a release of [3H]norepinephrine. The results of the present study suggest that beta-amyrin palmitate might release norepinephrine from newly synthesized pools, and thus, it might activate noradrenergic activity.

[Blood concentrations of futraful, uracil and 5-fluorouracil (5-FU) after UFT administration in the various reconstructions after gastrectomy. Saitama UFT Research Group].

The study was undertaken in the total of 58 gastric cancer patients among which 17 of Billroth (BI), 14 of Billroth II (B II) anastomosis after subtotal gastrectomy, and 7 of jejunal interposition, 9 of double tract and 11 of Roux en Y anastomosis after total gastrectomy were included. Blood samples were taken before 200 mg of per oral UFT administration and after 1, 2, 3, 5 and 7hrs. consecutively. The blood Futraful (FT) level in the total gastrectomy groups reached peak concentration within 1hr and kept in relatively high level during the observation period of 7hrs. The time to maximum FT concentration delayed in almost of B I and a few of B II patients. The concentration curves of uracil (URA) and 5-FU were similar in shape, revealing steep increase and decrease except B I anastomosis which showed gentle course. The plotted maximum concentrations of URA and 5-FU in the every type of reconstruction showed a significant correlation in the regression line. In the analysis of AUC, URA/FT was under 10%, suggesting the longer retention of the unmetabolite type of FT and early disappearance of URA. The ratio of 5-FU/FT was indifferent in each reconstruction. 5-FU/URA was higher in subtotal rather than total gastrectomy groups. From the data obtained, blood concentration of 5-FU after UFT administration was considered to depend on the emptying status in the gastrectomies. And moreover, it depended on blood URA level, since FT from which 5-FU was derived, was kept still sufficiently remained during observation period.

An antidepressant principle of Lobelia inflata L. (Campanulaceae).

A crude methanolic extract of the leaves of Lobelia inflata exhibited antidepressant activity in mice. The extract was fractionated, monitored by the activity, to give beta-amyrin palmitate as an active component.

Jatamols A and B: Sesquiterpenoids of Nardostachys jatamansi Roots1.

From the roots and rhizomes of NARDOSTACHYS JATAMANSI, two new eudesmanes jatamols A and B were isolated, and their structures were determined by spectral analysis and chemical evidence.

Isolation and hypoglycemic activity of trichosans A, B, C, D, and E: glycans of Trichosanthes kirilowii roots.

The non-dialyzable portion of the water extract of the Oriental crude drug "karokon", the roots of Trichosanthes kirilowii, was found to reduce the plasma glucose level in mice. Activity-guided fractionation of this non-dialyzable portion led to the isolation of five glycans termed as trichosans A, B, C, D and E, showing hypoglycemic actions in normal mice. The main glycan, trichosan A, also exhibited activity in alloxan-induced hyperglycemic mice.

Sagittatins A and B, Flavonoid Glycosides of Epimedium sagittatum Herbs1.

Two new flavonoid glycosides sagittatins A and B were isolated from EPIMEDIUM SAGITTATUM and their structures were fully characterized by chemical and spectroscopic means.

Schizonodiol, Schizonol, and Schizonepetosides D and E, Monoterpenoids of Schizonepeta tenuifolia Spikes1.

Four new monoterpenoids, shizonodiol, shizonol, and shizonepetosides D and E, have been isolated from SCHIZONEPETA TENUIFOLIA spikes along with the known flavonoids, diosmetin, hesperetin, and luteolin.