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Correlation of the glycoside response, the force staircase, and the action potential configuration in the neonatal rat heart.

The rat heart demonstrates marked alterations in its responses to ouabain and increased frequencies of stimulation and in the duration of its action potential during the initial 21 days of life. At an age of 6.2 days 5 times 10- minus 5M ouabain produced a 158.2% increase in dP/dt compared with a 17.2% increase at 21.1 days (P less than 0.001). At 6.2 days dP/dt increased by 53.4% when the heart rate was accelerated from 30 to 90 beats/min compared with an increase of 12.2% at 21.1 days (P less than 0.005). The positive glycoside and staircase responses at the younger age were virtually eliminated when the hearts were perfused with a solution containing 50% [Na+]o and 25% [Ca-2+]o ([Ca-2+]o/[Na+]o-2 maintained constant). The duration of the ventricular action potential progressively decreased from 350-400 msec at birth to 100-150 msec at 21 days of life. This decrease was due to a shortening and a decrease in the potential level of the plateau phase. The prominent plateau typical of the early neonatal period was significantly diminished by perfusion with 50% [Na+]o. The results suggest that Na+ flux through a slow membrane channel plays a significant role in the positive staircase and glycoside responses of the early neonatal rat heart. As the heart matures and becomes functionally anomalous relative to other mammalian species, the slow channel progressively closes.

Action Potentials↗

Membrane currents and tension in cat ventricular muscle treated with cardiac glycosides.

The effect of cardiac glycosides on membrane currents and tension in cat ventricular muscle was studied using the single sucrose gap voltage clamp method. Complete tension-voltage and current-voltage relations were obtained in five preparations before and during treatment with dihydro-ouabain (DHO, 1.7 X 10(-5)M). After 1-2 minutes of DHO, the developed tension was 15% greater than control, but there was no change in either the slow inward (calcium) current (Ica) or the level of the outward current flowing at the end of a 300-msec depolarization (Iout). After 6-8 minutes of DHO, there was a 60% increase in developed tension, a noticeable increase in resting tension, a 20% decrease in Ica, and a smaller increase in Iout. It seems possible that the reduction of Ica was due to a reduced driving force. In preparations treated with ouabain (5 X 10(-7)M, 3-5 minutes), developed tension was 45-150% greater than control with no change in Ica or Iout between -45 and + 15 mv. We conclude that the inotropic action of these cardiac glycosides is not mediated by an increase in Ica.

Animals↗

Two new triterpenoidal glycosides from Medicago polymorpha L.

Two new triterpenoid glycosides called medicago-saponins P1 (1) and P2 (2) were isolated together with five known glycosides from the aerial parts of Medicago polymorpha L. (Leguminosae). The structures of 1 and 2 were determined to be 3-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl caulophyllogenin 28-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside and the desglucoside of 1.

Carbohydrate Sequence↗

New bioactive monoterpene glycosides from Paeoniae Radix.

Bioassay-guided separation of MeOH extract of Japanese Paeoniae Radix inhibiting contractile responses of guinea pig ileum stimulated with electric field disclosed a new monoterpene glycoside, 6-O-beta-D-glucopyranosyl-lactinolide (1), as an active constituent together with two new monoterpene glycosides (3 and 4) and two new monoterpenes (2 and 5). Furthermore, 1-O-beta-D-glucopyranosyl-paeonisuffrone (2) was found to inhibit histamine release from rat peritoneal exudate cells induced by antigen-antibody reaction.

Animals↗

Bioactive saponins and glycosides. VII. On the hypoglycemic principles from the root cortex of Aralia elata Seem.: structure related hypoglycemic activity of oleanolic acid oligoglycoside.

The hypoglycemic component, elatoside E, was isolated from the root cortex of Aralia elata SEEM. (Araliaceae) together with elatoside F and eight known oleanolic acid glycosides, elatosides A and C, oleanolic acid 3-O-[alpha-L-arabinofuranosyl (1-->4)]-beta-D-glucopyranosiduronic acid, oleanolic acid 3-O-beta-D-glucopyranosiduronic acid, stipuleanosides R1 and R2, and chikusetsusaponins IV and IVa. The structures of elatosides E and F were determined on the basis of chemical and physicochemical evidence as oleanolic acid 3-O-[beta-D-xylopyranosyl (1-->2)][beta-D-glucopyranosyl (1-->3)]-alpha-L-arabinopyranoside and its 28-O-beta-D-glucopyranosyl ester, respectively. The hypoglycemic activity of oleanolic acid and nine oleanolic acid oligoglycosides from the root cortex of Aralia elata was determined by monitoring inhibition effect on the elevation of plasma glucose level by oral sucrose tolerance test in rats, and some structure-activity relationships of oleanolic acid glycoside were obtained.

Animals↗

Antidiabetic principles of natural medicines. III. Structure-related inhibitory activity and action mode of oleanolic acid glycosides on hypoglycemic activity.

We examined the structure-related activity of oleanolic acid glycosides with respect to their inhibitory effect on the increase in serum glucose in oral glucose-loaded rats and their mechanism of action using oleanolic acid 3-O-glucuronide and momordin Ic. Both the 3-O-monodesmoside structure and 28-carboxyl group were confirmed to be essential for such activity, and the 3-O-glucuronide was more potent than 3-O-glucoside. On the other hand, the 28-ester glucoside moiety and 6'-methyl ester of the glucuronide moiety reduced such activity. Oleanolic acid 3-O-glucuronide and momordin Ic, both of which inhibited the increase in serum glucose in oral glucose-loaded rats, did not lower serum glucose in normal or intraperitoneal glucose-loaded rats, or alloxan-induced diabetic mice. These glycosides were found to suppress gastric emptying in rats, and also inhibit glucose uptake in the rat small intestine in vitro. These results indicate that oleanolic acid 3-O-glucuronide and momordin Ic, given orally, have neither insulin-like activity nor insulin releasing-activity. They exhibit their hypoglycemic activity by suppressing the transfer of glucose from the stomach to the small intestine and by inhibiting glucose transport at the brush border of the small intestine.

Administration, Oral↗

Lupane-triterpene glycosides from the leaves of Acanthopanax gracilistylus.

A novel lupane-triterpene glycoside, called wujiapioside B (1), was isolated from the leaves of Acanthopanax gracilistylus (Araliaceae) together with three known lupane-triterpene glycosides, acankoreoside C (2), acantrifoside A (3) and 3-epibetulinic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester (4). Based on spectroscopic data, the chemical structure of 1 was determined as 3alpha,23-dihydroxy-lup-20(29)-en-28-oic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester. Compounds 2-3 were obtained for the first time from this plant and compound 4 has not been isolated from Acanthopanax genus yet.

Eleutherococcus↗

Studies on the constituents of Syringa species. X. Five new iridoid glycosides from the leaves of Syringa reticulata (Blume) Hara.

Five new iridoid glycosides, (8Z)-ligstroside (1), (8Z)-nüzhenide (3), 6'-O-alpha-D-glucopyranosylsyringopicroside (4), 3'-O-beta-D-glucopyranosylsyringopicroside (5) and 4'-O-beta-D-glucopyranosylsyringopicroside (6) were isolated, together with a known one, (8E)-nüzhenide (2), from the leaves of Syringa reticulata. Their structures were established on the basis of chemical and spectral data. Compounds 1 and 3 are the first findings of a (8Z)-oleoside-type secoiridoid. Compound 4 is the first naturally occurring iridoid di-glycoside having an isomaltose.

Iridoids↗

A new iridoid glycoside with nerve growth factor-potentiating activity, gelsemiol 6'-trans-caffeoyl-1-glucoside, from Verbena littoralis.

A new iridoid glycoside, gelsemiol 6'-trans-caffeoyl-1-glucoside (1), was isolated from Verbena littoralis, together with four known phenylethanoid glycosides, acteoside (2), 2'-acetylacteoside (3), jionoside (4), and isoverbascoside (5). Their structures were elucidated by spectral data. Compound 1 showed weak enhancement of nerve growth factor (NGF)-mediated neurite outgrowth from PC12D cells.

Caffeic Acids↗

[Seasonal fluctuation of flavonol glycosides in Epimedium species].

The seasonal fluctuation of flavonol glycosides in the leaves of Epimedium grandiflorum var. thunbergianum, E. cremeum and E. sempervirens (Berberidaceae) was investigated. The total content of glycosides was shown in the highest quantity at the flowering time, and as the leaves mature it has become stable amount with a little decrease. The suitable period for the harvest of Epimedium leaves was concluded to be two or three months after the flowering time.

Drugs, Chinese Herbal↗

Suppression of D-galactosamine-induced rat liver injury by glycosidic flavonoids-rich fraction from green tea.

Tea constituents that had a preventive effect on D-galactosamine-induced liver injury in rats were partially purified by column chromatography from a n-butanol-soluble fraction of green tea. The fraction containing glycosidic flavonoids was found to suppress the D-galactosamine-induced increase of plasma alanine aminotransferase and aspartate aminotransferase activities. These results indicate that glycosidic flavonoids contribute, at least in part, to the liver injury-preventive effect of green tea.

Alanine Transaminase↗

Juvenile hormone activity of some glycosidic juvenogens.

In a search for new hormonogen compounds related to insect juvenile hormones we have prepared and bioassayed several beta-D-glucosides of some selected secondary juvenoid alcohols. Due to localization of the activating enzyme beta-D-glucopyranosidase in the epithelium and in the lumen of the digestive tract, the glycosidic juvenogens exhibit juvenile hormone activity in insects only when ingested. They are completely inactive in topical application as well as when injected into the haemolymph. It is suggested that the highly specific and selective action of the hydrophilic, nonvolatile, glycosidic juvenogens could be of practical importance.

Animals↗

Structural studies on O- and N-glycosidically linked carbohydrate chains on Collocalia mucin.

Oligosaccharides, which are O- and N-glycosidically linked on salivary glycoproteins from the edible bird's nest of chinese swallows, were released by alkaline borohydride treatment of the asialoglycoproteins and fractionated by gel chromatography. Fract. VN1 (oligosaccharides greater than 2 000 dalton) apparently represented a mixture of saccharides derived from complex, N-glycosidically linked glycans (molar ratio Man/GlcNAc/Gal 3:4:8), while fractions VN2 (tetra- to hexasaccharides), VN3 (trisaccharide) and VN4 (disaccharide) were free of mannose, but did contain all the N-acetylgalactosamine released from the protein as its alditol. Oligosaccharides in Fract. VN2 and VN4 were purified by high-performance liquid chromatography, paper chromatography and thin-layer chromatography, methylated and analysed after total or partial acid hydrolysis by gas-liquid chromatography-mass spectrometry. The structures of a hexasaccharide in Fract. VN2/6 and of a tetrasaccharide in fraction VN2/4 were finally established after methylation through direct-probe mass spectrometry: Gal(1----4)GlcNAc(1----3)Gal(1----4)GlcNAc(1----3)Gal(1----3)GalNAc- ol and Gal(1----4)GlcNAc(1----6)[Gal(1----3)]GalNAc-ol. Mass spectrometrical and gas-chromatographical data obtained for a disaccharide in Fract. VN4 were identical with those for Gal(beta 1----3)GalNAc-ol.

Animals↗

Conformation about the glycosidic bond and susceptibility to 5'-nucleotidase of 8-substituted analogues of 5'-GMP.

Susceptibilities to snake venom 5'-nucleotidase (EC 3.1.3.5) have been evaluated for several 8-substituted analogues of 5'-GMP with varying populations of syn/anti conformations about the glycosidic bond. Improved syntheses of some of these are described, including direct chlorination of 5'-GMP to give 8-chloro-5'-GMP, a procedure which should be applicable to other purine nucleotides. The conformations of the various analogues were determined by means of 1H NMR spectroscopy, with particular emphasis on the glycosidic bond conformations. All the 8-substituted derivatives of 5'-GMP were relatively poor substrates of 5'-nucleotidase. This was shown to result largely from steric effects and the nature of the 8-substituent, and consistent with a requirement for the anti conformation. Although ribose-5-phosphate was not a substrate, it was a weak inhibitor, and its inhibitory properties account in part for the weak inhibitory properties of the 8-substituted 5'-GMP, and other, analogues. Attention is drawn to the hitherto largely neglected differences in properties of 5'-nucleotidases from different sources and their relevance to the present findings.

5'-Nucleotidase↗

Comparison between urinary pyridinium cross-links and hydroxylysine glycosides in monitoring the effects of ovariectomy and 17 beta-estradiol replacement in aged rats.

This study was undertaken to assess the sensitivity of hydroxylysylpyridinoline (HP), lysylpyridinoline (LP), galactosylhydroxylysine (GHyl) and glucosylgalactosylhydroxylysine (GGHyl) to monitor bone response to estrogen deficiency and replacement by comparing their excretory patterns in ovariectomized aged (11-14 months old) rats. The ovariectomized (OVX) rats were randomized into two groups: (1) OVX plus vehicle; (2) OVX plus 17 beta-estradiol (17-beta E, 10 micrograms/kg, s.c., 4 days/week). Treatment with 17-beta E started immediately after OVX and continued for 60 days. The collagen catabolites were measured in urine for 1 month before OVX and thereafter for 60 days. In temporal coincidence with urine collection, bone area and bone mineral density (BMD) of lumbar vertebrae, femoral diaphysis and distal metaphysis were measured by dual-energy X-ray absorptiometry. In the untreated rats, BMD of the femoral metaphysis and lumbar vertebrae decreased significantly and the urinary excretion of LP, HP, GHyl and GGHyl increased with different patterns. In the treated rats, 17-beta E replacement prevented the increment in LP excretion, partially prevented the increase in HP excretion, but had no effect on the excretion of GHyl and GGHyl. In conclusion pyridinolines and glycosides have different sensitivities to the bone response to OVX. Glycoside excretion after OVX also reflects metabolic processes not strictly related to bone loss and, in contrast with LP, is not sensitive to estrogen replacement.

Absorptiometry, Photon↗

Use of galactose oxidase in labelling hydroxylysine glycosides of collagen.

Commercial preparations of galactose oxidase were shown to contain a proteolytic component active against collagen and collagen CNBr peptides which could not be inhibited by reagents such as EDTA, PMSF, PCMB and TLCK nor activated by Ca++ or Mn++. 30% of the total galactose oxidase activity could be recovered free of proteolytic activity in a simple one-step combined gel filtration/affinity chromatography procedure. The biological activity of such preparations was tested with reference to collagen hydroxylysine glycosides. It was shown that over 70% of the covalently linked tritium label introduced by KB3H4 reduction after galactose oxidase treatment was not associated with galactose but was present in the same non-specifically labelled components in control experiments. The enzyme could be used in a controlled manner to label hydroxylysine glycosides in collagen by immobilising it on agarose beads. In this form it was easy to store, re-usable and retained 95% of its original activity even after prolonged (18 h) incubation with substrates.

Collagen↗

Glycosidation of chlormadinol acetate alters its actions on Na+/K+-transporting ATPase and cardiac contractility: a contribution to the endogenous digitalis problem.

Compared to the progesterone derivative chlormadinol acetate 1, the arabinofuranoside 2, rhamnoside 3 and glucoside 4 of 1 are less potent in the Na/K-ATPase assay, but evoke, contrary to 1, positive inotropy in vivo. In anaesthetized cats the circulation effects of 2 and 3 appear to be more favourable than those of the digitalis glycoside digitoxin. Hence, the progestin 1 is transformed through glycosidation into an interesting cardioactive steroid.

Animals↗

Bioavailability of anthocyanidin-3-glycosides following consumption of elderberry extract and blackcurrant juice.

Pharmacokinetic parameters and the bioavailability of several dietary anthocyanins following consumption of blackcurrant juice and elderberry extract were compared exploratorily in 6 healthy volunteers. They were given a single oral dose of either 137 ml of blackcurrant juice (144.8 mg total anthocyanins) or 30 ml of elderberry extract (147.3 mg total anthocyanins). Within 7 hours, the urinary excretion of total anthocyanins (i.e. the sum of all assayed anthocyanidin glycosides) was 0.04% and 0.37% of the administered dose following blackcurrant juice and elderberry extract ingestion, respectively. Pharmacokinetic parameters based on non-compartmental methods for plasma and urine concentrations exhibited higher variability in urinary excretion after ingestion of elderberry extract. Anthocyanin absorption was significantly greater following the intake of elderberry extract than after the intake of blackcurrant juice as shown by the 5.3- and 6.2-fold higher estimates of dose-normalized Cmax and AUC(0-tZ) of total anthocyanins, respectively. The geometric means of t(1/2) were not significantly different following elderberry extract (1.74 h) and blackcurrant juice ingestion (1.73 h, p > 0.05). The urinary excretion rate of intact anthocyanins was fast, appeared to be monoexponential for both blackcurrant juice and elderberry extract. However, in order to evaluate the contribution of anthocyanins to the health-protecting effects of blackcurrant juice and elderberry extract it will be necessary to perform further studies on the unchanged glycosides and their in vivo metabolites in human plasma and urine.

Adult↗