Cocaine self-administration reinforced on a progressive ratio schedule decreases with continuous d-amphetamine treatment in rats

Rationale

To date, there is no medication specifically approved for cocaine addiction. Agonist medications are used clinically in the treatment of other addictions, which suggests that this method of drug therapy could potentially be successful in treating cocaine addiction as well.

Objective

The objective of this study was to determine the effect of extended d-amphetamine treatment on responding on a progressive ratio (PR) schedule reinforced by cocaine.

Materials and methods

Rats were trained to self-administer cocaine (0.19, 0.38, 0.75, or 1.5 mg/kg/injection) or food on a PR schedule. After stable baseline breakpoints (the number of reinforcers earned in one session) were established over 3 days, animals were implanted with osmotic mini-pumps that continuously delivered d-amphetamine (5 mg/kg/day) for a duration of either 7 or 14 days. Breakpoints were then determined during and/or after this treatment period.

Results

Rats demonstrated dose-dependent decreases in cocaine-reinforced responding over the d-amphetamine treatment period. Breakpoints for doses of 0.75 mg/kg/injection and below decreased significantly when compared to baseline and remained decreased for up to 14 days after mini-pump removal, whereas those for the highest dose of cocaine remained unchanged. Additionally, d-amphetamine treatment during a 14-day abstinence period from cocaine self-administration had no effect on breakpoints when tested the day after mini-pump removal.

Conclusions

These data suggest that the reduction in cocaine-reinforced responding after continuous d-amphetamine treatment cannot be accounted for by tolerance alone. Instead, the roles of learning and the interaction between cocaine and d-amphetamine must be considered and examined in future studies.     

Effects of coincident 5-HT1A receptor stimulation and NMDA receptor antagonism on l-DOPA-induced dyskinesia and rotational behaviors in the hemi-parkinsonian rat

Rationale

Serotonin 1A receptor (5-HT1AR) agonists reduce l-DOPA-induced dyskinesia and enhance motor function in experimental and clinical investigations of Parkinson’s disease (PD). While the mechanism(s) by which these effects occur are unclear, recent research suggests that modulation of glutamate neurotransmission contributes.

Objective

To further delineate the relationship between 5-HT_1A receptors and glutamate, the current study examined the effects of the 5-HT_1AR agonist, ±8-OH-DPAT and the N-methyl-d-aspartic acid receptor (NMDAR) antagonist, MK-801, on l-DOPA-induced motor behavior.

Materials and methods

Unilateral 6-hydroxydopamine lesioned male Sprague–Dawley rats were rendered dyskinetic with 1 week of daily l-DOPA (12 mg/kg, i.p.) + benserazide (15 mg/kg, i.p.). On test days, one group of rats received pretreatments of: ±8-OH-DPAT (0, 0.03, 0.1, 0.3 mg/kg, i.p.) or MK-801 (0, 0.03, 0.1, 0.3 mg/kg, i.p.). A second group was administered combined ±8-OH-DPAT (0, 0.03 or 0.1 mg/kg, i.p.) + MK-801 (0, 0.1 mg/kg, i.p.). Pretreatments were followed by l-DOPA administration, after which, abnormal involuntary movements (AIMs) and rotations were monitored. To investigate effects on motor performance, subthreshold doses of ±8-OH-DPAT (0.03 mg/kg, i.p.) + MK-801 (0.1 mg/kg, i.p.) were administered to l-DOPA-naïve hemiparkinsonian rats before the forepaw adjusting steps test.

Results

Individually, both ±8-OH-DPAT and MK-801 dose-dependently decreased l-DOPA-induced AIMs without affecting rotations. Combined subthreshold doses of ±8-OH-DPAT+MK-801 reduced l-DOPA-induced AIMs and potently enhanced contralateral rotations without altering l-DOPA-induced motor improvements.

Conclusions

The current results indicate a functional interaction between 5-HT_1AR and NMDAR that may improve pharmacological treatment of PD patients.     

Triterpenoid saponins from the root of Anemone tomentosa

Three new triterpenoid saponins, tomentoside A (1), B (2) and C (3), along with four known saponins (4?C7) were isolated from the root of Anemone tomentosa. The structures of the new compounds were elucidated as 3-O-??-d-ribopyranosyl-(1??3)-??-l-rhamnopyranosyl-(1??2)-[??-d-glucopyranosyl-(1??4)]-??-l-arabinopyranosyl hederagenin 28-O-??-l-rhamnopyranosyl-(1??4)-??-d-glucopyranosyl-(1??6)-??-d-glucopyranoside (1), 3-O-??-d-ribopyranosyl-(1??3)-??-l-rhamnopyranosyl-(1??2)-[??-d-glucopyranosyl-(1??4)]-??-d-xylopyranosyl hederagenin 28-O-??-l-rhamnopyranosyl-(1??4)-??-d-glucopyranosyl-(1??6)-??-d-glucopyranoside (2) and 3-O-??-d-galactopyranosyl-(1??3)-??-l-rhamnopyranosyl-(1??2)-??-d-xylopyranosyl oleanolic acid 28-O-??-l-rhamnopyranosyl-(1??4)-??-d-glucopyranosyl-(1??6)-??-d-glucopyranoside (3) on the basis of chemical and spectral evidence. In the oligosaccharide chains of compound 3, the characteristic d-galactose residue is a rare structural feature and secondly encountered among triterpenoid saponins from Anemone.     

A novel saponin from Manilkara hexandra seeds and anti-inflammatory activity

Chromatographic separation of acetone precipitate of the seeds of Manilkara hexandra has resulted in a novel saponin, 3-O-(β-d-apiofuranosyl-(1 → 3)-β-d-glucopyranosyl)-28-O-(α-l-rhamnopyranosyl(1 → 3)-β-d-xylopyranosyl(1 → 4)-α-l-rhamnopyranosyl(1 → 2)-α-l-arabinopyranosyl)-16-α-hydroxyprotobassic acid (Saponin 3), together with two known saponins isolated for the first time from the family Sapotaceae, viz, 3-O-β-d-glucopyranosyl(1 → 6)[(β-d-apiofuranosyl-(1 → 3)]-β-d-glucopyranosyl)-28-O-(α-l-rhamnopyranosyl(1 → 3)-β-d-xylopyranosyl(1 → 4)-α-l-rhamnopyranosyl(1 → 2)-α-l-arabinopyranosyl)-16α-hydroxyprotobassic acid (Saponin 1), 3-O-(β-d-glucopyranosyl)-28-O-(α-l-rhamnopyranosyl(1 → 3)-β-d-xylopyranosyl(1 → 4)-α-l-rhamnopyranosyl(1 → 2)-α-l-arabinopyranosyl)-protobassic acid, and 3-O-(β-d-glucopyranosyl)-28-O-(α-l-rhamnopyranosyl(1 → 3)-β-d-xylopyranosyl(1 → 4)-α-l-rhamnopyranosyl(1 → 2)-α-l-arabinopyranosyl)-protobassic acid (Saponin 2). Also, three known phenolic compounds were isolated for the first time from the species hexandra, viz, gallic acid, myrecetin, and quercetin. The chemical structures of the isolated saponin compounds were established by spectral techniques (UV, ¹H, ¹³C NMR, and MS). The acetone fraction containing the crude saponin mixture possessed a significant inhibitory effect on LPS-induced nitric oxide to the extent of 60 % compared to the LPS-stimulated cells and to the extent of 20 % compared to the control level showing significant anti-inflammatory activity. Acetone and MeOH seed extracts as well as the crude saponin fraction of M. hexandra showed no antioxidant activity as measured by DPPH assay (SC₅₀ = 217.65, 496.68, and 562.38 μg/ml, respectively) compared to that of ascorbic acid (SC₅₀ = 12.9). The MeOH seed extract showed no cytotoxic activity against three different human cancer cell lines, viz, colon carcinoma (HCT-116), hepatocellular carcinoma (Hep-G2), and breast adenocarcinoma (MCF-7), estimated by MTT assay (IC₅₀ = 95.20, 73.39, and 79.15 μg/ml, respectively).     

Evaluation of antioxidant activity of new constituents from the fruits of Lycium chinense

Two new compounds as labd-7,11-dien-3β, 13α-diol-3α-l-arabinopyranosyl-(2a → 1b)-α-l-arabinopyranosyl-(2b → 1c)-α-l-arabinopyranosyl-(2c → 1d)-α-l-arabinopyranosyl-(2d → 1e)-α-l-arabinopyranosyl-(2e → 1f)-α-l-arabinopyranosyl-(2f → 1g)-α-l-arabinopyranoside (1), and 5 (6), 11 (12), 15 (15′), 5′ (6′), 11′ (12′)-decadehydro-β-carotenyl-4β,4′β-diol-4-α-l-arabinopyranosyl-(2a → 1b)-α-l-arabinopyranosyl-(2b → 1c)-α-l-arabinopyranosyl-(2c → 1d)-β-l-arabinopyranosido-4′-α-l-arabinopyranosyl-(2e → 1f)-α-l-arabinopyranosyl-(2f → 1g)-α-l-arabinopyranosyl-(2g → 1h)-α-l-arabinopyranosyl-(2h → 1i)-β-l-arabinopyranoside (2) along with known compound have been isolated from the methanol extract of fruits of Lycium chinense. Their chemical structures were established with the help of physical, chemical, and spectroscopic methods. The compounds 1 and 2 were investigated for scavenging of the diphenylpicrylhydrazyl (DPPH) radical scavenging activity, reducing power, and the phosphomolybdenum activity, and the results demonstrate that the compound (1) has potential as a natural antioxidant whereas the compound (2) exhibited moderate antioxidant activity.     

Inotropic effects of l-lysine in the mammalian heart

We studied the effects of l-lysine in cardiac preparations of mice and men. Of note, l-lysine increased force of contraction in a concentration- and time-dependent manner in isolated electrically paced left atrium of mouse and in human right atrium. It further increased heart rate and left ventricular pressure in the isolated perfused mouse heart. In isolated adult mouse cardiomyocytes, the contractility as assessed by edge detection was increased as well as the Ca²⁺ transients after electrically pacing by field stimulation. However, using the patch clamp technique, no effect of l-lysine on action potential duration from a constant holding potential or on current through l-type calcium channels could be observed. However, l-lysine led to a depolarization of unclamped cells. Furthermore, effects of l-lysine were stereospecific, as they were not elicited by d-lysine. The inotropic effects of l-lysine were not abrogated by additionally applied l-ornithine or l-arginine (known inhibitors of lysine transport). However, l-lysine (5 mM) shifted the concentration–response curve for a positive inotropic effect of 5-hydroxytryptamine (5-HT; serotonin) in atrium of transgenic mice (with cardiac specific overexpression of 5-HT₄ receptors) to higher concentrations. In summary, we describe a novel positive inotropic effect of an essential amino acid, l-lysine, in the mammalian heart. One might speculate that l-lysine treatment under certain conditions could sustain cardiac performance. Moreover, l-lysine is able to block, at least in part, cardiac 5-HT₄ receptors.     

Involvement of nucleus accumbens AMPA receptor trafficking in augmentation of D- amphetamine reward in food-restricted rats

Rationale

Chronic food restriction (FR) increases behavioral responsiveness to drugs of abuse and associated environments. Pre- and postsynaptic neuroadaptations have been identified in the mesoaccumbens dopamine pathway of FR subjects but the mechanistic basis of increased drug reward magnitude remains unclear.

Objectives

Effects of FR on basal and d-amphetamine-induced trafficking of AMPA receptor subunits to the nucleus accumbens (NAc) postsynaptic density (PSD) were examined, and AMPA receptor involvement in augmentation of d-amphetamine reward was tested.

Materials and methods

FR and ad libitum fed (AL) rats were injected with d-amphetamine (2.5 mg/kg, i.p.) or vehicle. Brains were harvested and subcellular fractionation and Western analyses were used to assess AMPA receptor abundance in NAc homogenate and PSD fractions. A follow-up experiment used a curve-shift protocol of intracranial self-stimulation to assess the effect of 1-naphthylacetyl spermine (1-NASPM), a blocker of Ca²⁺-permeable AMPA receptors, on rewarding effects of d-amphetamine microinjected in NAc shell.

Results

FR increased GluA1 in the PSD, and d-amphetamine increased p-Ser845-GluA1, GluA1, GluA2, but not GluA3, with a greater effect in FR than AL rats. d-amphetamine lowered reward thresholds, with greater effects in FR than AL rats, and 1-NASPM selectively reversed the enhancing effect of FR.

Conclusions

Results suggest that FR leads to increased synaptic incorporation of GluA1 homomers to potentiate rewarding effects of appetitive stimuli and, as a maladaptive byproduct, d-amphetamine. The d-amphetamine-induced increase in synaptic p-Ser845-GluA1, GluA1, and GluA2 may contribute to the rewarding effect of d-amphetamine, but may also be a mechanism of synaptic strengthening and behavior modification.     

Population pharmacokinetic modeling and deconvolution of enantioselective absorption of eflornithine in the rat

Enantioselective pharmacokinetics and absorption of eflornithine in the rat was investigated using population pharmacokinetic modeling and a modified deconvolution method. Bidirectional permeability of l- and d-eflornithine was investigated in Caco-2 cells. The rat was administered racemic eflornithine hydrochloride as a single oral dose [40–3,000 mg/kg bodyweight (BW)] or intravenously (IV) (100–2,700 mg/kg BW infused over 60–400 min). Serial arterial blood samples were collected and l- and d-eflornithine were quantitated with a previously published chiral bioanalysis method. The D:L concentration ratio was determined in rat faeces. Intravenous l-and d-eflornithine plasma concentration–time data was analyzed using population pharmacokinetic modeling and described with a 3-compartment pharmacokinetic model with saturable binding to one of the peripheral compartments. Oral plasma concentration–time data was analyzed using a modified deconvolution method accounting for nonlinearities in the eflornithine pharmacokinetics. Clearance was similar for both enantiomers (3.36 and 3.09 mL/min). Oral bioavailability was estimated by deconvolution at 30 and 59 % for l- and d-eflornithine. The D:L concentration ratio in feces was 0.49 and the Caco-2 cell permeability was similar for both enantiomers (6–10 × 10^?8 cm/s) with no evident involvement of active transport or efflux. The results presented here suggest that the difference in the bioavailability between eflornithine enantiomers is caused by a stereoselective difference in extent rather than rate of absorption. The presented modified deconvolution method made it possible to account for the non-linear component in the suggested three-compartment pharmacokinetic model thus rapidly estimating eflornithine oral bioavailability.     

Reduction of the reinforcing effectiveness of cocaine by continuous d-amphetamine treatment in rats: importance of active self-administration during treatment period

Rationale

Continuous administration of d-amphetamine has shown promise as a treatment for psychostimulant addiction. In rodent studies, constant infusion of d-amphetamine (5 mg/kg/day) has been shown to reduce cocaine-reinforced responding in the dose range of 0.19–0.75 mg/kg/inf.

Objectives

The present study tested whether these effects were a reflection of pharmacological interactions between d-amphetamine and cocaine or if they resulted from associative learning mechanisms

Methods

After stable progressive ratio (PR) baselines were established, rats were implanted with subcutaneous osmotic minipumps filled with either d-amphetamine (5 mg/kg/day—groups 1 and 2) or saline (group 3). During the treatment period, groups 1 and 3 self-administered cocaine at a dose that was previously shown to produce the most robust effects in combination with d-amphetamine treatment (0.19 mg/kg/inf), while group 2 received passive cocaine infusions.

Results

In replication of previous studies, d-amphetamine treatment resulted in a significant (35 %) decrease in breakpoints relative to saline controls. By contrast, no reductions in breakpoints were observed in animals that received passive cocaine infusions during the treatment period (group 2).

Conclusions

Active self-administration of cocaine during the treatment period appears to be an important factor in reducing cocaine-reinforced breakpoints. These findings suggest learning mechanisms are involved in the therapeutic effects of continuous d-amphetamine, and pharmacological interaction mechanisms such as cross-tolerance cannot completely account for the observed decreases in cocaine seeking.     

New cycloartane glycosides from the aerial part of Thalictrum fortunei

Four new cycloartane glycosides, 3-O-β-d-xylopyranosyl-(1 → 6)-β-d-glucopyranosyl-(1 → 4)-β-d-fucopyranosyl (22S,24Z)-cycloart-24-en-3β,22,26-triol 26-O-(6-O-acetyl)-β-d-glucopyranoside (1), 3-O-α-l-arabinopyranosyl-(1 → 6)-β-d-glucopyranosyl-(1 → 4)-β-d-fucopyranosyl (22S,24Z)-cycloart-24-en-3β,22,26-triol 26-O-(6-O-acetyl)-β-d-glucopyranoside (2), 3-O-β-d-glucopyranosyl (24S)-cycloartane-3β,16β,24,25,30-pentaol 25-O-β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranoside (3) and 3-O-β-d-glucopyranosyl (24S)-cycloartane-3β,16β,24,25,30-pentaol 25-O-β-d-glucopyranosyl-(1 → 4)-β-d-glucopyranoside (4), were isolated from the aerial parts of Thalictrum fortunei. Their structures were established on the basis of extensive NMR and HR-ESI-MS analyses, along with acid hydrolysis.     

Antihepatotoxic, nephroprotective, and antioxidant activities of phenolic compounds from Satureja macrostema leaves against carbon tetrachloride-induced hepatic damage in mice

Satureja macrostema (SM) is used with culinary and medicinal purposes. Methanol extract from SM was investigated for its phenolic content, antioxidant, hepatoprotective, and kidney protective activities. Liver and kidney damage were induced in rats with CCl₄. Hepatoprotective efficacy was measured by the activity of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, cholesterol, high density lipoprotein and total protein, and lipid peroxidation. Kidney function was evaluated by measuring plasma urea and creatinine. Antioxidant activity was evaluated by measuring blood glutathione content, superoxide dismutase and catalase activities, and malondialdehyde equivalent; their activity was comparable to that of silymarin, a well-known hepatoprotective agent. Methanol extracts of S. macrostema showed potent antioxidant, kidney protective, and hepatoprotective activities; in-depth chromatographic investigation resulted in the identification of six new flavonoid glycosides: 5-hydroxy-3,6,4′-trimethoxyflavonol-7-C-α-l-rhamnopyranosyl-(1 → 3)-β-d-glucopyranoside (2), 4′-methoxy-5,7,3′,5′-tetra-hydroxyflavanone-3-O-β-d-rhamnopyranosyl-(1 → 2)-β-d-rhamnopyranoside (3), 5,4′-dimethoxy-7,3′,5′-trihydroxyflavanone-3-O-β-d-rhamnopyranoside (4), 5,3′,4′,5′-tetrahydroxyflavanone-7-O-β-d-rhamnopyranoside (5), 5,3′,4′,5′-tetramethoxyflavanone-7-O-β-d-rhamnopyranoside (6), and 5,4′-dimethoxy-3′-hydroxyflavone-7-β-d-rhamnopyranoside (8) along with three known compounds: 5-hydroxy-7,4′-dimethoxyflavone (1), prunin (7), and diosmin (9) that were isolated. Structural elucidation of the new compounds was established based on the spectral data. The present study revealed that S. macrostema leaves have a significant radical scavenging and hepatoprotective activity.     

Phytochemical study onRandia siamensis

From the roots ofRandia siamensis,d-mannitol, a mixture of β-sitosterol and campesterol, oleanolic acid acetate, oleanolic acid-3-α-l-arabinoside and mesembryanthemoidigenic acid as a sapogenin were isolated and characterized.     

The synthesis of pennogenin 3-O-β-d-glucopyranosyl-(1 → 3)-[α-l-rhamnopyranosyl-(1 → 2)]-β-d-glucopyranoside

Pennogenin 3-O-β-d-glucopyranosyl-(1 → 3)-[α-l-rhamnopyranosyl-(1 → 2)]-β-d-glucopyranoside, a monodesmosidic saponin isolated from Paris polyphylla Smith var. yunnanensis with promised antitumor activities, was firstly synthesized from glucoside thiol via nine steps and with 27% overall yield.     

The effects of BMY-14802 against l-DOPA- and dopamine agonist-induced dyskinesia in the hemiparkinsonian rat

Rationale

l-DOPA continues to be the primary treatment for patients with Parkinson’s disease; however, the benefits of long-term treatment are often accompanied by debilitating side effects known as dyskinesias. In recent years, several 5-HT_1A receptor agonists have been found to reduce dyskinesia in clinical and experimental models of PD. The purported sigma-1 antagonist, BMY-14802 has been previously demonstrated to reduce l-DOPA induced dyskinesia in a 5-HT_1A receptor dependent manner.

Objective

In the present study, we extend these findings by examining the anti-dyskinetic potential of BMY-14802 against l-DOPA, the D₁ receptor agonist SKF81297 and the D₂ receptor agonist, quinpirole, in the hemi-parkinsonian rat model. In addition, the receptor specificity of BMY-14802’s effects was evaluated using WAY-100635, a 5-HT_1A receptor antagonist.

Results

Results confirmed the dose-dependent (20?>?10?>?5 mg/kg) anti-dyskinetic effects of BMY-14802 against l-DOPA with preservation of anti-parkinsonian efficacy at 10 mg/kg. BMY-14802 at 10 and 20 mg/kg also reduced dyskinesia induced by both D₁ and D₂ receptor agonists. Additionally, BMY-14802’s anti-dyskinetic effects against l-DOPA, but not SKF81297 or quinpirole, were reversed by WAY-100635 (0.5 mg/kg).

Conclusion

Collectively, these findings demonstrate that BMY-14802 provides anti-dyskinetic relief against l-DOPA and direct DA agonist in a preclinical model of PD, acting via multiple receptor systems and supports the utility of such compounds for the improved treatment of PD.     

Interactive effects of methylphenidate and alcohol on discrimination, conditioned place preference and motor coordination in C57BL/6J mice

Introduction

Prior research indicates methylphenidate (MPH) and alcohol (ethanol, EtOH) interact to significantly affect responses humans and mice. The present studies tested the hypothesis that MPH and EtOH interact to potentiate ethanol-related behaviors in mice.

Methods

We used several behavioral tasks including: drug discrimination in MPH-trained and EtOH-trained mice, conditioned place preference (CPP), rota-rod and the parallel rod apparatus. We also used gas chromatographic methods to measure brain tissue levels of EtOH and the d- and l-isomers of MPH and the metabolite, ethylphenidate (EPH).

Results

In discrimination, EtOH (1 g/kg) produced a significant leftward shift in the MPH generalization curve (1–2 mg/kg) for MPH-trained mice, but no effects of MPH (0.625–1.25 mg/kg) on EtOH discrimination in EtOH-trained mice (0–2.5 g/kg) were observed. In CPP, the MPH (1.25 mg/kg) and EtOH (1.75 g/kg) combination significantly increased time on the drug paired side compared to vehicle (30.7 %), but this was similar to MPH (28.8 %) and EtOH (33.6 %). Footslip errors measured in a parallel rod apparatus indicated that the drug combination was very ataxic, with footslips increasing 29.5 % compared to EtOH. Finally, brain EtOH concentrations were not altered by 1.75 g/kg EtOH combined with 1.25 mg/kg MPH. However, EtOH significantly increased d-MPH and l-EPH without changing l-MPH brain concentrations.

Conclusions

The enhanced behavioral effects when EtOH is combined with MPH are likely due to the selective increase in brain d-MPH concentrations. These studies are consistent with observations in humans of increased interoceptive awareness of the drug combination and provide new clinical perspectives regarding enhanced ataxic effects of this drug combination.     

Alkaloids from Clematis manshurica Rupr.

Three new alkaloids together with two known compounds have been isolated from the roots of Clematis manshurica. On the basis of their spectroscopic and chemical evidence, the new compounds were elucidated as methyl 7-ethoxy-3-indolecarbonate (2), methyl 7-O-α-l-rhamnopyranosyl-(1 → 6)-β-d-glucopyranosyl 3-indolecarbonate (3) and α-l-rhamnopyranosyl-(1 → 6)-β-d-glucopyranosyl 3-indolecarbonate (4).     

Selective potentiations in opioid analgesia following scopolamine pretreatment

The effects of the muscarinic receptor antagonist scopolamine upon analgesia induced by d-ala-d-leu-enkephalin (DADL), beta-endorphin (BEND) and morphine were examined. While scopolamine (10 mg/kg, IP) significantly potentiated the analgesic responses following DADL (40 g, ICV) and morphine (5 mg/kg, SC) on the jump test, it failed to alter significantly BEND (1 g, ICV) analgesia.     

Novel quercetin glucosides from Helminthostachys zeylanica root and acceleratory activity of melanin biosynthesis

Two novel quercetin glucosides, namely 4′-O-β-d-glucopyranosyl-quercetin-3-O-β-d-glucopyranosyl-(1→4)-β-d-glucopyranoside (compound 1) and 4′-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranosyl-quercetin-3-O-β-d-glucopyranosyl-(1→4)-β-d-glucopyranoside (compound 2), were isolated from Helminthostachys zeylanica root 50 % EtOH extract. Structural analysis of isolated compounds was achieved mainly by 600 MHz and 800 MHz NMR, UPLC–TOFMS and GC–MS. Of the two quercetin glucosides, compound 1 showed a high melanogenic acceleratory effect, 2.7 times higher than control, at 10 μM concentration in murine B16 melanoma cells, with no cytotoxic effect.     

Phenylethanoid and flavone glycosides from Ruellia tuberosa L.

A new phenylethanoid glycoside, isocassifolioside (8), and two new flavone glycosides, hispidulin 7-O-α-l-rhamnopyranosyl-(1′″ → 2″)-O-β-d-glucuronopyranoside (11) and pectolinaringenin 7-O-α-l-rhamnopyranosyl-(1′″ → 2″)-O-β-d-glucuronopyranoside (12) were isolated from the aerial portions of Ruellia tuberosa L., together with verbascoside (1), isoverbascoside (2), nuomioside (3), isonuomioside (4), forsythoside B (5), paucifloside (6), cassifolioside (7), hispidulin 7-O-β-d-glucuronopyranoside (9) and comanthoside B (10). The structure elucidations were based on analyses of chemical and spectroscopic data including 1D- and 2D-NMR. The isolated compounds 1–12 exhibited radical scavenging activity using ORAC assay.     

(−)-Catechin glycosides from Ulmus davidiana

Extensive chromatographic separation of the n-BuOH soluble fraction obtained from the stem and root barks of U. davidiana resulted in five hitherto unknown compounds together with a known one (?)-catechin 1. Structures of the five compounds were elucidated by chemical and spectroscopic analyses, to be (?)-catechin-7-O-gallate-5-O-(5″″-trans-caffeoyl)-β-d-apiofuranoside-3-O-β-d-apiofuranosyl-(1 → 2)-β-d-glucopyranoside 2, (?)-catechin-7-O-gallate-5-O-(5″″-trans-caffeoyl)-β-d-apiofuranoside-3-O-β-d-glucopyranoside 3, (?)-catechin-7-O-gallate-5-O-β-d-apiofuranoside-3-O-(2″-O-galloyl)-β-d-glucopyranoside 4, (?)-catechin-7-O-gallate-5-O-(5″″-trans-caffeoyl)-β-d-apiofuranoside 5, and (?)-catechin-7-O-gallate-5-O-(5″″-trans-feruloyl)-β-d-apiofuranoside 6.