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Effect of Polygala tenuifolia root on behavioral disorders by lesioning nucleus basalis magnocellularis in rat.

UNLABELLED: We investigated whether an aqueous extract of Polygala tenuifolia Willd (PTW) could improve the rats' memory and behavioral disorders produced by lesioning nucleus basalis magnocellularis (NBM) in rats. The animals were divided into four groups for surgery, and following that they were orally administered PTW extract for 7 and 21 days. Each group consisted of eight male Sprague-Dawley rats and were treated as follows: CONTROL: no surgery (n = 8), PBS: 1M (mol/L) phosphate buffered saline (n = 8), IBO: 0.12 M (n = 8), QUIS: 0.12 M (n = 8). Two 0.5 microL injections were made in the vicinity of the bilateral side of the nucleus basalis magnocellularis (NBM). All rats were tested in the neurological tests and the step-through passive avoidance memory test during pre-surgery, surgery and post-surgery drug treatment. The results suggest that PTW extract has some repairing effects on the memory and behavioral disorders produced by lesioning of the NBM in rats.

Animals↗

Antagonistic effects of methanolic extract of Polygala telephioides on morphine responses in mice.

The present study was undertaken to investigate the antagonistic effects of the methanolic extract of Polygala telephioides (PT) on morphine responses in mice. Single administration of PT tended to antagonize the morphine-induced analgesia in a hot-plate test. Moreover, PT (300 mg/kg, p.o.) improved the morphine-induced memory impairment in an elevated plus maze test. However, PT alone had no effect on behaviors in the open-field, hot-plate and elevated plus maze tests. We investigated the effects of PT on naloxone-induced jumping (as withdrawal sign) in morphine-dependent mice. To induce dependence, mice were twice daily treated with morphine (10-45 mg/kg, s.c.) for 5 days. Co-administrations of PT (10, 100 and 300 mg/kg, p.o.) during repeated morphine treatments significantly suppressed the naloxone (10 mg/kg, i.p.)-induced jumping. However, the naloxone-induced jumping was not affected by a single large administration of PT on the 5th day. The inhibitory effect of PT on the naloxone-induced jumping was due to the development of dependence rather than expression of withdrawal sign. Moreover, single administration of PT (30 mg/kg, p.o.) decreased the morphine levels in plasma. These results indicate that PT may be useful in facilitating narcotic detoxification.

Animals↗

Quality evaluation of Polygala japonica through simultaneous determination of six bioactive triterpenoid saponins by HPLC-ELSD.

Polygala japonica Houtt (Polygalaceae), a traditional Chinese herb, has been used as expectorant, anti-inflammatory, antibacterial and antidepressant agent. To evaluate the quality of P. japonica, a high performance liquid chromatography (HPLC) with evaporative light scattering detector (ELSD) method was developed for the simultaneous determination of six active triterpenoid saponins. With a Discovery C(18) analytical column, the analytes were separated efficiently using acetonitrile-methanol-0.05% trifluoroacetic acid (TFA) as mobile phase in a gradient program. The evaporator tube temperature of ELSD was set at 105 degrees C, and with the nebulizing gas flow-rate of 2.6l/min. All calibration curves showed good linear regression (gamma>0.9991) within the tested range. Additionally, reproducibility for the quantification of six saponins in P. japonica with intra- and inter-day variations of less than 5.0% was observed. Quantification of the six active saponins in P. japonica from different locations was performed by this newly developed method, which provides a new tool for the assessment of quality of P. japonica.

Chromatography, High Pressure Liquid↗

Attenuation of cocaine-induced conditioned place preference by Polygala tenuifolia root extract.

A recent investigation indicated that Polygala tenuifolia Willdenow extract (PTE) possesses a potential antipsychotic effect. In this study, we examined the effects of PTE on the cocaine-induced changes in locomotor activity, conditioned place preference (CPP), fos-related antigen-immunoreactivity (FRA-IR), and activator protein (AP)-1 DNA binding activity. Cocaine-induced behavioral effects (hyperlocomotion and CPP) occurred in parallel with increases in FRA-IR and AP-1 DNA binding activity in the nucleus accumbens. These responses induced by cocaine were consistently attenuated by concurrent treatment with PTE (25 mg or 50 mg/kg/day, i.p. x 7). The adenosine A2A receptor antagonist, 1,3,7-trimethyl-8-(3-chlorostyrl)xanthine (0.5 or 1.0 mg/kg, i.p.), reversed the PTE-mediated pharmacological action in a dose related manner; neither the adenosine A(1) receptor antagonist, 8-cyclopentyl-1,3-dimethylxanthine (0.5 or 1.0 mg/kg, i.p.) nor the A2B receptor antagonist, alloxazine (1.5 or 3.0 mg/kg, i.p.) significantly affected this pharmacological action. Our results suggest that PTE prevents cocaine-induced behavioral effects, at least in part, via the activation of the adenosine A2A receptor.

Analysis of Variance↗

New phenolics from Polygala fallax.

Two new phenolic compounds, polygalolide A (1) and polygalolide B (2), together with three known xanthones were isolated from the roots and stems of Polygala fallax. The structures of 1 and 2 were elucidated on the basis of spectroscopic evidence.

Drugs, Chinese Herbal↗

Xanthone glycosides from Polygala tenuifolia and their conformational analyses.

Seven xanthone glycosides were isolated from the cortexes of Polygala tenuifolia, and their structures were identified as polygalaxanthones VIII-XI (1-4), sibiricoxanthone B (5), 7-O-methylmangiferin (6), and lancerin (7), on the basis of spectroscopic analyses. Compounds 1-4 are new xanthone glycosides, and compounds 4 and 5 exist as rotamers. To explain this phenomenon, conformational analyses were performed on compounds 4 and 5 and other compounds with similar skeletons that were isolated from P. tenuifolia.

Glycosides↗

Saponins from Polygala japonica and their effects on a forced swimming test in mice.

Five new triterpenoid saponins, polygalasaponins E (1), F (2), G (3), H (4), and J (5), along with eight known ones (6-13), were isolated from the aerial parts of Polygala japonica. Their structures were established by chemical and spectroscopic means. Forced swimming tests on mice showed that saponins 1 and 4 significantly reduce the immobility status by 58.1% and 51.3% at a dosage of 100 mg/kg administrated orally once daily for 5 days, respectively.

Animals↗

Antidepressant principles of the roots of Polygala tenuifolia.

[(125)I]RTI-55-membrane binding assay-guided fractionation and separation of a water-soluble extract of the roots of Polygala tenuifolia gave five new oligosaccharide derivatives, polygalatenosides A-E (1-5). The structures of these new oligosaccharides were established on the basis of spectroscopic evidence. Polygalatenosides A and B (1 and 2) showed significant inhibitory activity, with IC(50) values of 30.0 and 6.04 microM, respectively, in this membrane binding assay and acted as norepinephrine reuptake inhibitors through blocking norepinephrine transport.

Antidepressive Agents↗

Xanthones from the roots of Polygala caudata and their antioxidation and vasodilatation activities in vitro.

Three new xanthones, 2-hydroxy-1,6,7-trimethoxyxanthone (1), 1,4-dimethoxy-2,3-methylenedioxyxanthone (2), and 7-hydroxy-1,2-dimethoxyxanthone (3), together with five known compounds, 2,7-dihydroxy-1-methoxyxanthone (4), 1-methoxy-2,3-methylenedioxyxanthone (5), 7-hydroxy-1-methoxyxanthone (6), euxanthone (1,7-dihydroxyxanthone) (7), and gentitein (1,3,7-trihydroxyxanthone) (8), were isolated from the roots of Polygala caudata. Their structures were established on the basis of spectral evidence. In the antioxidation activity screening in vitro with luminol chemiluminescence methods, compounds 1 - 5 and 7 and 8 showed H2O2 scavenger activity, with a scavenging effect of 58.4 - 94.5% at 10 microg/mL, and 26.0 - 84.7% at 2 microg/mL. Compounds 4 and 8 also exhibited scavenging effects on the reactive oxygen free radicals produced by macrophage respiratory bursts, with a scavenging effect of 71.7% and 63.4% at 10 microg/mL, 41.2% and 47.8% at 2 microg/mL, respectively. In the vasodilatation assay, compounds 4 - 7 exhibited relaxing activity on the contractions evoked by KCl in Wistar rat thoracic aorta rings in a dose-dependent manner.

Animals↗

Induction of NGF synthesis in astrocytes by onjisaponins of Polygala tenuifolia, constituents of kampo (Japanese herbal) medicine, Ninjin-yoei-to.

The effect of a kampo medicine, Ninjin-yoei-to (NYT; Ren-shen-yang-rong-tang in Chinese) on nerve growth factor (NGF) secretion from the cultured rat astrocytes was examined in vitro. When rat embryo astrocytes were cultured in the presence of NYT for 24 h, the amount of NGF in the medium was significantly increased in a dose dependent manner. Among 14 kinds of component herbs in NYT, the roots of Polygala tenuifolia and roots of Panax ginseng extracts increased NGF levels from the astrocytes. Saponin fraction from the roots of P. tenuifolia enhanced the production of NGF, however phenolic glycoside fraction showed no effect. Onjisaponins A, B, E, F and G as major saponins of the root of P. tenuifolia strongly increased the NGF level, whereas ginsenosides Rb1 and Rg1 did not affect the NGF level. Onjisaponin F also induced ChAT mRNA level in rat basal forebrain cells. These results indicate the possibility that NYT and/or onjisaponins in P. tenuifolia may have potential therapeutic effects for the treatment of Alzheimer disease patients.

Animals↗

New flavonol glycosides and new xanthone from Polygala japonica.

Three new flavonol glycosides and a new xanthone were isolated from Polygala japonica HOUTT. with eight known compounds. Their structures were identified as 1,7-dihydroxy-3,4-dimethoxy-xanthone (1), kaempferol-7,4'-dimethyl ether (2), physcion (3), guazijinxanthone (4), rhamnetin (5), polygalin A (6), 3,5,7-trihydroxy-4'-methoxy-flavone-3-O-beta-d-galactopyranoside (7), 3,5,3'-trihydoxy-7,4'-dimethoxy-flavone-3-O-beta-d-galactopyranoside (8), 3,5,3',4'-tetrahydroxy-7-methoxy-flavone-3-O-beta-d-galactopyranoside (9), 3,5,3',4'-tetrahydroxy-7-methoxy-flavone-3-O-beta-d-glucopyranoside (10), polygalin B (11), polygalin C (12). Among them, compound 4 is a new xanthone, and 6, 11 and 12 are new flavonol glycosides. Compounds 1, 4, 7 and 8 were tested for cytotoxic activity with MTT assays on five human tumor cell lines, K562, A549, PC-3M, HCT-8 and SHG-44. Compound 4 showed cytotoxic activity against all the five cell lines.

Antineoplastic Agents, Phytogenic↗

New acylated triterpene saponins from Polygala tenuifolia willd.

Two new acylated presenegenin glycosides E-onjisaponin H (5) and Z-onjisaponin (6) together with seven known saponins were isolated from the roots of Polygala tenuifolia Willd. Compounds 5 and 6 were obtained as a pair of isomers due to trans and cis-p-methoxycinnamoyl. Their structures were elucidated mainly by 2D-NMR techniques including 1H-1HCOSY, TOCSY, HSQC, HMBC as 3-O-(beta-D-glucopyranosyl) presenegenin 28-[O-beta-D-apiofuranosyl-(1 --> 3)-O-[beta-D-xylopyranosyl-(1 --> 4)]-O-alpha-L-rhamnopyranosyl-(1 --> 2)-O-[alpha-L-rhamnopyranosyl-(1 --> 3)]-4-O-[(E)-p-methoxycinnamoyl]-beta-D-fucopyranosyl] ester (5) and its (Z)-isomer (6).

Acylation↗

Three new xanthones from the roots of Polygala japonica Houtt.

Three new xanthones, 3, 6-dihydroxy-1, 2, 7-trimethoxyxanthone (2), 3, 7-dihydroxy- 1, 2-dimethoxyxanthone (4) and 1, 2, 7-trihydroxy-3-methoxyxanthone (9), together with seven known compounds were isolated from the roots of Polygala japonica Houtt. Their structures were determined on the basis of spectroscopic data.

Magnetic Resonance Spectroscopy↗

Pharmacological properties of N-095, a drug containing red ginseng, polygala root, saffron, antelope horn and aloe wood.

This study sought to establish a pharmacological profile for N-095, a crude drug containing red ginseng, polygala root, saffron, antelope horn and aloe wood. Our studies on rats and mice revealed a number of pharmacological properties of this novel drug. N-095 increased the forced swimming time in mice and prevented gastric ulcers in rats under restraint and water immersion stress conditions at 100 mg/kg or higher. It also prevented footpad swelling in rats treated with lambda-carrageenin and histamine-induced gastric ulcers in rats at 300 mg/kg or higher. Furthermore, N-095 augmented the sedative effect in mice induced by hexobarbital, which is characterized by a decreased spontaneous motor activity and a prolongation of sleeping time. N-095 also stimulated spontaneous contractility of the uterus in rats at 1000 mg/kg and 2000 mg/kg and prevented hemolysis of erythrocytes by heating. In contrast, N-095 had no effect on the respiratory or cardiovascular system or on water and electrolyte regulation in rats or mice. These results show that N-095 is a relatively safe drug for use as a nutrient or tonic.

Animals↗

Effect of Polygala tenuifolia root extract on cerebral ischemia and reperfusion.

In this study, the effects of Polygala tenuifolia root extract on brain ischemia/reperfusion injury in Mongolian gerbils were investigated. The gerbils were administered ethanol extract of P. tenuifolia and its four sub-fractions orally 2 hours prior to ischemia, and were subjected to a 20-minute no-flow cerebral ischemia in vivo. Thirty minutes and 72 hours after reperfusion, the brain was removed and the ATP, lactate and lipid peroxide levels were determined, and the neurons in the hippocampal CA1 subfield were examined. In the vehicle-treated ischemic gerbils, the brain ATP levels decreased significantly, but this decrease was prevented by pre-treatment with an n-butanol fraction of P. tenuifolia. In contrast, both the lactate content and lipid peroxidation levels were elevated in the vehicle-treated ischemic animals, but this elevation was inhibited by ethanol extract and n-butanol fraction of P. tenuifolia, respectively. Both the ethanol extract and n-butanol fraction of P. tenuifolia attenuated post-ischemic neuronal necrosis in the hippocampal CA1 subfield. Our findings suggest that both ethanol extract and n-butanol fraction of P. tenuifolia root can reduce brain damage during ischemia and reperfusion, and prevent lipid peroxidation and preserve the energy metabolism.

Adenosine Triphosphate↗