Root Of Polygala Tenuifolia Willd Research Articles

A review of the botany, metabolites, pharmacology, toxicity, industrial applications, and processing of Polygalae Radix: the "key medicine for nourishing life".

Polygalae radix (PR) is the dried root of Polygala tenuifolia Willd. and Polygala sibirica L. and enjoys the reputation as the "key medicine for nourishing life." In this study, information about "Polygala tenuifolia Willd.," "Polygala sibirica L.," and "Yuanzhi" was retrieved from scientific databases, including Google Scholar, Baidu Scholar, Web of Science, PubMed, CNKI, and Wan Fang Data. Information from Chinese herbal medicine classics, Yaozhi Data, and the Gaide Chemical Network was also collected. Information related to botany, phytochemistry, pharmacology, toxicity, industrial applications, and processing is summarized in this paper to tap its potentialities and promote its further development and clinical application. More than 320 metabolites have been isolated from PR; saponins, xanthones, and oligosaccharide esters are the main functional metabolites. Pharmacological research shows that its pharmacological action mainly focuses on resisting nervous system diseases, and it also has the functions of anti-oxidation, anti-inflammation, anti-tumor, anti-pathogenic microorganisms and others. The gastrointestinal irritation of its saponins impeded its application, but this irritation can be reduced by controlling the dosage, compatibility with other herbs, or processing. The future progress of PR faces opportunities and challenges. More attention should be paid to the traditional application and processing methods of PR recorded in ancient books. The lack of safety and clinical studies has limited its application and transformation of achievements. Moreover, it is one-sided to take the content of only a few metabolites as the index of processing optimization and quality control, which cannot reflect the full pharmacological and toxicological activities of PR.

Combination of tenuigenin-based Polygala tenuifolia willd. root extract and forsythoside a improved Alzheimer’s disease

Tenuigenin is a kind of the main active ingredients in roots of Polygala tenuifolia Willd. (a species in the genus Polygala, family Polygalaceae) and forsythoside A (FA) is one of the main active ingredients of Forsythia suspensa (Thunb.) Vahl. (a species in the genus Forsythia, family Meliaceae). The studies have shown that tenuigenin-based Polygala tenuifolia Willd. extract (YZ) and FA have protective effects on nervous damage. In the study the combination (YF) of YZ and FA showed synergistic neuro-protective effects on PC12 cell model of Alzheimer’s disease (AD). YF (2:1) which was made up of 2/3 YZ and 1/3 FA increased cell viability, inhibited AChE expression and activity, alleviated apoptosis and slowed Aβ aggregation, while YF (1:2) which consisted of 1/3 YZ and 2/3 FA depressed inflammation and oxidative stress. There was no obvious synergistic effect of YF on Tau phosphorylation.

Polygalae Radix: review of metabolites, pharmacological activities and toxicology.

Polygalae Radix: is the dried root of Polygala tenuifolia Willd. or Polygala sibirica L., which has the effect of improving memory and cognitive function in traditional Chinese medicine. Modern pharmacological studies indicated that Polygalae Radix has rich pharmacological activities in vitro and in vivo, including protective effects on the nervous system, immune system, cardiovascular system and respiratory system, as well as antioxidant and antiepileptic pharmacological activities. Up to now, more than 160 metabolites from Polygalae Radix were identified, including triterpenoid saponins, xanthones, oligosaccharide esters and et al. The clinical practice of traditional Chinese medicine has proved that Polygalae Radix has a certain irritation to the throat, and a large or long-term use will stimulate the digestive tract, and the main toxic metabolite is saponins. Therefore, Polygalae Radix should be pr ocessed or used in combination with other Chinese herbal medicines to reduce the irritation to the throat and reduce gastrointestinal irritation. This article provides a review of the metabolites, pharmacological activity, and toxicology of Polygalae Radix. It also discusses the future research prospects and existing problems of Polygalae Radix, providing reference for further research on Polygalae Radix.

Chemical Constituents of the Roots of Polygala tenuifolia and Their Anti-Inflammatory Effects

Increasing scientific evidence has demonstrated that the roots of Polygala tenuifolia Willd. have pharmacological effects related to anti-inflammation. Therefore, the aim of this study is to investigate the chemical constituents from P. tenuifolia roots as anti-inflammatory drug candidates. In the present work, twenty-three compounds were isolated from P. tenuifolia roots, including three saponins (1-3), ten phenylpropanoid sucrose esters (4-12), one benzoic acid sugar ester derivative (13), four xanthones (14-17), two hydroxy benzophenone derivatives (18 and 19), two phenolic derivatives (20 and 21), and two ionones (22 and 23). All isolates were tested for their inhibitory effects of LPS-stimulated NO and PGE2 production in RAW 264.7 macrophages. Among these, 3-O-(3,4,5-trimethoxy-cinnamoyl),6'-O-(p-methoxybenzoyl) sucrose ester (TCMB; 11) together with compounds 3 and 21 exhibited significant inhibitory effects on NO production, while TCMB and compounds 17, 19, and 21 showed strong inhibitory effects on PGE2 production. Specifically, TCMB (11) downregulated the protein levels of iNOS and COX-2 in LPS-induced RAW 264.7 macrophages. In addition, TCMB (11) dose-dependently diminished the relative mRNA expression levels of iNOS, PGE2, and proinflammatory cytokines (TNF-α, IL-1β, and IL-6). A molecular docking study showed that TCMB (11) has strong binding affinities with iNOS and COX-2.

Sugar easters and xanthones from the roots of Polygala tenuifolia Willd. and their cytoprotective activity

Six new sugar esters (1–6), named tenuifolisides F-G (1–2) and tenuifolioses W-Z (3–6), together with 16 known compounds (7–22) were isolated from the roots of Polygala tenuifolia. The chemical structures of the new compounds were elucidated by 1D, 2D NMR and HRESIMS techniques together with chemical methods. All the compounds were evaluated for the cytoprotective activity against hydrogen peroxide (H2O2)-induced oxidative stress in human keratinocyte HaCaT cells. Compounds 4, 5, 13, 20 and 22 showed strong cytoprotective effect.

Neuroprotective Effects and Mechanisms of Senegenin, an Effective Compound Originated From the Roots of Polygala Tenuifolia.

Senegenin is the main bioactive ingredient isolated from the dried roots of Polygala tenuifolia Willd. In recent years, senegenin has been proved to possess a variety of pharmacological activities, such as anti-oxidation, anti-inflammation, anti-apoptosis, enhancement of cognitive function. Besides, it has a good development prospect for the treatment of neurodegenerative diseases, depression, osteoporosis, cognitive dysfunction, ischemia-reperfusion injury and other diseases. However, there is no systematic literature that fully demonstrates the pharmacological effects of senegenin. In order to meet the needs of new drug research and precise medication, this review summarized the neuroprotective effects, mechanisms and gastrointestinal toxicity of senegenin based on the literatures published from the past 2 decades. In addition, an in-depth analysis of the existing problems in the current research as well as the future research directions have been conducted in order to provide a basis for the clinical application of this important plant extract.

Comparative Study on the Chemical Components and Gastrointestinal Function on Rats of the Raw Product and Licorice-Simmered Product of Polygala tenuifolia

The root of Polygala tenuifolia Willd. (Polygalaceae) (PT) has been listed as a nootropic, anti-inflammatory, and antipsychotic medicine that can cure insomnia. Raw PT (RPT) is toxic and must be processed before clinical use. Licorice-simmered PT (LPT) is one of the most common processed products. We conducted this study in order to investigate the differences in chemical components and gastrointestinal function between RPT and LPT. We used principal component analysis (PCA) and quantitative analysis to study the differences in the chemical components. Animal experiments were conducted to evaluate the effects of PT on the gastrointestinal function of rats before and after simmering. Pathological sections of gastrointestinal tissues, serum hormone levels, and inflammatory cytokines were observed. The PCA results demonstrated that obvious separation was achieved between the RPT and LPT samples. Tenuifoliside B (TFSB), 3,6'-disinapoyl sucrose (DSS), tenuifoliose A (TFOA), tenuifoliose H (TFOH), onjisaponin B (OJB), onjisaponin Z (OJZ), and total saponins levels were decreased after licorice processing, while glomeratose A (GA) and 3,4,5-trimethoxycinnamic acid (TMCA) levels were markedly increased. Compared to the control group, the RPT groups exhibited dramatically lower levels of gastrin (GAS), motilin (MTL), and substance P (SP) and markedly higher levels of vasoactive intestinal peptide (VIP) and somatostatin (SS), but the LPT groups exhibited no significant differences in the above indexes. The levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) in gastrointestinal tissue were markedly increased in the low RPT (L-RPT), high RPT (H-RPT), and H-LPT groups, showing a certain inflammatory effect, but the inflammatory effect in the L-LPT group was relatively weak. Licorice simmering can effectively reduce the inhibitory effect of RPT on gastrointestinal function in rats and reduce damage to gastrointestinal tissue. This study provides a scientific basis for research on the processing mechanism and clinical application of PT.

Protective effects of tenuifolin isolated from Polygala tenuifolia Willd roots on neuronal apoptosis and learning and memory deficits in mice with Alzheimer's disease.

The roots of Polygala tenuifolia Willd have a long history of being used as a traditional Chinese medicine for the treatment of insomnia, forgetfulness, sorrow and depression. Tenuifolin (TEN) has been isolated from Polygala tenuifolia Willd roots, and this study was carried out to investigate the potential beneficial effects of TEN on neuronal apoptosis and memory deficits in a mouse model of Alzheimer's disease (AD). TEN treatment reversed spatial learning and memory deficits, as well as neuronal apoptosis in hippocampal areas, in APP/PS1 transgenic AD mice. TEN treatment protected against Aβ25-35-induced apoptosis, loss of mitochondria-membrane potential, and activation of caspases-3 and -9 in SH-SY5Y cells. TEN has potential benefit in treating learning and memory deficits in APP/PS1 transgenic AD mice, and its effects may be associated with reversing AD pathology-induced neuronal apoptosis. These insights pave the way for further analysis of the potential of TEN as an AD therapeutic agent.

Polygalacic acid inhibits MMPs expression and osteoarthritis via Wnt/β-catenin and MAPK signal pathways suppression

Osteoarthritis (OA) is a chronic degenerative joint disease that has been shown to be closely related to the over expression of matrix metalloproteinases (MMPs). Polygalacic acid is a triterpene isolated from the root of Polygala tenuifolia Willd. In the present study, the anti-inflammatory effect of polygalacic acid in OA was investigated as well as its in vitro and in vivo mechanism. In vitro, rat chondrocytes were induced with interleukin-1beta (IL-1β) and treated with different concentrations of polygalacic acid; real-time PCR and Western blotting were performed to evaluate the expressions of MMP-3, MMP-9, MMP-13, and COX-2. In addition, the MAPK and Wnt/β-catenin signaling pathways were analyzed via Western blotting and immunofluorescence staining. In vivo, a rat OA model was treated with polygalacic acid. Gross morphological and histological assessments were performed to evaluate the resulting cartilage damage. Polygalacic acid significantly reduced the expression of MMPs and COX-2, which could be induced by IL-1β in rat chondrocytes. Furthermore, polygalacic acid treatment prevented the degeneration of cartilage in the rat OA model. To investigate the underlying mechanism, we found that polygalacic acid suppressed both the IL-1β-induced activation of Wnt/β-catenin and the mitogen-activated protein kinase (MAPK) signal pathway in chondrocytes. These results suggest that polygalacic acid may have a therapeutic effect in OA treatment.

Illumination on "Reserving Phloem and Discarding Xylem" and Quality Evaluation of Radix polygalae by Determining Oligosaccharide Esters, Saponins, and Xanthones.

The root of Polygala tenuifolia Willd. or Polygala sibirica L. exhibits protective effects on the central nervous system and is frequently used to treat insomnia, amnesia, and other cognitive dysfunction. In our study, we studied nine bioactive compounds spanning oligosaccharide esters, saponins, and xanthones by using a sensitive, efficient, and validated method established on ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry. The quantified result of interesting compounds proved that accumulation of those compounds were found in phloem rather than in xylem. By taking the standardized result of nine compound contents into account, the “Spider-web” analytical result of xylem and phloem from Radix polygalae (RP) unveiled the rationality of RP’s classical use in clinic including discarding the xylem and reserving the phloem. Moreover, the remarkable variation was also revealed from the quantitative result of 45 samples with different diameters from the different origins, which did not significantly correlate with the variation of RP’s diameter. Our study could shed the light on the quality assessment of RP for further research and illustrate the scientific connotation of the processing method of “discarding the xylem and reserving the phloem”.

Soluble epoxide hydrolase inhibitory activity of phenolic glycosides from Polygala tenuifolia and in silico approach

The goal of this study was to identify soluble epoxide hydrolase (sEH) inhibitors from plants. Our efforts led to the isolation of nine phenolic glycosides 1–9 from the roots of Polygala tenuifolia Willd. The structures of compounds were determined by spectroscopic methods, including mass spectroscopy and one-dimensional and two-dimensional nuclear magnetic resonance, and compared with published data. All the isolated compounds were evaluated for their inhibitory activity against sEH. The IC50 values for inhibition ranged 6.4 ± 0.4 to 27.2 ± 0.3 µM. Inhibitors 2–9 were confirmed the interaction with receptor as competitive type. Molecular docking demonstrated that inhibitors 2–9 could bind sufficiently to the right pocket. Additionally, potential inhibitors (5, 6, and 8) were confirmed to show the flexible movement with the protein in these sites of receptor.

Synergistic Neuroprotective Effects of Two Herbal Ingredients via CREB-Dependent Pathway.

As two natural oligosaccharide esters, 3,6’-Disinapoyl sucrose (DISS) and tenuifolisideA (TFSA) are originating from the root of Polygala tenuifolia Willd, a traditional Chinese medicine used in treatment of mental disorders. Previous reports have shown that both of them possess in vitro neuroprotective effects by stimulating different upstream pathways related with cyclic AMP-responsive element-binding protein (CREB). In the present study, we investigated the additive neuroprotective effects of DISS and TFSA on Glu-induced damage of SY5Y cells and purposed the possible underlying mechanism. The interaction between DISS and TFSA showed a clear-cut synergistic effect as evidenced by combination index (CI). Additional evidence from biochemical (NOS activity) assays confirmed their additive inhibition on the Glu-induced NOS hyperactivation. Moreover, we showed that co-treatment of DISS and TFSA resulted in an additively up-regulated phosphorylation of CREB as well as increased expressions of CRTC1 and BDNF. Neuroprotective effects of DISS and TFSA on Glu-induced decrease in cell viability were blocked by MAPK/ERK1/2 inhibitor (U0126) and PI3-K inhibitor (LY290042). Nevertheless, the CRTC1 or BDNF expression induced by these two compounds was significantly reduced in the presence of either ERK or PI3-K inhibitor, indicating that the two oligosaccharide esters shared some common pathways in the regulation of CREB-BDNF pathway. Taken together, we, for the first time, showed that DISS and TFSA exerted the additive neuroprotective effects on CREB-BDNF signaling pathway through complementary mechanisms.

The inhibition of JNK MAPK and NF-κB signaling by tenuifoliside A isolated from Polygala tenuifolia in lipopolysaccharide-induced macrophages is associated with its anti-inflammatory effect

The root of Polygala tenuifolia Willd. (Polygalaceae) is well known for its use in the treatment of neurasthenia, amnesia, and inflammation. In this study, we isolated phenyl propanoid type metabolite tenuifoliside A, one of the phenylpropanoids from P. tenuifolia, and investigated its anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW264.7 and murine peritoneal macrophages. The results showed that tenuifoliside A inhibited the production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), prostaglandin E2 (PG E2), and cyclooxygenase (COX)-2. In addition, tenuifoliside A suppressed the production of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β. We also evaluated the effects of tenuifoliside A on the activation of nuclear factor-kappaB (NF-κB). Tenuifoliside A inhibited the translocation of the NF-κB subunit p65 into the nucleus by interrupting the phosphorylation and degradation of inhibitor kappa B (IκB)-α in LPS-stimulated murine peritoneal macrophages. Moreover, we confirmed that the suppression of the inflammatory process by tenuifoliside A was mediated through the mitogen-activated protein kinases (MAPKs) pathway based on the fact that tenuifoliside A significantly decreased p-c-Jun N-terminal kinase (p-JNK) protein expression in LPS-stimulated murine peritoneal macrophages. Taken together, the anti-inflammatory effects of tenuifoliside A were mediated by the inhibition of the NF-κB and MAPK pathways. This study is the first report on the anti-inflammatory effects of tenuifoliside A, and the strong anti-inflammatory effects of tenuifoliside A provide potential compound to be developed as therapeutic for inflammatory diseases.

Potential Antiarrhythmic Effect of Methyl 3,4,5-Trimethoxycinnamate, a Bioactive Substance from Roots of <i>Polygalae Radix</i>: Suppression of Triggered Activities in Rabbit Myocytes

3,4,5-Trimethoxycinnamic acid (TMCA), methyl 3,4,5-trimethoxycinnamate (M-TMCA) and p-methoxycinnamic acid (PMCA) have been identified as the major bioactive components in the serum collected from rats treated with oral administration of Polygalae Radix ("YuanZhi," the roots of Polygala tenuifolia WILLD.), a traditional Chinese medicine used to relieve insomnia, anxiety and heart palpitation. The present study was designed to investigate its direct electrophysiological effects on isolated ventricular myocytes from rabbits. Whole-cell configuration of the patch-clamp technique was used to measure action potential (AP) and membrane currents in single ventricular myocytes enzymatically isolated from adult rabbit hearts. Ca(2+) transients were recorded in myocytes loaded with the Ca(2+) indicator Fluo-4AM. Among three bioactive substances of Polygala metabolites, only M-TMCA (15-30 µM) significantly shortened action potential duration at 50% and 90% repolarization (APD(50) and APD(90)) in cardiomyocytes in a concentration-dependent and a reversible manner. M-TMCA also inhibited L-type calcium current (I(Ca,L)), but showed effect on neither transient outward potassium current (I(to)) nor steady-state potassium current (I(K,SS)). Furthermore, M-TMCA abolished isoprenaline plus BayK8644-induced early afterdepolarizations (EADs) and suppressed delayed afterdepolarizations (DADs) and triggered activities (TAs). This potential anti-arrhythmic effects were likely attributed by the inhibition of I(Ca,L) and the suppression of intracellular Ca(2+) transients, which consequently suppress the generation of transient inward current (I(ti)). These findings suggest that M-TMCA may protect the heart from arrhythmias via its inhibitory effect on calcium channel.

Study on the anti-dementia and neural protection effects of ethamol soluble extract of Polygalae Radix

Polygalae radix, the root of Polygala tenuifolia Willd, has been widely used as a drug for the treatment of amnesia, calm, convulsions, aging, physical weakness, abnormal intelligence, etc, in traditional Chinese medicine. Recent research indicated that Polygalae radix has the function of neural protection. Extractions and fractionation of Polygalae radix were used as effective compounds in this research, which mainly focused on the expression of Tau and BACE1, symbolic markers for Alzheimer's disease. The result indicated that Polygalae radix could reduce the expression of Tau and BACE1 after the treatment. This may improve and protect the normal function of the nervous system and reduce the harm of Alzheimer's disease. Amyloid plaques are characteristic features of Alzheimer’s disease and believed to be neurotoxic,which could be stained with Thioflavin S. The result indicated that the amyloid plaques were reduced significantly, this suggested that the symptom of Alzheimer’s disease was improved and the neurotoxic effect reduced. By Morris water maze tests, the study and memory ability of mice were improved after the treatment of Polygalae radix. Key words: Polygalae radix, dementia, Morris water maze tests, BACE-1, Tau, amyloid plaques, Thioflavin S staining.

Triterpenoid Saponins and Oligosaccharides from the roots of Polygala tenuifolia Willd.

Aim To study the chemical constituents and bioactivities of the roots of Polygala tenuifolia Willd. Methods Bioactivity-guide was applied to study the chemical constituents of P. tenuifolia, and the chemical structures were determined by application of spectroal data (NMR, MS). Results One new, four known triterpenoid saponins and six oligosaccharides were obtained and their structures were identified as 3- O-β-D-glucopyranosyl-presenegenin 28- O-α-L-arabinopyranosyl-(1→ 3)-β-D-xylopyranosyl-(1→4)-[β-D-apiofuranosyl-(1→3)]-α-L-rhamnopyranosyl-(1→2)-[3- O-3, 4, 5-trimethoxycinnamoyl]-β-D-fucopyranosyl ester (onjisaponin Wg, 1), onjisaponins Fg ( 2), Ng ( 3), R ( 4), and O ( 5), tenuifolioses A ( 6), B ( 7), C( 8), I ( 9), K ( 10), and G ( 11). Conclusion Compound 1 is a new saponin. Compounds 6 and 7 showed neuroprotective activity against glumate and serum deficiency at the concentration of 1×10 −5 mol·L −1. Compounds 7 and 8 potentiated basal synaptic transmission in the dentate gyrus of anesthetized rats. The NMR data of 2–5 were reported for the first time.

Anti-inflammatory effects of Polygala tenuifolia root through inhibition of NF-κB activation in lipopolysaccharide-induced BV2 microglial cells

Ethnopharmacological relevanceThe root of Polygala tenuifolia Willd is a well-known traditional Oriental medicine and has been prescribed for treatment of dysfunction in memorial systems and various brain inflammatory diseases. The present study was designed to validate the anti-inflammatory effects of the water extract of Polygala tenuifolia root (WEPT). Materials and methodsThe anti-inflammatory properties of WEPT were studied using lipopolysaccharide (LPS)-stimulated murine BV2 microglia model. As inflammatory parameters, the production of nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase (COX)-2, prostaglandin E2 (PGE2), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β were evaluated. We also examined the extract's effect on the activity of nuclear factor-kappaB (NF-κB), and toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (Myd-88) expression. ResultsWEPT suppressed LPS-induced production of NO, PGE2, and expression of iNOS and COX-2 in a dose-dependent manner, without causing cytotoxicity. It also significantly reduced generation of proinflammatory cytokines, including IL-1β and TNF-α. In addition, WEPT suppressed NF-κB translocation by blockade of IkappaB-α (IκB-α) degradation and inhibited TLR4 and Myd-88 expression in LPS-stimulated BV2 cells. ConclusionsThese results indicate that the inhibitory effects of WEPT on LPS-stimulated inflammatory mediator production in BV2 microglia are associated with suppression of the NF-κB and toll-like receptor signaling pathways. Therefore, Polygala tenuifolia extracts may be useful in treatment of neurodegenerative diseases by inhibition of inflammatory mediator production in activated microglia.

Effects of the crude extract of Polygala tenuifolia Willd on human sperm in vitro

The aim of the present study is to analyze sperm membrane changes and the spermicidal effect in treatment with the crude extract from Polygala tenuifolia Willd (PTW) in vitro. The root of PTW was extracted in distilled water. Normal human spermatozoa were used to assess the spermicidal activity (Sander-Cramer assay) of the extract from the PTW root. The hypo-osmotic swelling (HOS) test and the eosin Y (EY) staining were used to detect the integrity of sperm membrane and vitality. The sperm chromatin dispersion (SCD) test was performed to determine sperm DNA integrity. N-9 was used as a reference standard and semen added to physiological saline was used as the control. Semen samples were donated by 42 healthy fertile men. The crude extract from the root of PTW could immobilize and kill 100% spermatozoa within 20 s in vitro at the concentrations of 20.0 and 10.0 mg/ml; at the concentration of 5.0 mg/ml, spermatozoa were immobilized in (39.5±3.2) s. In the groups of the crude extract from the root of PTW and N-9 solution, the rate of the normal HOS (tails swollen) and the white head (unstained) was 0%, and the rate of the abnormal HOS (tails unswollen) and red head (stained) was 100%. Sperm DNA fragmentation showed no change in exposure to the crude extract from the root of PTW and N-9 solution. The sperm revival test did not show any spermatozoa that recovered their motilities. The rapid spermicidal activity of the crude extract from the root of PTW in vitro may occur by the disruption of the sperm membrane integrity.

Polygalae radix inhibits toxin-induced neuronal death in the Parkinson's disease models

Polygalae radix, the root of Polygala tenuifolia Willd, has commonly been used for the treatment of amnesia and anxiety in traditional Korean medicine. The aim of this study was to investigate its neuroprotective effects and possible mechanisms of action in models of Parkinson's disease. This study utilized a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, a reactive oxygen species (ROS) assay, a nitric oxide (NO) production assay, and a caspase-3 activity test as measures of cell viability in PC12 cells damaged by 6-hydroxydopamine (6-OHDA). The protective effects of PRE against 1-methyl-4-phenylpyridium (MPP(+))-induced neurotoxicity were assessed in rat primary dopaminergic neurons and in a mouse PD model in which PRE was administered (100mg/kg/day, 3 days, p.o.) before acute 1-mehtyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity. Finally, TH immunohistochemistry tests were conducted in the substantia nigra pars compacta (SNpc) and striatum (ST). PRE significantly inhibited 6-OHDA-induced cell damage at doses of 0.05-1μg/ml with a maximal effect at 0.1μg/ml. Caspase-3 activity and the production of ROS and NO were alleviated at 0.1μg/ml. Also at this dose, PRE protected mesencephalic dopaminergic neurons from MPP(+)-induced toxicity. In an in vivo mouse model of PD, PRE protected dopaminergic neurons and fibers from MPTP-induced toxicity in the SNpc and ST. These results demonstrate that PRE has protective effects on dopaminergic neurons via its anti-oxidant and anti-apoptotic activity.

Antioxidant activity of oligosaccharide ester extracted from Polygala tenuifolia roots in senescence-accelerated mice

The constituents of the ethanol extract from the root of Polygala tenuifolia Willd. (Polygalaceae) were investigated for antioxidant activity in senescence-accelerated mice. Consequently, two relevant samples were obtained, a fraction separated by macroporous resin (YZ-OE), and a major pure crystal of 3,6′-disinapoyl sucrose (DISS). Based on HPLC-ESI-MS analysis, the most constituents in the YZ-OE fraction from the extract of P. tenuifolia were oligosaccharide esters. The antioxidant activities of these two samples were evaluated using the accelerated senescence-prone, short-lived mice (SAMP) in vivo. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were increased significantly in SAMP mice fed oligosaccharide esters (YZ-OE 50 mg/kg) and its constituents (DISS 50 mg/kg). However, the content of malondialdehyde (MDA) was increased in the blood and liver of SAMP mice. But when given YZ-OE, it could be decreased, by 44.3% and 47.5%, respectively, compared with the SAMP model. Results from the analyses indicated that the oligosaccharide esters (YZ-OE) from roots of P. tenuifolia had a high in vivo antioxidant activity.