Preparation, structural characteristics and pharmacological activity of polysaccharides from Polygala tenuifolia: A review.

Polygala tenuifolia is a traditional Chinese medicine with a long history of application, with the efficacy of suppressing cough, calming asthma, tranquilizing the mind, and benefiting the intellect. It is classified as a top-quality medicine in Shennong's Classic of Materia Medica. Polysaccharide is an important active ingredient in Polygala tenuifolia, which consists of several monosaccharides, including Ara, Gal, Glc, and so on. In this review, the preparation methods, structural characteristics, and biological activities of polysaccharides from Polygala tenuifolia are summarized, and the problems in the current studies are discussed to support further research, development, and utilization.

Glycyrrhizae radix et rhizoma processing ameliorates adverse reactions of polygalae radix in zebra fish and rabbit models.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygala tenuifilia Willd (Polygalaceae), a traditional Chinese medicine, has been used for a long time to treat various illnesses with serious adverse reactions. Glycyrrhizae radix et rhizoma processing is generally used to reduce the adverse reactions. AIM OF THE STUDY: The aim of this study was to validate the irritation caused by raw Polygalaceae (RPA), to investigate whether processed Polygalaceae (PGA) was less irritating, and to screen and validate irritant properties of virgaureagenin G (polygala acid, PA), 3,6'-disinapoylsucrose (DSS), Tenuifolia (TEN) and polygalaxanthone III (POL), which had pharmacologically active in Polygalaceae. Zebrafish model, Draize test and High-Performance Liquid Chromatography (HPLC) were utilized to achieve the aim. MATERIALS AND METHODS: Scanning Electron Microscopy (SEM) and optical microscope were used to determine the presence of calcium oxalate needle crystal in RPA and PGA. Zebrafish egg spinning changes and zebrafish embryo behavior were used for irritation validation, irritation comparison and irritant screening. For additional evidence, the Draize test, HE staining of rabbit eyes and ELISA kit were used. Finally, changes in the composition of RPA and PGA were investigated using HPLC. RESULTS: SEM and optical microscopy revealed no calcium oxalate needle crystals in Polygalaceae. RPA, PGA, PA and DSS were able to accelerate the spinning of zebrafish eggs and the movement of embryos, while TEN and POL were not. RPA, PGA, DSS and PA may cause rabbit eyes to become hyperemic and swollen, resulting in damage to the iris, cornea and conjunctiva and increased levels of interleukin-6 (IL-6) and interleukin-10 (IL-10). Comparatively, the effects caused by PGA were less severe than those caused by RPA. In addition, compared to RPA, PGA had lower levels of DSS and PA. CONCLUSIONS: RPA, PGA, DSS, and PA were irritating. However, processing and curing could reduce the irritation by reducing the levels of DSS and PA. DSS and PA could be two potential irritants of Polygalaceae.

Polysaccharide from Polygala tenuifolia alleviates cognitive decline in Alzheimer's disease mice by alleviating Aß damage and targeting the ERK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygala tenuifolia is used in a variety of Chinese medicine prescriptions for the classic dementia treatment, and polysaccharide is an important active component in the herb. AIM OF THE STUDY: This study investigated the in vivo anti-Alzheimer's disease (AD) activity of the polysaccharide PTPS from Polygala tenuifolia using the senescence-accelerated mouse/prone8 (SAMP8) model and explored its molecular mechanism to lay the foundation for the development of polysaccharide-based anti-AD drugs. MATERIALS AND METHODS: The Morris water maze test (MWM)was used to detect changes in the spatial cognitive ability of mice, and Nissl staining was applied to observe the state of neurons in the classic hippocampus. The levels of acetylcholine (ACh) and acetylcholinesterase (AChE) were measured by ELISA. Immunofluorescence was used to reflect ß-amyloid (Aß) levels in brain tissue. Apoptosis was evaluated by TdT-mediated dUTP Nick-End Labeling (TUNEL) method. The status of dendritic branches and spines was observed by Golgi staining. Meanwhile, the expression levels of recombinant human insulin-degrading enzyme (IDE), brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB), extracellular regulated protein kinases (ERK), and cAMP-response element binding protein (CREB) proteins were determined by Western blotting. RESULTS: PTPS improves spatial cognitive deficits in AD mice, reduces cellular damage in the CA3 region of the hippocampus, maintains the balance of the cholinergic system, and exerts an anti-AD effect in vivo. The molecular mechanism of its action may be related to the reduction of Aß deposition as well as the activation of ERK pathway-related proteins with enhanced synaptic plasticity. CONCLUSIONS: PTPS is able to exert anti-AD activity in vivo by mitigating Aß damage and targeting the ERK pathway.

Extract identification and evaluation of the cytotoxic activity of Polygala fallax Hemsl in Heilongjiang ethnic medicine against tumors.

BACKGROUND: Heilongjiang Province is a frontier province with distinctive characteristics, fertile land and rich products. OBJECTIVE: This study provides a new method for qualitatively studying flavonoids in traditional Chinese medicine and a new auxiliary means for identifying flavonoid isomers. METHODS: The flavonoids in Polygala fallax Hemsl were identified by ultra-performance liquid chromatography-photo-diode array (PDA)-quadrupole-electro- static field orbitrap mass spectrometry tandem by UV Spectrum, primary and secondary high-resolution mass spectrometry (MS1/MS2) cleavage of fragments combined with databases, mass spectrometry cleavage patterns and literature. RESULTS: The established QSRR model was used to verify the flavonoids identified from the Polygala fallax Hemsl. CONCLUSION: The structure of multiple Polygala fallax Hemsl has been identified using various spectral methods. The tumor cytotoxic activity of the isolated compounds was evaluated. This paper is of great significance for further elucidating the pharmacodynamic substance basis and further developing and utilizing Polygala fallax Hemsl.

Development of an online UPLC-PDA-ESI-Q-TOF-MS-LOX-FLD system for rapid screening of anti-inflammatory compounds in Polygala tenuifolia Willd.

In this study, the first ultra-high performance liquid chromatography-photo-diode array-electrospray ionization-quadrupole-time-of-flight-mass spectrometry-lipoxygenase-fluorescence detector (UPLC-PDA-ESI-Q-TOF-MS-LOX-FLD) online system was developed for the identification and evaluation of anti-inflammatory active ingredients in Polygala tenuifolia Willd. Using this system, the UPLC fingerprints, mass fragments and LOX-binding peak profiles in the samples were rapidly and simultaneously obtained. A total of 101 compounds were isolated and identified and 38 compounds (11 oligosaccharide esters, nine xanthones, 17 saponins, and one glycosyloxyflavone) showed strong LOX-binding activity. Six compounds were selected to study their LOX-binding ability, and the results indicated that the content of the six compounds had a good linear relationship with the LOX-binding ability, and it was found that the substitution position, the type of substituent and the number of glycosyl groups all had a certain influence on the LOX-binding ability of the compounds. The LOX-binding activities of 10 compounds were verified by the surface plasmon resonance (SPR) technique and the activity results were consistent with the online system. After validation, we identified 7 active compounds that combined with LOX to exert anti-inflammatory effects for the first time. All the results fully demonstrate the efficiency, stability and reliability of the online system and this work provides an exemplary and useful method for the rapid screening of potential anti-inflammatory active compounds in P. tenuifolia and other traditional Chinese medicines. At the same time, it provides a new direction for screening small molecule inhibitors of enzymes like LOX.

The Antinociceptive Effect of a Hydroalcoholic Extract of Polygala altomontana and Its Chemical Profile Using UPLC-ESI-QTOF-HR-MS.

The hydroalcoholic extract of Polygala altomontana (30, 100, and 300 mg/kg, i.g.) showed a dose-dependent antinociceptive action during the inflammatory phase of the formalin test. In addition, the preparation (30 and 300 mg/kg, i.g.) showed anti-hyperalgesic action when tested on a mechanical nociception model. UPLC-ESI-QTOF-MS data indicated the active extract contained phenylpropanoid sucrose esters, glycosylated quercetin derivatives, styrylpyrones, and coumarins. Some identified compounds, including styrylpyrones and coumarins, have previously demonstrated antinociceptive action. The results also show that P. altomontana shows potential for developing pain-relieving herbal remedies and drugs.

Structural elucidation and anti-neuroinflammatory activity of Polygala tenuifolia polysaccharide.

Polygala tenuifolia is extensively used to treat amnesia in traditional Chinese medicine, and pharmacological studies have reported the beneficial effects of P. tenuifolia on intelligence and cognition. In the present study, the crude polysaccharide alkali-extracted from P. tenuifolia roots (PTB) inhibited lipopolysaccharide-induced microglia/astrocyte activation and significantly improved the learning and memory ability of Alzheimer's disease (AD) rats. To determine its bioactive components, a heteropolysaccharide (PTBP-1-3) was isolated from PTB. Structural analysis showed that PTBP-1-3 was composed of α-L-Araf-(1→, â†’3)-α-L-Araf-(1→, →5)-α-L-Araf-(1→, →3,5)-α-L-Araf-(1→, →2,5)-α-L-Araf-(1→, ß-D-Xylp-(1→, →2,3,4)-ß-D-Xylp-(1→, α-L-Rhap-(1→, ß-D-Galp-(1→, →4)-α-D-Galp-(1→, →6)-α-D-Galp-(1→, →6)-α-D-Glcp-(1→, →3,6)-α-D-Glcp-(1→, →6)-α-D-Manp-(1→, and →2,4)-ß-D-Manp-(1→ residues. PTBP-1-3 decreased the production of NO, TNF-α, and IL-1ß in lipopolysaccharide-activated BV2 microglia cells in a manner similar to that of minocycline. In conclusion, PTBP-1-3 exhibited a potent inhibitory effect on neuroinflammation, and could be one of the bioactive ingredients in PTB for anti-neuroinflammation. PTB and PTBP-1-3 may be potential therapeutic agents for the treatment of AD.

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.

Antitumor activity and immunomodulation mechanism of a novel polysaccharide extracted from Polygala tenuifolia Willd. evaluated by S180 cells and S180 tumor-bearing mice.

We recently isolated a polysaccharide from Polygala tenuifolia Willd. (PTP) and reported that such a PTP could induce cell apoptosis with FAS/FAS-L-mediated death receptor pathway in human lung cancer cells. Herein, we indicate antitumor activity and immunoregulation of PTP for S180 sarcoma cells by in vitro and in vivo targeting. In vitro, S180 cells took on prominent characteristics of apoptosis under-treated with PTP in follow-up antitumor activity studies, including irregular shrinkage and fragmentation nuclear, apoptotic bodies formation, and reduction of mitochondrial membrane potential (MMP). Additionally, flow cytometry indicated that the number of normal cells (FITC-/PI-) gradually decreased from 98.08% to 16.31%, while the number of apoptotic cells (FITC+/PI- or FITC+/PI+) increased from 0.87% to 54.84%. The ratio of BAX and Bcl-2 increased, which promoted the release of Cytochrome C (CytC), and it further maximized the expression of activated-caspase-9/-3. Additionally, the PTP revised the immune organ indexes, the activities of NK cells and lymphocytes, and induced the secretion of IL-2 (7.34-16.17%), IFN-γ (14.34-20.85%) and TNF-α (12.32-22.58%) in vivo. Thus, PTP can induce cell apoptosis and activate the immunoregulation mechanism thereby exhibiting biological activity.

Active constituent of Polygala tenuifolia attenuates cognitive deficits by rescuing hippocampal neurogenesis in APP/PS1 transgenic mice.

BACKGROUND: Alzheimer's disease (AD) is the most common dementia worldwide, and there is still no satisfactory drug or therapeutic strategy. Polygala tenuifolia is a traditional Chinese medicine with multiple neuroprotective effects. In present study, we investigated the effects of three active constituents [3,6'-disinapoyl sucrose (DISS), onjisaponin B (OB) and tenuifolin (TEN)] of Polygala tenuifolia (PT) on the proliferation and differentiation of neural stem cells (NSCs) to identify the potential active constituent of PT promoting hippocampal neurogenesis. METHODS: NSCs were isolated from hippocampi of newborn C57BL/6 mice, and transfected with mutant amyloid precursor protein (APP) gene to establish an AD cell model (APP-NSCs). 3-(4,5- Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays were performed, and the proliferation and differentiation of NSCs were assessed by neurosphere formation assay, 5-bromo-2'-deoxyuridine (BrdU) incorporation assay and immunofluorescence (IF) staining analysis. APP/PS1 transgenic mice were administrated with the potential active constituent DISS for 4 weeks. Morris water maze (MWM), Nissl staining assay and IF staining assays were carried out to evaluate the cognitive function, neural damages and hippocampal neurogenesis, respectively. RESULTS: DISS exerted the optimal ability to strengthen APP-NSCs proliferation and neuronal differentiation, followed by OB and TEN. Furthermore, DISS treatment for 4 weeks strikingly rescued the cognitive deficits, neuronal injures, and neurogenesis disorder in adult APP/PS1 transgenic mice. CONCLUSIONS: Our findings demonstrated that DISS is the constituent of PT that triggers the most potent increase of hippocampal neurogenesis in our mouse model of AD.

Polygalaxanthone III downregulates inflammation in the lipopolysaccharide-stimulated RAW264.7 macrophages: A quantibody array analysis.

Polygala japonica Houtt. (PJ), a member of the Polygala L. family that is suggested to exhibit detoxification properties in traditional Chinese medicine, is often used to treat upper respiratory tract infections. The anti-inflammatory effects of four main components of PJ (POL, PS-XLIX, PS-E, and PS-F) were examined using the LPS(0.3 µg·mL-1)-stimulated RAW264.7 macrophage model. The levels of NO, ROS, and iNOS were examined to analyze the anti-inflammatory activity of POL. Additionally, the levels of extracellular inflammation-related cytokines and chemokines were measured using quantibody array. The KEGG pathway analysis was performed to examine the anti-inflammatory mechanism of POL. The levels of NO in the POL-pretreated group were significantly downregulated when compared with those in the PS-E-pretreated, PS-F-pretreated, and PS-XLIX-pretreated groups. POL significantly inhibited the changes of iNOS, ROS, and inflammatory factors caused by LPS stimulation (p < 0.001). The expression levels of IL21 and GM-CSF were examined using qPCR, while those of JAK-STAT signaling pathway-related proteins in the LPS-stimulated RAW264.7 macrophages were analyzed using western blotting. POL significantly downregulated the expression of IL-21 and GM-CSF. The anti-inflammatory mechanism of POL is mediated through the JAK-STAT pathway. Thus, this study demonstrated that POL is an anti-inflammatory component of PJ and elucidated its mechanism.

Saponins isolated from Radix polygalae extent lifespan by modulating complement C3 and gut microbiota.

With the increase in human lifespan, population aging is one of the major problems worldwide. Aging is an irreversible progressive process that affects humans via multiple factors including genetic, immunity, cellular oxidation and inflammation. Progressive neuroinflammation contributes to aging, cognitive malfunction, and neurodegenerative diseases. However, precise mechanisms or drugs targeting age-related neuroinflammation and cognitive impairment remain un-elucidated. Traditional herbal plants have been prescribed in many Asian countries for anti-aging and the modulation of aging-related symptoms. In general, herbal plants' efficacy is attributed to their safety and polypharmacological potency via the systemic manipulation of the body system. Radix polygalae (RP) is a herbal plant prescribed for anti-aging and the relief of age-related symptoms; however, its active components and biological functions remained un-elucidated. In this study, an active methanol fraction of RP containing 17 RP saponins (RPS), was identified. RPS attenuates the elevated C3 complement protein in aged mice to a level comparable to the young control mice. The active RPS also restates the aging gut microbiota by enhancing beneficial bacteria and suppressing harmful bacteria. In addition, RPS treatment improve spatial reference memory in aged mice, with the attenuation of multiple molecular markers related to neuroinflammation and aging. Finally, the RPS improves the behavior and extends the lifespan of C. elegans, confirming the herbal plant's anti-aging ability. In conclusion, through the mouse and C. elegas models, we have identified the beneficial RPS that can modulate the aging process, gut microbiota diversity and rectify several aging-related phenotypes.

Combination of urine and faeces metabolomics to reveal the intervention mechanism of Polygala tenuifolia compatibility with Magnolia officinalis on gastrointestinal motility disorders.

OBJECTIVES: To explore the intervention mechanism of combining Polygala tenuifolia (PT) with Magnolia officinalis (MO) on gastrointestinal motility disorders caused by PT. METHODS: Urine and faeces of rats were collected; the effects of PT and MO on the gastric emptying and small intestine advancing rates in mice were analysed via ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) to determine the potential metabolites. Changes in the metabolic profiles of the urine and faeces were revealed by untargeted metabolomics, followed by multivariate statistical analysis. The integration of urine and faeces was applied to reveal the intervention mechanism of PT-MO on PT-induced disorders. KEY FINDINGS: PT + MO (1:2) improved the gastrointestinal function in mice suffering from PT-induced gastrointestinal motility disorder. Metabolomics indicated that the PT-MO mechanism was mainly associated with the regulations of 17 and 12 metabolites and 11 and 10 pathways in urine and faeces, respectively. The common metabolic pathways were those of tyrosine, purine, tricarboxylic acid cycle, pyruvate and gluconeogenesis, which were responsible for the PT-MO intervention mechanism. CONCLUSIONS: The PT-MO (1:2) couple mechanism mitigated the PT-induced disorders, which were related to the energy, amino acid and fatty metabolisms.

Extract of Polygala tenuifolia, Angelica tenuissima, and Dimocarpus longan Reduces Behavioral Defect and Enhances Autophagy in Experimental Models of Parkinson's Disease.

The 20% ethanol extract of Polygala tenuifolia, Angelica tenuissima, and Dimocarpus longan (WIN-1001X) was derived from a modified version of Korean traditional herbal formula 'Chungsimyeolda-tang' which has been used for the treatment of cerebrovascular disorders. The Parkinson's disease presents with impaired motor functions and loss of dopaminergic neurons. However, the treatment for Parkinson's disease is not established until now. This study aims to elucidate the therapeutic advantages of WIN-1001X on animal models of Parkinson's disease. WIN-1001X administration successfully relieved the Parkinsonism symptoms in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mice tested by rota-rod and pole tests. The loss of tyrosine hydroxylase activities in substantia nigra and striatum was also attenuated by administration of WIN-1001X. In mice with sub-chronical MPTP injections, autophagy-related proteins, such as LC3, beclin-1, mTOR, and p62, were measured using the immunoblot assay. The results were favorable to induction of autophagy after the WIN-1001X administration. WIN-1001X treatment on 6-hydroxydopamine-injected rats also exhibited protective effects against striatal neuronal damage and loss of dopaminergic cells. Such protection is expected to be due to the positive regulation of autophagy by administration of WIN-1001X with confirmation both in vivo and in vitro. In addition, an active compound, onjisaponin B was isolated and identified from WIN-1001X. Onjisaponin B also showed significant autophagosome-inducing effect in human neuroblastoma cell line. Our study suggests that relief of Parkinsonism symptoms and rescue of tyrosine hydroxylase activity in dopaminergic neurons are affected by autophagy enhancing effect of WIN-1001X which the onjisaponin B is one of the major components of activity.

The antidepressant-like effects of the water extract of Panax ginseng and Polygala tenuifolia are mediated via the BDNF-TrkB signaling pathway and neurogenesis in the hippocampus.

ETHNOPHARMACOLOGY RELEVANCE: The water extract of Panax ginseng (GT) and Polygala tenuifolia (YT), the main constituents of the commonly used kai-xin-san formula of traditional Chinese medicine, represents SY. It possesses strong neuroprotective effects. Using behavioural tests, we have previously established that the SY formulation exerts superior antidepressant activity than that of GT or YT. AIM: To elucidate the impact of SY treatment on chronic unpredictable mild stress (CUMS)-induced depressive-like behaviours and the prospective mechanism related to hippocampal neurogenesis and the BDNF signaling pathway. METHODS: We exposed Sprague-Dawley rats (male; 180-200 g) to CUMS for 35 days. The rats in the experimental treatment groups were daily treated with either fluoxetine (10 mg kg-1d-1) or SY (67.5, 135, or 270 mg kg-1d-1) orally until the behavioural tests (tail suspension test [TST], novelty-suppressed feeding test [NSFT], sucrose preference test [SPT], and forced swim test [FST]) were completed. We assessed the modifications in the hippocampal neurogenesis and the BDNF signaling pathway post-treatment with CUMS and SY. Additionally, K252a, a tyrosine protein kinase inhibitor, was utilized to evaluate the antidepressant mechanisms of SY. RESULT: s: The results of SPT, NSFT, FST, and TST in CUMS-exposed rats confirmed the antidepressant actions of SY. Additionally, SY treatment induced the BDNF signaling pathway and reversed the hippocampal neurogenesis caused by CUMS. Moreover, we found that the TrkB antagonist K252a blocked SY effects on behavioural improvement, inhibited the incremental effects of SY on hippocampal neurogenesis, and eliminated the impact of SY on BDNF-TrkB signaling activation. Thus, the impact of SY treatment on BDNF signaling molecules (pAkt, pERK1/2, and pCREB) were significantly inhibited by K252a. CONCLUSIONS: This study showed that SY acted as an antidepressant in rats exhibiting CUMS-induced depressive-like behaviours, and was facilitated by promoting hippocampal neurogenesis and the BDNF signaling pathway activation. Thus, SY could act as a potential novel supplement or adjuvant to prevent or treat clinical depressive disorders.

Protein unbound pharmacokinetics of ambroxol in the blood and brains of rats and the interaction of ambroxol with Polygala tenuifolia by multiple microdialysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ambroxol elevates glucocerebrosidase (GCase) activity and reduces nigrostriatal alpha-synuclein burden to better ameliorate motor function in Parkinson's disease (PD). Polygala tenuifolia is a potential alternative botanical medicine for the treatment of many nonmotor symptoms of PD commonly used in Taiwanese patients. Co-administration of these two medicines pose potential herb-drug interaction. AIM OF THE STUDY: Our hypothesis is that ambroxol and P. tenuifolia may potentially possess herbal drug synergetic effects in the blood and brain. MATERIALS AND METHODS: To investigate this hypothesis, a multiple microdialysis system coupled with validated ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for rat blood and brain samples. Experimental rats were divided into three groups: low-dose and high-dose ambroxol alone (10 mg/kg, i.v. and 30 mg/kg, i.v., respectively) and ambroxol (10 mg/kg, i.v.) pretreated with P. tenuifolia extract (1 g/kg, p.o. for 5 consecutive days). RESULTS: Ambroxol easily penetrated into the brain and reached a maximum concentration in the striatum at approximately 60 min after low- and high-dose treatment. The area under the concentration curve (AUC) ratio increased proportionally at the doses of 10 and 30 mg/kg, which suggested a linear pharmacokinetic manner of ambroxol. The brain penetration of ambroxol was approximately 30-34%, which was defined as the ambroxol AUC blood-to-brain distribution ratio (AUCbrain/AUCblood). The P. tenuifolia extract did not significantly alter the pharmacokinetics of ambroxol in the blood and brain of rats. CONCLUSION: The present study suggests that it is safety without pharmacokinetic interactions for this dosing regimen to use P. tenuifolia extract and ambroxol together.

Polygalae Radix: A review of its traditional uses, phytochemistry, pharmacology, toxicology, and pharmacokinetics.

Polygalae Radix (Polygalaceae), the dried root of Polygala tenuifolia Willd. and Polygala sibirica L., has been widely used as a medicine for improving cognitive function. In China, Polygalae Radix has been widely used in the treatment of insomnia, forgetfulness, depression, cough, palpitation, and other diseases. More than 140 compounds have been isolated from Polygalae Radix, including saponins, xanthones, oligosaccharide esters, and so on. The compounds and extracts isolated from Polygalae Radix possess wide-ranging pharmacological activities, such as neuroprotective, antidepressant, hypnotic-sedative, anti-inflammatory, antiviral, antitumor, antioxidant, antiaging, and antiarrhythmic effects, among others. The clinical practice of traditional Chinese medicine has proved that raw Polygalae Radix can irritate the throat. Modern studies have found that raw Polygalae Radix exhibits a certain degree of toxicity to the gastrointestinal tract after long-term use or excessive doses and that its main toxic components are saponins. Thus, Polygalae Radix is usually processed, and/or combined with other herbs to reduce gastrointestinal irritation. This review investigated the pharmacokinetics of Polygalae Radix. Future research perspectives and the existing problems of Polygalae Radix were also discussed. This review can broaden the understanding regarding Polygalae Radix and provide references for further research.

UHPLC-MS/MS method for pharmacokinetic and bioavailability determination of five bioactive components in raw and various processed products of Polygala tenuifolia in rat plasma.

CONTEXT: Sibiricose A5 (A5), sibiricose A6 (A6), 3,6'-disinapoyl sucrose (DSS), tenuifoliside A (TFSA) and 3,4,5-trimethoxycinnamic acid (TMCA) are the main active components of Polygala tenuifolia Willd. (Polygalaceae) (PT) that are active against Alzheimer's disease. OBJECTIVE: To compare the pharmacokinetics and bioavailability of five active components in the roots of raw PT (RPT), liquorice-boiled PT (LPT) and honey-stir-baked PT (HPT). MATERIALS AND METHODS: The median lethal dose (LD50) was evaluated through acute toxicity test. The pharmacokinetics of five components after oral administration of extracts of RPT, LPT, HPT (all equivalent to 1.9 g/kg of RPT extract for one dose) and 0.5% CMC-Na solution (control group) were investigated, respectively, in Sprague-Dawley rats (four groups, n = 6) using UHPLC-MS/MS. In addition, the absolute bioavailability of A5, A6, DSS, TFSA and TMCA after oral administration (7.40, 11.60, 16.00, 50.00 and 3.11 mg/kg, respectively) and intravenous injection (1/10 of the corresponding oral dose) in rats (n = 6) was studied. RESULTS: The LD50 of RPT, LPT and HPT was 7.79, 14.55 and 15.99 g/kg, respectively. AUC 0- t of RPT, LPT and HPT were as follows: A5 (433.18 ± 65.48, 680.40 ± 89.21, 552.02 ± 31.10 ng h/mL), A6 (314.55 ± 62.73, 545.76 ± 123.16, 570.06 ± 178.93 ng h/mL) and DSS (100.30 ± 62.44, 232.00 ± 66.08, 197.58 ± 57.37 ng h/mL). The absolute bioavailability of A5, A6, DSS, TFSA and TMCA was 3.25, 2.95, 2.36, 1.17 and 42.91%, respectively. DISCUSSION AND CONCLUSIONS: The pharmacokinetic and bioavailability parameters of each compound can facilitate future clinical studies.

Research on anti-hepatocellular carcinoma activity and mechanism of Polygala fallax Hemsl.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygala fallax Hemsl. is a kind of traditional medicine of Yao Minority in China. In Chinese medicine practice, Polygala fallax Hemsl. is commonly prescribed to treat all kinds of acute and chronic hepatitis. AIM OF THE STUDY: The present study aimed at investigating the effects and its possible mechanism of Polygala fallax Hemsl. on the proliferation and apoptosis of HepG2 cells (a kind of human hepatoma cell). MATERIALS AND METHODS: Through a variety of experimental methods, including MTT technique and Hoechst staining to detect apoptosis in Hepatocyte HepG2 cells, flow cytometry to observe the pro-apoptotic and circulatory arrest effects as well as real-time fluorescence quantitative polymerase chain reaction (q-PCR) technique to examine the expression levels of Bcl-2/Bax gene and prote Western blot to examine the expression levels of bcl-2/bax,caspase3,8,9,CyclinA,p21,p27,ERK.Phospho-ERK and AKT, Phospho-AKT in HepG2 cells. RESULTS: The results showed that compared with the control group, all polarity fractions of P. fallax had inhibitory effects on HepG2 cells, among which the inhibition effect of ethyl acetate fraction in 0.036 ± 0.001 mg/mL of IC50 for 24 h was the most obvious (P < 0.01). And the HepG2 cells induced at the ethyl acetate fraction could up-regulate Bax gene and protein, while down-regulating Bcl-2 gene and protein (P < 0.05) during S phase in a dose-dependent manner. In addition, the ethyl acetate site of Larch can also down regulate the expression of ERK, AKT and activate caspase 3, 8 and 9. CONCLUSION: It could be concluded that the ethyl acetate fraction of Polygala fallax Hemsl. can significantly prohibit the proliferation of HepG2 cells. The possible mechanism is to promote the expression of Bax, inhibit the expression of Bcl-2, and down regulate the expression of AKT and ERK.

A pectin-like polysaccharide from Polygala tenuifolia inhibits pancreatic cancer cell growth in vitro and in vivo by inducing apoptosis and suppressing autophagy.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant carcinomas, which is characterized by apoptosis- and autophagy-dependent tumorigenic growth. Autophagy constitutes a stress adaptation that suppresses apoptosis. To explore new leading compound against PDAC, a pectin-like polysaccharide named RP02-1, was purified from roots of Polygala tenuifolia. Bioactivity test showed that RP02-1 might inhibit pancreatic cancer cells growth in vitro and in vivo. RP02-1 could inhibit pancreatic cancer cell (AsPC-1 and BxPC-3) proliferation, migration and colony formation. Mechanism study suggested that RP02-1 induced pancreatic cancer cells apoptosis, which was detected by Bcl-2 down-regulation, Bax up-regulation and conversion from Caspase 3 to Cleaved Caspase 3. Interestingly, autophagy was suppressed by RP02-1 treatment concentration-dependently through affenuatingBeclin-1, ATG5 and LC3B expression in BxPC-3 cells. In addition, RP02-1 could inhibit autophagy induced by Pennogenin 3-O-beta-chacotrioside. However, RP02-1 had almost no toxicity both in vitro and in vivo. The above results suggested that RP02-1 might be a potential leading compound for new drug candidate development for human PDAC treatment via inducing apoptosis and against autophagy.