Polygala Tenuifolia Research Articles

Medicinal Herbs with Anti-Inflammatory Activities for Natural and Organic Healing

One of the principal causes of different disorders is an uncontrolled inflammatory response. Alkaloids, flavonoids, polyphenolic, proanthocyanidin, terpenoid, and steroid compounds are the main reasons for the anti-inflammatory activities of medicinal herbs and plants. The current manuscript introduces a series of potential anti-inflammatory plants, particularly those which are routines in Iranian and Chinese traditional herbal medicine, and simplifies the function and mechanisms of natural constituents for the prevention and treatment of inflammatory disorders. PubMed, Science Direct, Google Scholar, Wiley Online Library, Springer, Taylor, Francis, etc., have been used to search for collecting of scientific publications for a full evaluation of current documentation in the literature showing the importance of medicinal plants with anti-inflammatory characteristics and natural medicines. The most notable medicinal plants with anti-inflammatory activities are Baccharis dracunculifolia, Aconitum bulleyanum, Crateya adansonii, Alliums spp., Centella asiatica, Flos lonicerae, Corydalis dubia, Syringae folium, Coptis chinensis, Casearia decandra, Nigella sativa, Cannabis sativa, Tamarindus indica L., Glycyrrhiza glabra, Panax ginseng, Panax notoginseng, Pistacia vera, Smilax china, Scutellaria baicalensis, Rosemarinus officinalis, Moringa olifera, Pulsatilla radix, Pistacia atlantica, Rullia tuberose, Canarium album, Dodonaea polyandra, Forsythia suspense, Polygala tenuifolia, Radiz Isatidis, Hypericum sampsonii, Geranium koreanum, Typha capensis, Isatidis folium, Ginkgo biloba, Houttuynia cordata, snow lotus, etc. Herbal medicine mainly uses numerous parts of plants or combinations of them to prevent and remedy diseases and promote health. More investigations and clinical experiments are needed to provide more information on the importance of medicinal plants as well as their roles in the treatment and prevention of inflammatory diseases.

Inhibitory Activity of 4-O-Benzoyl-3'-O-(OMethylsinapoyl) Sucrose from Polygala tenuifolia on Escherichia coliβ-Glucuronidase.

Bacterial β-glucuronidase in the intestine is involved in the conversion of 7-ethyl-10- hydroxycamptochecin glucuronide (derived from irinotecan) to 7-ethyl-10-hydroxycamptothecin, which causes intestinal bleeding and diarrhea (side effects of anti-cancer drugs). Twelve compounds (1-12) from Polygala tenuifolia were evaluated in terms of β-glucuronidase inhibition in vitro. 4-O-Benzoyl-3'-O-(O-methylsinapoyl) sucrose (C3) was highly inhibitory at low concentrations. C3 (an uncompetitive inhibitor) exhibited a ki value of 13.4 μM; inhibitory activity increased as the substrate concentration rose. Molecular simulation revealed that C3 bound principally to the Gln158-Tyr160 enzyme loop. Thus, C3 will serve as a lead compound for development of new β- glucuronidase inhibitors.

PTP70-2, a novel polysaccharide from Polygala tenuifolia, prevents neuroinflammation and protects neurons by suppressing the TLR4-mediated MyD88/NF-κB signaling pathway

PTP70-2, a novel polysaccharide isolated from Polygala tenuifolia in our previous publication, exhibits potential anti-inflammatory effects. Here, we investigate the mechanisms underlying these effects and the neuroprotective activity of PTP70-2 in lipopolysaccharide (LPS)-damaged BV2 microglial cells and neuroinflammation-injured primary cortical neurons. The results suggest that PTP70-2 dramatically reduces the LPS-stimulated inflammatory cytokines overexpression, as well as down-regulates the levels of TLR4-, MyD88-, and NF-κB-related proteins. The effect of PTP70-2 in down-regulation of proinflammatory cytokines and downstream proteins implicated in MyD88 and NF-κB signaling is related to the TLR4 pathway. Furthermore, this effect is enhanced by the co-incubation of BV2 cells with PTP70-2 and TAK242, a TLR4 inhibitor, before exposure to LPS. Importantly, PTP70-2 prevents neuroinflammation-induced neurotoxicity by mitigating ROS overproduction and MMP dissipation. Overall, the PTP70-2's anti-neuroinflammation and neuroprotection are involved to the modulation of the TLR4-mediated MyD88/NF-κB signaling pathway.

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

BackgroundAlzheimer’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.MethodsNSCs 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.ResultsDISS 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.ConclusionsOur findings demonstrated that DISS is the constituent of PT that triggers the most potent increase of hippocampal neurogenesis in our mouse model of AD.

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.

Qisheng Wan formula ameliorates cognitive impairment of Alzheimer's disease rat via inflammation inhibition and intestinal microbiota regulation

Ethnopharmacology relevanceQisheng Wan formula (QWF) was first described in the book Sheng Ji Zong Lu in 1117. The book states that QWF can cure forgetfulness, improve the mind, and make people smart. Hence, QWF has been widely used to treat patients with forgetfulness or dementia. QWF, a classic Chinese formulation, comprises seven herbal drugs: the sclerotium of Poria cocos (Schw.) Wolf, bark of Cinnamomum cassia Presl, root of Polygala tenuifolia Willd., root and rhizome of Panax ginseng C. A. Mey., root of Asparagus cochinchinensis (Lour.) Merr., root and rhizome of Acorus tatarinowii Schott, and root bark of Lycium chinense Mill. Aim of the studyThis study aimed to utilize modern pharmacological methods to evaluate the therapeutic effects and explore the underlying mechanism of QWF action on rats with Alzheimer's disease (AD). Materials and methodsThe chemical profile of QWF was characterized using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The AD rat model was established via a bilateral intraventricular injection of amyloid-β (1–42) (Aβ1–42). The rats were subsequently treated daily with QWF for 4 weeks. The Morris water maze test was performed to evaluate the cognition processes in the rats, whereas histological changes in the hippocampus were observed using hematoxylin and eosin staining. The expression levels of Aβ1–42, nuclear factor-kappa B (NF-κB), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in the hippocampus and colon were assessed. Moreover, the diversity and composition of the intestinal microbiota were analyzed using 16S rDNA gene sequencing. ResultsOne hundred and fourteen compounds were characterized in QWF. QWF significantly ameliorated the cognition processes and histopathological damages due to AD in rats by decreasing the deposition of Aβ1-42 and downregulating the expression of NF-κB, TNF-α, and IL-6. QWF also modulated changes in the diversity and composition of intestinal microbiota to suppress the relative abundance of inflammation-associated microbiota. ConclusionThis study showed that QWF can suppress proinflammatory factors and modulate the intestinal microbiota in AD rats.

Direct infusion–tandem mass spectrometry combining with data mining strategies enables rapid chemome characterization of medicinal plants: A case study of Polygala tenuifolia

Data-independent MS2 spectrum acquisition after fragmenting the precursor ion cohort with 1 Da bin, termed as MS/MSALL ®, offers an opportunity to achieve rapid chemome characterization when being coupled with direct infusion (DI). Some post-acquisition data processing strategies, such as mass defect filtering (MDF), diagnostic fragment ion filtering (DFIF), and neutral loss filtering (NLF), facilitate data extraction from massive dataset, and moreover, molecular weight (MW) imprinting allows rapid capturing those reported components. Here, DI–MS/MSALL ® was employed to acquire cubic spectral dataset, and the strategies such as MW imprinting, MDF, DFIF, and NLF, were subsequently applied to filter the structural information. The integrated pipeline was utilized for the chemome characterization of Polygala tenuifolia, a famous edible medicinal plant. To aid information filtering, an in-house chemical library was built by comprehensively collecting structural information from some available databases. A single analytical run was completed within 5 min. For MS1 spectrum processing, MW imprinting was firstly applied to capture the compounds in the chemical library, and “five-point” MDF frames were employed to pursue saponins, oligosaccharide esters, and xanthones. Regarding MS2 spectral plot, DFIF and NLF were deployed to search information-of-interest. Structural identification was accomplished by carefully correlating precursor ions and MS2 spectra, applying the well-defined mass cracking rules, and referring to literature information as well as available databases. A total of 109 compounds, mainly saponins (40 ones), oligosaccharide esters (29 ones), and xanthones (19 ones), were captured and structurally annotated. MS1 spectra were also implemented for chemome comparison between Polygala tenuifolia and several similar plants belonging to Polygala genus, resulting in the observation of significant inter- and intra-species differences. Above all, DI–MS/MSALL ® is a promising choice for high-throughput chemome profiling of, but not limited to, medicinal plants, in particular when being integrated with post-acquisition data processing strategies.

Comparison of anti-inflammatory effects of Mecasin and its constituents on lipopolysaccharide-stimulated BV2 cells.

Mecasin, a traditional medicine, contains nine herbal constituents: Curcuma longa, Salvia miltio rhiza, Gastrodia elata, Chaenomeles sinensis, Polygala tenuifolia, Paeonia japonica, Glycyrrhiza uralensis, Atractylodes japonica and processed Aconitum carmichaeli. Several biological effects of mecasin have been described both in vivo and in vitro. Previous studies have demonstrated that mecasin has anti-inflammatory effects. The purpose of the present study was to determine anti-inflammatory effects of mecasin and its natural product constituents on lipopolysaccharide (LPS)-stimulated BV2 cells by measuring nitrite and nitric oxide contents. Nitrite production levels in LPS-stimulated BV2 cells incubated with mecasin and each individual constituent of mecasin were measured. The results suggested that C. longa, P. tenuifolia and P. japonica inhibited nitrite production in a pattern similar to that of mecasin. The effect of mecasin was likely a result of synergistic effects of its natural herb constituents.

The Antidepressant-Like Effects of Shen Yuan in a Chronic Unpredictable Mild Stress Rat Model.

Depression is a common yet severe neuropsychiatric condition that causes imposes considerable personal, economic, and social burdens worldwide. Medicinal plant species (e.g., Panax ginseng and Polygala tenuifolia) demonstrate potent antidepressant-like effects with less toxicity and other side effects. Shen yuan prescription (SY), composed of Panax ginseng (GT) and Polygala tenuifolia (YT). The present study aimed to elucidate the effects of SY treatment on chronic unpredictable mild stress (CUMS) rats and study the underlying mechanism. Our results indicated that SY (67.5, 135, or 270 mg/kg) significantly reverses the depressive-like behaviors in rats with a 5-week CUMS exposure, as demonstrated by increased sucrose consumption in the sucrose preference test, and decreased immobility time in the tail suspension and forced swim test. Moreover, SY altered serum corticosterone levels, pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α), and oxidative markers (SOD, CAT, and MDA), and increased the levels of hippocampal neurotransmitters (5-HT, DA, and NE) in rats exposed to CUMS. Furthermore, rats treated with SY showed a reduction in the protein expression of BDNF, p-TrkB, p-Akt, and p-mTOR proteins induced by CUMS exposure in the hippocampus. In conclusion, SY prevented depressive-like behaviors in CUMS-exposed rats by preventing hypothalamus-pituitary-adrenal axis dysfunction, decreasing the levels of the neurotransmitters, minimizing oxidative stress, suppressing neuroinflammation, and activating the PI3K/Akt/mTOR-mediated BDNF/TrkB pathway, all of which are the key players in the pathological basis of depression.

The antidepressant-like effects of Shen Yuan: Dependence on hippocampal BDNF-TrkB signaling activation in chronic social defeat depression-like mice.

The Shen Yuan prescription (SY) comprises Panax ginseng (GT) and Polygala tenuifolia (YT), elicited superior antidepressant activity compared with that of GT or YT alone. The aim of this paper is to elucidate the effects of SY treatment on chronic social defeat stress (CSDS)-induced depression-like symptoms and the related mechanism. Our results indicated that SY treatment reverses the depressive-like behaviors induced by CSDS as measured by the social interaction test, sucrose preference test, forced swim test, and tail suspension test. SY decreased the serum levels of CORT and increased hippocampal neurotransmitters (5-HT, DA, and NE) in CSDS mice. Meanwhile, SY upregulated the brain-derived neurotrophic factor (BDNF) signaling pathway and reversed the decreased hippocampal neurogenesis caused by CSDS. In addition, we found that the TrkB antagonist K252a fully blocked the SY effects on behavioral improvement and eliminated the promoting effects of SY on hippocampal neurogenesis and BDNF-TrkB signaling (including the downstream ERK and Akt pathways) activation, thus further demonstrating that BDNF-TrkB signaling was necessary for the SY effects. In conclusion, our study showed that SY acted as an antidepressant in mice exhibiting CSDS-induced depression-like symptoms, and its effect was facilitated by promoting hippocampal neurogenesis and BDNF signaling pathway activation.

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.

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.

Oligosaccharides from Traditional Chinese Herbal Medicines: A Review of Chemical Diversity and Biological Activities.

Most of traditional Chinese herbal medicine (TCHM) substances come from medicinal plants, among which oligosaccharides have gradually attracted widespread attention at home and abroad due to their important biological activities and great medicinal potential. Numerous in vitro and in vivo experiments exhibited that oligosaccharides possess various activities, such as antitumor, anti-oxidation, modulate the gut microflora, anti-inflammatory, anti-infection, and immune-regulatory activities. Generally, biological activities are closely related to chemical structures, including molecular weight, monosaccharide composition, glycosidic bond connection, etc. The structural analysis of oligosaccharides is an important basis for studying their structure-activity relationship, but the structural diversity and complexity of carbohydrate compounds limit the study of oligosaccharides activities. Understanding the structures and biological functions of oligosaccharides is important for the development of new bioactive substances with natural oligosaccharides. This review provides a systematic introduction of the current knowledge of the chemical structures and biological activities of oligosaccharides. Most importantly, the reported chemical characteristics and biological activities of the famous TCHM oligosaccharides were briefly summarized, including Morinda officinalis, Rehmannia glutinosa, Arctium lappa, Polygala tenuifolia, Panax ginseng, Lycium barbarum and Astragalus membranaceus. TCHM oligosaccharides play an important role in nutrition, health care, disease diagnosis and prevention as well as have broad application prospects in the field of medicine.

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

To explore the intervention mechanism of combining Polygala tenuifolia (PT) with Magnolia officinalis (MO) on gastrointestinal motility disorders caused by PT. 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. 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. The PT-MO (1:2) couple mechanism mitigated the PT-induced disorders, which were related to the energy, amino acid and fatty metabolisms.

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

Ethnopharmacological relevanceAmbroxol 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 studyOur hypothesis is that ambroxol and P. tenuifolia may potentially possess herbal drug synergetic effects in the blood and brain. Materials and methodsTo 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). ResultsAmbroxol 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. ConclusionThe present study suggests that it is safety without pharmacokinetic interactions for this dosing regimen to use P. tenuifolia extract and ambroxol together.

Cloning, Yeast Expression, and Characterization of a β-Amyrin C-28 Oxidase (CYP716A249) Involved in Triterpenoid Biosynthesis in Polygala tenuifolia.

Polygala tenuifolia Willd. is a traditional Chinese herbal medicine that is widely used in treating nervous system disorders. Triterpene saponins in P. tenuifolia (polygala saponins) have excellent biological activity. As a precursor for the synthesis of presenegin, oleanolic acid (OA) plays an important role in the biosynthesis of polygala saponins. However, the mechanism behind the biosynthesis of polygala saponins remains to be elucidated. In this study, we found that CYP716A249 (GenBank: ASB17946) oxidized the C-28 position of β-amyrin to produce OA. Using quantitative real-time PCR, we observed that CYP716A249 had the highest expression in the roots of 2-year-old P. tenuifolia, which provided a basis for the selection of samples for gene cloning. To identify the function of CYP716A249, the strain R-BE-20 was constructed by expressing β-amyrin synthase in yeast. Then, CYP716A249 was co-expressed with β-amyrin synthase to construct the strain R-BPE-20 by using the lithium acetate method. Finally, we detected β-amyrin and OA by ultra-HPLC-Q Exactive hybrid quadrupole-Orbitrap high-resolution accurate mass spectrometry and GC-MS. The results of this study provide insights into the biosynthesis pathway of polygala saponins.

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 relevanceThe 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. AimTo 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. MethodsWe 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. Results: 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. ConclusionsThis 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.

Bioactive Compounds from Polygala tenuifolia and Their Inhibitory Effects on Lipopolysaccharide-Stimulated Pro-inflammatory Cytokine Production in Bone Marrow-Derived Dendritic Cells.

The roots of Polygala tenuifolia Wild (Polygalaceae), which is among the most important components of traditional Chinese herbal medicine, have been widely used for over 1000 years to treat a variety of diseases. In the current investigation of secondary metabolites with anti-inflammatory properties from Korean medicinal plants, a phytochemical constituent study led to the isolation of 15 compounds (1–15) from the roots of P. tenuifolia via a combination of chromatographic methods. Their structures were determined by means of spectroscopic data such as nuclear magnetic resonance (NMR), 1D- and 2D-NMR, and liquid chromatography-mass spectrometry (LC-MS). As the obtained results, the isolated compounds were divided into two groups—phenolic glycosides (1–9) and triterpenoid saponins (10–15). The anti-inflammatory effects of crude extracts, fractions, and isolated compounds were investigated on the production of the pro-inflammatory cytokines interleukin (IL)-12 p40, IL-6, and tumour necrosis factor-α in lipopolysaccharide-stimulated bone marrow-derived dendritic cells. The IC50 values, ranging from 0.08 ± 0.01 to 21.05 ± 0.40 μM, indicated potent inhibitory effects of the isolated compounds on the production of all three pro-inflammatory cytokines. In particular, compounds 3–12, 14, and 15 showed promising anti-inflammatory activity. These results suggest that phenolic and triterpenoid saponins from P. tenuifolia may be excellent anti-inflammatory agents.

Neuroprotective effects of the aerial parts of Polygala tenuifolia Willd extract on scopolamine-induced learning and memory impairments in mice.

Alzheimer's disease is a common neurodegenerative disease characterized by progressive cognitive dysfunction and behavioral impairment. Aerial parts of Polygala tenuifolia Willd (APT) is a traditional Chinese medicine used for the treatment of amnesia. The present study aimed to investigate the protective effects of APT on scopolamine-induced learning and memory impairments in mice. Scopolamine-induced mice were used to determine the effects of APT on learning and memory impairment. Mice were orally administered with APT (25, 50 and 100 mg/kg) and piracetam (750 mg/kg) for 14 days, and intraperitoneally injected with scopolamine (2 mg/kg) from days 8 to 14. Morris water maze and step-down tests were performed to evaluate learning and memory. Levels of acetylcholine (ACh), choline acetyltransferase (ChAT), acetylcholinesterase (AChE), interleukin (IL)-1β, IL-10 and brain-derived neurotrophic factor (BDNF) in the hippocampus and frontal cortex were measured by ELISA. Superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) were measured via biochemical detection. The results demonstrated that APT ameliorated learning and memory impairment in scopolamine-induced mice. Correspondingly, APT significantly increased ACh and ChAT levels in the hippocampus and prefrontal cortex of scopolamine-induced mice. Additionally, treatment with APT significantly increased BDNF and IL-10 levels, and decreased IL-1β and AChE levels in the same mice. Furthermore, APT significantly increased SOD activity and GSH content, and decreased MDA levels in brain tissue. These results indicated that APT may ameliorate learning and memory impairment by regulating cholinergic activity, promoting BDNF and inhibiting neuroinflammation and oxidative stress.

Extract of the Aerial Part of Polygala tenuifolia Attenuates d-Galactose/NaNO2-induced Learning and Memory Impairment in Mice.

Alzheimer's disease, one of the most common types of age-related dementia, is characterized by memory deterioration and behavior disorder. The aboveground part of Polygala tenuifolia is a traditional Chinese medicine used for the treatment of amnesia. This study was conducted to investigate the ameliorating effect of the aerial part of P. tenuifolia on d-galactose/NaNO2-induced learning and memory impairment in mice. d-galactose (120 mg/kg) and NaNO2 (90 mg/kg) were injected intraperitoneally for 60 days to induce learning and memory impairment in mice. The aerial part of P. tenuifolia (25, 50, and 100 mg/kg) and piracetam (200 mg/kg) were simultaneously administered orally on days 15 - 60. Results of this study showed that aerial part of P. tenuifolia significantly decreased the latency time and increased the number of platform crossings in the Morris water maze compared with the Model group. Moreover, the aerial part of P. tenuifolia significantly increased the latency time and decreased the error frequency in the step-down and step-through tests compared with the Model group. Meanwhile, the aerial part of P. tenuifolia was able to regulate the cholinergic system by increasing the levels of ACh and ChAT and decreasing the level of AChe. The aerial part of P. tenuifolia also significantly attenuated the levels of interleukin-1 beta and malonaldehyde and enhanced the interleukin-10 and glutathione levels and superoxide dismutase activity. Furthermore, treatment with aerial part of P.tenuifolia increased the protein and mRNA expression of brain-derived neurotrophic factor and tropomyosin receptor kinase B in the hippocampus. These results suggest that the aerial part of P. tenuifolia can ameliorate learning and memory impairments by modulating cholinergic activity, inhibiting neuroinflammation and oxidative stress, and regulating the brain-derived neurotrophic factor and tropomyosin receptor kinase B signaling pathway.