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1.
Molecules ; 27(10)2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35630542

RESUMO

Dried roots of Polygala tenuifolia (YuanZhi in Chinese) are widely used in Chinese herbal medicine. These components in YuanZhi have significant anti-oxidation properties owing to high levels of 3,6'-disinapoylsucrose (DISS) and Polygalaxanthone III (PolyIII). In order to efficiently extract natural medicines, response surface methodology (RSM) and least squares support vector machine (LSSVM) were used for the modeling and optimization of ultrasound-assisted extraction of DISS and PolyIII together to determine the antioxidant activity of the extracts obtained from YuanZhi. For the optimal combination of the comprehensive yield of DISS and PolyIII (Y), the Box-Behnken design (BBD) was used to improve extraction time (X1), extraction temperature (X2), liquid-solid ratio (X3), and ethanol concentration (X4). The optimal process parameters were determined to be as follows: extraction time, 93 min; liquid-solid ratio, 40 mL/g; extraction temperature, 48 °C; and ethanol concentration, 67%. With these conditions, the predictive optimal combination comprehensive evaluation value is 13.0217. It was clear that the LS-SVM model had higher accuracy in predictive and optimization capabilities, with higher antioxidant activity and lower relative deviations values, than did RSM. Hence, the LS-SVM model proved to be more effective for the analysis and improvement of the extraction process.


Assuntos
Antioxidantes , Polygala , Antioxidantes/farmacologia , Etanol , Análise dos Mínimos Quadrados , Máquina de Vetores de Suporte , Ultrassom
2.
Pharm Biol ; 60(1): 689-698, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35298359

RESUMO

CONTEXT: The mammalian circadian clock system regulates physiological function. Crude drugs, containing Polygalae Radix, and Kampo, combining multiple crude drugs, have been used to treat various diseases, but few studies have focussed on the circadian clock. OBJECTIVE: We examine effective crude drugs, which cover at least one or two of Kampo, for the shortening effects on period length of clock gene expression rhythm, and reveal the mechanism of shortening effects. MATERIALS AND METHODS: We prepared 40 crude drugs. In the in vitro experiments, we used mouse embryonic fibroblasts from PERIOD2::LUCIFERASE knock-in mice (background; C57BL/6J mice) to evaluate the effect of crude drugs on the period length of core clock gene, Per2, expression rhythm by chronic treatment (six days) with distilled water or crude drugs (100 µg/mL). In the in vivo experiments, we evaluated the free-running period length of C57BL/6J mice fed AIN-93M or AIN-93M supplemented with 1% crude drug (6 weeks) that shortened the period length of the PERIOD2::LUCIFERASE expression rhythm in the in vitro experiments. RESULTS: We found that Polygalae Radix (ED50: 24.01 µg/mL) had the most shortened PERIOD2::LUCIFERASE rhythm period length in 40 crude drugs and that the CaMKII pathway was involved in this effect. Moreover, long-term feeding with AIN-93M+Polygalae Radix slightly shortened the free-running period of the mouse locomotor activity rhythm. DISCUSSION AND CONCLUSIONS: Our results indicate that Polygalae Radix may be regarded as a new therapy for circadian rhythm disorder and that the CaMKII pathway may be regarded as a target pathway for circadian rhythm disorders.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/fisiologia , Relógios Circadianos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Polygala , Animais , Relação Dose-Resposta a Droga , Masculino , Medicina Kampo , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Transdução de Sinais/efeitos dos fármacos
3.
Phytother Res ; 36(3): 1402-1412, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35129236

RESUMO

The general consensus is that stress affects the central nervous system and can lead to cognitive problems. The root of Polygala tenuifolia (P. tenuifolia) is a well-known traditional Chinese medicine used for improving brain function. Tenuifolin (TEN) is the major constituent of P. tenuifolia and has a promising neuroprotective property. The purpose of this study was to investigate the alleviating effect of TEN on cognitive impairment induced by chronic restraint stress (CRS) and its mechanism. Our results showed that CRS exposure resulted in impaired cognitive performance in C57BL/6J mice, as indicated by decreased responses in Y-maze, novel objects recognition, and step-through passive avoidance tests. TEN treated daily orally (10 and 20 mg/kg) for 30 days reversed these behavior changes. Meanwhile, TEN could significantly regulate interleukin (IL)-6 and IL-10 levels in the hippocampus. TEN inhibited the toll-like receptor 4/nuclear factor-kappa B-mediated inflammation, as well as adrenocorticotropic hormone and corticosterone levels in serum. Most importantly, we found that TEN also upregulated the expressions of brain-derived neurotrophic factor, tropomyosin kinase B, glucocorticoid receptor, glutamate receptor 1, and synapse-associated proteins. Collectively, these data suggest that TEN has a potential improvement effect on memory loss caused by CRS.


Assuntos
Disfunção Cognitiva , Diterpenos do Tipo Caurano , Polygala , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Diterpenos do Tipo Caurano/farmacologia , Hipocampo , Camundongos , Camundongos Endogâmicos C57BL , Polygala/metabolismo
4.
Molecules ; 27(3)2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35163950

RESUMO

Polygala species are frequently used worldwide in the treatment of various diseases, such as inflammatory and autoimmune disorders as well as metabolic and neurodegenerative diseases, due to the large number of secondary metabolites they contain. The present study was performed on Polygala inexpectata, which is a narrow endemic species for the flora of Turkey, and resulted in the isolation of nine known compounds, 6,3'-disinapoyl-sucrose (1), 6-O-sinapoyl,3'-O-trimethoxy-cinnamoyl-sucrose (tenuifoliside C) (2), 3'-O-(O-methyl-feruloyl)-sucrose (3), 3'-O-(sinapoyl)-sucrose (4), 3'-O-trimethoxy-cinnamoyl-sucrose (glomeratose) (5), 3'-O-feruloyl-sucrose (sibiricose A5) (6), sinapyl alcohol 4-O-glucoside (syringin or eleutheroside B) (7), liriodendrin (8), and 7,4'-di-O-methylquercetin-3-O-ß-rutinoside (ombuin 3-O-rutinoside or ombuoside) (9). The structures of the compounds were determined by the spectroscopic methods including 1D-NMR (1H NMR, 13C NMR, DEPT-135), 2D-NMR (COSY, NOESY, HSQC, HMBC), and HRMS. The isolated compounds were shown in an in silico setting to be accommodated well within the inhibitor-binding pockets of myeloperoxidase and inducible nitric oxide synthase and anchored mainly through hydrogen-bonding interactions and π-effects. It is therefore plausible to suggest that the previously established anti-inflammatory properties of some Polygala-derived phytochemicals may be due, in part, to the modulation of pro-inflammatory enzyme activities.


Assuntos
Compostos Fitoquímicos/análise , Extratos Vegetais/farmacologia , Polygala/metabolismo , Anti-Inflamatórios/análise , Cromatografia Líquida de Alta Pressão/métodos , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Glucosídeos/isolamento & purificação , Glucosídeos/farmacologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Fenilpropionatos/isolamento & purificação , Fenilpropionatos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Raízes de Plantas/química , Polygala/genética , Sacarose/isolamento & purificação , Sacarose/metabolismo , Turquia
5.
Int J Biol Macromol ; 194: 546-555, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34801584

RESUMO

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.


Assuntos
Microglia/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Polygala/metabolismo , Polissacarídeos/farmacologia , Animais , Linhagem Celular , Camundongos , Fator 88 de Diferenciação Mieloide/metabolismo
6.
Free Radic Biol Med ; 179: 76-94, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34933095

RESUMO

Activation of the NLRP3 inflammasome and its mediated neuroinflammation are implicated in neurodegenerative diseases, while mitophagy negatively regulates NLRP3 inflammasome activation. SHP-2, a protein-tyrosine phosphatase, is critical for NLRP3 inflammasome regulation and inflammatory responses. In this study, we investigated whether triterpenoid saponins in Radix Polygalae inhibit the NLRP3 inflammasome via mitophagy induction. First, we isolated the active fraction (polygala saponins (PSS)) and identified 17 saponins by ultra-performance liquid chromatography coupled with diode-array detection and tandem quadrupole time-of-flight mass spectrometry (UHPLC-DAD-Q/TOF-MS). In microglial BV-2 cells, PSS induced mitophagy as evidenced by increased co-localization of LC3 and mitochondria, as well as an increased number of autophagic vacuoles surrounding the mitochondria. Furthermore, the mechanistic study found that PSS activated the AMPK/mTOR and PINK1/parkin signaling pathways via the upregulation of SHP-2. In Aß(1-42)-, A53T-α-synuclein-, or Q74-induced BV-2 cells, PSS significantly inhibited NLRP3 inflammasome activation, which was attenuated by bafilomycin A1 (an autophagy inhibitor) and SHP099 (an SHP-2 inhibitor). In addition, the co-localization of LC3 and ASC revealed that PSS promoted the autophagic degradation of the NLRP3 inflammasome. Moreover, PSS decreased apoptosis in conditioned medium-induced PC-12 cells. In APP/PS1 mice, PSS improved cognitive function, ameliorated Aß pathology, and inhibited neuronal death. Collectively, the present study, for the first time, shows that PSS inhibit the NLRP3 inflammasome via SHP-2-mediated mitophagy in vitro and in vivo, which strongly suggests the therapeutic potential of PSS in various neurodegenerative diseases.


Assuntos
Polygala , Saponinas , Animais , Inflamassomos , Camundongos , Mitofagia , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Saponinas/farmacologia
7.
Zhongguo Zhong Yao Za Zhi ; 46(22): 5744-5759, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34951162

RESUMO

Polygalae Radix has long been used in China for calming the mind, promoting intelligence, communicating the heart and kidney, eliminating phlegm, and reducing swelling. At present, it is used to treat amnesia, insomnia, and malaise. Modern research has revealed that Polygalae Radix mainly contains triterpenoid saponins, xanthone, oligosaccharide esters, etc., with the activities of improving memory, resisting dementia, protecting the brain, relieving cough, and removing phlegm, as well as sedation and hypnosis. The present study reviews the research progress on chemical composition, pharmacological action, quality control, and metabolism of Polygalae Radix in the past 30 years, to provide a theoretical basis for further research and development.


Assuntos
Medicamentos de Ervas Chinesas , Polygala , Oligossacarídeos , Raízes de Plantas , Controle de Qualidade
8.
J Org Chem ; 86(23): 16268-16277, 2021 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-34730980

RESUMO

An improved process for preparing tenuifolin (presenegenin 3-ß-d-glucopyranoside) from the root of Polygala senega L. was developed. A crude saponin mixture extracted from P. senega was subjected to hydrolysis, and the reactivity of compounds in the extract was controlled by utilizing the combination of a flow reactor and experimental design. In addition, column chromatography with HP 20, a synthetic polystyrenic adsorbent, allowed the gram-scale preparation of tenuifolin in a continuous manner with fewer steps. This approach shortens the total time required for gram-scale preparation from 16 to 5 h in a continuous manner while improving the yield from 0.59% to 2.08% (w/w).


Assuntos
Polygala , Diterpenos do Tipo Caurano , Hidrólise , Raízes de Plantas , Temperatura
9.
Int J Mol Sci ; 22(19)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34638751

RESUMO

Obesity is a risk factor for metabolic diseases including type 2 diabetes, nonalcoholic steatohepatitis (NASH), heart diseases, and cancer. This study aimed to investigate the anti-obesity effect of Polygalin C (PC) isolated from Polygala japonica Houtt. in 3T3-L1 adipocytes. Based on Oil Red O assay results, PC significantly decreased lipid accumulation compared to the control. We found that PC suppressed adipogenesis transcription factors including peroxisome proliferator-activated receptor γ (PPAR γ) and CCAAT/enhancer-binding protein (C/EBP) α, and lipogenic factors such as sterol regulatory element-binding protein 1c (SREBP 1c) and fatty acid synthase (FAS), in 3T3-L1 adipocytes using Western blotting and real-time polymerase chain reaction (PCR). Moreover, PC inhibited the differentiation of 3T3-L1 cells by regulating the AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) and mitogen-activated protein kinase/protein kinase B (MAPK/Akt) signaling pathways. Additionally, we confirmed that PC inhibited early adipogenesis factors C/EBP ß and C/EBP δ. Therefore, PC inhibited adipogenesis and lipogenesis in vitro. Thus, PC appears to exert potential therapeutic effects on obesity by suppressing lipid metabolism.


Assuntos
Adipogenia/efeitos dos fármacos , Flavonóis/farmacologia , Lipogênese/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Obesidade , Polygala/química , Células 3T3-L1 , Animais , Ácido Graxo Sintase Tipo I/biossíntese , Flavonóis/química , Flavonóis/isolamento & purificação , Camundongos , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Obesidade/patologia , PPAR gama/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
10.
Int J Biol Macromol ; 192: 546-556, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34648800

RESUMO

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.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Fatores Imunológicos/farmacologia , Extratos Vegetais/farmacologia , Polygala/química , Polissacarídeos/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Biomarcadores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Humanos , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Imunofenotipagem , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Espécies Reativas de Oxigênio/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
11.
BMC Complement Med Ther ; 21(1): 267, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34696749

RESUMO

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.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Medicina Tradicional Chinesa/métodos , Células-Tronco Neurais/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Estrutura Molecular , Teste do Labirinto Aquático de Morris , Polygala/química
12.
J Microbiol Biotechnol ; 31(11): 1576-1582, 2021 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-34528918

RESUMO

Bacterial ß-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 ß-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 ß- glucuronidase inhibitors.


Assuntos
Inibidores Enzimáticos/farmacologia , Escherichia coli/enzimologia , Glucuronidase/antagonistas & inibidores , Polygala/química , Sacarose/farmacologia , Proteínas de Escherichia coli/antagonistas & inibidores , Irinotecano , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Terciária de Proteína
13.
J Pharmacol Sci ; 147(2): 184-191, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34384566

RESUMO

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.


Assuntos
Anti-Inflamatórios , Medicamentos de Ervas Chinesas/farmacologia , Glicosídeos/farmacologia , Inflamação/genética , Polygala/química , Xantonas/farmacologia , Animais , Citocinas/genética , Citocinas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Inflamação/etiologia , Mediadores da Inflamação/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Lipopolissacarídeos/efeitos adversos , Camundongos , Óxido Nítrico/genética , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
J Pharm Biomed Anal ; 204: 114281, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34333452

RESUMO

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.


Assuntos
Medicamentos de Ervas Chinesas , Plantas Medicinais , Polygala , Cromatografia Líquida de Alta Pressão , Mineração de Dados , Humanos , Espectrometria de Massas em Tandem
15.
Dev Biol ; 479: 1-10, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34314693

RESUMO

Along with a strict determinism of early embryogenesis in most living organisms, some of them exhibit variability of cell fates and developmental pathways. Here we discuss the phenomena of determinism and variability of developmental pathways, defining its dependence upon cell potency, cell sensitivity to the external signals and cell signaling. We propose a set of conjectures on the phenomenon of variability of developmental pathways, and denote a difference between a normal (local) variability, leading to an invariant final structure (e.g., embryo shape), and fundamental one, which is a switching between different developmental pathways, leading to different possible structures. For illustrating our conjectures, we analyzed early developmental stages of plant embryos with different levels of variability of morphogenesis pathways, and provide a set of computational experiments by Morphogenesis Software.


Assuntos
Diferenciação Celular/fisiologia , Linhagem da Célula/fisiologia , Desenvolvimento Vegetal/fisiologia , Arabidopsis/embriologia , Fumaria/embriologia , Morfogênese/fisiologia , Desenvolvimento Vegetal/genética , Polygala/embriologia , Pulsatilla/embriologia
16.
Pharmacol Res ; 170: 105697, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34062240

RESUMO

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.


Assuntos
Envelhecimento/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Complemento C3/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Polygala , Saponinas/farmacologia , Fatores Etários , Envelhecimento/genética , Envelhecimento/imunologia , Envelhecimento/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Caenorhabditis elegans/genética , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo , Longevidade/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos Endogâmicos C57BL , /imunologia , /prevenção & controle , Fármacos Neuroprotetores/isolamento & purificação , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Raízes de Plantas , Polygala/química , Saponinas/isolamento & purificação , Memória Espacial/efeitos dos fármacos , Transcriptoma
17.
J Pharm Pharmacol ; 73(2): 247-262, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33793803

RESUMO

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.


Assuntos
Motilidade Gastrointestinal/efeitos dos fármacos , Magnolia/química , Extratos Vegetais/farmacologia , Polygala/química , Aminoácidos/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Metabolismo Energético/efeitos dos fármacos , Ácidos Graxos/metabolismo , Fezes , Feminino , Masculino , Espectrometria de Massas , Metabolômica/métodos , Camundongos , Extratos Vegetais/toxicidade , Ratos , Ratos Sprague-Dawley
18.
Metab Brain Dis ; 36(3): 453-462, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33394286

RESUMO

Stroke is considered one of the leading causes of death worldwide. The treatment is limited; however, the Brazilian flora has a great source of natural products with therapeutic potentials. Studies with the medicinal plant Polygala sabulosa W. Bennett provided evidence for its use as an anti-inflammatory and neuroprotective drug. In the case of ischemic stroke due to lack of oxygen, both acute and chronic inflammatory processes are activated. Thus, we hypothesized that P. sabulosa (HEPs) has the potential to treat the motor and cognitive deficits generated by ischemic stroke. Male mice were subjected to global ischemia for 60 min, followed by reperfusion and orally treated with HEPs (100 mg/kg in saline + 3% tween 20) twice a day (12 h apart) for 48 h starting 3 h after surgery. Motor skills were assessed using grip force and open field tasks. Hippocampi were then collected for mRNA quantification of the cytokines IL-1-ß and TNF-α levels. After 48 h of acute treatment, spatial reference memory was evaluated in a Morris water maze test for another group of animals. We show that HEPs treatment significantly prevented motor weakness induced by ischemia. Brain infarct area was reduced by 22.25% with downregulation of the levels of IL-1ß and TNF-α mRNA. Learning performance and memory ability on Morris water maze task were similar to the sham group. Our data demonstrates the neuroprotective properties of HEPs through its anti-inflammatory activities, which prevent motor and cognitive impairments, suggesting that HEPs may be an effective therapy for ischemic stroke.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Transtornos Motores/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Extratos Vegetais/uso terapêutico , Polygala , Animais , Isquemia Encefálica/metabolismo , Cognição/efeitos dos fármacos , Disfunção Cognitiva/metabolismo , Modelos Animais de Doenças , Força da Mão , Interleucina-1beta/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Transtornos Motores/metabolismo , Destreza Motora/efeitos dos fármacos , Força Muscular/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
19.
Neuromolecular Med ; 23(3): 428-443, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33432492

RESUMO

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.


Assuntos
Angelica/química , Autofagia/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Transtornos Parkinsonianos/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Polygala/química , Sapindaceae/química , Animais , Apomorfina/farmacologia , Linhagem Celular Tumoral , Corpo Estriado/enzimologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/enzimologia , Avaliação Pré-Clínica de Medicamentos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Neuroblastoma/patologia , Fármacos Neuroprotetores/farmacologia , Oxidopamina/toxicidade , Extratos Vegetais/farmacologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Teste de Desempenho do Rota-Rod , Saponinas/química , Saponinas/farmacologia , Saponinas/uso terapêutico , Substância Negra/enzimologia , Triterpenos/química , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Tirosina 3-Mono-Oxigenase/análise
20.
J Ethnopharmacol ; 269: 113764, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33383115

RESUMO

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.


Assuntos
Ambroxol/farmacocinética , Encéfalo/metabolismo , Corpo Estriado/metabolismo , Medicamentos de Ervas Chinesas/farmacocinética , Transtornos Parkinsonianos/tratamento farmacológico , Polygala/química , Ambroxol/metabolismo , Ambroxol/uso terapêutico , Animais , Área Sob a Curva , Análise Química do Sangue , Barreira Hematoencefálica , Encéfalo/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Interações Ervas-Drogas , Masculino , Microdiálise/métodos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem
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