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The hard clam Meretrix meretrix, which has been traditionally used as medicine and seafood, was used in this study to isolate antioxidant peptides. First, a peptide-rich extract was tested for its protective effect against paraquat-induced oxidative stress using the nematode model Caenorhabditis elegans. Then, three novel antioxidant peptides; MmP4 (LSDRLEETGGASS), MmP11 (KEGCREPETEKGHR) and MmP19 (IVTNWDDMEK), were identified and were found to increase the resistance of nematodes against paraquat. Circular dichroism spectroscopy revealed that MmP4 was predominantly in beta-sheet conformation, while MmP11 and MmP19 were primarily in random coil conformation. Using transgenic nematode models, the peptides were shown to promote nuclear translocation of the DAF-16/FOXO transcription factor, a pivotal regulator of stress response and lifespan, and induce the expression of superoxide dismutase 3 (SOD-3), an antioxidant enzyme. Analysis of DAF-16 target genes by real-time PCR reveals that sod-3 was up-regulated by MmP4, MmP11 and MmP19 while ctl-1 and ctl-2 were also up-regulated by MmP4. Further examination of daf-16 using RNA interference suggests that the peptide-increased resistance of C. elegans to oxidative stress was DAF-16 dependent. Taken together, these data demonstrate the antioxidant activity of M. meretrix peptides, which are associated with activation of the stress response factor DAF-16 and regulation of the antioxidant enzyme genes.
Assuntos
Antioxidantes/farmacologia , Fatores Biológicos/farmacologia , Bivalves/metabolismo , Caenorhabditis elegans/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Animais Geneticamente Modificados , Antioxidantes/química , Antioxidantes/isolamento & purificação , Bioensaio/métodos , Fatores Biológicos/química , Fatores Biológicos/isolamento & purificação , Caenorhabditis elegans/efeitos dos fármacos , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Modelos Animais , Estresse Oxidativo/genética , Paraquat/toxicidade , Peptídeos/química , Peptídeos/isolamento & purificação , Peptídeos/farmacologia , Interferência de RNA , Espécies Reativas de Oxigênio/metabolismoRESUMO
Immunity due to immune balance contributes to disease prevention and treatment. Radix Codonopsis polysaccharide (RCP) is isolated from the root of the Chinese herb Codonopsis pilosula. Previous studies have indicated that RCP has immunomodulatory activities; however, the effects of RCP on immunity, especially immune balance, are still largely unknown. In the present study, we investigated the effects of RCP on T-cell balance in mice. The mice were pretreated intragastrically with or without RCP for 15 days and injected with hydrocortisone on days 10-15 to disturb the immune system. The spleen and thymus were weighed and used to calculate immune organ indexes. The percentages of CD4+ T cells, CD8+ T cells, Th1 cells, Th2 cells, regulatory T cells (Tregs) and Th17 cells in peripheral blood were assayed by flow cytometry. Pro-inflammatory and anti-inflammatory cytokines, TNF-α, IL-1ß and IL-10, in serum were determined by enzyme-linked immunosorbent assay (ELISA) kits. The results showed that RCP pretreatment could maintain the homeostasis of CD8+ T cells, Tregs, Th17 cells, TNF-α, IL-1ß and IL-10 in hydrocortisone-treated mice. Furthermore, RCP pretreatment maintained the immune balance of CD4+/CD8+ T cells, Th1/Th2 cells, Tregs/Th17 cells, IL-10/TNF-α and IL-10/IL-1ß. Taken together, RCP pretreatment had beneficial effects on the maintenance of T-cell balance against hydrocortisone disturbance in mice and potential to be developed into novel functional food.
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Codonopsis , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Animais , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/isolamento & purificação , Polissacarídeos/isolamento & purificação , Linfócitos T/metabolismoRESUMO
The efficacy of polysaccharides is widespread, especially in immune regulation. However, the genetic basis of the changes in polysaccharides regulating immunity is unclear. To obtain genome-wide insights into transcriptome changes and regulatory networks, we designed a polysaccharide formula, comprising lentinan, pachymaran and tremelia, to increase the availability of their optimized active sites. In this case, we focused on a model of immunosuppression to investigate genes by digital gene expression (DGE) tag profiling in T and B cells. These genes were further validated by qRT-PCR and Western blot experiments. Consequently, polysaccharide formula treatment helped to recover the expression of immune-related genes, including CADM1, CCR2, IGLL1, LIGP1, and FCGR3, FCGR2 in B cells, as well as S100A8, S100A9, ChIL3, MMP8 and IFITM3 in T cells. These results suggest that treatment with polysaccharides improves the immunity of immunosuppressive mice by regulating genes associated with T and B cell functions.
Assuntos
Imunidade/efeitos dos fármacos , Terapia de Imunossupressão , Imunossupressores/farmacologia , Linfócitos T/efeitos dos fármacos , Animais , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Glucanos/farmacologia , Humanos , Imunidade/genética , Lentinano/farmacologia , Camundongos , Ortópteros/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Linfócitos T/imunologiaRESUMO
The purpose of this study is to investigate the effects of probiotics combined with prebiotics (PP) supplementation on weaned rat metabolism. A metabonomic strategy employing 1H-NMR spectroscopy and multivariate data analysis was used to examine weaned rat biological responses to PP supplementation. Male Sprague-Dawley rats (post-natal day 21, PD 21) received probiotics (Lactobacillus acidophilus NCFM (L-NCFM) and Bifidobacterium lactis Bi-07 (B-LBi07), 1 : 1, 1.0 × 1011 cfu kg-1) and prebiotics (Lycium barbarum polysaccharides (LBP), Poria cocos polysaccharides (PCPs) and Lentinan, 1 : 1 : 1, 24 g kg-1) via intragastric administration for 28 consecutive days. Urine and feces were collected for analysis. Significant topographical metabolic variations were present in urine and feces. Urinary metabolites upregulated by PP treatment included alanine, N-acetylglycine, glutamine, dimethylamine, phosphorylcholine, ethylene glycol, mannitol, phenylacetylglycine and glycoate, which were related to alanine, aspartate and glutamate metabolism, and choline metabolism. Feces-derived metabolites, including caproate, valerate, butyrate, propionate, lactate, acetate, succinate, methanol, threonine and methionine, were significantly increased, which were related to short-chain fatty acid (SCFA) metabolism and TCA cycle metabolism. These results indicate that dietary PP supplementation can regulate common systemic metabolic processes, including energy metabolism, amino acid metabolism, lipid metabolism, nucleic acid metabolism, and gut microbiota-related metabolism. This study also illuminates the vital role of PP supplementation in regulating the metabolism of weaned rats.
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BACKGROUND AND PURPOSE: Increasing energy expenditure through adipocyte thermogenesis is generally accepted as a promising strategy to mitigate obesity and its related diseases. However, few clinically effective and safe agents are known to promote adipocyte thermogenesis. In this study, 20 traditional Chinese herbal medicines were screened to examine whether they induced adipocyte thermogenesis. EXPERIMENTAL APPROACH: The effects of Chinese herbal medicines or components isolated from extracts of A. membranaceus, on adipocyte thermogenesis were analysed by assessing expression of uncoupling protein 1 (UCP1) by qPCR. Eight-week-old C57BL6/J male mice were fed a high-fat diet for 8 weeks and then randomized to two groups treated with vehicle or formononetin for another 8 weeks. Glucose tolerance tests and staining of adipose tissue with haematoxylin and eosin were carried out. Whole-body oxygen consumption was measured with an open-circuit indirect calorimetry system. KEY RESULTS: Extracts of A. membranaceus increased expression of Ucp1 in primary cultures of mouse adipocytes. Formononetin was the only known component of A. membranaceus extracts to increase adipocyte Ucp1 expression. Diet-induced obese mice treated with formononetin gained less weight and showed higher energy expenditure than untreated mice. In addition, formononetin binds directly with PPARγ. CONCLUSIONS AND IMPLICATION: Taken together, our study demonstrates that the Chinese herbal medicine from A. membranaceus and its constituent formononetin have the potential to reduce obesity and associated metabolic disorders. Our results suggest that formononetin regulates adipocyte thermogenesis as a non-classical PPARγ agonist.
Assuntos
Adipócitos/efeitos dos fármacos , Astragalus propinquus/química , Isoflavonas/isolamento & purificação , Isoflavonas/farmacologia , PPAR gama/metabolismo , Termogênese/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/farmacologia , Metabolismo Energético/efeitos dos fármacos , Teste de Tolerância a Glucose , Masculino , Camundongos , Obesidade/induzido quimicamente , Obesidade/prevenção & controle , Consumo de Oxigênio/efeitos dos fármacos , PPAR gama/fisiologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Cultura Primária de Células , RNA Interferente Pequeno/farmacologia , Termogênese/fisiologia , Proteína Desacopladora 1/biossínteseRESUMO
Epimedium has been traditionally used to treat a variety of medical conditions, including neurological disorders. In this study, an acidic polysaccharide EbPS-A1 is isolated from Epimedium brevicornum and found to contain mainly galacturonic acid, galactose, and rhamnose but also arabinose and glucuronic acid. Using Caenorhabditis elegans models, we show that EbPS-A1 is capable of inhibiting behavioral dysfunction mediated by polyglutamine (polyQ), which is implicated in several neurodegenerative disorders such as Huntington's disease. Interestingly, EbPS-A1 does not inhibit polyQ aggregation or extend lifespan in the nematodes; it does, however, improve the survival under increased oxidative stress of both polyQ and wild-type nematodes intoxicated by paraquat. Further studies reveal that EbPS-A1 is capable of not only scavenging free radicals in vitro but also reducing reactive oxygen species levels, enhancing antioxidant enzyme activities, and decreasing lipid peroxidation product in C. elegans models. Together, these results suggest that the protective effect of Epimedium polysaccharide against polyQ-mediated neurotoxicity is likely due to its antioxidant function.
Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Epimedium/química , Neurotoxinas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Peptídeos/toxicidade , Polissacarídeos/farmacologia , Animais , Antioxidantes/metabolismo , Comportamento Animal/efeitos dos fármacos , Fracionamento Químico , Sequestradores de Radicais Livres/farmacologia , Malondialdeído/metabolismo , Agregados Proteicos/efeitos dos fármacos , Análise de SobrevidaRESUMO
Overweight or obese adults aged 20~55 years and living in Beijing more than one year were randomly divided into different management groups. A one-year integrated health management intervention was applied in the health management groups. The physical indicators and metabolic indicators changed after one-year intervention on the overweight and obese adults. The annual reduction of the physical indicators was significant in all groups (p < 0.05) except the weight loss in the placebo + general management group. The health management and the dietary supplement have statistically significant (p < 0.001, p < 0.001) effects on the annual reduction of these indicators and interactive effect between them was found on some of these indicators such as bodyweight, body mass index (BMI), body fat ratio (BFR), and hipline (p < 0.05). The dietary supplement + health management group had the best annual reduction effects for the indicators among the groups. Integrated health management interventions including both dietary supplements intervention and health management could improve metabolic indicators in overweight and obese adults together with the physical indicators, suggesting the intermediated role of metabolic indictors in controlling obesity.
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An integrative metabolomics and proteomics approach can provide novel insights in the understanding of biological systems. We have integrated proteome and metabolome data sets for a holistic view of the molecular mechanisms in disease. Using quantitative iTRAQ-LC-MS/MS proteomics coupled with UPLC-Q-TOF-HDMS based metabolomics, we determined the protein and metabolite expression changes in the kidney-yang deficiency syndrome (KYDS) rat model and further investigated the intervention effects of the Jinkui Shenqi Pill (JSP). The VIP-plot of the orthogonal PLS-DA (OPLS-DA) was used for discovering the potential biomarkers to clarify the therapeutic mechanisms of JSP in treating KYDS. The results showed that JSP can alleviate the kidney impairment induced by KYDS. Sixty potential biomarkers, including 5-l-glutamyl-taurine, phenylacetaldehyde, 4,6-dihydroxyquinoline, and xanthurenic acid etc., were definitely up- or down-regulated. The regulatory effect of JSP on the disturbed metabolic pathways was proved by the established metabonomic method. Using pathway analyses, we identified the disturbed metabolic pathways such as taurine and hypotaurine metabolism, pyrimidine metabolism, tyrosine metabolism, tryptophan metabolism, histidine metabolism, steroid hormone biosynthesis, etc. Furthermore, using iTRAQ-based quantitative proteomics analysis, seventeen differential proteins were identified and significantly altered by the JSP treatment. These proteins appear to be involved in Wnt, chemokine, PPAR, and MAPK signaling pathways, etc. Functional pathway analysis revealed that most of the proteins were found to play a key role in the regulation of metabolism pathways. Bioinformatics analysis with the IPA software found that these differentially-expressed moleculars had a strong correlation with the α-adrenergic signaling, FGF signaling, etc. Our data indicate that high-throughput metabolomics and proteomics can provide an insight on the herbal preparations affecting the metabolic disorders using high resolution mass spectrometry.
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Doenças Metabólicas/metabolismo , Metaboloma , Metabolômica , Preparações de Plantas/farmacologia , Proteoma , Proteômica , Animais , Biomarcadores , Masculino , Espectrometria de Massas/métodos , Doenças Metabólicas/tratamento farmacológico , Redes e Vias Metabólicas , Metabolômica/métodos , Preparações de Plantas/uso terapêutico , Análise de Componente Principal , Proteômica/métodos , Ratos , Transdução de SinaisRESUMO
Myeloid-derived suppressor cells (MDSCs) are well known for their capacity to suppress antitumor T-cell responses, but their effects on B-cell function and antibody production remain unclear. Here, we found that MDSCs that accumulated around the germinal center in the spleen of tumor-bearing mice co-located with B cells. In the presence of MDSCs, the antibody reaction to a surrogate antigen was significantly enhanced in mice, especially the immunoglobulin (Ig)A subtype. Co-culture with MDSCs promoted both proliferation and differentiation of B cells into IgA-producing plasma cells in vitro. Interestingly, the cross talk between MDSCs and B cells required cell-cell contact. MDSCs from tumor necrosis factor receptor (TNFR) 2-/- mice, but not from TNFR1-/- mice, failed to promote B-cell responses. Further investigation suggested that interleukin-10 and transforming growth factor-ß1 were crucial for the MDSC-mediated promotion of IgA responses. These results demonstrate a novel mechanism of MDSC-mediated immune regulation during tumor growth.
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Linfócitos B/metabolismo , Imunoglobulina A/biossíntese , Células Supressoras Mieloides/metabolismo , Receptores Tipo II do Fator de Necrose Tumoral/metabolismo , Animais , Formação de Anticorpos , Proliferação de Células , Interleucina-10/metabolismo , Ativação Linfocitária , Camundongos Endogâmicos C57BL , Baço/metabolismo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
This work was designed to explore the effective components and targets of herbal medicine AS1350 and its effect on "Kidney-Yang Deficiency Syndrome" (KYDS) based on a chinmedomics strategy which is capable of directly discovering and predicting the effective components, and potential targets, of herbal medicine. Serum samples were analysed by UPLC-MS combined with pattern recognition analysis to identify the biomarkers related to the therapeutic effects. Interestingly, the effectiveness of AS1350 against KYDS was proved by the chinmedomics method and regulated the biomarkers and targeting of metabolic disorders. Some 48 marker metabolites associated with alpha-linolenic acid metabolism, fatty acid metabolism, sphingolipids metabolism, phospholipid metabolism, steroid hormone biosynthesis, and amino acid metabolism were identified. The correlation coefficient between the constituents in vivo and the changes of marker metabolites were calculated by PCMS software and the potential effective constituents of AS1350 were also confirmed. By using chinmedomics technology, the components in AS1350 protecting against KYDS by re-balancing metabolic disorders of fatty acid metabolism, lipid metabolism, steroid hormone biosynthesis, etc. were deduced. These data indicated that the phenotypic characterisations of AS1350 altering the metabolic signatures of KYDS were multi-component, multi-pathway, multi-target, and overall regulation in nature.
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Medicamentos de Ervas Chinesas/administração & dosagem , Doenças Metabólicas/tratamento farmacológico , Metaboloma/genética , Deficiência da Energia Yang/tratamento farmacológico , Ácido alfa-Linolênico/genética , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Hormônios Esteroides Gonadais/sangue , Hormônios Esteroides Gonadais/genética , Humanos , Nefropatias , Espectrometria de Massas , Doenças Metabólicas/sangue , Metaboloma/efeitos dos fármacos , Fosfolipídeos/sangue , Fosfolipídeos/genética , Esfingolipídeos/sangue , Esfingolipídeos/genética , Deficiência da Energia Yang/sangue , Deficiência da Energia Yang/genética , Ácido alfa-Linolênico/sangueRESUMO
Since excessive reactive oxygen species (ROS) is known to be associated with aging and age-related diseases, strategies modulating ROS level and antioxidant defense systems may contribute to the delay of senescence. Here we show that the protein hydrolyzate from Angelica sinensis was capable of increasing oxidative survival of the model animal Caenorhabditis elegans intoxicated by paraquat. The hydrolyzate was then fractionated by ultrafiltration, and the antioxidant fraction (<3 kDa) was purified by gel filtration to obtain the antioxidant A. sinensis peptides (AsiPeps), which were mostly composed of peptides with <20 amino acid residues. Further studies demonstrate that AsiPeps were able to reduce the endogenous ROS level, increase the activities of the antioxidant enzymes superoxide dismutase and catalase, and decrease the content of the lipid peroxidation product malondialdehyde in nematodes treated with paraquat or undergoing senescence. AsiPeps were also shown to reduce age pigments accumulation and extend lifespan but did not affect the food-intake behavior of the nematodes. Taken together, our results demonstrate that A. sinensis peptides (AsiPeps) are able to delay aging process in C. elegans through antioxidant activities independent of dietary restriction.
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Envelhecimento/fisiologia , Angelica sinensis/química , Antioxidantes/farmacologia , Caenorhabditis elegans/fisiologia , Peptídeos/farmacologia , Hidrolisados de Proteína/farmacologia , Envelhecimento/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/enzimologia , Bovinos , Cromatografia Líquida , Malondialdeído/metabolismo , Dados de Sequência Molecular , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Paraquat/toxicidade , Peptídeos/química , Pigmentos Biológicos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Espectrometria de Massas em TandemRESUMO
This paper was designed to investigate the phenotypic characterization of Nanshi Oral Liquid (NOL) alters metabolic signatures of the 'Kidney Yang Deficiency syndrome' (KYDS). Urine metabolites were profiled by UPLC-ESI-Q-TOF-HDMS. The significantly changed metabolites such as xanthurenic acid, 4,8-dihydroxyquinoline, 3-methyldioxyindole, 4,6-dihydroxyquinoline, kynurenic acid, hippuric acid, taurine, tyramine, and 3-metanephrine, had been identified, and were related to the disturbance in tyrosine metabolism, steroid hormone biosynthesis, taurine and hypotaurine metabolism, tryptophan metabolism, phenylalanine metabolism and lysine degradation, which were helpful to further understanding the KYDS and intervention mechanism of NOL. The biochemical result showed that NOL can alleviate the kidney impairment induced by KYDS. Metabolomics results indicated the significantly changed metabolites were found to be reasonable in explaining the action mechanism of NOL. Interestingly, the effectiveness of NOL against KYDS was proved using the established metabolomics method and regulated the biomarkers as well as adjusted the metabolic disorder pathways. NOL had potentially pharmacological effect through regulating multiple perturbed pathways to normal state. This work showed that the metabolomics method was a powerful approach for studying the phenotypic characterization of disease's syndrome during disease prevention and its intervention mechanism.
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Medicamentos de Ervas Chinesas/administração & dosagem , Nefropatias/tratamento farmacológico , Nefropatias/metabolismo , Metaboloma , Metabolômica , Deficiência da Energia Yang/tratamento farmacológico , Deficiência da Energia Yang/metabolismo , Animais , Biomarcadores , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Humanos , Nefropatias/patologia , Masculino , Espectrometria de Massas , Medicina Tradicional Chinesa , Redes e Vias Metabólicas , Metabolômica/métodos , Análise de Componente Principal , Ratos , Síndrome , Deficiência da Energia Yang/patologiaRESUMO
Polysaccharide compounds (PCs), which composed of different kinds of polysaccharides always isolated from different kinds of traditional Chinese medicine, are now attracting more and more attentions due to their strong immunomodulatory activities beyond the corresponding one-component polysaccharides. In this study, we demonstrated for the first time that PCs-1 and PCs-2 had strong immunomodulatory effects on macrophages both in in vitro and in vivo models by atomic force microscopy (AFM). By high resolution AFM imaging, PCs-1 and PCs-2 were found to inhibit LPS induced cell surface particle size and roughness increase in RAW264.7 macrophages, demonstrating the anti-inflammatory effects of PCs-1 and PCs-2 on macrophages. PCs-1 and PCs-2 were also proved to increase the particle size and roughness of resting RAW264.7 macrophages, which suggested that PCs could activate resting RAW264.7 macrophages. And additionally, PCs-1 and PCs-2 were also found to reverse the surface particle size and roughness decrease of peritoneal macrophages isolated from cyclophosphamide induced immunosuppressive mice, suggesting the activation effects of PCs-1 and PCs-2 on immunosuppressive macrophages. These results further enhanced our understanding of macrophage activations by direct imaging of cell surface ultrastructure and also highlighted AFM as a novel nanotool for macrophage detections. And most importantly, these results also indicated the outstanding immunomodulatory effects of PCs on macrophages, which therefore suggested that PCs could be served as a kind of novel immunomodulatory agents that would benefit human health. SCANNING 38:792-801, 2016. © 2016 Wiley Periodicals, Inc.
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Fatores Imunológicos/farmacologia , Macrófagos/efeitos dos fármacos , Polissacarídeos/farmacologia , Animais , Células Cultivadas , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/ultraestrutura , Camundongos , Camundongos Endogâmicos BALB C , Microscopia de Força AtômicaRESUMO
Ginseng occupies a prominent position in the list of best-selling natural products worldwide. Asian ginseng (Panax ginseng) and American ginseng (Panax quinquefolius) show different properties and medicinal applications in pharmacology, even though the main active constituents of them are both thought to be ginsenosides. Metabolomics is a promising method to profile entire endogenous metabolites and monitor their fluctuations related to exogenous stimulus. Herein, an untargeted metabolomics approach was applied to study the overall urine metabolic differences between Asian ginseng and American ginseng in mice. Metabolomics analyses were performed using gas chromatography-mass spectrometry (GC-MS) together with multivariate statistical data analysis. A total of 21 metabolites related to D-glutamine and D-glutamate metabolism, glutathione metabolism, TCA cycle and glyoxylate and dicarboxylate metabolism, differed significantly under the Asian ginseng treatment; 34 metabolites mainly associated with glyoxylate and dicarboxylate metabolism, TCA cycle and taurine and hypotaurine metabolism, were significantly altered after American ginseng treatment. Urinary metabolomics reveal that Asian ginseng and American ginseng can benefit organism physiological and biological functions via regulating multiple metabolic pathways. The important pathways identified from Asian ginseng and American ginseng can also help to explore new therapeutic effects or action targets so as to broad application of these two ginsengs.
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Cromatografia Gasosa-Espectrometria de Massas , Ginsenosídeos , Metaboloma , Panax/química , Urina , Animais , Ginsenosídeos/química , Ginsenosídeos/farmacocinética , Ginsenosídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos ICRRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Dictyophora indusiata is a medicinal mushroom traditionally used in China for a variety of conditions, including inflammatory and neural diseases. D. indusiata polysaccharides (DiPS) are shown to have in vitro antioxidant activity but in vivo evidence is lacking. This study aimes to explore the antioxidant capacity and related neuroptotective activities of DiPS using wild-type and neurodegenerative Caenorhabditis elegans models. MATERIALS AND METHODS: The antioxidant capacities of DiPS were first determined using paraquat survival and Pgst-4::GFP expression assays in wild-type and transgenic C. elegans models, respectively, and then further investigated by determining reactive oxygen species (ROS) level, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity as well as functional parameters of mitochondria. The activation of stress response transcription factors and neuroptotective activities were examined using nuclear localization and chemosensory behavioral assays in transgenic nematodes, respectively. RESULTS: DiPS was shown not only to increase survival rate and reduce stress level under paraquat-induced oxidative conditions but also to decrease ROS and MDA levels and increase SOD activity in C. elegans models. Moreover, DiPS was also able to restore the functional parameters of mitochondria, including membrane potential and ATP content, in paraquat-stressed nematodes. In addition, nuclear translocation assays demonstrate that the stress response transcription factor DAF-16/FOXO was involved in the antioxidant activity of the polysaccharide. Further experiments reveal that DiPS was capable of reducing ROS levels and alleviating chemosensory behavior dysfunction in transgenic nematode models of neurodegenerative diseases mediated by polyglutamine and amyloid-ß protein. CONCLUSIONS: These findings demonstrate the antioxidant and neuroprotective activities of the D. indusiata polysaccharide DiPS in wild-type and neurodegenerative C. elegans models, and thus provide an important pharmacological basis for the therapeutic potential of D. indusiata in neurodegeneration.
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Agaricales/química , Antioxidantes/farmacologia , Caenorhabditis elegans/efeitos dos fármacos , Degeneração Neural , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Síndromes Neurotóxicas/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/farmacologia , Trifosfato de Adenosina/metabolismo , Peptídeos beta-Amiloides/toxicidade , Animais , Animais Geneticamente Modificados , Antioxidantes/isolamento & purificação , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Relação Dose-Resposta a Droga , Metabolismo Energético/efeitos dos fármacos , Malondialdeído/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/isolamento & purificação , Síndromes Neurotóxicas/genética , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Paraquat/toxicidade , Peptídeos/toxicidade , Polissacarídeos/isolamento & purificação , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Fatores de TempoRESUMO
Astragalus membranaceus is a medicinal plant traditionally used in China for a variety of conditions, including inflammatory and neural diseases. Astragalus polysaccharides are shown to reduce the adverse effect of levodopa which is used to treat Parkinson's disease (PD). However, the neuroprotective effect of Astragalus polysaccharides per se in PD is lacking. Using Caenorhabditis elegans models, we investigated the protective effect of astragalan, an acidic polysaccharide isolated from A. membranaceus, against the neurotoxicity of 6-hydroxydopamine (6-OHDA), a neurotoxin that can induce parkinsonism. We show that 6-OHDA is able to degenerate dopaminergic neurons and lead to the deficiency of food-sensing behavior and a shorter lifespan in C. elegans. Interestingly, these degenerative symptoms can be attenuated by astragalan treatment. Astragalan is also shown to alleviate oxidative stress through reducing reactive oxygen species level and malondialdehyde content and increasing superoxide dismutase and glutathione peroxidase activities and reduce the expression of proapoptotic gene egl-1 in 6-OHDA-intoxicated nematodes. Further studies reveal that astragalan is capable of elevating the decreased acetylcholinesterase activity induced by 6-OHDA. Together, our results demonstrate that the protective effect of astragalan against 6-OHDA neurotoxicity is likely due to the alleviation of oxidative stress and regulation of apoptosis pathway and cholinergic system and thus provide an important insight into the therapeutic potential of Astragalus polysaccharide in neurodegeneration.
Assuntos
Astragalus propinquus/química , Neurônios Dopaminérgicos/efeitos dos fármacos , Quempferóis/farmacologia , Fármacos Neuroprotetores/farmacologia , Síndromes Neurotóxicas/prevenção & controle , Polissacarídeos/farmacologia , Acetilcolinesterase/metabolismo , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Comportamento Animal/efeitos dos fármacos , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/metabolismo , Citoproteção , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Relação Dose-Resposta a Droga , Quempferóis/isolamento & purificação , Peroxidação de Lipídeos , Longevidade/efeitos dos fármacos , Degeneração Neural , Fármacos Neuroprotetores/isolamento & purificação , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Síndromes Neurotóxicas/psicologia , Estresse Oxidativo/efeitos dos fármacos , Oxidopamina , Fitoterapia , Plantas Medicinais , Polissacarídeos/isolamento & purificação , Espécies Reativas de Oxigênio/metabolismo , Proteínas Repressoras/metabolismo , Fatores de TempoRESUMO
Correction for 'Rapidly improved determination of metabolites from biological data sets using the high-efficient TransOmics tool' by Aihua Zhang et al., Mol. BioSyst., 2014, 10, 2160-2165.
RESUMO
Metabolomics is a new approach based on the systematic study of the full complement of metabolites in a biological sample. Extracting biomedical information from large datasets is of considerable complexity. Furthermore, the traditional method of assessing metabolomics data is not only time-consuming but it is often subjective work. Here we used sensitive ultra-performance LC-ESI/Q-TOF high-definition mass spectrometry (UPLC-ESI-Q-TOF-MS) in positive ion mode coupled with a new developed software program TransOmics for widely untargeted metabolomics, which incorporates novel nonlinear alignment, deconvolution, matched filtration, peak detection, and peak matching to characterize metabolites as a case study. The TransOmics method can facilitate prioritization of the data and greatly increase the probability of identifying metabolites related to the phenotype of interest. By this means, 17 urinary differential metabolites were identified (less than 10 min) involving the key metabolic pathways including tyrosine metabolism, glutathione metabolism, phenylalanine metabolism, ascorbate and aldarate metabolism, arginine and proline metabolism, and so forth. Metabolite identification has also been significantly improved, using the correlation peak patterns in contrast to a reference metabolite panel. It can detect and identify metabolites automatically and remove background noise, and also provides a user-friendly graphical interface to apply principal component analyses, correlation analysis and compound statistics. This investigation illustrates that metabolomics combined with the proposed bioinformatic approach (based on TransOmics) is important to elucidate the developing biomarkers and the physiological mechanism of disease, and has opened the door for the development of a new genre of metabolite identification methods.
Assuntos
Biomarcadores/urina , Biologia Computacional/métodos , Redes e Vias Metabólicas , Metabolômica/métodos , Animais , Cromatografia Líquida de Alta Pressão , Bases de Dados de Proteínas , Humanos , Ratos , Ratos Wistar , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Recent studies have uncovered important aging clues, including free radicals, inflammation, telomeres, and life span pathways. Strategies to regulate aging-associated signaling pathways are expected to be effective in the delay and prevention of age-related disorders. For example, herbal polysaccharides with considerable anti-oxidant and anti-inflammation capacities have been shown to be beneficial in aging and age-related neurodegenerative diseases. Polysaccharides capable of reducing cellular senescence and modulating life span via telomere and insulin pathways have also been found to have the potential to inhibit protein aggregation and aggregation-associated neurodegeneration. Here we present the current status of polysaccharides in anti-aging and anti-neurodegenerative studies.
Assuntos
Envelhecimento/efeitos dos fármacos , Envelhecimento/patologia , Degeneração Neural/tratamento farmacológico , Plantas Medicinais/química , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Humanos , Doenças Neurodegenerativas/tratamento farmacológicoRESUMO
Anti-aging Chinese medicines have been used in traditional beverages to promote health and prevent diseases. Interestingly, these functional beverages may be used differently between men and women, reflecting the "yin-yang" philosophy of Chinese medicine. Modern studies have revealed that some dietary natural products can slow aging in model organisms, and functional beverages containing such products have recently emerged in Chinese market, challenging the dominance of traditional functional beverages. Here we summarize both traditional anti-aging herbs and modern natural dietary compounds currently used in functional beverages in China, and also briefly outline the underlying mechanisms of the beverages in slowing aging process.