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1.
Water Res ; 201: 117323, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34139511

RESUMO

Natural Deep Eutectic Solvents (NADES) are composed of supramolecular interactions of two or more natural compounds, such as organic acids, sugars, and amino acids, and they are being used as a new media alternative to conventional solvents. In this study, a new application of NADES is presented as a possible technology for biofilm structural breaker in complex systems since the current solvents used for biofilm cleaning and extraction of biofilm components use hazardous solutions. The NADES (betaine:urea:water and lactic acid:glucose:water) were analyzed before and after the biofilm treatment by attenuated total reflection Fourier-transform infrared spectroscopy and fluorescence excitation-emission matrix spectroscopy. Our results indicate that the green solvents could solubilize up to ≈70 percent of the main components of the biofilms extracellular matrix. The solubilization of the biomolecules weakened the biofilm structure, which could enhance the biofilm solubilization and removal. The NADES have the potential to be an environment-friendly, green solvent to extract valuable compounds and break the main structure from the biofilm, leading to a greener method for extracellular polymeric substance (EPS) extraction and biofilm treatment in various water treatment systems.


Assuntos
Matriz Extracelular de Substâncias Poliméricas , Extratos Vegetais , Solventes , Água
2.
Molecules ; 26(9)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946576

RESUMO

Some medicines are poorly soluble in water. For tube feeding and parenteral administration, liquid formulations are required. The discovery of natural deep eutectic solvents (NADES) opened the way to potential applications for liquid drug formulations. NADES consists of a mixture of two or more simple natural products such as sugars, amino acids, organic acids, choline/betaine, and poly-alcohols in certain molar ratios. A series of NADES with a water content of 0-30% (w/w) was screened for the ability to solubilize (in a stable way) some poorly water-soluble pharmaceuticals at a concentration of 5 mg/mL. The results showed that NADES selectively dissolved the tested drugs. Some mixtures of choline-based NADES, acid-neutral or sugars-based NADES could dissolve chloral hydrate (dissociated in water), ranitidine·HCl (polymorphism), and methylphenidate (water insoluble), at a concentration of up to 250 mg/mL, the highest concentration tested. Whereas a mixture of lactic-acid-propyleneglycol could dissolve spironolacton and trimethoprim at a concentration up to 50 and 100 mg/mL, respectively. The results showed that NADES are promising solvents for formulation of poorly water-soluble medicines for the development of parenteral and tube feeding administration of non-water-soluble medicines. The chemical stability and bioavailability of these drug in NADES needs further studies.


Assuntos
Produtos Biológicos/química , Composição de Medicamentos , Preparações Farmacêuticas/química , Solventes/química , Betaína/química , Colina/química , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Estrutura Molecular , Solubilidade
3.
J Chem Ecol ; 47(6): 564-576, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33881708

RESUMO

Based on the hypothesis that the variation of the metabolomes of latex is a response to selective pressure and should thus be affected differently from other organs, their variation could provide an insight into the defensive chemical selection of plants. Metabolic profiling was used to compare tissues of three Euphorbia species collected in diverse regions. The metabolic variation of latexes was much more limited than that of other organs. In all the species, the levels of polyisoprenes and terpenes were found to be much higher in latexes than in leaves and roots of the corresponding plants. Polyisoprenes were observed to physically delay the contact of pathogens with plant tissues and their growth. A secondary barrier composed of terpenes in latex and in particular, 24-methylenecycloartanol, exhibited antifungal activity. These results added to the well-known role of enzymes also present in latexes, show that these are part of a cooperative defense system comprising biochemical and physical elements.


Assuntos
Euphorbia/metabolismo , Euphorbia/microbiologia , Geografia , Herbivoria , Látex/metabolismo , Metabolômica , Euphorbia/fisiologia , Especificidade da Espécie
4.
Food Res Int ; 141: 110170, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33642026

RESUMO

Xanthine oxidase (XO) inhibition is a major strategy for preventing hyperuricemia and associated comorbidities, such as gout. Alfalfa extract has been demonstrated to possess XO-inhibiting activity; however, the elaborate conventional fraction-by-fraction analyses hindered the identification of the active components. In this study, we established a streamlined approach to rapidly screen, identify, and characterize XO-interacting compounds in alfalfa, by incorporating protein-subtraction, mass profiling, and molecular docking analysis. Crude extract was incubated with or without XO protein before UPLC-ESI-Q-TOF-MS/MS composition profiling. By dereplicating the component profile of XO-subtracted extract from that of untreated extract, the targets were rapidly narrowed down to twelve XO-interacting compounds, regarded as potential xanthine oxidase inhibitors (XOIs). Molecular docking analysis revealed that nine of these compounds, namely salicylic acid, tricin 7-O-glucuronopyranoside, chrysoeriol-7-glucoside, ferulic acid, apigenin 7-O-ß-glucuronopyranoside, apigenin, tricin, chrysoeriol, and liquiritigenin, exhibited high affinity with XO, and depicted the possible mechanisms of inhibition. In vitro bioassay further verified the XO inhibitory activities of selected compounds, among which apigenin, chrysoeriol and liquiritigenin were more potent XO inhibitors (XOIs), with IC50 of 0.25, 0.5 and 1 µM, respectively, compared to allopurinol (IC50 = 1.41 µM), the well-known XO-inhibiting drug. Together, the results demonstrated that alfalfa is a promising natural source for potent XOIs which might be applied for nutraceuticals development and that the approach used is applicable for efficient screening, identification, and mechanistic analyses of enzyme-inhibiting compounds from plant-based resources.


Assuntos
Medicago sativa , Xantina Oxidase , Metabolômica , Simulação de Acoplamento Molecular , Espectrometria de Massas em Tandem
5.
Crit Rev Food Sci Nutr ; : 1-15, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33749380

RESUMO

Metabolomics of human biological fluids or tissues is used to discover markers for diseases by comparing the metabolome of the patients against healthy individuals. Ultimately, these markers can be used in drug discovery to determine how medications normalize (at least in part) the human metabolome at specific disease stages to homeostatic. Likewise, the health effects of food can be studied. Even metabolomics of the food can be combined with metabolomics of the treated patients to correlate compounds from food with measurable health effects from clinical studies. Various chemometric analyses of these metabolomics data are used to identify markers for diseases and to obtain evidence for health effects. This review discusses recent researches (published from 2013 to 2021) on whether specific dietary intervention to humans suffering from metabolic disorders may improve their pathological status. The scope is limited to those associated with major lifestyle diseases such as diabetes, obesity, and cardiovascular diseases, for which food is thought may have detrimental as well as beneficial effects on human health. It includes metabolites characterization of different biological samples such as the human serum/plasma, urine, saliva, feces, or ileal fluid. Whether the study results supported the claimed health benefits and whether the research was conducted with appropriate study design, was criticized.

6.
J Ethnopharmacol ; 268: 113636, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33271247

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: In the ethnomedicine of Russia, the Eleutherococcus senticosus (Rupr. et Maxim.) Maxim. fruits and roots are used to treat immune-related diseases. Because of the overexploitation of the roots, the species is considered to be endangered and is put on the Red List in some countries (e.g. the Republic of Korea). Therefore, the aerial parts of E. senticosus might be explored as a new sustainable source of compounds with an adaptogenic activity. AIM OF THE STUDY: This study is aimed to evaluate the adaptogenic activity of the Eleutherococcus senticosus fruits intractum to support the use of the fruits in folk medicine of Russia. MATERIALS AND METHODS: The effect on IL-2 and IL-10 release by peripheral blood leukocytes (PBLs) was measured by the ELISA, the CPE on the A549 and PBLs were determined with trypan blue and the MTT. The innate immunity assay was done in the VSV-PBLs model. Metabolic profiling was done using HPLC-DAD and HPLC-RID. RESULTS: We report for the first time that the intractum (300 µg/mL) and eleutheroside E (100 µg/mL) and B (100 µg/mL) do not act as a virucidal agent (VSV). The intractum and eleutherosides E and B caused the increase of the PBLs proliferation up to 24.61 and 100%, resp. The decreased viral replication in the VSV-PBLs-Int model might be associated with an increased secretion of IL-10 (328 pg/mL). Eleutheroside E and B did not affect the innate immunity. No eleutherosides were determined in the intractum, the ethyl acetate layer contained caffeic and protocatechuic acids. A large amount of myo-inositol and D-mannitol was found (267.5 and 492.5 mg/g DE). CONCLUSIONS: Our observations justify the traditional use of the fruits in Russia in immune-related diseases. The results mean that there are other compounds than eleutherosides responsible for the adaptogenic effect, probably myo-inositol and caffeic acid, for which an immunostimulatory activity has already been confirmed.


Assuntos
Eleutherococcus , Medicina Baseada em Evidências/métodos , Imunidade Inata/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Medicina Tradicional/métodos , Extratos Vegetais/farmacologia , Células A549 , Frutas , Humanos , Imunidade Inata/imunologia , Leucócitos/imunologia , Extratos Vegetais/imunologia , Extratos Vegetais/isolamento & purificação
7.
Molecules ; 25(3)2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32023899

RESUMO

Natural deep eutectic solvents (NADES) are a type of ionic liquid (IL) or deep eutectic solvent (DES), the ingredients of which are exclusively natural products (non-toxic and environmentally friendly). Here, we explore the potential of NADES as an alternative to conventional organic solvents (e.g., aqueous methanol or ethanol) for the extraction of flavonoids from Scutellaria baicalensis stem bark to investigate their extractability depending on structural variation. Four NADES, each containing citric acid in combination with ß-alanine, glucose, xylitol, or proline (at a molar ratio of 1:1), and a variable amount of water, were used to extract the flavonoid aglycones: baicalein (1), scutellarein (3), wogonin (5), and oroxylin A (7), and their glycosides, baicalin (2), scutellarin (4), wogonoside (6) and oroxyloside (8) from the powdered bark of S. baicalensis. The chemical profile and yield of the extracts were determined using HPTLC and HPLC. The extractability of individual flavonoids was found to be influenced by the concentration of water (20-60%, w/w) in the NADES. Among the tested flavonoids, the extraction yield of baicalein (1), scutellarein (3), wogonin (5), oroxylin A (7) with NADES was 2 to 6 times that of aqueous methanol. However, the amount of their corresponding glycosides (baicalin (2), wogonoside (6) and oroxyloside (8)) extracted with NADES was only 1.5-1.8 times higher than with aqueous methanol. Interestingly, the more hydrophilic glycosides were less extracted than their corresponding aglycones despite the high hydrophilicity of the NADES. These results prove that NADES may be used for extraction of compounds with a wide range of hydrophilicity.


Assuntos
Ácido Cítrico/química , Flavonoides/análise , Scutellaria baicalensis/química , Solventes/química , Água/química , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Delgada , Glucose/química , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular , Extratos Vegetais/química , Prolina/química , Xilitol/química , beta-Alanina/química
8.
Crit Rev Food Sci Nutr ; 60(15): 2564-2592, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31407921

RESUMO

The principles of 'green chemistry' are gaining importance in agri-food sector due to the need to reduce pollution from toxic chemicals, make industrial processes safer and more sustainable, and to offer 'clean-labeled products' required by the consumers. The application of natural deep eutectic solvents (NADES) - natural product-based green liquids is considered the promising alternative to conventional organic solvents. This review is intended to summarize and discuss recent advances related to physicochemical properties of NADES, their applications, compatibility with analytic techniques and toxicological profile, pointing out the challenges and necessary improvements for their wider utilization in agri-food sector. NADES allow extraction of wide range of food compounds and they are proven to be convenient for food-related applications. However, their potential for industrial scale-up utilization is not completely investigated. Examined NADES are readily biodegradable, but only preliminary studies on NADES toxicity which include limited number of NADES molecules are available. Apart from fundamental research dealing with NADES formation and the nature of the interactions and structure underpinning the liquid phase formation, the question of purity of NADES obtained by different synthetic methodologies need to be addressed in the future. Data on physicochemical properties of synthetized NADES are still needed as they are relevant for industrial applications.


Assuntos
Produtos Biológicos , Indústria Alimentícia , Química Verde , Solventes , Produtos Biológicos/química , Humanos , Solventes/química
9.
J Ethnopharmacol ; 250: 112460, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-31837415

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Honey, an important additive with natural deep eutectic solvent (NADES) characteristics, has been used in traditional medicine for thousands of years. AIM OF THE STUDY: We investigated the quality-improving effects of honey on Astragali Radix (Mikvetch Root) (RA) as an example. MATERIALS AND METHODS: Decoctions of raw RA, fried RA, honey-fried RA, and a man-made- honey-fried RA were prepared and compared in cell-based bioactivity tests, chemical composition tests, as well as a bioavailability test with calycosin-7-O-ß-D-glucoside. RESULTS: The addition of honey increased the concentrations of active compounds and their oral bioavailability, provided protection against acetylation, and consequently increased their bioactivity. These changes were also observed when a pure NADES-mimicking honey was used. CONCLUSION: Our findings provide a potential explanation as to why honey has long been used as traditional medicine additives and rationalize the application of honey and honey-like substance in producing pharmaceuticals.


Assuntos
Astrágalo (Planta) , Mel , Extratos Vegetais/farmacologia , Raízes de Plantas , Acetilação , Animais , Disponibilidade Biológica , Feminino , Células HEK293 , Temperatura Alta , Humanos , Masculino , Medicina Tradicional , Metabolômica , Camundongos Endogâmicos ICR , Extratos Vegetais/farmacocinética , Ratos Sprague-Dawley , Solventes
10.
Sci Rep ; 9(1): 8878, 2019 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-31222034

RESUMO

Numerous aquatic invertebrates survive harsh environments by displaying dormancy as encysted embryos. This study aimed at determining whether metabolomics could provide molecular insight to explain the "dormancy syndrome" by highlighting functional pathways and metabolites, hence offering a novel comprehensive molecular view of dormancy. We compared the metabolome of morphologically distinct dormant encysted embryos (resting eggs) and non-dormant embryos (amictic eggs) of a rotifer (Brachionus plicatilis). Metabolome profiling revealed ~5,000 features, 1,079 of which were annotated. Most of the features were represented at significantly higher levels in non-dormant than dormant embryos. A large number of features was assigned to putative functional pathways indicating novel differences between dormant and non-dormant states. These include features associated with glycolysis, the TCA and urea cycles, amino acid, purine and pyrimidine metabolism. Interestingly, ATP, nucleobases, cyclic nucleotides, thymidine and uracil, were not detected in dormant resting eggs, suggesting an impairment of response to environmental and internal cues, cessation of DNA synthesis, transcription and plausibly translation in the dormant embryos. The levels of trehalose or its analogues, with a role in survival under desiccation conditions, were higher in resting eggs. In conclusion, the current study highlights metabolomics as a major analytical tool to functionally compare dormancy across species.


Assuntos
Embrião não Mamífero , Hidrobiologia , Invertebrados/embriologia , Metabolômica , Animais
11.
Viruses ; 11(5)2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31091764

RESUMO

Benzothiadiazole (BTH) is a functional analogue of the phytohormone salycilic acid (SA) involved in the plant immune response. NahG tomato plants are unable to accumulate SA, which makes them hypersusceptible to several pathogens. Treatments with BTH increase the resistance to bacterial, fungal, viroid, or viral infections. In this study, metabolic alterations in BTH-treated Money Maker and NahG tomato plants infected by citrus exocortis viroid (CEVd) were investigated by nuclear magnetic resonance spectroscopy. Using multivariate data analysis, we have identified defence metabolites induced after viroid infection and BTH-treatment. Glycosylated phenolic compounds include gentisic and ferulic acid accumulated in CEVd-infected tomato plants, as well as phenylalanine, tyrosine, aspartate, glutamate, and asparagine. Besides, an increase of γ-aminobutyric acid (GABA), glutamine, adenosine, and trigonelline, contributed to a clear discrimination between the metabolome of BTH-treated tomato leaves and their corresponding controls. Among them, GABA was the only metabolite significantly accumulated in both genotypes after the chemical treatment. In view of these results, the addition of GABA was performed on tomato plants infected by CEVd, and a reversion of the NahG hypersusceptibility to CEVd was observed, indicating that GABA could regulate the resistance to CEVd induced by BTH.


Assuntos
Lycopersicon esculentum/efeitos dos fármacos , Lycopersicon esculentum/metabolismo , Metaboloma/efeitos dos fármacos , Doenças das Plantas/imunologia , Tiadiazóis/farmacologia , Viroides/imunologia , Citrato (si)-Sintase/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genes de Plantas/genética , Lycopersicon esculentum/imunologia , Lycopersicon esculentum/virologia , Oxigenases de Função Mista/metabolismo , Doenças das Plantas/terapia , Doenças das Plantas/virologia , Imunidade Vegetal/efeitos dos fármacos , RNA Viral , Viroides/patogenicidade
12.
J Ethnopharmacol ; 237: 47-54, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-30898554

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The quality control of Traditional Chinese medicine (TCM) is a scientific problem and an industrial issue, which hampers the development of evidence based TCM. The concept of quality markers (Q-markers) is proposed and has been applied to the quality evaluation of TCM based on its clinical efficacy. However, more specific methods are needed to put this idea into practice. The standard decoction is a representative of decoction used in clinical practice and it can be used for the discovery of Q-markers related to the clinical efficacy of TCM. AIM OF THE STUDY: In this study, a systemic strategy was established to discover Q-markers related to the clinical efficacy of TCM Ephedrae Herba (EH), dried stem of Ephedra sinica Stapf. The different processed materials of EH have different clinical applications, though originating from the same medicinal herb. MATERIALS AND METHODS: The standard decoction of each of the processed materials was prepared and a 1HNMR metabolomics approach and total polysaccharide analysis were used to identify potential Q-markers related to the different clinical applications of EH. Correlation analysis was made of the measured biological activity and the holistic chemical profile. RESULTS: The results showed that total polysaccharides and alkaloids were Q-markers for EH preparations. CONCLUSION: This study demonstrates that the standard decoction is a reasonable research objective to explore chemical markers that correlate with the clinical efficacy of TCM.


Assuntos
Ephedra , Extratos Vegetais/farmacologia , Caules de Planta , Controle de Qualidade , Células HEK293 , Humanos , Luciferases/fisiologia , Metabolômica , Regiões Promotoras Genéticas , Receptor 2 Toll-Like/fisiologia , Fator de Transcrição AP-1/fisiologia , Resultado do Tratamento
13.
ChemSusChem ; 12(7): 1310-1315, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30741473

RESUMO

The use of natural deep eutectic solvents (NADES) as multifunctional solvents for limonene bioprocessing was reported. NADES were used for the extraction of limonene from orange peel wastes, as solvent for the chemoenzymatic epoxidation of limonene, and as sacrificial electron donor for the in situ generation of H2 O2 to promote the epoxidation reaction. The proof-of-concept for this multifunctional use was provided, and the scope and current limitations of the concept were outlined.

14.
Methods Mol Biol ; 1815: 437-455, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29981141

RESUMO

The plant Catharanthus roseus is a rich source of terpenoid indole alkaloids (TIA). Some of the TIA are important as antihypertensive (ajmalicine) and anticancer (vinblastine and vincristine) drugs. However, production of the latter is very low in the plant. Therefore, in vitro plant cell cultures have been considered as a potential supply of these chemicals or their precursors. Some monomeric alkaloids can be produced by plant cell cultures, but not on a level feasible for commercialization, despite extensive studies on this plant that deepened the understanding of the TIA biosynthesis and its regulation. In order to analyze the metabolites in C. roseus cell cultures, this chapter presents the method of TIA, carotenoids, and phytosterols analyses. Furthermore, an NMR-based metabolomics approach to study C. roseus cell culture is described.


Assuntos
Carotenoides/análise , Catharanthus/metabolismo , Técnicas de Cultura de Células/métodos , Espectroscopia de Ressonância Magnética/métodos , Metabolômica/métodos , Fitosteróis/análise , Células Vegetais/metabolismo , Alcaloides de Triptamina e Secologanina/análise , Cromatografia Líquida de Alta Pressão , Padrões de Referência , Espectrofotometria Ultravioleta , Suspensões
15.
J Food Drug Anal ; 26(2S): S96-S114, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29703391

RESUMO

Processing of Chinese medicines is a pharmaceutical technique that transforms medicinal raw materials into decoction pieces for use in different therapies. Various adjuvants, such as vinegar, wine, honey, and brine, are used in the processing to enhance the efficacy and reduce the toxicity of crude drugs. Proper processing is essential to ensure the quality and safety of traditional Chinese medicines (TCMs). Therefore, sound knowledge of processing principles is crucial to the standardized use of these processing adjuvants and to facilitate the production and clinical use of decoction pieces. Many scientific reports have indicated the synergistic effects of processing mechanisms on the chemistry, pharmacology, and pharmacokinetics of the active ingredients in TCMs. Under certain conditions, adjuvants change the content of active or toxic components in drugs by chemical or physical transformation, increase or decrease drug dissolution, exert their own pharmacological effects, or alter drug pharmacokinetics. This review summarizes various processing methods adopted in the last two decades, and highlights current approaches to identify the effects of processing parameters on TCMs.


Assuntos
Adjuvantes Farmacêuticos/química , Composição de Medicamentos/métodos , Medicamentos de Ervas Chinesas/química , Animais , Composição de Medicamentos/normas , Humanos , Medicina Tradicional Chinesa
16.
J Chromatogr A ; 1532: 198-207, 2018 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-29229334

RESUMO

Natural deep eutectic solvents (NADES) made mainly with abundant primary metabolites are being increasingly applied in green chemistry. The advantages of NADES as green solvents have led to their use in novel green products for the food, cosmetics and pharma markets. However, one of the main difficulties encountered in the development of novel products and their quality control arises from their low vapour pressure and high viscosity. These features create the need for the development of new analytical methods suited to this type of sample. In this study, such a method was developed and applied to analyse the efficiency of a diverse set of NADES for the extraction of compounds of interest from two model plants, Ginkgo biloba and Panax ginseng. The method uses high-performance thin-layer chromatography (HPTLC) coupled with multivariate data analysis (MVDA). It was successfully applied to the comparative quali- and quantitative analysis of very chemically diverse metabolites (e.g., phenolics, terpenoids, phenolic acids and saponins) that are present in the extracts obtained from the plants using six different NADES. The composition of each NADES was a combination of two or three compounds mixed in defined molar ratios; malic acid-choline chloride (1:1), malic acid-glucose (1:1), choline chloride-glucose (5:2), malic acid-proline (1:1), glucose-fructose-sucrose (1:1:1) and glycerol-proline-sucrose (9:4:1). Of these mixtures, malic acid-choline chloride (1:1) and glycerol-proline-sucrose (1:1:1) for G. biloba leaves, and malic acid-choline chloride (1:1) and malic acid-glucose (1:1) for P. ginseng leaves and stems showed the highest yields of the target compounds. Interestingly, none of the NADES extracted ginkgolic acids as much as the conventional organic solvents. As these compounds are considered to be toxic, the fact that these NADES produce virtually ginkgolic acid-free extracts is extremely useful. The effect of adding different volumes of water to the most efficient NADES was also evaluated and the results revealed that there is a great influence exerted by the water content, with maximum yields of ginkgolides, phenolics and ginsenosides being obtained with approximately 20% water (w/w).


Assuntos
Cromatografia em Camada Delgada/métodos , Extratos Vegetais/química , Solventes/química , Análise Discriminante , Análise dos Mínimos Quadrados , Panax/química , Análise de Componente Principal , Viscosidade , Água/química
17.
Plant Cell Tissue Organ Cult ; 134(1): 41-53, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-31007320

RESUMO

Previous studies showed that geraniol could be an upstream limiting factor in the monoterpenoid pathway towards the production of terpenoid indole alkaloid (TIA) in Catharanthus roseus cells and hairy root cultures. This shortage in precursor availability could be due to (1) limited expression of the plastidial geraniol synthase resulted in a low activity of the enzyme to catalyze the conversion of geranyl diphosphate to geraniol; or (2) the limitation of geraniol transport from plastids to cytosol. Therefore, in this study, C. roseus's geraniol synthase (CrGES) gene was overexpressed in either plastids or cytosol of a non-TIA producing C. roseus cell line. The expression of CrGES in the plastids or cytosol was confirmed and the constitutive transformation lines were successfully established. A targeted metabolite analysis using HPLC shows that the transformed cell lines did not produce TIA or iridoid precursors unless elicited with jasmonic acid, as their parent cell line. This indicates a requirement for expression of additional, inducible pathway genes to reach production of TIA in this cell line. Interestingly, further analysis using NMR-based metabolomics reveals that the overexpression of CrGES impacts primary metabolism differently if expressed in the plastids or cytosol. The levels of valine, leucine, and some metabolites derived from the shikimate pathway, i.e. phenylalanine and tyrosine were significantly higher in the plastidial- but lower in the cytosolic-CrGES overexpressing cell lines. This result shows that overexpression of CrGES in the plastids or cytosol caused alteration of primary metabolism that associated to the plant cell growth and development. A comprehensive omics analysis is necessary to reveal the full effect of metabolic engineering.

18.
Saudi Pharm J ; 25(5): 734-743, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28725146

RESUMO

Nature is a source of many plant-based molecules used as pro- or drugs. Eleutherococcus species are native to Asia and the North Russia, and are traditionally used to treat various diseases. In turn, neither secondary metabolites of the species cultivated in the West Europe nor the bioactivity is known. No differences in the phenols and flavonoids content in the inflorescences were found. The richest in polyphenols was E. giraldii (5.18 mg/g), while in flavonoids it was E. gracilistylus (1.80 mg/g). Using LC-ESI-MS/MS, protocatechuic and trans-caffeic acids have been identified as the most abundant compounds in E. gracilistylus, E. giraldii, E. senticosus (833.4; 855.6; 614.7 and 280.8; 156.0; 167.6 µg/g DE). It was observed that all species were able to chelate Fe2+ with the EC50 value of 0.2, 0.6, 0.3 mg/mL for E. gracilistylus, E. giraldii, E. senticosus, respectively. E. gracilistylus exhibited the strongest antiperoxidation and anti-DPPH∗ activity (EC50 3.2 and 0.48 mg/mL). The weak inhibitory potential has been observed in case of AChE inhibition at the level of 16.17 and 12.2% for E. gracilistylus, E. giraldii. We report for the first time that the extracts inhibited Hyal activity in the range from 16.4 to 60.7%. To our best knowledge, no information was available on this activity of the inflorescences and this provides a background to study inflorescences in more detail. Considering the SAR, an antioxidant activity may be correlated with a high amount of protocatechuic and trans-caffeic acids and their chemical structure.

19.
Biochem Pharmacol ; 139: 94-104, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28636884

RESUMO

A long history of use and extensive documentation of the clinical practices of traditional Chinese medicine resulted in a considerable number of classical preparations, which are still widely used. This heritage of our ancestors provides a unique resource for drug discovery. Already, a number of important drugs have been developed from traditional medicines, which in fact form the core of Western pharmacotherapy. Therefore, this article discusses the differences in drug development between traditional medicine and Western medicine. Moreover, the article uses the discovery of artemisinin as an example that illustrates the "bedside-bench-bedside" approach to drug discovery to explain that the middle way for drug development is to take advantage of the best features of these two distinct systems and compensate for certain weaknesses in each. This article also summarizes evidence-based traditional medicines and discusses quality control and quality assessment, the crucial steps in botanical drug development. Herbgenomics may provide effective tools to clarify the molecular mechanism of traditional medicines in the botanical drug development. The totality-of-the-evidence approach used by the U.S. Food and Drug Administration for botanical products provides the directions on how to perform quality control from the field throughout the entire production process.


Assuntos
Doença Crônica/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Drogas em Investigação/uso terapêutico , Medicina Baseada em Evidências , Medicina Tradicional Chinesa , Qualidade da Assistência à Saúde , Pesquisa Médica Translacional , Animais , China , Doença Crônica/prevenção & controle , Desenho de Fármacos , Descoberta de Drogas , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Drogas em Investigação/efeitos adversos , Drogas em Investigação/química , Drogas em Investigação/farmacologia , Humanos , Medicina Tradicional Chinesa/normas , Medicina Tradicional Chinesa/tendências , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Garantia da Qualidade dos Cuidados de Saúde/tendências , Controle de Qualidade , Melhoria de Qualidade/tendências , Qualidade da Assistência à Saúde/tendências , Pesquisa Médica Translacional/tendências , Ocidente
20.
Sci Rep ; 7(1): 3777, 2017 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-28630440

RESUMO

The spread of multidrug-resistant Staphylococcus aureus strains, including methicillin-resistant S. aureus (MRSA), has shortened the useful life of anti-staphylococcal drugs enormously. Two approaches can be followed to address this problem: screening various sources for new leads for antibiotics or finding ways to disable the resistance mechanisms to existing antibiotics. Plants are resistant to most microorganisms, but despite extensive efforts to identify metabolites that are responsible for this resistance, no substantial progress has been made. Plants possibly use multiple strategies to deal with microorganisms that evolved over time. For this reason, we searched for plants that could potentiate the effects of known antibiotics. From 29 plant species tested, Cytisus striatus clearly showed such an activity and an NMR-based metabolomics study allowed the identification of compounds from the plant extracts that could act as antibiotic adjuvants. Isoflavonoids were found to potentiate the effect of ciprofloxacin and erythromycin against MRSA strains. For the structure-activity relationship (SAR), 22 isoflavonoids were assessed as antibiotic adjuvants. This study reveals a clear synergy between isoflavonoids and the tested antibiotics, showing their great potential for applications in the clinical therapy of infections with antibiotic-resistant microorganisms such as MRSA.


Assuntos
Antibacterianos/farmacologia , Ciprofloxacina/farmacologia , Cytisus/química , Eritromicina/farmacologia , Isoflavonas/farmacologia , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Folhas de Planta/química , Antibacterianos/química , Ciprofloxacina/agonistas , Sinergismo Farmacológico , Eritromicina/agonistas , Isoflavonas/agonistas , Isoflavonas/química
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