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1.
J Agric Food Chem ; 68(7): 2146-2154, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-31984739

RESUMO

Flavonoids are valuable natural products widely used in human health and nutrition applications. Engineering microbial consortia to express complex flavonoid biosynthetic pathways is a promising approach for flavonoid production. In this study, the entire flavonoid biosynthetic pathway was split into two independent pathways, each of which was contained in separate Saccharomyces cerevisiae cells. The first cell type, sNAR5, which was genetically engineered to express the naringenin biosynthetic pathway, produced 144.1 mg/L naringenin. The second cell type was genetically modified with the heterologous naringenin-to-delphinidin pathway. A coculture produced a delphinidin titer, significantly higher than that produced in a monoculture of strain sDPD2, harboring the entire pathway. Furthermore, we successfully employed this coculture platform for the production of 3 flavonols and 2 anthocyanidins in flask-scale culture. This coculture platform paves the way for the development of an economical and efficient process for microbial flavonoid production.


Assuntos
Flavonoides/biossíntese , Engenharia Metabólica , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Antocianinas/química , Antocianinas/metabolismo , Vias Biossintéticas , Técnicas de Cocultura , Flavanonas/química , Flavanonas/metabolismo , Flavonoides/química
2.
Eur J Med Chem ; 186: 111829, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31757526

RESUMO

The implication of DNA methylation in cancer is today clearly established. Despite that nucleoside analogues are currently used for leukaemia treatment, their low stability in physiological conditions and their lack of selectivity arise the need for the identification of non-nucleoside DNA methyltransferase inhibitors. Here, we describe the synthesis and pharmacological characterisation of a novel class of DNA methyltransferase inhibitors: the 3-halo-3-nitroflavanones. We showed that 3-bromo-3-nitroflavanones 3b and 4a have a micromolar DNMT inhibition and an increased potency in a cell reporter model. Interestingly they are significantly more stable than the reference compounds and induce a low cytotoxicity, supporting them as new candidates for the development of non-cytotoxic cell-reprogramming epi-drugs for anticancer treatment.


Assuntos
Antineoplásicos/farmacologia , DNA (Citosina-5-)-Metiltransferases/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Flavanonas/farmacologia , Nitrocompostos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , DNA (Citosina-5-)-Metiltransferases/metabolismo , Metilação de DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Flavanonas/química , Células HCT116 , Humanos , Estrutura Molecular , Nitrocompostos/síntese química , Nitrocompostos/química , Relação Estrutura-Atividade
3.
J Agric Food Chem ; 68(1): 409-417, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31833363

RESUMO

Naringin has been documented to possess various bioactivities. Due to thorny endogenous interferences, the metabolism pathways of naringin and exact amounts of derived phenolic catabolites have not been definitely assigned. In this work, stable isotope-labeling-based liquid chromatography-mass spectrometry methods were developed to eliminate the endogenous interferences. [2',3',5',6'-D4]-naringin was orally administrated to rats. Urine and feces samples were collected and then analyzed with ultrahigh-performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS). A total of 21 flavonoid metabolites and 11 phenolic catabolites were screened. The metabolism and catabolism pathways were proposed. Furthermore, deuterated naringin and its main metabolites were determined with rapid resolution liquid chromatography tandem triple quadrupole mass spectrometry (RRLC-QqQ-MS/MS). The overall recovery of ingested deuterated naringin was calculated as 56.9% without endogenous interferences. The obtained results provide essential information for further pharmacological studies of naringin.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Fezes/química , Flavanonas/química , Flavanonas/metabolismo , Marcação por Isótopo/métodos , Espectrometria de Massas/métodos , Animais , Medicamentos de Ervas Chinesas/metabolismo , Feminino , Flavanonas/urina , Masculino , Ratos , Ratos Sprague-Dawley
4.
Food Chem ; 311: 125902, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31865113

RESUMO

Phosphate buffered saline (PBS) is a commonly used buffer in biological research. Herein, the stability of a series of flavonoids, i.e. myricetin, kaempferol, baicalein, luteolin and quercetin, were assessed in PBS within 5 s. Apigenin proved very stable in PBS and was therefore used as a control. Kaempferol and baicalein were less stable with small amounts of oxidized and hydroxylated products being detected. The other flavonoids were unstable and their dimers were identified in PBS at 4 °C under normal atmospheric conditions. Flavonols with a catechol or pyrogallol substitution pattern on ring B readily formed stable dimers and oxidized products in PBS (pH = 7.4) at 4 °C within 5 s. The chosen experimental conditions improved the stability of dimers and allowed their detection.


Assuntos
Catecóis/química , Flavonóis/química , Pirogalol/química , Tampões (Química) , Temperatura Baixa , Dimerização , Flavanonas/química , Flavonoides , Quempferóis/química , Luteolina/química , Estrutura Molecular , Oxirredução , Fosfatos/química , Quercetina/química
5.
Artigo em Inglês | MEDLINE | ID: mdl-31881511

RESUMO

Systemic dry syndrome affects quality of life, and various effective methods are being developed for its treatment. We recently found that rooibos (Aspalathus linearis) extract activates muscarinic M3 receptor and improves dryness in mice and humans. We identified eriodictyol-6-C-ß-D-glucoside (E6CG) as the active component affecting the secretory functions of exocrine glands; however, the pharmacokinetics and distribution of E6CG in exocrine glands have not been elucidated in mice receiving rooibos extract. We have developed a quantification method using LC-MS/MS to detect E6CG without an internal standard. Experiments on C57BL/6 mice administered rooibos extract showed that E6CG was transferred into blood plasma, with its concentration levels peaking 19.3 min after treatment. Substantial levels of E6CG were detected in the submandibular, sublingual, parotid, and lacrimal glands and in the sweat glands in palm skin. This study reports that rooibos extracts containing E6CG can be used as functional foods for improving systemic dryness.


Assuntos
Aspalathus/química , Flavanonas/análise , Flavanonas/farmacocinética , Glucosídeos/análise , Glucosídeos/farmacocinética , Administração Oral , Animais , Flavanonas/química , Glucosídeos/química , Limite de Detecção , Modelos Lineares , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Reprodutibilidade dos Testes , Glândulas Salivares/química , Pele/química , Distribuição Tecidual
6.
Molecules ; 24(20)2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31614687

RESUMO

The demand for licorice and its natural product derivatives in domestic and foreign market is considerably huge. The core production areas of licorice are covered with salinity and drought land in northwestern China. Studies have shown that suitable environmental stress can promote the accumulation of glycyrrhizin and liquiritin to improve its quality as medicinal materials. However, there are few reports on other bioactive constituents of licorice, not to mention their dynamic accumulation under stressed conditions. To explore the quality formation of licorice from the perspective of salt influence, a reliable method based on ultra-fast liquid chromatography tandem triple quadrupole mass spectrometry (UFLC-MS/MS) was established for simultaneous determination of sixteen bioactive constituents, including triterpenoids, flavonoids, chalcones and their glycosides. Physiological experiments were performed to investigate salt tolerance of licorice under different salinity treatments. The expressions of crucial genes (bAS and CHS), key enzymes of triterpenoid and flavonoid synthesis, were also tested by qRT-PCR. Our study found that 50 mM NaCl treatment (low stress) was the most favorable to promote the accumulation of bioactive constituents in the long term, without harming the plants. Flavonoid accumulation of non-stressed and low-stressed groups became different in the initial synthesis stage, and glycosyltransferases may have great influence on their downstream synthesis. Furthermore, bAS and CHS also showed higher levels in low-stressed licorice at harvest time. This work provides valuable information on dynamic variations in multiple bioactive constituents in licorice treated by salt and insight into its quality formation under stressed conditions.


Assuntos
Medicamentos de Ervas Chinesas/química , Flavonoides/química , Glycyrrhiza/química , Extratos Vegetais/química , Chalconas/química , Chalconas/metabolismo , Cromatografia Líquida , Medicamentos de Ervas Chinesas/metabolismo , Flavanonas/química , Flavanonas/metabolismo , Flavonoides/metabolismo , Glucosídeos/química , Glucosídeos/metabolismo , Ácido Glicirrízico/química , Ácido Glicirrízico/metabolismo , Humanos , Extratos Vegetais/metabolismo , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Folhas de Planta/metabolismo , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Estresse Salino , Espectrometria de Massas em Tandem , Triterpenos/química , Triterpenos/metabolismo
7.
Molecules ; 24(20)2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31601055

RESUMO

Baicalein, a famously effective component of the traditional Chinese medicine Rhizoma Huang Qin (Scutellaria altissima L.), has been proved to have potent neuroprotection and anti-platelet aggregation effects with few side effects. Meanwhile, recent studies have revealed that the introduction of amino acid to baicalein could improve its neuroprotective activity. In the present study, a series of novel baicalein amino acid derivatives were designed, synthesized, and screened for their neuroprotective effect against tert-butyl, hydroperoxide-induced, SH-SY5Y neurotoxicity cells and toxicity on the normal H9C2 cell line by standard methylthiazol tetrazolium (MTT) assay. In addition, all of the newly synthesized compounds were characterized by 1H-NMR, 13C-NMR, and high resolution mass spectrometry (HR-MS). The results showed that most of the compounds provided more potent neuroprotection than baicalein, and were equivalent to the positive drug edaravin. They showed no obvious cytotoxicity on normal H9C2 cells. Notably, the most active compound 8 displayed the highest protective effect (50% effective concentration (EC50) = 4.31 µM) against tert-butyl, hydroperoxide-induced, SH-SY5Y neurotoxicity cells, which was much better than the baicalein (EC50 = 24.77 µM) and edaravin (EC50 = 5.62 µM). Further research on the chick chorioallantoic membrane (CAM) model indicated that compound 8 could significantly increase angiogenesis, which might promote neurovascular proliferation. The detection of apoptosis analysis showed that compound 8 could dramatically alleviate morphological manifestations of cell damage. Moreover, the benzyloxycarbonyl (cbz)-protected baicalein amino acid derivatives showed better neuroprotective activity than the t-Butyloxy carbonyl (boc)-protected derivatives.


Assuntos
Aminoácidos/química , Flavanonas/síntese química , Flavanonas/farmacologia , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/farmacologia , Indutores da Angiogênese/química , Indutores da Angiogênese/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Química Sintética , Embrião de Galinha , Relação Dose-Resposta a Droga , Flavanonas/química , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Fármacos Neuroprotetores/química , Relação Estrutura-Atividade
8.
Zhongguo Zhong Yao Za Zhi ; 44(17): 3653-3661, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31602937

RESUMO

For the effects of multi-component environment on the solubility and permeability of single components,and the problems of biopharmaceutical attribute classification of single components in the compound prescriptions environment,baicalein was used as the research object in this study to investigate the biopharmaceutic attributes of single-component and their traditional Chinese medicine( TCM) biopharmaceutic attributes in the multi-component environment of Gegen Qilian Decoction. Shaking flask method,intrinsic dissolution rate test and HPLC were used to determine solubility of baicalein. Markers specified by FDA were utilized as permeable boundary reference materials to verify the applicability of the single-pass intestinal perfusion method( SPIP),and the quantitative research on the permeability of baicalein was also conducted. It is concluded that baicalein could be categorized as BCS-Ⅱ drug based on its low solubility and high intestinal permeability values,and it may be categorized into CMMBCS-I in the multi-component environment of Gegen Qilian Decoction due to its poor solubility but enhanced solubility and permeability in compound environment. This study could provide verification ideas for clinical determination of the best human oral dose of baicalein,and provide the data basis for the study of biopharmaceutics classification system of Chinese materia medica( CMMBCS).


Assuntos
Biofarmácia/classificação , Medicamentos de Ervas Chinesas/química , Flavanonas/química , Materia Medica/classificação , Humanos , Absorção Intestinal , Permeabilidade , Solubilidade
9.
J Mater Sci Mater Med ; 30(9): 107, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31512084

RESUMO

In the present study, collagen hydrogel containing naringin was fabricated, characterized and used as the scaffold for peripheral nerve damage treatment. The collagen was dissolved in acetic acid, naringin added to the collagen solution, and cross-linked with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide powder (EDC; 0.10 mM) to form the hydrogel. The microstructure, swelling behavior, biodegradation, and cyto/hemocompatibility of the fabricated hydrogels were assessed. Finally, the healing efficacy of the prepared collagen hydrogel loaded with naringin on the sciatic nerve crush injury was assessed in the animal model. The characterization results showed that the fabricated hydrogels have a porous structure containing interconnected pores with the average pore size of 90 µm. The degradation results demonstrated that about 70% of the primary weight of the naringin loaded hydrogel had been lost after 4 weeks of storage in PBS. The in vitro study showed that the proliferation of Schwann cells on the collagen/naringin hydrogel was higher than the control group (tissue culture plate) at both 48 and 72 h after cell seeding and even significantly higher than pure collagen 72 h after cell seeding (*p < 0.005, **p < 0.001). The animal study implied that the sciatic functional index reached to -22.13 ± 3.00 at the end of 60th days post-implantation which was statistically significant (p < 0.05) compared with the negative control (injury without the treatment) (-82.60 ± 1.06), and the pure collagen hydrogel (-59.80 ± 3.20) groups. The hot plate latency test, the compound muscle action potential, and wet weight-loss of the gastrocnemius muscle evaluation confirmed the positive effect of the prepared hydrogels on the healing process of the induced nerve injury. In the final, the histopathologic examinations depicted that the collagen/naringin hydrogel group reduced all the histological changes induced from the nerve injury and showed more resemblance to the normal sciatic nerve, with well-arranged fibers and intact myelin sheath. The overall results implied that the prepared collagen/naringin hydrogel can be utilized as a sophisticated alternative to healing peripheral nerve damages.


Assuntos
Colágeno Tipo I/química , Flavanonas/farmacologia , Regeneração Tecidual Guiada/métodos , Hidrogéis/farmacologia , Regeneração Nervosa/efeitos dos fármacos , Nervo Isquiático/lesões , Nervo Isquiático/fisiologia , Animais , Células Cultivadas , Colágeno Tipo I/farmacologia , Flavanonas/química , Humanos , Hidrogéis/química , Masculino , Teste de Materiais , Traumatismos dos Nervos Periféricos/patologia , Traumatismos dos Nervos Periféricos/terapia , Ratos , Ratos Wistar , Células de Schwann/citologia , Células de Schwann/efeitos dos fármacos , Células de Schwann/fisiologia , Nervo Isquiático/efeitos dos fármacos , Tecidos Suporte/química , Cicatrização/efeitos dos fármacos
10.
J Agric Food Chem ; 67(42): 11650-11656, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31554401

RESUMO

Occurring in hops (Humulus lupulus) and beer as a racemic mixture, (2R,2S)-8-prenylnaringenin (8-PN) is a potent phytoestrogen in hop dietary supplements used by women as alternatives to conventional hormone therapy. With a half-life exceeding 20 h, 8-PN is excreted primarily as 8-PN-7-O-glucuronide or 8-PN-4'-O-glucuronide. Human liver microsomes and 11 recombinant human UDP-glucuronosyltransferases (UGTs) were used to catalyze the formation of the two oxygen-linked glucuronides of purified (2R)-8-PN and (2S)-8-PN, which were subsequently identified using mass spectrometry and nuclear magnetic resonance spectroscopy. Formation of (2R)- and (2S)-8-PN-7-O-glucuronides predominated over the 8-PN-4'-O-glucuronides except for intestinal UGT1A10, which formed more (2S)-8-PN-4'-O-glucuronide. (2R)-8-PN was a better substrate for all 11 UGTs except for UGT1A1, which formed more of both (2S)-8-PN glucuronides than (2R)-8-PN glucuronides. Although several UGTs conjugated both enantiomers of 8-PN, some conjugated just one enantiomer, suggesting that human phenotypic variation might affect the routes of metabolism of this chiral estrogenic constituent of hops.


Assuntos
Flavanonas/química , Glucuronídeos/química , Glucuronosiltransferase/química , Extratos Vegetais/química , Biocatálise , Flavanonas/metabolismo , Glucuronídeos/metabolismo , Glucuronosiltransferase/metabolismo , Humanos , Humulus/química , Humulus/metabolismo , Espectrometria de Massas , Microssomos Hepáticos/química , Microssomos Hepáticos/metabolismo , Extratos Vegetais/metabolismo , Estereoisomerismo
11.
Biophys Chem ; 254: 106246, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31426023

RESUMO

The inhibitory effect of the flavonoid naringenin on plant and human Two-Pore Channels (TPCs) was assessed by means of electrophysiological measurements. By acting on human TPC2, naringenin, was able to dampen intracellular calcium responses to VEGF in cultured human endothelial cells and to impair angiogenic activity in VEGF-containing matrigel plugs implanted in mice. Molecular docking predicts selective binding sites for naringenin in the TPC structure, thus suggesting a specific interaction between the flavonoid and the channel.


Assuntos
Canais de Cálcio/química , Flavanonas/química , Plantas/metabolismo , Animais , Sítios de Ligação , Cálcio/química , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Colágeno/química , Combinação de Medicamentos , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Flavanonas/metabolismo , Humanos , Laminina/química , Camundongos , Simulação de Acoplamento Molecular , Técnicas de Patch-Clamp , Proteínas de Plantas/antagonistas & inibidores , Proteínas de Plantas/metabolismo , Proteoglicanas/química
12.
Molecules ; 24(17)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443449

RESUMO

Structure-related biological activities of flavanones are still considered largely unexplored. Since they exhibit various medicinal activities, it is intriguing to enter deeper into their chemical structures, electronic transitions or interactions with some biomolecules in order to find properties that allow us to better understand their effects. Little information is available on biological activity of flavanone and its monohydroxy derivatives in relation to their physicochemical properties as spectral profiles, existence of protonated/deprotonated species under pH changes or interaction with Calf Thymus DNA. We devoted this work to research demonstrating differences in the physicochemical properties of the four flavanones: flavanone, 2'-hydroxyflavanone, 6-hydroxyflavanone and 7-hydroxyflavanone and linking them to their biological activity. Potentiometric titration, UV-Vis spectroscopy were used to investigate influence of pH on acid-base and spectral profiles and to propose the mode of interaction with DNA. Cyclic voltammetry was applied to evaluate antioxidant potentiality and additionally, theoretical DFT(B3LYP) method to disclose electronic structure and properties of the compounds. Molecular geometries, proton affinities and pKa values have been determined. According to computational and cyclic voltammetry results we could predict higher antioxidant activity of 6-hydroxyflavanone with respect to other compounds. The values of Kb intrinsic binding constants of the flavanones indicated weak interactions with DNA. Structure-activity relationships observed for antioxidant activity and DNA interactions suggest that 6-hydroxyflavanone can protect DNA against oxidative damage most effectively than flavanone, 2'-hydroxyflavanone or 7-hydroxyflavanone.


Assuntos
DNA/química , Flavanonas/química , Algoritmos , Animais , Bovinos , Modelos Moleculares , Modelos Teóricos , Conformação Molecular , Estrutura Molecular , Relação Estrutura-Atividade
13.
Food Chem ; 298: 125086, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31272050

RESUMO

Methylglyoxal (MGO) is a highly reactive ɑ-dicarbonyl compound that may adversely impact food quality and human health by modifying proteins. The kinetics of the reaction of naringenin with MGO was studied at pH 6-8 and 37 °C by UV-Vis spectrophotometry and reaction products were characterized by liquid chromatography-mass spectrometry (LC-MS/MS). The apparent second order rate constant (k2) increased at pH above the lowest pKa value of naringenin, indicating deprotonated naringenin as the main reactant. A Lederer-Manasse type reaction mechanism is suggested, with dehydration of the MGO-dihydrate as a rate determining step. The quantitative data obtained in the present study was used to simulate the competitive reaction between MGO and nucleophilic amino acid residues (Lys, Arg and Cys) and naringenin in milk. It is predicted that naringenin will be able to efficiently trap MGO during storage of milk, although the reversible trapping of MGO by Cys residues is initially kinetically favourable.


Assuntos
Flavanonas/química , Aldeído Pirúvico/química , Aminoácidos/química , Cromatografia Líquida , Concentração de Íons de Hidrogênio , Cinética , Proteínas do Leite/química , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Ultravioleta , Espectrometria de Massas em Tandem
14.
Enzyme Microb Technol ; 129: 109361, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31307576

RESUMO

Amylosucrase (ASase) is a unique multifunctional enzyme exhibiting transglycosylation activity. In this study, the specificity of the transglycosylation activity of ASase was evaluated using several hydroxyflavones (HFVOs) and hydroxyflavanones (HFVAs). Our results reveal that the 3-OH and 7-OH positions of the mono-HFVOs and -HFVAs are resistant to transglycosylation by Deinococcus geothermalis ASase (DGAS), whereas the 6-OH and 4'-OH positions of the mono-HFVOs and -HFVAs exhibit relatively strong transglycosylation reactivities with the glucose donors released from sucrose by DGAS. Particularly, the 6-OH position is considerably more reactive (54-fold higher kcat) than the 4'-OH position in both HFVOs and HFVAs. Further, the transglycosylation reactions with di- and tri-HFVOs and HFVAs were also investigated and observed to exhibit similar results to those observed for the mono-HFVO and -HFVA molecules. The pH of the reaction influences the reactivity of certain hydroxyl residues, indicating that the pKa values of the hydroxyl groups may be crucial factors in the transglycosylation reactions. These observations help us understand the specificity of the transglycosylation activity of ASase and to predict the transglycosylation products of flavonoids.


Assuntos
Deinococcus/enzimologia , Flavanonas/metabolismo , Flavonas/metabolismo , Glucosiltransferases/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Deinococcus/química , Deinococcus/metabolismo , Flavanonas/química , Flavonas/química , Glucose/metabolismo , Glucosiltransferases/química , Glicosilação
15.
J Pharm Biomed Anal ; 175: 112734, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31330286

RESUMO

A rapid and reliable LC-MS/MS method was developed for the quantitation of major components in Folium Artemisiae Argyi (mugwort), a widely used traditional Chinese herbal medicine. A total of 5 phenolic acids and 17 flavonoids were separated and simultaneously determined by using a Shiseido C18 column (150 × 3.0 mm, 3 µm) and gradient elution of acetonitrile-aqueous formic acid (100:0.1, v/v) at a 0.5 mL min-1 flow rate, via multiple reaction monitor (MRM) in polarity switching mode. The quantitative method was validated in terms of sensitivity, linearity, precision, accuracy and stability, which proved to be sensitive, accurate and reproducible. Then 65 samples collected from different areas were selected for component analysis by LC-MS/MS and assessment of antioxidant activity using DPPH, ABTS, FRAP, O2- and OH scavenging assays. Grey relational analysis and partial least square regression were used to evaluate the relevance between chemicals and bioactivities, and the results indicated chlorogenic acid, isochlorogenic acid B, A, C, eriodictyol, jaceosidin and eupatilin made the key contribution to antioxidant activity. The present study combines chemical analysis and bioassay to identify bioactive markers, which possesses potential value for the activity-oriented quality control of mugwort.


Assuntos
Antioxidantes/química , Medicamentos de Ervas Chinesas/química , Flavonoides/química , Hidroxibenzoatos/química , Ácido Clorogênico/análogos & derivados , Ácido Clorogênico/química , Cromatografia Líquida de Alta Pressão/métodos , Flavanonas/química , Controle de Qualidade , Espectrometria de Massas em Tandem/métodos
16.
Biomed Res Int ; 2019: 1395480, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31341887

RESUMO

In peach orchards, birds severely damage flowers during blossom season, decreasing the fruit yield potential. However, the wild peach species Prunus mira shows intraspecific variations of bird damage, indicating that some of the wild trees have developed strategies to avert bird foraging. Motivated by this observation, we formulated the present study to identify the potential flower metabolites mediating the bird's selective feeding behavior in P. mira flowers. The birds' preferred (FG) and avoided (BFT) flowers were collected from wild P. mira trees at three different locations, and their metabolite contents were detected, quantified, and compared. The widely-targeted metabolomics approach was employed to detect a diverse set of 603 compounds, predominantly, organic acids, amino acid derivatives, nucleotide and its derivatives, and flavones. By quantitatively comparing the metabolite contents between FG and BFT, three candidate metabolites, including Eriodictiol 6-C-hexoside 8-C-hexoside-O-hexoside, Luteolin O-hexosyl-O-hexosyl-O-hexoside, and Salvianolic acid A, were differentially accumulated and showed the same pattern across the three sampling locations. Distinctly, Salvianolic acid A was abundantly accumulated in FG but absent in BFT, implying that it may be the potential metabolite attracting birds in some P. mira flowers. Overall, this study sheds light on the diversity of the floral metabolome in P. mira and suggests that the bird's selective feeding behavior may be mediated by variations in floral metabolite contents.


Assuntos
Aves/fisiologia , Comportamento Alimentar , Flores/química , Prunus persica/metabolismo , Animais , Ácidos Cafeicos/química , Ácidos Cafeicos/metabolismo , Flavanonas/química , Flavanonas/metabolismo , Flores/metabolismo , Lactatos/química , Lactatos/metabolismo , Luteolina/química , Luteolina/metabolismo , Metaboloma , Prunus persica/química
17.
Phytomedicine ; 63: 153033, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31352284

RESUMO

BACKGROUND: The emergence of antibiotic resistant microorganisms presents a worldwide problem that requires novel antibiotic and non-antibiotic strategies, and biofilm formation is a mechanism of drug resistance utilized by diverse microorganisms. The majority of microorganisms live in biofilms that help their survival against starvation, antimicrobial agents, and immunological defense systems. Therefore, it is important novel compounds be identified that inhibit biofilm formation and cell survival without drug resistance. STUDY DESIGN: In this study, the antimicrobial and antibiofilm activities of five prenylated flavanones (Okinawan propolins) isolated from fruits of Macaranga tanarius (L.) were investigated against 14 microorganisms including 10 pathogens. RESULTS: Of these five propolins, propolin D at 5-10 µg/ml significantly inhibited biofilm formation by three Staphylococcus aureus strains, a Staphylococcus epidermidis strain, and a Candida albicans with MICs from 10 to 50 µg/ml, and in C. albicans, propolin D was found to inhibit biofilm formation by reducing cell aggregation and downregulated the expressions of hypha/biofilm-related genes including ECE1 and HWP1. Interestingly, at sub-MIC concentrations (10-50 µg/ml), propolin D significantly inhibited biofilm formation by enterohemorrhagic E. coli O157:H7, uropathogenic E. coli O6:H1, and Acinetobacter baumannii without affecting planktonic cell growth, but did not inhibit biofilm formation by a commensal E. coli K-12 strain, three probiotic Lactobacillus plantarum strains, or two Pseudomonas aeruginosa strains. And, propolin D reduced fimbriae production by E. coli O157:H7 and repressed gene expression of curli fimbriae genes (csgA and csgB). Also, propolin D was minimally toxic in a Caenorhabditis elegans nematode model. CONCLUSION: These findings show that prenylated flavanones, especially propolin D from Macaranga tanarius (Okinawan propolis), should be considered potential candidates for the development of non-toxic antibacterial and antifungal agents against persistent microorganisms.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Euphorbiaceae/química , Flavanonas/farmacologia , Flavonoides/farmacologia , Animais , Antibacterianos/química , Antibacterianos/toxicidade , Antifúngicos/química , Antifúngicos/toxicidade , Biofilmes/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candida albicans/fisiologia , Avaliação Pré-Clínica de Medicamentos , Escherichia coli O157/efeitos dos fármacos , Flavanonas/química , Flavanonas/toxicidade , Flavonoides/química , Flavonoides/toxicidade , Testes de Sensibilidade Microbiana , Prenilação , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Testes de Toxicidade
18.
Int J Pharm ; 567: 118490, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31271814

RESUMO

The possibility of newly developed α-glycosylated naringin (Naringin-G) as a solubilizing agent was investigated against pranlukast hemihydrate (PLH), a model drug with extremely low water solubility. The physical mixtures (PMs) of PLH/Naringin-G increased the solubility of PLH compared with PLH crystals and PMs with other additives, such as α-glycosylated rutin (Rutin-G) and sodium dodecyl sulfate (SDS). Naringin-G did not decrease the surface tension, whereas SDS showed a surface-active property and critical micelle concentration. The apparent solubility of PLH increased in proportion to the concentration of Naringin-G, and similarly for SDS, indicating that constant amounts of Naringin-G molecules interacted with PLH molecules. There was no change in the Caco-2 cell viability following contact with a high concentration of Naringin-G solution (10% (w/v)). The oral absorption of PLH in a rat animal model was improved when administrated with Naringin-G. The value for the area under plasma concentration-time curve from PMs of PLH/Naringin-G was 2.2 times higher than that from PLH crystals alone. Together, these results suggested that newly synthesized Naringin-G would be a promising solubilizing agent as an alternative to surfactants.


Assuntos
Cromonas , Flavanonas , Administração Oral , Animais , Disponibilidade Biológica , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Cromonas/administração & dosagem , Cromonas/química , Cromonas/farmacocinética , Flavanonas/administração & dosagem , Flavanonas/química , Flavanonas/farmacocinética , Glicosilação , Humanos , Absorção Intestinal , Masculino , Ratos Sprague-Dawley , Solubilidade
19.
Molecules ; 24(12)2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31238565

RESUMO

Pinocembrin is one of the most abundant flavonoids in propolis, and it may also be widely found in a variety of plants. In addition to natural extraction, pinocembrin can be obtained by biosynthesis. Biosynthesis efficiency can be improved by a metabolic engineering strategy and a two-phase pH fermentation strategy. Pinocembrin poses an interest for its remarkable pharmacological activities, such as neuroprotection, anti-oxidation, and anti-inflammation. Studies have shown that pinocembrin works excellently in treating ischemic stroke. Pinocembrin can reduce nerve damage in the ischemic area and reduce mitochondrial dysfunction and the degree of oxidative stress. Given its significant efficacy in cerebral ischemia, pinocembrin has been approved by China Food and Drug Administration (CFDA) as a new treatment drug for ischemic stroke and is currently in progress in phase II clinical trials. Research has shown that pinocembrin can be absorbed rapidly in the body and easily cross the blood-brain barrier. In addition, the absorption/elimination process of pinocembrin occurs rapidly and shows no serious accumulation in the body. Pinocembrin has also been found to play a role in Parkinson's disease, Alzheimer's disease, and specific solid tumors, but its mechanisms of action require in-depth studies. In this review, we summarized the latest 10 years of studies on the biosynthesis, pharmacological activities, and pharmacokinetics of pinocembrin, focusing on its effects on certain diseases, aiming to explore its targets, explaining possible mechanisms of action, and finding potential therapeutic applications.


Assuntos
Produtos Biológicos/metabolismo , Produtos Biológicos/farmacologia , Flavanonas/biossíntese , Flavanonas/farmacologia , Animais , Produtos Biológicos/química , Produtos Biológicos/farmacocinética , Vias Biossintéticas , Avaliação Pré-Clínica de Medicamentos , Fermentação , Flavanonas/química , Flavanonas/farmacocinética , Humanos , Relação Estrutura-Atividade
20.
J Nat Med ; 73(4): 847-854, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31218551

RESUMO

Two new flavonoid glycosides, 2',4'-dihydroxydihydrochalcone-4-O-ß-D-glucopyranoside (1) and medicarpin-3-O-ß-D-apiofuranosyl (1 → 2)-ß-D-glucopyranoside (2), together with 34 known flavonoids were isolated from the 75% EtOH extract of the dried roots of Glycyrrhiza uralensis Fisch. Their structures were elucidated on the basis of spectroscopic analyses. The flavonoids were classified into ten sub-types, namely, dihydrochalcone (1), pterocarpans (2-4), flavones (5-6), flavanones (7-11), chalcones (12-15), retro-chalcones (16-18), isoflavans (19-21), isoflavones (22-28), 3-arylcoumarins (29-30), and coumestans (31-36). The isolated flavonoids were evaluated for in vitro hepatoprotective activity against D-galactosamine-induced toxicity in human hepatoma HepG2 cells.


Assuntos
Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Glycyrrhiza uralensis/química , Linhagem Celular Tumoral , Chalconas/química , Chalconas/isolamento & purificação , Cumarínicos/química , Cumarínicos/isolamento & purificação , Flavanonas/química , Flavanonas/isolamento & purificação , Flavonas/química , Flavonas/isolamento & purificação , Flavonoides/química , Glicosídeos/química , Glycyrrhiza/química , Células Hep G2 , Humanos , Isoflavonas/química , Isoflavonas/isolamento & purificação , Raízes de Plantas/química , Pterocarpanos/química , Pterocarpanos/isolamento & purificação
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