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1.
J Agric Food Chem ; 69(35): 10272-10280, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34436886

RESUMO

Salt is very important for human health and food seasoning. Recently, several peptides isolated from natural food products have been reported exhibiting a salty taste or a saltiness-enhancing function. In this investigation, taste-active peptides occurring in commercial Chinese fermented soybean curd were isolated and identified using ultrafiltration, gel permeation chromatography, ion-exchange chromatography, and nano-LC/Q-TOF MS/MS. The salty taste-enhancing function of the target fractions was confirmed by both a rat taste cell model and/or human sensory evaluation. Four decapeptides were found as taste-active compounds. Among them, peptide E (EDEGEQPRPF) was the most potent saltiness-enhancing peptide: 0.4 mg/mL in 50 mmol/L NaCl solution could increase its salty perception equivalent to the salt level of 63 mmol/L NaCl reference solution. The sequence of the peptide has been found in the α'-subunit of ß-conglycinin [Glycine max]. The remaining peptides V (VGPDDDEKSW), DD (DEDEQPRPIP), and DG (DEGEQPRPFP) showed umami and kokumi tastes as well as a weak saltiness-enhancing sensation. These findings suggest that the decapeptide EDEGEQPRPF could be a possible alternative to partially reduce the amount of sodium intake without compromising for saltiness.


Assuntos
Cloreto de Sódio , Alimentos de Soja , Animais , China , Peptídeos , Ratos , Alimentos de Soja/análise , Espectrometria de Massas em Tandem , Paladar
2.
Int J Mol Sci ; 22(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202585

RESUMO

Cultured keratinocytes are desirable models for biological and medical studies. However, primary keratinocytes are difficult to maintain, and there has been little research on lingual keratinocyte culture. Here, we investigated the effect of Y-27632, a Rho kinase (ROCK) inhibitor, on the immortalization and characterization of cultured rat lingual keratinocyte (RLKs). Three Y-27632-supplemented media were screened for the cultivation of RLKs isolated from Sprague-Dawley rats. Phalloidin staining and TUNEL assay were applied to visualize cytoskeleton dynamics and cell apoptosis following Y-27632 removal. Label-free proteomics, RT-PCR, calcium imaging, and cytogenetic studies were conducted to characterize the cultured cells. Results showed that RLKs could be conditionally immortalized in a high-calcium medium in the absence of feeder cells, although they did not exhibit normal karyotypes. The removal of Y-27632 from the culture medium led to reversible cytoskeletal reorganization and nuclear enlargement without triggering apoptosis, and a total of 239 differentially expressed proteins were identified by proteomic analysis. Notably, RLKs derived from the non-taste epithelium expressed some molecular markers characteristic of taste bud cells, yet calcium imaging revealed that they rarely responded to tastants. Collectively, we established a high-calcium and feeder-free culture method for the long-term maintenance of RLKs. Our results shed some new light on the immortalization and differentiation of lingual keratinocytes.


Assuntos
Amidas/farmacologia , Cálcio/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Quinases Associadas a rho/antagonistas & inibidores , Animais , Técnicas de Cultura de Células , Células Cultivadas , Ratos
3.
Phytomedicine ; 76: 153253, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32531699

RESUMO

BACKGROUND: Cyperenoic acid, one of the main chemical constituents of the root of Croton crassifolius, exhibited potent anti-angiogenic property on the zebrafish embryo model with little cytotoxicity. Nevertheless, its anti-angiogenic mechanism and anti-tumor effect have not been investigated. PURPOSE: To investigate the anti-angiogenic mechanisms of cyperenoic acid and evaluate it whether could exert anti-tumor effect by inhibiting angiogenesis. STUDY DESIGN: Targeting vascular endothelial growth factor receptor-2 (VEGFR2) pathway to inhibit tumor angiogenesis is a significant strategy for cancer treatment. Initially, the anti-angiogenic effect of cyperenoic acid as well as the mechanisms of the action was studied using both in-vitro and in-vivo methodologies. Then, its anti-tumor effect through anti-angiogenesis by attenuating VEGFR2 signaling pathway was evaluated. METHODS: The in-vitro inhibitory effect of cyperenoic acid on the vascular endothelial growth factor (VEGF)-induced angiogenesis was evaluated using human umbilical vein endothelial cells (HUVECs) model. Moreover, its ex-vivo and in-vivo effects were evaluated using the aortic ring assay and the matrigel plug assay. The influence of the cyperenoic acid on tyrosine phosphorylation of VEGFR2 was studied by western blotting assay and the influence on downstream signaling pathway of VEGFR2 also be detected. Computer-docking simulations were carried out to study the interaction between cyperenoic acid and VEGFR2. Finally, its inhibitory effect on tumor growth was studied using breast cancer xenograft model. RESULTS: Cyperenoic acid possessed little toxicity to HUVECs, but it significantly inhibited VEGF-induced proliferation, invasion, migration and tube formation of HUVECs. Moreover, it inhibited VEGF-induced sprout formation ex vivo and vessel formation in vivo. Further mechanistic study showed that cyperenoic acid could suppress VEGFR2 tyrosine kinase activity and alter its downstream signaling pathways in VEGF-induced HUVECs. In addition, it could form two hydrogen bonds with the ATP binding pocket of the VEGFR2 kinase domain by docking. For breast cancer xenograft model, cyperenoic acid suppressed tumor growth, but no obvious toxic pathologic changes were observed in mice. Besides, it suppressed the phosphorylation of VEGFR2 in tumor, demonstrating its anti-angiogenic ability in vivo partly targeting the VEGFR2. CONLUSION: Cyperenoic acid could exert anti-tumor effect in breast cancer by inhibiting angiogenesis via VEGFR2 signaling pathway.

4.
Food Microbiol ; 90: 103408, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32336369

RESUMO

This study aimed to explore the core functional microbiotas related to flavor compounds involving in a naturally fermented soybean curd (plain sufu). Properties such as physicochemical parameters, flavor compounds (17 free amino acids, 21 fatty acids, and 14 aroma volatiles) and microbiota profiles were investigated, and their correlations were explored at 8 stages during production. Results from principal component analysis, multiple factor analysis, and partial least squares-discrimination analysis showed that these properties varied significantly in the eight stages. Furthermore, based on Pearson correlation coefficients and Variable importance for predictive components values between the microbiota profiles and flavor compounds, nine bacterial (Bacillus, Enterobacter, Lactobacillus, Sphingobacterium, Stenotrophomonas, Tetragenococcus, Trabulsiella, Unclassified, and Weissella) and six fungal (Alternaria, Sterigmatomyces, Actinomucor, Fusarium, Debaryomyces, Candida) genera were identified as core functional microbiotas significantly affecting the production of flavor compounds during the natural production. Overall, this study provided a comprehensive description of the dynamic changes of physicochemical parameters, flavor compounds, and microbiota profiles throughout the natural production of plain sufu. The similarities and variations among different stages, as well as correlation between flavor compounds and microbiotas would help to understand the mechanism of plain sufu production, and further to enhance the quality control of plain sufu.


Assuntos
Bactérias/metabolismo , Fermentação , Aromatizantes/análise , Fungos/metabolismo , Microbiota , Alimentos de Soja/microbiologia , Aminoácidos/análise , Bactérias/classificação , Bactérias/isolamento & purificação , Fenômenos Fisiológicos Bacterianos , China , Ácidos Graxos/análise , Alimentos e Bebidas Fermentados/microbiologia , Fungos/classificação , Fungos/isolamento & purificação , Odorantes/análise , Compostos Orgânicos Voláteis/análise
5.
J Food Biochem ; 44(5): e13185, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32162705

RESUMO

Miracle fruit (Synsepalum dulcificum) is famous for its uniqueness of modifying sour taste to sweetness. However, its cholesterol-lowering activity has not been reported. This study investigated the effect of S. dulcificum on the compositional changes of plasma lipids in hamsters fed a high-cholesterol control diet. Six groups of hamsters were fed either a control diet or one of the five experimental diets containing 2% ethanol extract of leaves, 2% water extract of leaves, 2% ethanolic extract of seeds (ES), 2% water extract of seeds, or 2% dry pulp. Results showed that ES decreased the plasma total cholesterol (TC). Two triterpenoids (lupeol acetate and ß-amyrin acetate) were isolated from the ES and they added to a diet could decrease TC by 15%-20% in hamsters. It was concluded that ES showed potent TC-lowering activity and triterpenoid was one of the active components of ES. PRACTICAL APPLICATIONS: In recent years, people are more interested in phytochemicals from functional foods treated for hyperlipidemia because they possessed fewer side effects than the synthetic drugs. The triterpenoids isolated from the miracle fruit may be promising candidates for the development of cholesterol-lowering agent, especially for patients whose blood cholesterol level and body weight are high. Meanwhile, the miracle fruit have a good potential as cholesterol-lowering functional food or a natural source of cholesterol-lowering agent.


Assuntos
Synsepalum , Colesterol , Humanos , Triterpenos Pentacíclicos , Paladar
6.
Molecules ; 25(1)2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31947901

RESUMO

Atractylodes macrocephala is known to exhibit multi-arrays of biologic activity in vitro. However, detail of its anti-tumor activity is lacking. In this study, the effects of atractylenolide I (AT-I), a bio-active compound present in Atractylodes macrocephala rhizome was studied in the human colorectal adenocarcinoma cell line HT-29. The results showed that AT-I induced apoptosis of human colon cancer cells through activation of the mitochondria-dependent pathway. The IC50 of AT-I was 277.6 µM, 95.7 µM and 57.4 µM, after 24, 48 and 72 h of incubation with HT-29, respectively. TUNEL and Annexin V-FITC/PI double stain assays showed HT-29 DNA fragmentation after cell treatment with various AT-I concentrations. Western blotting analysis revealed activation of both initiator and executioner caspases, including caspase 3, caspase 7, and caspase 9, as well as PARP, after HT-29 treatment with AT-I via downregulation of pro-survival Bcl-2, and upregulation of anti-survival Bcl-2 family proteins, including Bax, Bak, Bad, Bim, Bid and Puma. The studies show for the first time that AT-I is an effective drug candidate towards the HT-29 cell.


Assuntos
Adenocarcinoma/metabolismo , Neoplasias do Colo/metabolismo , Lactonas/farmacologia , Sesquiterpenos/farmacologia , Apoptose/efeitos dos fármacos , Western Blotting , Caspase 3/metabolismo , Caspase 7/metabolismo , Caspase 9/metabolismo , Caspases/metabolismo , Fragmentação do DNA/efeitos dos fármacos , Células HT29 , Humanos , Marcação In Situ das Extremidades Cortadas
7.
Food Res Int ; 125: 108548, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31554058

RESUMO

Selected physico- (texture and color) chemical (salt, protein, and moisture content) properties and 20 targeted volatile compounds (TVCs) from 12 commercial red sufus were investigated to identify correlations with sensory attributes obtained by either QDA or Flash Profile (FP). The intensities of 15 attributes from QDA and the ranking values of 19 attributes from FP of red sufus were evaluated, and a higher variance was generally found in the results from FP than those from QDA among the 12 samples. Principal component analysis (PCA) of TVCs showed that both the concentration and the ratio of volatile compounds influenced the flavor quality and the discrimination among the samples. Multiple factor analysis (MFA) was used to associate the sensory data from either FP or QDA with the physicochemical properties and TVCs of red sufus. The results showed that both FP and QDA data associated well with the physicochemical and TVC data, and the intensity of the sensory attributes could be predicted from the properties of red sufus. Pearson correlation coefficients between the sensory attributes (aroma/flavor) and TVCs pinpointed that a sulfur-like aroma was a key attribute in red sufus, and it might be a result of the comprehensive combination of different TVCs. The information reported here could be important for the quality control of traditional and new variants of red sufu products by providing an approach to substitute the sensory measurements with the instrumental measurements, and to strengthen the interpretation of sensory data by showing how they are affected by the physicochemical properties.


Assuntos
Odorantes/análise , Alimentos de Soja/análise , Compostos Orgânicos Voláteis/análise , Fenômenos Químicos , Cromatografia Gasosa-Espectrometria de Massas , Análise de Componente Principal , Compostos Orgânicos Voláteis/química
8.
Molecules ; 24(15)2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31387305

RESUMO

New quantitative structure-activity relationship (QSAR) models for bitter peptides were built with integrated amino acid descriptors. Datasets contained 48 dipeptides, 52 tripeptides and 23 tetrapeptides with their reported bitter taste thresholds. Independent variables consisted of 14 amino acid descriptor sets. A bootstrapping soft shrinkage approach was utilized for variable selection. The importance of a variable was evaluated by both variable selecting frequency and standardized regression coefficient. Results indicated model qualities for di-, tri- and tetrapeptides with R2 and Q2 at 0.950 ± 0.002, 0.941 ± 0.001; 0.770 ± 0.006, 0.742 ± 0.004; and 0.972 ± 0.002, 0.956 ± 0.002, respectively. The hydrophobic C-terminal amino acid was the key determinant for bitterness in dipeptides, followed by the contribution of bulky hydrophobic N-terminal amino acids. For tripeptides, hydrophobicity of C-terminal amino acids and the electronic properties of the amino acids at the second position were important. For tetrapeptides, bulky hydrophobic amino acids at N-terminus, hydrophobicity and partial specific volume of amino acids at the second position, and the electronic properties of amino acids of the remaining two positions were critical. In summary, this study not only constructs reliable models for predicting the bitterness in different groups of peptides, but also facilitates better understanding of their structure-bitterness relationships and provides insights for their future studies.


Assuntos
Aminoácidos/química , Dipeptídeos/química , Peptídeos/química , Relação Quantitativa Estrutura-Atividade , Paladar
9.
Food Chem ; 275: 32-40, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30724202

RESUMO

A rapid headspace solid-phase microextraction method was optimized to detect volatile components in three commercial plain sufu samples. The method was then used to qualify 14 aroma impact components that contribute significantly to the volatile profile in 12 commercial samples produced at three locations and laboratory-scale fermented samples aged for 3, 15, 30, and 90 days. Principal component analysis (PCA) was subsequently used to group the samples. The optimized method identified 148 volatile compounds in three commercial samples, and the concentrations of 14 aroma impact compounds varied significantly among commercial and laboratory samples. PCA confirmed that these samples could be discriminated according to their production location and aging time, thereby rendering this method a simple strategy for sample discrimination.


Assuntos
Alimentos e Bebidas Fermentados/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Microextração em Fase Sólida/métodos , Soja , Compostos Orgânicos Voláteis/análise , Análise de Alimentos/métodos , Análise de Alimentos/estatística & dados numéricos , Odorantes/análise , Análise de Componente Principal
10.
J Sci Food Agric ; 99(6): 3024-3033, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30488614

RESUMO

BACKGROUND: Red sufu is a type of sufu produced by solid-state fermentation of soybean curd and coloration with red mold rice. The purposes of this study were: (i) to characterize commercial red sufu samples using the quantitative descriptive analysis (QDA) and flash profile (FP) by ten trained and ten untrained panelists, respectively; (ii) to compare the differences in panel performance, descriptive abilities and sensory maps between the two methodologies; and (iii) to compare the efficiency between QDA and FP using red sufu as the matrix. Techniques in multivariate analysis were utilized to explore the data. RESULTS: Results from generalized procrustes analysis (GPA) showed that panel performance by QDA was more repeatable and reached higher homogeneity than that by FP. Despite the confidence ellipse results of the 12 red sufus being better discriminated by QDA, the RV coefficient was high (RV = 0.852) between the configurations of the two-dimensional model (F1 and F2) of the two methodologies, indicating that the two methods are similar and closely related. Overall, QDA provided more accurate and detailed information, while FP provided a similar sensory map on product location and descriptive results. CONCLUSION: The FP technique appeared to be an efficient alternative approach to quickly evaluate sensory properties, including appearance, flavor, aroma and textural properties of an array of red sufu products. © 2018 Society of Chemical Industry.


Assuntos
Alimentos e Bebidas Fermentados/análise , Alimentos de Soja/análise , Adulto , Feminino , Alimentos e Bebidas Fermentados/economia , Humanos , Masculino , Alimentos de Soja/economia , Paladar , Adulto Jovem
11.
J Sci Food Agric ; 98(11): 4216-4226, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29406615

RESUMO

BACKGROUND: Sufu is a fermented soybean food with unique odor, flavor, and texture, which might not be appreciated by nonregular consumers. To identify the attributes that nonregular consumers appreciated, 12 commercial products bought from a Hong Kong market were tested by 113 consumers according to the ideal profile method (IPM), and rated on 22 attributes. RESULTS: Data provided from nonregular consumers were consistent at both panel and consumer levels. The predicted ideal profile received a higher hedonic score (7.0) than the tested products (6.0). Compared with commercial samples, the ideal sufu has low intensity in the attributes of fermented (aroma and flavor), moldy (aroma), and hard (texture), but high intensity in the soybean-like (aroma and flavor) and sesame oil-like (aroma and flavor) attributes. CONCLUSION: IPM could be used as an alternative approach to collect sensory profiles and preference data directly from consumers for product characterization. It could also be applied to identify the attributes that nonregular consumers appreciated. © 2018 Society of Chemical Industry.


Assuntos
Comportamento do Consumidor/estatística & dados numéricos , Inquéritos sobre Dietas/métodos , Aromatizantes/análise , Alimentos de Soja/análise , Adolescente , Adulto , Feminino , Alimentos e Bebidas Fermentados/análise , Preferências Alimentares , Humanos , Masculino , Pessoa de Meia-Idade , Odorantes/análise , Análise de Componente Principal , Soja/química , Paladar , Adulto Jovem
12.
Food Chem ; 239: 1117-1125, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-28873530

RESUMO

Lipid oxidation-a major cause of food product deterioration-necessitates the use of food additives to inhibit food oxidation. Ginger extract (GE) has been reported to possess antioxidant properties. However, components isolated from ginger have been rarely reported to inhibit fat oxidation. Herein, antioxidant properties of GE and four pure components derived from it (6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol) were examined and their properties were compared to those of butylated hydroxytoluene. GE and the constituent components exhibited antioxidant properties that might be attributed to their hydroxyl groups and suitable solubilizing side chains. 6-Shogaol and 10-gingerol exhibited higher activity at 60°C than 6-gingerol and 8-gingerol. Low antioxidant activity was detected at high temperatures (120/180°C). Overall, GE displayed the strongest dose-dependent antioxidant properties, especially at high temperatures, thereby demonstrating that GE can be employed as a natural antioxidant in lipid-containing processed foods.


Assuntos
Gengibre , Catecóis , Álcoois Graxos , Lipídeos , Extratos Vegetais
13.
Sci Rep ; 7(1): 7483, 2017 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-28790369

RESUMO

Salty taste is one of the five basic tastes and is often elicited by NaCl. Because excess sodium intake is associated with many health problems, it could be useful to have salt taste enhancers that are not sodium based. In this study, the regulation of NaCl-induced responses was investigated in cultured human fungiform taste papillae (HBO) cells with five arginyl dipeptides: Ala-Arg (AR), Arg-Ala (RA), Arg-Pro (RP), Arg-Glu (RE), and Glu-Arg (ER); and two non-arginyl dipeptides: Asp-Asp (DD) and Glu-Asp (ED). AR, RA, and RP significantly increased the number of cell responses to NaCl, whereas no effect was observed with RE, ER, DD, or ED. We also found no effects with alanine, arginine, or a mixture of both amino acids. Pharmacological studies showed that AR significantly increased responses of amiloride-sensitive but not amiloride-insensitive cells. In studies using small interfering RNAs (siRNAs), responses to AR were significantly decreased in cells transfected with siRNAs against epithelial sodium channel ENaCα or ENaCδ compared to untransfected cells. AR dramatically increased NaCl-elicited responses in cells transfected with NHE1 siRNA but not in those transfected with ENaCα or ENaCδ siRNAs. Altogether, AR increased responses of amiloride-sensitive cells required ENaCα and ENaCδ.


Assuntos
Arginina/química , Dipeptídeos/farmacologia , Canais Epiteliais de Sódio/genética , Cloreto de Sódio/farmacologia , Papilas Gustativas/efeitos dos fármacos , Amilorida/farmacologia , Arginina/farmacologia , Cálcio/metabolismo , Canais Epiteliais de Sódio/metabolismo , Regulação da Expressão Gênica , Humanos , Cultura Primária de Células , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Salinidade , Transdução de Sinais , Trocador 1 de Sódio-Hidrogênio/antagonistas & inibidores , Trocador 1 de Sódio-Hidrogênio/genética , Trocador 1 de Sódio-Hidrogênio/metabolismo , Papilas Gustativas/citologia , Papilas Gustativas/metabolismo , Percepção Gustatória/fisiologia
14.
Int J Oncol ; 51(1): 213-222, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28534941

RESUMO

Eudesmane-type sesquiterpenes are natural sesquiterpenes with anti-inflammatory properties, but their anti-angiogenic activities are not known. The present study demonstrated that 5α-hydroxycostic acid and hydroxyisocostic acid, two eudesmane-type sesquiterpenes (ETSs), isolated from the herb Laggera alata, possessed anti-angiogenic effects. Under non-toxic dosage, ETSs suppressed VEGF­induced proliferation in human umbilical vein endothelial cells (HUVECs) and vessel formation in zebrafish embryos. Moreover, ETSs inhibited VEGF-stimulated HUVEC migration, stress fibers and tube formation. Results from real­time PCR analysis involving in vivo and in vitro experiments indicated that pro-angiogenic-related mRNA levels were downregulated, including VEGFA, VEGFR2 and Tie2 genes after ETS treatments. Western blot analysis showed that ETSs suppressed VEGF-stimulated VEGFR2 phosphorylation and activation of its downstream molecules, such as Src/AKT/eNOS, FAK, PLCγ/ERK1/2 and p38. Moreover, the VEGF-stimulation of angiopoietin 2 (Ang2) mRNA level increase was significantly downregulated in the presence of ETSs. ETSs inhibited Ang2-induced phosphorylation of the receptor Tie2 in HUVECs, which indicated that ETSs not just suppressed VEGF/VEGFR2 axis, but also the Ang2/Tie2 one. Furthermore, the wound-healing assay revealed that ETSs reduced the migration of Ang2-stimulated human breast cancer (MCF-7) cells. Mechanistically, the anti-migration effect of ETSs correlated with the blockade of Ang2-induced E-cadherin loss and AKT activation. Collectively, the present study suggests that ETSs possess anti-angiogenic ability by interfering the VEGF- and Ang2-related pathways, and they may be good drug candidates.


Assuntos
Inibidores da Angiogênese/farmacologia , Asteraceae/química , Neoplasias da Mama/prevenção & controle , Movimento Celular/efeitos dos fármacos , Neovascularização Patológica/prevenção & controle , Sesquiterpenos de Eudesmano/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Animais , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Embrião não Mamífero/citologia , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Transdução de Sinais , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo
15.
J Breath Res ; 10(4): 046004, 2016 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-27677705

RESUMO

Selected ion flow tube-mass spectrometry (SIFT-MS) provides rapid, non-invasive measurements of a full-mass scan of volatile compounds in exhaled breath. Although various studies have suggested that breath metabolites may be indicators of human disease status, many of these studies have included few breath samples and large numbers of compounds, limiting their power to detect significant metabolites. This study employed a least absolute shrinkage and selective operator (LASSO) approach to SIFT-MS data of breath samples to preliminarily evaluate the ability of exhaled breath findings to monitor the efficacy of dialysis in hemodialysis patients. A process of model building and validation showed that blood creatinine and urea concentrations could be accurately predicted by LASSO-selected masses. Using various precursors, the LASSO models were able to predict creatinine and urea concentrations with high adjusted R-square (>80%) values. The correlation between actual concentrations and concentrations predicted by the LASSO model (using precursor H3O+) was high (Pearson correlation coefficient = 0.96). Moreover, use of full mass scan data provided a better prediction than compounds from selected ion mode. These findings warrant further investigations in larger patient cohorts. By employing a more powerful statistical approach to predict disease outcomes, breath analysis using SIFT-MS technology could be applicable in future to daily medical diagnoses.


Assuntos
Testes Respiratórios/métodos , Expiração , Espectrometria de Massas/métodos , Modelos Teóricos , Diálise Renal , Adulto , Creatinina/sangue , Humanos , Monitorização Fisiológica , Projetos Piloto , Reprodutibilidade dos Testes , Ureia/sangue , Compostos Orgânicos Voláteis/análise
16.
Nat Prod Commun ; 11(4): 435-8, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27396185

RESUMO

Centipeda minima is a Chinese herbal medicine used in the treatment of various diseases including cancer. An ethanol extract of the herb, its four fractions with different polarities, and two volatile oils prepared by steam distillation (SD) and supercritical fluid extraction (SFE) were investigated for their anti-angiogenic activity in a wild-type zebrafish model using a quantitative endogenous alkaline phosphatase (EAP) assay. The SFE oil displayed potent anti-angiogenic activity. Fifteen sesquiterpene lactones (SLs; compounds 1-15) isolated from the SFE oil were evaluated for their anti-angiogenic effect. Results revealed that pseudoguaianolide type SLs (1-8) inhibited vessel formation in the zebrafish embryos while guaianolide type SLs (9-15) showed little effect. Among the active ones, 6-O-angeloylenolin (1), a major component of SFE oil, possessed the strongest effect by reducing vessel formation in zebrafish embryos to 40% of the control value at 29.7 µM. Further study using the Tg (fli1a:EGFP) y1-type zebrafish model revealed that it blocked both intersegmental blood vessels (ISVs) and subintestinal vessels plexus (SIVs) formation in zebrafish embryos. Real-time polymerase chain reaction assay on the wild-type zebrafish embryos suggested that 6-O-angeloylenolin affected multiple molecular targets related to angiogenesis including VEGF receptor, angiopoietin, and its receptors. Taken together, our findings demonstrate that C. minima possesses anti-angiogenic activity, and 6-O-angeloylenolin is a promising candidate for the development of an anti-angiogenic agent.


Assuntos
Inibidores da Angiogênese/análise , Asteraceae/química , Lactonas/isolamento & purificação , Lactonas/farmacologia , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Inibidores da Angiogênese/farmacologia , Animais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Peixe-Zebra
17.
Phytomedicine ; 23(3): 283-92, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26969382

RESUMO

BACKGROUND: Wedelia chinensis is a traditional medicinal herb used in Asia and it has been reported to possess various bioactivities including anti-inflammatory and anticancer effects. However, its anti-angiogenic activity has never been reported. PURPOSE: To determine the most potent anti-angiogenic component in W. chinensis and its molecular mechanism of action. STUDY DESIGN: Initially, the active fraction of the plant was studied. Then, we determined the active components of the fraction and explored the mechanism of the most active compound. METHODS: The ethanol extract of W. chinensis and its four fractions with different polarities were evaluated for their anti-angiogenic activity in the Zebrafish model using quantitative endogenous alkaline phosphatase (EAP) assay. The molecular mechanism of the most active compound from the active fraction was studied using the real-time polymerase chain reaction (PCR) assay on Zebrafish embryos. The inhibitory effect of the most active compound on the proliferation, invasion and tube formation steps of angiogenesis was evaluated using the vascular endothelial growth factor (VEGF)-induced human umbilical vein endothelial cells (HUVECs) model, and the influences of the active compound on tyrosine phosphorylation of VEGF receptor (VEGFR-2) and its downstream signal pathway were evaluated by western blotting assay. Moreover, its anti-angiogenic effect was further evaluated by the VEGF-induced sprouts formation on aortic ring assay and the VEGF-induced vessel formation of mice on matrigel plug assay, respectively. RESULTS: Petroleum ether (PE) fraction of the plant displayed potent anti-angiogenic activity. Twelve kaurane diterpenoids (1-12) isolated from this fraction showed quite different effects. Compounds 9-12 could dose-dependently inhibit vessel formation in the Zebrafish embryos while the others showed little inhibitory effect. Among the active diterpenoids, compound 10, 3α-cinnamoyloxy-9ß-hydroxy-ent-kaura-16-en-19-oic acid (CHKA), possessed the strongest effect, and it affected multiple molecular targets related to angiogenesis including VEGF and angiopoietin in Zerbrafish. Moreover, CHKA significantly inhibited a series of VEGF-induced angiogenesis processes including proliferation, invasion, and tube formation of endothelial cells. Besides, it directly inhibited VEGFR-2 tyrosine kinase activity and its downstream signaling pathways in HUVECs. CHKA also obviously inhibited sprouts formation of aortic ring, and block vessel formation in mice. CONCLUSION: Our findings demonstrate that kaurane diterpenoids is one of anti-angiogenic components in W. chinensis, and CHKA may become a promising candidate for the development of anti-angiogenic agent.


Assuntos
Inibidores da Angiogênese/farmacologia , Diterpenos do Tipo Caurano/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Wedelia/química , Animais , Aorta/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Embrião não Mamífero/efeitos dos fármacos , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Neovascularização Patológica/tratamento farmacológico , Fosforilação , Extratos Vegetais/farmacologia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/farmacologia , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Peixe-Zebra
18.
Phytochemistry ; 122: 270-275, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26725185

RESUMO

Six diterpenoids [crassifolin J, K, L, M, N and O] along with eleven known ones were isolated from the supercritical fluid extract (SFE) of the roots of Croton crassifolius (Euphorbiaceae). Their structures were elucidated using spectroscopic methods (IR, UV, HRESIMS, 1D and 2D NMR). The structure and stereochemistry of crassifolin J was confirmed by single-crystal X-ray diffraction analysis, and the absolute configurations of crassifolin K-M were determined by CD spectra. Twenty-three diterpenoids from this plant were screened for their anti-angiogenic activity using a wild-type zebrafish in vivo model. Four of the known compounds were active, of which penduliflaworosin possessed the best activity relative to the positive control (SU5416). Further study demonstrated that penduliflaworosin could inhibit vessel formation on Tg(fli1a:EGFP)y1-type zebrafish embryos.


Assuntos
Inibidores da Angiogênese/isolamento & purificação , Inibidores da Angiogênese/farmacologia , Croton/química , Diterpenos Clerodânicos/isolamento & purificação , Diterpenos Clerodânicos/farmacologia , Inibidores da Angiogênese/química , Animais , Cristalografia por Raios X , Diterpenos , Diterpenos Clerodânicos/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Raízes de Plantas/química , Peixe-Zebra
19.
J Agric Food Chem ; 63(43): 9520-7, 2015 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-26468759

RESUMO

Human respiratory syncytial virus (RSV) is a common pathogen that causes pneumonia and bronchiolitis in infants and young children. Our previous study showed that tangeretin from Citrus reticulate possessed potent in vitro anti-RSV effects comparable to that of ribavirin. Therefore, in this study, we investigated the in vivo anti-RSV activity of tangeretin in 3-week-old male BALB/c mice. A plaque reduction assay and fluorescence quantitative polymerase chain reaction (FQ-PCR) showed that tangeretin inhibited RSV replication in the lung of mice. Moreover, a luminex assay indicated tangeretin relieved RSV-induced lung inflammation by attenuating interleukin (IL)-1ß secretion. Possible anti-inflammatory mechanisms of tangeretin were preliminarily explored using a RSV-infected macrophage model. A FQ-PCR, enzyme-linked immunosorbent assay (ELISA), and luciferase assay revealed that tangeretin inhibited RSV-induced inflammation by suppressing nuclear factor-κB (NF-κB) activation. This study demonstrates that tangeretin inhibited RSV replication and RSV-induced lung inflammation in vivo and may be useful in preventing and treating RSV infections and inflammation.


Assuntos
Antivirais/administração & dosagem , Citrus/química , Flavonas/administração & dosagem , Extratos Vegetais/administração & dosagem , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sinciciais Respiratórios/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Humanos , Pulmão/imunologia , Pulmão/virologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/imunologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/fisiologia , Replicação Viral/efeitos dos fármacos
20.
J Ethnopharmacol ; 175: 185-91, 2015 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-26386379

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The root of Croton crassifolius Geisel is traditionally used in China for the treatment of snake bites, stomach ache, sternalgia, joint pain, pharyngitis, jaundice and rheumatoid arthritis, while in Thailand, it has been used as an anticancer herbal medicine by the indigenous people. Yet, its pharmacological studies are still limited, especially towards its anticancer property. Anti-angiogenesis is a promising therapeutic strategy in the anti-cancer treatment. Previous studies have shown strong anti-angiogenic activity in the low polar fraction of the herb. Nevertheless, the potent compound which is responsible for the anti-angiogenesis, and its molecular mechanism have never been reported. AIM OF THE STUDY: To determine the potent anti-angiogenic component in C. crassifolius and its molecular mechanism of action. MATERIALS AND METHODS: C. crassifolius was extracted using supercritical fluid extraction and steam distillation. The anti-angiogenic activities of the two extracts were evaluated in the zebrafish model by quantitative endogenous alkaline phosphatase assay. The chemical compounds in the active extract were isolated using chromatographic methods, and their structures were elucidated using different spectroscopic techniques. The content/quantity of the active compounds in this extract was determined with HPLC analysis. The molecular mechanism of the most active compound was further studied using the real-time PCR assay. Besides, its cytotoxicity on various cancer and normal cell lines was evaluated using the cell-counting kit. RESULTS: Supercritical fluid extract (SFE) of C. crassifolius showed better anti-angiogenic activity than that of steam distillation extract (SDE). Three sesquiterpenes, namely, cyperenoic acid, 8-hydroxy-α-guaiene and (+)-guaia-l(10),ll-dien-9-one, were isolated and identified in the SFE. Among them, cyperenoic acid displayed the strongest anti-angiogenic activity by 51.7% of the control at 10µM, while the others showed little effect. HPLC results showed that cyperenoic acid was the major component in the SFE with 9.97% (w/w). Results of the real-time PCR assay suggested that the cyperenoic acid affected multiple molecular targets related to angiogenesis including vascular endothelial growth factor (Vegfa), angpiopoietin (Angpt), and their receptors. Cytotoxicity assay showed cyperenoic acid possessed little toxicity toward cancer and normal cells. CONCLUSIONS: Cyperenoic acid is an important anti-angiogenic component present in C. crassifolius and serve as a potent inhibitor in the angiogenesis in the zebrafish embryo model. The anti-angiogenic property, but not the cytotoxicity, of C. crassifolius provides a scientific basis for its traditional use in cancer treatment.


Assuntos
Inibidores da Angiogênese/farmacologia , Croton , Extratos Vegetais/farmacologia , Angiopoietina-1/genética , Angiopoietina-2/genética , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Embrião não Mamífero , Humanos , Raízes de Plantas , Receptor de TIE-1/genética , Receptor TIE-2/genética , Fator A de Crescimento do Endotélio Vascular/genética , Células Vero , Peixe-Zebra
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