Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 18.667
Filtrar
1.
Rinsho Ketsueki ; 60(9): 1108-1119, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31597834

RESUMO

Conventional chemotherapy with cytarabine and anthracycline (often referred to as "7+3") has been used for many years in the treatment of acute myeloid leukemia (AML). Despite meaningful advances in areas of supportive care and transplantation, little progress has been made in developing new chemotherapy options. In 2018, The Food and Drug Administration (FDA) of the US approved several novel agents for AML treatment as follows: ivosidenib, an inhibitor of isocitrate dehydrogenase-1; venetoclax, a potent inhibitor of bcl2; and glasdegib, an inhibitor of hedgehog signaling pathway. Moreover, clinical trials of alvocidib (flavopiridol), an inhibitor of the CDK9, pevonedistat, an inhibitor of NEDD8, and APR-246, a reactivator of mutant p53, are in progress. These agents will either be incorporated into the conventional 7+3 regimen or combined with hypomethylating agents to improve the outcome of AML therapy, and the results will guide the next stage of precision medicine in the treatment of AML.


Assuntos
Leucemia Mieloide Aguda/tratamento farmacológico , Benzimidazóis/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Ciclopentanos/farmacologia , Aprovação de Drogas , Flavonoides/farmacologia , Glicina/análogos & derivados , Glicina/uso terapêutico , Humanos , Terapia de Alvo Molecular , Compostos de Fenilureia/uso terapêutico , Piperidinas/farmacologia , Piridinas/uso terapêutico , Pirimidinas/farmacologia , Sulfonamidas/uso terapêutico , Estados Unidos , United States Food and Drug Administration
2.
Biol Res ; 52(1): 54, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31581950

RESUMO

BACKGROUND: IcarisideII (ICAII) could promote the differentiation of adipose tissue-derived stem cells (ADSCs) to Schwann cells (SCs), leading to improvement of erectile function (EF) and providing a realistic therapeutic option for the treatment of erectile dysfunction (ED). However, the underlying molecular mechanisms of ADSCs and ICAII in this process remain largely unclear. METHODS: ADSCs were treated with different concentrations of ICAII. Cell proliferation was determined by MTT assay. qRT-PCR and western blot were performed to detect expressions of SCs markers, signal transducer and activator of transcription-3 (STAT3), and microRNA-let-7i (let-7i). Luciferase reporter assay was conducted to verify the regulatory relationship between let-7i and STAT3. The detection of intracavernosal pressure (ICP) and the ratio of ICP/mean arterial pressure (MAP) were used to evaluate the EF in bilateral cavernous nerve injury (BCNI) rat models. RESULTS: ICAII promoted cell proliferation of ADSCs in a dose-dependent manner. The mRNA and protein levels of SCs markers were increased by ICAII treatment in a dose-dependent manner in ADSCs. Moreover, let-7i was significantly decreased in ICAII-treated ADSCs and upregulation of let-7i attenuated ICAII-induced promotion of SCs markers. In addition, STAT3 was a direct target of let-7i and upregulated in ICAII-treated ADSCs. Interestingly, overexpression of STAT3 abated the let-7i-mediated inhibition effect on differentiation of ADSCs to SCs and rescued the ICAII-mediated promotion effect on it. Besides, combination treatment of ADSCs and ICAII preserved the EF of BCNI rat models, which was undermined by let-7i overexpression. CONCLUSION: ICAII was effective for preserving EF by promoting the differentiation of ADSCs to SCs via modulating let-7i/STAT3 pathway.


Assuntos
Tecido Adiposo/citologia , Diferenciação Celular/efeitos dos fármacos , Disfunção Erétil/tratamento farmacológico , Flavonoides/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células de Schwann/efeitos dos fármacos , Animais , Western Blotting , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley , Transfecção
3.
Zhongguo Zhong Yao Za Zhi ; 44(15): 3335-3342, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602892

RESUMO

Based on pharmacodynamics-component correlation analysis,the best effective part of hyperlipidemia of Pericarpium Citri Reticulatae( PCR) was screened out to confirm the possible constituents with the lipid regulating effect,in order to provide a basis for the development of new drugs. Hyperlipidemia rats induced by fat emulsion were used to screen out the best hypolipidemic parts of PCR with TC,LDL-c as the index. HPLC-ESI-MS were used to analyze common constituents of the different solvent extracts from PCR. The constituents were classified and identified based on the retention time,m/z and UV spectra. And the HPLC-DAD were used to determine the contents of flavonoids( narirutin,hesperidin,didymin,nobiletin,tangeretin,3,5,6,7,8,3',4'-heptemthoxyflavone).Correlation analysis was conducted on the constituents and efficacy with the method of SPSS ANOVA bivariate correlation. Five extracts could significantly decrease the content of TC,LDL-c of hyperlipemia rats induced by fat emulsion,and the best effective part were95% ethanol and ethyl acetate. There were 19 common peaks in five different solvent extracts from PCR,and 17 flavonoids were identified and classified,including 10 polymethoxyflavonoids and 7 other flavonoids. According to the raw material quantity,the order of content of flavonones arranged from high to low: n-butyl alcohol part> 95% ethanol part> water part> ethyl acetate part> petroleum ether part; and the order of PMFs arranged from high to low: n-butyl alcohol part≈95% ethanol part≈ethyl acetate part > petroleum ether part > water part. The decreased percentage of TC,LDL-c was positively correlated with 10 common PMFs constituents,which suggested that PMFs may be the effective components for reducing blood lipid.


Assuntos
Citrus/química , Medicamentos de Ervas Chinesas/farmacologia , Hipolipemiantes/farmacologia , Animais , Cromatografia Líquida de Alta Pressão , Flavonoides/farmacologia , Ratos
4.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3478-3485, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602912

RESUMO

Tripterygium Glycosides Tablets has good anti-inflammatory and immunomodulatory activities,but its reproductive damage is significant. Previous studies of the research group have found that Cuscutae Semen flavonoids can improve spermatogenic cell damage caused by Tripterygium Glycosides Tablets by regulating spermatogenic cell cycle,apoptosis and related protein expression,but the mechanism of action at the gene level is still unclear. In this study,Illumina high-throughput sequencing platform was applied in transcriptional sequencing of spermatogenic cells of rats after the intervention of Cuscutae Semen flavonoids and Tripterygium Glycosides Tablets. Differentially expressed genes were screened out and the GO enrichment and KEGG pathway analysis of differentially expressed genes were conducted to explore the mechanism of Cuscutae Semen flavonoids in improving reproductive injury caused by Tripterygium Glycosides Tablets. The results showed that 794 up-regulated genes and 491 down-regulated genes were screened in Tripterygium Glycosides Tablets group compared with the blank group. Compared with Tripterygium Glycosides Tablets,440 up-regulated genes and 784 down-regulated genes were screened in the Cuscutae Semen flavonoids+Tripterygium Glycosides Tablets group. Among them,the gene closely related to reproductive function is DNMT3 L. Analysis of GO function and KEGG signaling pathway enrichment showed that the above differentially expressed genes were mainly enriched in cell,cell process,catalytic activity,binding,ovarian steroid synthesis,thyroid hormone and other functions and pathways. The thyroid hormone signaling pathway was the common enrichment pathway of the two control groups. In a word,Cuscutae Semen flavonoids has a good treatment effect on male reproductive damage caused by Tripterygium Glycosides Tablets. The mechanism may be closely related to up-regulation of DNMT3 L genes and intervention of thyroid hormone signaling pathway. At the same time,the discovery of many different genes provides valuable information for study on the mechanism of Cuscutae Semen flavonoids and Tripterygium Glycosides Tablets compatibility decreasing toxicity and increasing efficiency.


Assuntos
Cuscuta/química , Flavonoides/farmacologia , Genitália/efeitos dos fármacos , Glicosídeos/toxicidade , Tripterygium/toxicidade , Animais , DNA (Citosina-5-)-Metiltransferases/genética , Feminino , Genitália/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Masculino , Ratos , Sementes/química , Transdução de Sinais , Comprimidos , Hormônios Tireóideos/genética , Transcriptoma
5.
J Agric Food Chem ; 67(42): 11684-11693, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31564105

RESUMO

Enzymatic acylation is commonly used to increase the lipophilicity of flavonoids. However, the absence of primary hydroxyl groups makes it challenging to acylate baicalin using traditional acylation methods. In this study, an enzymatic esterification strategy was developed to introduce fatty-acid chains into baicalin at its carboxyl group, hence successfully synthesizing a new series of baicalin ester derivatives in nonaqueous media. Under the optimal reaction conditions, up to 95% conversion of baicalin was achieved. Antimicrobial evaluation of the baicalin ester derivatives indicated a corresponding increase to that of C log P values, with a cutoff effect at C log P = 5.2. Baicalin ester derivatives with C log P values of 4.9-5.2 exhibited the most potent antimicrobial activity. Interestingly, the introduction of medium-length fatty alcohol chains not only increased lipophilicity but also endowed them with membrane-disrupting properties. This study, therefore, provides an understanding of the esterification of flavonoid glycosides and a prospective application of the ester derivatives.


Assuntos
Anti-Infecciosos/química , Flavonoides/química , Lipase/química , Acilação , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Biocatálise , Esterificação , Ácidos Graxos/química , Flavonoides/farmacologia , Leveduras/efeitos dos fármacos
6.
Life Sci ; 235: 116797, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31472146

RESUMO

Chrysin is a promising phytochemical that is categorized under the class of flavonoids based on its chemical structure. Naturally, it is widely present in propolis, honey, passion fruit, and even in mushrooms and other plant sources, whereas its synthetic counterparts are also being employed for pharmacological purposes. It has widely been employed in treatment of various degenerative disorders and provides cytotoxic and anti-inflammatory functions. Its antioxidant and disease preventing abilities are attributed to its structural diversity arising in ring-A and absence of oxygenation in B and C ring. In this review, the scientific studies are being reported emphasizing benefits and its allied health claims on chrysin in numerous metabolic malfunctions.


Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Antivirais/farmacologia , Flavonoides/farmacologia , Humanos
7.
J Agric Food Chem ; 67(40): 11119-11128, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31525874

RESUMO

Xanthohumol (Xan) is a prenylated chalcone mainly found in hops; it has been demonstrated to function against hypercholesterolemia, hyperlipidemia, and atherosclerosis. In this study, we focused on the hypocholesterolemic effect of Xan on cholesterol uptake and the underlying molecular mechanisms of Xan in human intestinal Caco-2 cells. The microarray data showed that Niemann-Pick C1-like 1 (NPC1L1), an essential transporter for dietary cholesterol absorption, was significantly downregulated in Xan-treated Caco-2 cells. We demonstrated that Xan (10 and 20 µM) suppressed the mRNA and protein expression of NPC1L1 by 0.65 ± 0.12-fold and 0.54 ± 0.15-fold and 0.72 ± 0.04-fold and 0.44 ± 0.12-fold, respectively, compared to that of the vehicle-treated Caco-2 cells. Moreover, Xan (10 and 20 µM) significantly inhibited cholesterol uptake by approximately 12 and 32% in Caco-2 cells. NPC1L1 promoter activity was significantly suppressed by Xan, and a DNA element within the NPC1L1 promoter involved in Xan-mediated NPC1L1 reduction located between the -120 and -20 positions was identified. Moreover, Xan markedly decreased the mRNA and protein levels of hepatocyte nuclear factor 4α (HNF-4α), a critical activator of NPC1L1 transcription, and subsequently attenuated HNF-4α/NPC1L1 promoter complex formation, resulting in the suppression of NPC1L1 gene expression. Finally, we demonstrated that Xan markedly abolished lovastatin-induced NPC1L1 overexpression in Caco-2 cells. These findings reveal that Xan suppresses NPC1L1 expression via downregulation of HNF-4α and exerts inhibitory effects on cholesterol uptake in the intestinal Caco-2 cells. Our findings suggest Xan could serve as a potential cholesterol-lowering agent and supplement for statin therapy.


Assuntos
Colesterol/metabolismo , Flavonoides/farmacologia , Fator 4 Nuclear de Hepatócito/metabolismo , Proteínas de Membrana/genética , Propiofenonas/farmacologia , Anticolesterolemiantes/farmacologia , Transporte Biológico/efeitos dos fármacos , Células CACO-2 , Regulação para Baixo/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Fator 4 Nuclear de Hepatócito/genética , Humanos , Proteínas de Membrana/metabolismo , Regiões Promotoras Genéticas
8.
J Agric Food Chem ; 67(36): 10222-10234, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31385700

RESUMO

The emergence and rapid spread of methicillin-resistant Staphylococcus aureus (MRSA) critically requires alternative therapeutic options. New antibacterial drugs and strategies are urgently needed to combat MRSA-associated infections. Here, we investigated the antibacterial activity of flavones from Morus alba and the potential mode of action against MRSA. Kuwanon G, kuwanon H, mulberrin, and morusin displayed high efficiency in killing diverse MRSA isolates. On the basis of structure-activity analysis, the cyclohexene-phenyl ketones and isopentenyl groups were critical to increase the membrane permeability and to dissipate the proton motive force. Meanwhile, mechanistic studies further showed that kuwanon G displayed rapid bactericidal activity in vitrowith difficulty in developing drug resistance. Kuwanon G targeted phosphatidylglycerol and cardiolipin in the cytoplasmic membrane through the formation of hydrogen bonds and electrostatic interactions. Additionally, kuwanon G promoted wound healing in a mouse model of MRSA skin infection. In summary, these results indicate that flavones are promising lead compounds to treat MRSA-associated infections through disrupting the proton motive force and membrane permeability.


Assuntos
Antibacterianos/farmacologia , Flavonas/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/metabolismo , Morus/química , Extratos Vegetais/farmacologia , Infecções Estafilocócicas/microbiologia , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Permeabilidade da Membrana Celular/efeitos dos fármacos , Feminino , Flavonas/química , Flavonas/isolamento & purificação , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Humanos , Masculino , Meticilina/farmacologia , Staphylococcus aureus Resistente à Meticilina/genética , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Raízes de Plantas/química , Força Próton-Motriz/efeitos dos fármacos
9.
J Agric Food Chem ; 67(37): 10521-10533, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31461284

RESUMO

This work was designed to comparatively investigate 27 dietary flavonoids that act as α-glucosidase inhibitors and insulin sensitizers. On the basis of the results of an in vitro experiment of α-glucosidase inhibition, myricetin (IC50 = 11.63 ± 0.36 µM) possessed the strongest inhibitory effect, followed by apigenin-7-O-glucoside (IC50 = 22.80 ± 0.24 µM) and fisetin (IC50 = 46.39 ± 0.34 µM). A three-dimensional quantitative structure-activity relationship model of α-glucosidase inhibitors with good predictive capability [comparative molecular field analysis, q2 = 0.529, optimum number of components (ONC) = 10, R2 = 0.996, F = 250.843, standard error of estimation (SEE) = 0.064, and two descriptors; comparative similarity index analysis, q2 = 0.515, ONC = 10, R2 = 0.997, F = 348.301, SEE = 0.054, and four descriptors] was established and indicated that meta positions of ring B favored bulky and minor, electron-withdrawing, and hydrogen bond donor groups. The presence of electron-donating and hydrogen bond acceptor groups at position 4' of ring B could improve α-glucosidase activity. Position 3 of ring C favored minor, electron-donating, and hydrogen bond donor groups, whereas position 7 of ring A favored bulky and hydrogen bond acceptor groups. Molecular docking screened five flavonoids (baicalein, isorhamnetin-3-O-rutinoside, apigenin-7-O-glucoside, kaempferol-7-O-ß-glucoside, and cyanidin-3-O-glucoside) that can act as insulin sensitizers and form strong combinations with four key protein targets involved in the insulin signaling pathway. Apigenin-7-O-glucoside (60 µM) can effectively improve insulin resistance, and glucose uptake increased by approximately 73.06% relative to the model group of insulin-resistant HepG2 cells. Therefore, apigenin-7-O-glucoside might serve as the most effective α-glucosidase inhibitor and insulin sensitizer. This work may guide diabetes patients to improve their condition through dietary therapy.


Assuntos
Flavonoides/química , Inibidores de Glicosídeo Hidrolases/química , Insulina/metabolismo , Flavonoides/metabolismo , Flavonoides/farmacologia , Inibidores de Glicosídeo Hidrolases/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Células Hep G2 , Humanos , Simulação de Acoplamento Molecular , Saccharomyces cerevisiae/enzimologia , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo , alfa-Glucosidases/química , alfa-Glucosidases/metabolismo
10.
Anticancer Res ; 39(8): 4043-4053, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366486

RESUMO

BACKGROUND/AIM: Triple-negative breast cancer (TNBC) is the most aggressive subtype, predominant in African American women. In this study, the antioxidant/anticancer activity of muscadine grape extracts and the role of their phenolic and flavonoid contents in exerting these properties were investigated in TNBC cells. MATERIALS AND METHODS: Berry extracts from muscadine genotypes were investigated for total phenolic content (TPC), total flavonoid content (TFC), antioxidant capacity, and anticancer effects using breast cancer cell lines, representing Caucasians and African Americans. RESULTS: The antioxidant activity was associated with high TPC content. Extracts showed cytotoxicity up to 78.6% in Caucasians and 90.7% in African American cells, with an association with high antioxidant capacity. There was a strong correlation between TPC and anticancer/antioxidant activities. CONCLUSION: The anticancer and antioxidant effects of muscadine grapes are attributed to the TPC of extracts, which showed a stronger positive correlation with growth inhibition of African American breast cancer cells compared to Caucasians.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Extratos Vegetais/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Vitis/química , Afro-Americanos/genética , Antineoplásicos Fitogênicos/química , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Feminino , Flavonoides/química , Flavonoides/farmacologia , Frutas/química , Humanos , Células MCF-7 , Fenóis/química , Fenóis/farmacologia , Extratos Vegetais/química , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia
11.
Life Sci ; 234: 116739, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31400352

RESUMO

AIM: This study aimed to investigate the effect of icariin (referred as ICA) on Alzheimer's disease (AD) model through endoplasmic reticulum (ER) stress pathway. MAIN METHODS: Nine months male APP/PS1 and wild-type (WT) mice were randomly divided into four groups: APP/PS1 control, APP/PS1 + ICA, WT control and WT + ICA groups. The treated mice were given ICA 60 mg/kg/d and control mice were received the same volume distilled water for consecutive 3 months. The Morris water maze and Novel object recognition were used to detect animals' behavior. Nissl staining was used to observe the neuronal morphology in hippocampus area. Aß deposition in hippocampal region was observed by immunofluorescence staining. TUNEL staining was used to observe apoptosis. Detection of expression of ER stress related factors by Western blot and real time RT-PCR. KEY FINDINGS: Chronically administrated with ICA compared with APP/PS1 control mice significantly improved the behavior performance, reduced neuronal apoptosis, as well as suppressing the ER stress signaling pathway, including that decreased the level of glucose-regulated protein 78, phosphorylated ER-regulated kinase and phosphorylated eukaryotic initiation factor α, as well activating transcription factor-4, C/EBP homologous protein, DNA damage inducible protein 34 and tribbles homologous protein 3. SIGNIFICANCE: Our data indicated that ICA suppressed the ER stress signaling to protect against AD animal model, these findings suggest that a potential point for researching the effect of ICA on neurodegeneration.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Precursor de Proteína beta-Amiloide/metabolismo , Cognição/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Flavonoides/uso terapêutico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Animais , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Masculino , Memória/efeitos dos fármacos , Camundongos
12.
J Enzyme Inhib Med Chem ; 34(1): 1481-1488, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31423846

RESUMO

Indoleamine 2,3-dioxygenase 1 (IDO1), a tryptophan catabolising enzyme, is known as a tumour cell survival factor that causes immune escape in several types of cancer. Flavonoids of Sophora flavescens have a variety of biological benefits for humans; however, cancer immunotherapy effect has not been fully investigated. The flavonoids (1-6) isolated from S. flavescens showed IDO1 inhibitory activities (IC50 4.3-31.4 µM). The representative flavonoids (4-6) of S. flavescens were determined to be non-competitive inhibitors of IDO1 by kinetic analyses. Their binding affinity to IDO1 was confirmed using thermal stability and surface plasmon resonance (SPR) assays. The molecular docking analysis and mutagenesis assay revealed the structural details of the interactions between the flavonoids (1-6) and IDO1. These results suggest that the flavonoids (1-6) of S. flavescens, especially kushenol E (6), as IDO1 inhibitors might be useful in the development of immunotherapeutic agents against cancers.


Assuntos
Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Sophora/química , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Flavonoides/química , Flavonoides/isolamento & purificação , Células HeLa , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Modelos Moleculares , Estrutura Molecular , Mutagênese Sítio-Dirigida , Relação Estrutura-Atividade , Células Tumorais Cultivadas
13.
Food Chem ; 299: 125124, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31288163

RESUMO

Inflammation plays a key role in diseases such as diabetes, asthma, cardiovascular diseases and cancer. Diet can influence different stages of inflammation and can have an important impact on several inflammatory diseases. Increasing scientific evidence has shown that polyphenolic compounds, such as flavonoids, which are found in fruits, vegetables, legumes, or cocoa, can have anti-inflammatory properties. Recent studies have demonstrated that flavonoids can inhibit regulatory enzymes or transcription factors important for controlling mediators involved in inflammation. Flavonoids are also known as potent antioxidants with the potential to attenuate tissue damage or fibrosis. Consequently, numerous studies in vitro and in animal models have found that flavonoids have the potential to inhibit the onset and development of inflammatory diseases. In the present review, we focused in flavonoids, the most abundant polyphenols in the diet, to give an overview of the most recent scientific knowledge about their impact on different inflammatory diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Flavonoides/farmacologia , Inflamação/tratamento farmacológico , Neoplasias/tratamento farmacológico , Animais , Anti-Inflamatórios/análise , Antioxidantes/análise , Cacau/química , Doenças Cardiovasculares/patologia , Dieta , Fabaceae/química , Flavonoides/análise , Frutas/química , Humanos , Neoplasias/patologia , Polifenóis/análise , Polifenóis/farmacologia , Verduras/química
14.
J Sci Food Agric ; 99(14): 6418-6430, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31294466

RESUMO

BACKGROUND: Dracocephalum kotschyi Boiss. is a valuable source of rosmarinic acid (RA) and methoxylated hydroxyflavones (such as xanthomicrol and cirsimaritin) with antioxidative and antiplatelet effects and with antiproliferative potential against various cancer cells. The extensive application of nanotechnology in hairy root cultures is a new sustainable production platform for producing these active constituents. In the present study, hairy roots derived from 4-week-old leaves and Agrobacterium rhizogenes strain ATCC15834 were used to investigate the impact of various concentrations of iron oxide nanoparticles (Fe NPs) in two elicitation time exposures (24 and 48 h) on growth, antioxidant enzyme activity, total phenolic and flavonoid content (TPC and TFC), and some polyphenols. Gene expression levels of phenylalanine ammonia-lyase (pal) and rosmarinic acid synthase (ras) were also analyzed. RESULTS: Iron nanoparticles enhanced biomass accumulation in hairy roots. The treatment time and Fe NP dosage largely improved the activity of antioxidant enzymes, TPC and TFC. The highest RA (1194 µg g-1 FW) content (9.7-fold), compared to controls, was detected with 24 h of exposure to 75 mg L-1 Fe NP, which was consistent with the expression of pal and ras genes under the influence of elicitation. The xanthomicrol, cirsimaritin, and isokaempferide content was increased 11.87, 3.85, and 2.27-fold, respectively. CONCLUSION: Stimulation of D. kotschyi hairy roots by Fe NPs led to a significant increase in the induction and production of important pharmaceutical compounds such as rosmarinic acid and xanthomicrol. © 2019 Society of Chemical Industry.


Assuntos
Antineoplásicos Fitogênicos/biossíntese , Compostos Férricos/farmacologia , Flavonoides/biossíntese , Lamiaceae/efeitos dos fármacos , Lamiaceae/metabolismo , Proteínas de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Flavonoides/farmacologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Humanos , Lamiaceae/genética , Lamiaceae/crescimento & desenvolvimento , Nanopartículas/química , Fenilalanina Amônia-Liase/genética , Fenilalanina Amônia-Liase/metabolismo , Proteínas de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Raízes de Plantas/metabolismo
15.
Zhongguo Zhong Yao Za Zhi ; 44(9): 1911-1920, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31342721

RESUMO

To study the binding capacity of active ingredients of Daidai lipid-lowering flavonoid extract and plasma protein,investigate the ways to improve the traditional formula for calculating protein binding rates based on ultrafiltration,and increase the stability and reliability of the experimental results. UPLC-MS/MS was used to establish a quantitative analysis method for simultaneous determination of active ingredients( neohesperidin and narngin) in ultrafiltrate. The protein binding rates were calculated by the traditional ultrafiltration formula. The correction factors( F) were introduced later,and the binding rates calculated with the correction factors were compared with those without the correction factors. The binding capacity of the extract and plasma protein was evaluated. The quantitative analysis method established by UPLC-MS/MS had a good specificity. The standard curve and linear range,method accuracy,precision and lower limit of quantitation all met the requirements. The method met the requirement for quantitative detection of the active ingredients in ultrafiltrate after the rat plasma was filtrated in the ultrafiltration tube. Under the experimental conditions,the binding rates of both active ingredients( neohesperidin and narngin) were higher than 90%. The active ingredients and rat plasma protein were bound in a concentration-dependent manner,with statistically significant differences( P<0. 01). There was no statistically significant difference between the protein binding abilities of the two active ingredients with rat plasma protein. Therefore,the active ingredients of Daidai lipid-lowering flavonoid extract had a relatively strong binding strength with rat plasma protein,and they were bound in a concentration-dependent manner. Additionally,when calculating protein binding rates by the traditional ultrafiltration formula,the correction factors could be introduced to effectively reflect the errors of multiple ingredient groups in traditional Chinese medicine extracts.This correction method could provide a reference thinking and practical reference for the improvement of the determination method of the traditional Chinese medicine plasma protein binding ability based on ultrafiltration.


Assuntos
Proteínas Sanguíneas , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/farmacologia , Hipolipemiantes/farmacologia , Animais , Cromatografia Líquida de Alta Pressão , Lipídeos , Ratos , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem
16.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(3): 283-288, 2019 May 28.
Artigo em Chinês | MEDLINE | ID: mdl-31257814

RESUMO

OBJECTIVE: To investigate the effects of tectochrysin on prostate cancer cell line 22Rv.1 and reveal its molecular mechanism. METHODS: Tectochrysin at the concentrations of 0~20 µg/ml was applied to 22Rv.1 cells and normal prostate cell RWPE-1. The proliferation activity of the cells was detected by MTS assay. Flow cytometry and hoechst 33342 staining were used to analyze the effects of drugs on cell apoptosis, death, cell cycle and nuclear type changes. LDH release test was used to analyze the cytotoxicity of the drug to 22Rv.1 cells. QPCR and Western blot were used to analyze the effects of the drug on the expressions of genes in 22Rv.1 cells. Finally, the tumor inhibited effect of the drug on the bearing tumor BALB/c mice were confirmed though anti-tumor experiment. RESULTS: Tectochrysin could significantly inhibit the proliferation activity of 22Rv.1 cells and induced their apoptosis, and promoted the expressions of genes dr4, dr5, trail, p53, caspase-3, caspase-8, caspase-9, bid, bax and foxo3, inhibited the expressions of anti-apoptotic genes akt, pi3k and bcl-2. CONCLUSION: Tectochrysin can induce prostate cancer cells apoptosis through affecting TRAIL and PI3K/AKT signaling pathways, and has anti-prostate cancer effect.


Assuntos
Apoptose , Flavonoides/farmacologia , Neoplasias da Próstata/patologia , Animais , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias da Próstata/tratamento farmacológico , Transdução de Sinais , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo
17.
BMC Complement Altern Med ; 19(1): 155, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31269947

RESUMO

BACKGROUND: Osteochondral defects mostly occur as a result of trauma or articular degeneration. The poor regenerative ability of articular cartilage remains osteochondral defects are a tricky problem to deal with. The modern treatment strategies mainly focus on cartilage tissue engineering with bioactive materials. In this study, we aimed to develop icariin conditioned serum (ICS) together with hyaluronic acid (HA) and determine their ability in reparing osteochondral tissue in a critical-sized defect in rabbit knees. METHODS: Primary chondrocytes were incubated with serum conditioned with icariin at different concentrations, then cell proliferation rates and glycosaminoglycan (GAG) secretion were detected. Rabbits were treated with intra-articular injection of 0.5 mL normal saline (NS), ICS, HA and ICS + HA in the right knee joint, respectively. ICRS scores were used to assess the macroscopic cartilage regeneration. Histological and immunohistochemical analysis including H&E, Safranin O, toluidine blue and collagen II staining were used to determine the repair of cartilage and the regeneration of chondrocytes. RESULTS: Icariin at a low dose of 0.94 g/kg was identified to have significantly promoted the proliferation of chondrocytes and enhance the secretion of GAG. Femoral condyle from rabbits treated by ICS together with HA was observed to be integrated with native cartilage and more subchondral bone regeneration. ICS together with HA could promote repair of the cartilage defect and increase the neoformation of cartilage. CONCLUSIONS: These results demonstrated the potential of ICS combined with HA to promote reparative response in cartilage defects and the possible application in bioactive material based cartilage regeneration therapies.


Assuntos
Cartilagem Articular/efeitos dos fármacos , Condrogênese/efeitos dos fármacos , Flavonoides/uso terapêutico , Animais , Condrócitos/efeitos dos fármacos , Epimedium , Flavonoides/farmacologia , Ácido Hialurônico/uso terapêutico , Fitoterapia , Coelhos , Soro , Viscossuplementos/uso terapêutico
18.
Chem Pharm Bull (Tokyo) ; 67(7): 640-647, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257319

RESUMO

Neuroinflammation manifested by over-activation of microglial cells plays an essential role in neurodegenerative diseases. Short-term activation of microglia can be beneficial, but chronically activated microglia can aggravate neuronal dysfunction possibly by secreting potentially cytotoxic substances such as tumor necrosis factor-alpha (TNF-α) and nitric oxide (NO), which can result in dysfunction and death of neurons. Therefore inhibiting over-activation of microglia and the production of cytotoxic intermediates may become an effective therapeutic approach for neuroinflammation. In this paper, we review our continuous research on natural inhibitors of over-activated microglia from traditional herbals, including flavonoids, lignans, sesquiterpene coumarins, and stilbenes.


Assuntos
Produtos Biológicos/química , Microglia/metabolismo , Animais , Produtos Biológicos/farmacologia , Cumarínicos/química , Cumarínicos/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Lignanas/química , Lignanas/farmacologia , Microglia/citologia , Microglia/efeitos dos fármacos , Óxido Nítrico/biossíntese , Estilbenos/química , Estilbenos/farmacologia , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/metabolismo
19.
Life Sci ; 232: 116618, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31265854

RESUMO

AIMS: Mitochondrial dysfunction has been regarded as one of the hallmarks of cerebral ischemia-reperfusion injury. In previous studies, we have provided evidence that the extracellular signaling pathway (ERK) 1/2 inhibitor PD98059 improved the neurological deficits by modulating antioxidant and anti-apoptotic activities in rats subjected to cardiac arrest/cardiopulmonary resuscitation (CA/CPR). Since oxidative stress can activate mitochondria-dependent apoptosis and autophagy, we further explored the effects of PD98059 on mitochondria involved with apoptosis and autophagy in rat CA model. MATERIALS AND METHODS: We disposed PD98059 in CA/CPR rats, tested the mitochondrial-mediated apoptosis pathway in brain tissues at 24 h post-resuscitation by mitochondrial permeability transition pores (MPTP), cytochrome c (CytC), BCL-2, BAX, caspase-3, as well as autophagy by LC3, Beclin-1, and p62. Furthermore, we explored the relationship of dynamin-related protein 1 (Drp1) with apoptosis and autophagy. KEY FINDINGS: Our study showed that PD98059 decreased the openings of MPTP, CytC release, caspase3 activation, apoptotic indices, LC3-II, Beclin-1and increased P62. PD98059 also inhibited mitochondria-dependent apoptosis and the activity of autophagy in a dose-dependent manner in rat cerebral cortices at 24 h post-resuscitation. The generation of phosphorylated Drp1-616 was down-regulated accompanied by a decrease of TUNEL-positive cells and LC3 in dual immunostaining after PD98059 inhibited activation of ERK signaling pathway in a dose-dependent manner in rat cerebral cortices at 24 h post-resuscitation. SIGNIFICANCE: PD98059 protects the brain against mitochondrial-mediated apoptosis and autophagy at 24 h post-resuscitation in rats subjected to CA/CPR, which is linked with the downregulation of Drp1 expression.


Assuntos
Flavonoides/farmacologia , Parada Cardíaca/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Reanimação Cardiopulmonar , Córtex Cerebral/metabolismo , Modelos Animais de Doenças , Flavonoides/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Mitocôndrias/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
20.
J Agric Food Chem ; 67(30): 8339-8347, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31291543

RESUMO

The dried seeds of Cuminum cyminum L. have been traditionally used as food and medicine. To explore its chemical composition and anti-inflammatory activity, four new compounds (1-4) along with five known compounds (5-9) were isolated from the seeds in the present study. The chemical structures of the new compounds were identified as follows: methyl 3-((7H-purin-2-yl) amino)-3-(4-isopropylphenyl) propanoate (1), 8-(amino(4-isopropylphenyl)methyl)-5-hydroxy-2-(4-hydroxyphenyl)-7-methoxy-4-oxo-4H-chromene-6-carboxylic acid (2), (3,4,5-trihydroxy-6-((4-isopropylbenzyl)oxy)tetrahydro-2H-pyran-2-yl)methyl (E)-3-(4-propoxyphenyl)acrylate (3), and (3,4,5-trihydroxy-6-((5-hydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-chromen-7-yl)oxy)tetrahydro-2H-pyran-2-yl)methyl 3-(4-isopropylphenyl)-2-methoxypropanoate (4). Compound 2, an atypical nitrogen-containing flavonoid, exhibited the most active inhibitory effect on nitride oxide, with IC50 of 5.25 µM in the lipopolysaccharide-stimulated RAW264.7 cell assay. Compound 2 was found to suppress the expression levels of inducible nitric oxide synthase and cyclooxygenase-2. Furthermore, it was revealed that both nuclear factor κB and mitogen-activated protein kinase were involved in the anti-inflammatory process of compound 2.


Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Cuminum/química , Flavonoides/química , Flavonoides/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Frutas/química , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/imunologia , Estrutura Molecular , NF-kappa B/genética , NF-kappa B/imunologia , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/imunologia , Células RAW 264.7 , Sementes/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA