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1.
Front Plant Sci ; 15: 1356922, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628367

RESUMO

Among the bioactive compounds, lipid-soluble tanshinone is present in Salvia miltiorrhiza, a medicinal plant species. While it is known that ethephon has the ability to inhibit the tanshinones biosynthesis in the S. miltiorrhiza hairy root, however the underlying regulatory mechanism remains obscure. In this study, using the transcriptome dataset of the S. miltiorrhiza hairy root induced by ethephon, an ethylene-responsive transcriptional factor EIN3-like 1 (SmEIL1) was identified. The SmEIL1 protein was found to be localized in the nuclei, and confirmed by the transient transformation observed in tobacco leaves. The overexpression of SmEIL1 was able to inhibit the tanshinones accumulation to a large degree, as well as down-regulate tanshinones biosynthetic genes including SmGGPPS1, SmHMGR1, SmHMGS1, SmCPS1, SmKSL1 and SmCYP76AH1. These are well recognized participants in the tanshinones biosynthesis pathway. Further investigation on the SmEIL1 was observed to inhibit the transcription of the CPS1 gene by the Dual-Luciferase (Dual-LUC) and yeast one-hybrid (Y1H) assays. The data in this work will be of value regarding the involvement of EILs in regulating the biosynthesis of tanshinones and lay the foundation for the metabolic engineering of bioactive ingredients in S. miltiorrhiza.

2.
J Sci Food Agric ; 103(15): 7381-7392, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37390299

RESUMO

BACKGROUND: Diabetes mellitus poses a substantial threat to public health due to rising morbidity and mortality. α-Glucosidase is one of the key enzymes affecting diabetes. Herein, (-)-epigallocatechin-3-gallate (EGCG) and (-)-epigallocatechin (EGC) were applied to clarify the role of the galloyl moiety of tea polyphenols in the inhibition of glycation and α-glucosidase activity. The structure-activity relationship of the galloyl moiety in EGCG on α-glucosidase was investigated in terms of inhibition kinetics, spectroscopy, atomic force microscopy and molecular docking. A bovine serum protein-fructose model was employed to determine the effect of the galloyl moiety on glycation. RESULTS: The results indicated that the introduction of a galloyl moiety enhanced the capacity of EGCG to inhibit glycation and α-glucosidase activity. The IC50 value of EGC is approximately 2400 times higher than that of EGCG. Furthermore, the galloyl moiety in EGCG altered the microenvironment and secondary structure of α-glucosidase, resulting in a high binding affinity of EGCG to α-glucosidase. The binding constant of EGCG to α-glucosidase at 298 K is approximately 28 times higher than that of EGC. CONCLUSION: Overall, the galloyl moiety of EGCG plays a crucial role in inhibiting glycation and α-glucosidase activity, which helps to enhance the molecular understanding of the structure and function of the polyphenol galloyl moiety in the science of food and agriculture. © 2023 Society of Chemical Industry.


Assuntos
Catequina , alfa-Glucosidases , alfa-Glucosidases/metabolismo , Simulação de Acoplamento Molecular , Catequina/farmacologia , Catequina/química , Polifenóis/química , Análise Espectral , Chá/química
3.
Genes Brain Behav ; 22(4): e12852, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37278348

RESUMO

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by atypical patterns of social interaction and communication, as well as restrictive and repetitive behaviors. In addition, patients with ASD often presents with sleep disturbances. Delta (δ) catenin protein 2 (CTNND2) encodes δ-catenin protein, a neuron-specific catenin implicated in many complex neuropsychiatric diseases. Our previous study demonstrated that the deletion of Ctnnd2 in mice led to autism-like behaviors. However, to our knowledge, no study has investigated the effects of Ctnnd2 deletion on sleep in mice. In this study, we investigated whether the knockout (KO) of exon 2 of the Ctnnd2 gene could induce sleep-wake disorders in mice and identified the effects of oral melatonin (MT) supplementation on Ctnnd2 KO mice. Our results demonstrated that the Ctnnd2 KO mice exhibited ASD-like behaviors and sleep-wake disorders that were partially attenuated by MT supplementation. Overall, our current study is the first to identify that knockdown of Ctnnd2 gene could induce sleep-wake disorders in mice and suggests that treatment of sleep-wake disturbances by MT may benefit to autism-like behaviors causing by Ctnnd2 gene deletion.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Melatonina , Transtornos do Sono-Vigília , Camundongos , Animais , Transtorno do Espectro Autista/tratamento farmacológico , Transtorno do Espectro Autista/genética , Camundongos Knockout , Melatonina/farmacologia , Melatonina/uso terapêutico , Transtornos do Sono-Vigília/tratamento farmacológico , Transtornos do Sono-Vigília/genética , Sono
4.
Aquat Toxicol ; 261: 106616, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37348385

RESUMO

Oxytetracycline (OTC), a commonly used tetracycline antibiotic in aquaculture, has been found to cause significant damage to the liver of largemouth bass (Micropterus salmoides). This study revealed that OTC can lead to severe histopathological damage, structural changes at the cellular level, and increased levels of reactive oxygen species (ROS) in M. salmoides. Meanwhile, OTC impairs the activities of antioxidant enzyme (such as T-SOD, CAT, GST, GR) by suppressing the activation of MAPK/Nrf2 pathway. OTC disrupts mitochondrial dynamics and mitophagy through via PINK1/Parkin pathway. The accumulation of damaged mitochondria, combined with the inhibition of the antioxidant enzyme system, contributes to elevated ROS levels and oxidative liver damage in M. salmoides. Further investigations demonstrated that an enzyme-treated soy protein (ETSP) dietary supplement can help maintain mitochondrial dynamic balance by inhibiting the PINK1/Parkin pathway and activate the MAPK/Nrf2 pathway to counteract oxidative damage. In summary, these findings highlight that exposure to OTC disrupts mitochondrial dynamics and inhibits the antioxidant enzyme system, ultimately exacerbating oxidative liver damage in M. salmoides. We propose the use of a dietary supplement as a preventive measure against OTC-related side effects, providing valuable insights into the mechanisms of antibiotic toxicity in aquatic environments.


Assuntos
Bass , Oxitetraciclina , Poluentes Químicos da Água , Animais , Antioxidantes/metabolismo , Bass/metabolismo , Oxitetraciclina/toxicidade , Dinâmica Mitocondrial , Espécies Reativas de Oxigênio/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Poluentes Químicos da Água/toxicidade , Estresse Oxidativo , Fígado , Antibacterianos/farmacologia , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/farmacologia , Proteínas Quinases/metabolismo , Proteínas Quinases/farmacologia
5.
Front Pharmacol ; 12: 721988, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34531747

RESUMO

Dihydrotanshinone I (DHT) is a natural component in Salvia miltiorrhiza and has been widely researched for its multiple bioactivities. However, poor solubility and biocompatibility of DHT limit its desirable application for clinical purposes. Herein, DHT was encapsulated with bovine serum albumin (BSA) to enhance bioavailability. Compared to free DHT, DHT-BSA NPs (nanoparticles) showed an improved solubility in normal saline and increased protection against hydrogen peroxide-induced oxidative damage in PC12 cells. In addition, DHT-BSA NPs administered by intravenous injection displayed a significant efficacy in the middle cerebral artery occlusion/reperfusion models, without any impact on the cerebral blood flow. In summary, DHT-BSA NPs show an enhanced bioavailability compared with free DHT and a successful penetration into the central nervous system for stroke therapy, demonstrating their application potential in cardio-cerebrovascular diseases.

6.
Life Sci ; 257: 118122, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32702446

RESUMO

AIMS: Berberine is an isoquinoline alkaloid extracted from the root, rhizome and stem bark of Coptidis Rhizoma. Previous studies have revealed the anti-tumor potential of berberine against various types of cancer cells. However, the underlying mechanisms are not yet fully understood. In this study, we focused on the effects of berberine on fatty acid synthesis and extracellular vesicles formation in cancer cells, and revealed the internal mechanism of berberine inhibition on cancer cell proliferation. MATERIALS AND METHODS: Anti-proliferative activity of berberine was determined by cell counting and microscope observation and cell cycle analysis. Activities of AMPK and ACC, expression of extracellular vesicles markers were detected by western blotting. 13C labeling metabolic flux analysis was used for determination of de novo synthesis of fatty acids. The excreted extracellular vesicles in culture mediums were separated by both polyethylene glycol enrichment of extracellular vesicles and differential centrifugation separation. KEY FINDINGS: Among our early experiments, 5-10 µmol/L berberine exhibited the substantial anti-proliferative effect against human colon cancer cell line HCT116, cervical cancer cell line HeLa and other cancer cells. It was also revealed that, through activating AMPK, berberine inhibited ACC activity then suppressed intracellular fatty acid synthesis, finally decreased the biogenesis of extracellular vesicles. Moreover, supplement with citrate acid, palmitic acid, as well as exogenous extracellular vesicles, could rescue the inhibitory effect of berberine on cell proliferation, suggesting that inhibited ACC activity, suppressed fatty acid synthesis and decreased extracellular vesicles production were important mechanisms account for berberine inhibiting cancer cell proliferation. SIGNIFICANCE: Our study indicates that berberine suppresses cancer cell proliferation through inhibiting the synthesis of fatty acids and decreasing biogenesis and secretion of extracellular vesicles, suggests that berberine is a promising candidate for the development of new therapies for cancer.


Assuntos
Antineoplásicos/farmacologia , Berberina/farmacologia , Vesículas Extracelulares/metabolismo , Ácidos Graxos/metabolismo , Neoplasias/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/metabolismo , Acetil-CoA Carboxilase/metabolismo , Western Blotting , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ácido Cítrico/farmacologia , Vesículas Extracelulares/efeitos dos fármacos , Células HCT116/efeitos dos fármacos , Células HeLa/efeitos dos fármacos , Humanos
7.
Drug Deliv ; 27(1): 983-995, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32611218

RESUMO

To improve synergistic anticancer efficacy and minimize the adverse effects of chemotherapeutic drugs, temozolomide (TMZ) and curcumin (CUR) co-loaded nanostructured lipid carriers (NLCs) were prepared by microemulsion in this study. And the physicochemical properties, drug release behavior, intracellular uptake efficiency, in vitro and in vivo anticancer effects of TMZ/CUR-NLCs were evaluated. TMZ/CUR-NLCs showed enhanced inhibitory effects on glioma cells compared to single drug loaded NLCs, which may be owing to that the quickly released CUR can sensitize the cancer cells to TMZ. The inhibitory mechanism is a combination of S phase cell cycle arrest associated with induced apoptosis. Notably, TMZ/CUR-NLCs can accumulate at brain and tumor sites effectively and perform a significant synergistic anticancer effect in vivo. More importantly, the toxic effects of TMZ/CUR-NLCs on major organs and normal cells at the same therapeutic dosage were not observed. In conclusion, NLCs are promising nanocarriers for delivering dual chemotherapeutic drugs sequentially, showing potentials in the synergistic treatment of tumors while reducing adverse effects both in vitro and in vivo.


Assuntos
Antineoplásicos/farmacologia , Curcumina/farmacologia , Portadores de Fármacos/química , Nanopartículas/química , Temozolomida/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular Tumoral , Química Farmacêutica/métodos , Curcumina/administração & dosagem , Curcumina/farmacocinética , Combinação de Medicamentos , Liberação Controlada de Fármacos , Glioma/tratamento farmacológico , Humanos , Lipídeos/química , Tamanho da Partícula , Fase S/efeitos dos fármacos , Temozolomida/administração & dosagem , Temozolomida/farmacocinética
8.
Food Chem ; 306: 125632, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31606634

RESUMO

In this study, we have developed a novel polyelectrolyte complex (PEC) hydrogel that could be easily prepared by self-assembly of two food-grade polysaccharides salecan and N,N,N-trimethyl chitosan (TMC). The electrostatic interactions between two polysaccharides were driving force in complexation processes and have been demonstrated by FTIR, XRD, XPS and TGA. The swelling capacity, morphology and rheological property of the hydrogels could be well tuned by controlling salecan/TMC ratio. Green tea polyphenols (GTP) was efficiently encapsulated into PEC hydrogels and liberated in a sustained pattern. The amount of GTP released in simulated intestinal fluid (SIF) was significantly higher than simulated gastric fluid (SGF). Increasing salecan/TMC ratio also markedly enhanced GTP release amount. Release exponent n obtained in SGF indicated a Fickian diffusion, while in SIF an anomalous transport occurred. The release mechanism was well-fitted with Ritger-Peppas model. Taken together, these PEC hydrogels could be suitable carriers for intestinal targeted nutrient delivery.


Assuntos
Polieletrólitos/química , Polifenóis/química , Polissacarídeos/química , Chá/química , Difusão , Hidrogéis/química , Concentração de Íons de Hidrogênio , beta-Glucanas/química
9.
J Cell Mol Med ; 23(8): 5715-5727, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31225721

RESUMO

Increase of myocardial oxidative stress is closely related to the occurrence and development of cardiac hypertrophy. Cordycepin, also known as 3'-deoxyadenosine, is a natural bioactive substance extracted from Cordyceps militaris (which is widely cultivated for commercial use in functional foods and medicine). Since cordycepin suppresses oxidative stress both in vitro and in vivo, we hypothesized that cordycepin would inhibit cardiac hypertrophy by blocking oxidative stress-dependent related signalling. In our study, a mouse model of cardiac hypertrophy was induced by aortic banding (AB) surgery. Mice were intraperitoneally injected with cordycepin (20 mg/kg/d) or the same volume of vehicle 3 days after-surgery for 4 weeks. Our data demonstrated that cordycepin prevented cardiac hypertrophy induced by AB, as assessed by haemodynamic parameters analysis and echocardiographic, histological and molecular analyses. Oxidative stress was estimated by detecting superoxide generation, superoxide dismutase (SOD) activity and malondialdehyde levels, and by detecting the protein levels of gp91phox and SOD. Mechanistically, we found that cordycepin activated activated protein kinase α (AMPKα) signalling and attenuated oxidative stress both in vivo in cordycepin-treated mice and in vitro in cordycepin treated cardiomyocytes. Taken together, the results suggest that cordycepin protects against post-AB cardiac hypertrophy through activation of the AMPKα pathway, which subsequently attenuates oxidative stress.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Cardiomegalia/tratamento farmacológico , Desoxiadenosinas/uso terapêutico , Transdução de Sinais , Angiotensina II/farmacologia , Animais , Cardiomegalia/diagnóstico por imagem , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico , Desoxiadenosinas/farmacologia , Fibrose , Hemodinâmica/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Modelos Biológicos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Pressão , Transdução de Sinais/efeitos dos fármacos
10.
Am J Transl Res ; 10(7): 2078-2086, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30093945

RESUMO

Sepsis, a life-threatening syndrome with uncontrolled inflammatory response, causes high morbidity and mortality worldwide. Currently, satisfactory treatments on sepsis are still lacking in clinic. Thus, new therapeutic strategies are urgently required. Recently, celastrol, a pentacyclic triterpene extracted from the traditional Chinese medicine Tripterygium Wilfordi plant, attracted great interest for its properties of anti-inflammation, anti-oxidative stress, and metabolism remodeling. However, the effect of celastrol on sepsis is still unclear. In this study, we investigated the effect of celastrol on lipopolysaccharides (LPS)-induced inflammation and organ injuries in mice. Following celastrol pretreatment, mice showed increased mortality rate and aggravated inflammation evidenced by further enhanced inflammatory markers of IL-6, IL-1ß, TNF-α, IL-18, MCP-1, and ICAM-1 in circulation, liver, and kidney after LPS treatment. The serum levels of ALT, AST, and LDH were further increased in parallel with the deteriorated liver morphological damage (H&E) and oxidative stress in celastrol-treated mice, indicating an aggravated liver injury. In kidney, the expressions of tubular injury markers of kidney injury molecule-1 (KIM-1) and gelatinase-associated lipocalin (NGAL) were further upregulated along with higher levels of blood urea nitrogen (BUN), creatinine (Cr), and MDA in celastrol-treated mice. These findings not only indicated a detrimental role of celastrol therapy in LPS-induced inflammation and organ injuries but also suggested the restriction of celastrol usage in sepsis patients.

11.
Food Funct ; 8(8): 2875-2885, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28726929

RESUMO

Myocardial infarction is a devastating event, especially when reperfusion is not performed. The inflammatory response has been associated with the pathogenesis of left ventricular remodeling after myocardial infarction. This study focused on the anti-apoptotic and anti-inflammatory effects of sesamin on ligation of the left anterior descending artery in an experimental mouse model and the potential mechanism underlying the activation of JNK and NF-κB pathways. Mice with MI induced by surgical left anterior descending coronary artery ligation were treated with sesamin by gavage for 1 week. Results showed that after treatment with sesamin, MI-induced cardiac damage was alleviated significantly, indicated by the histopathological examination. The myocardial apoptosis in the border zone was dramatically reduced by sesamin, resulting from the altered expression of apoptosis factors. Moreover, treatment with sesamin also mitigated the inflammatory response, decreased expression of cytokines and the inactivation of NF-κB (nuclear factor κB) signaling. Sesamin decreased the levels of p-JNK protein, which in turn inactivated pro-apoptotic signaling events by restoring the balance between mitochondrial pro-apoptotic Bcl-2 and Bax proteins. Thus, our study suggests that sesamin could alleviate MI-induced cardiac dysfunction through decrease of myocardial apoptosis and inflammatory response.


Assuntos
Apoptose/efeitos dos fármacos , Dioxóis/administração & dosagem , Lignanas/administração & dosagem , MAP Quinase Quinase 4/imunologia , Infarto do Miocárdio/tratamento farmacológico , NF-kappa B/imunologia , Extratos Vegetais/administração & dosagem , Sesamum/química , Animais , Modelos Animais de Doenças , Humanos , MAP Quinase Quinase 4/genética , Masculino , Camundongos , Infarto do Miocárdio/genética , Infarto do Miocárdio/imunologia , Infarto do Miocárdio/fisiopatologia , NF-kappa B/genética , Transdução de Sinais/efeitos dos fármacos , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/imunologia
12.
Pak J Pharm Sci ; 30(3): 747-753, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28653917

RESUMO

We determined the in vitro antioxidant and antimicrobial activities of Platycarya strobilacea infructescence (PSI) from various solvent extracts (methanol, ethyl acetate, water and tannin polymers) and quantified the content of total phenolic of each extract. The ethyl acetate extract was found to have the best radical-scavenging activity and ferric reducing power, as well as antimicrobial activity. In order to investigate the protective effect on oxidative stress in vivo, each extract was administered to rats, and the serum, liver and heart were analyzed. The water extract and tannin polymers significantly decreased malonyldialdehyde (MDA) concentrations in serum, liver and heart compared to the control group (P<0.01). Furthermore, super oxide dismutase (SOD) and glutathione per oxidase (GSH-Px) activities were increased by administration of all extracts. We concluded that the ethyl acetate extract of PSI has strong antioxidant activity in vitro and possesses antimicrobial activity. These results indicated PSI the potential of medicinal uses and food preservation.


Assuntos
Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Juglandaceae/química , Extratos Vegetais/farmacologia , Animais , Cromatografia Líquida de Alta Pressão , Técnicas In Vitro , Masculino , Testes de Sensibilidade Microbiana , Ratos , Ratos Sprague-Dawley
13.
Data Brief ; 10: 474-477, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28054010

RESUMO

This data article contains complementary results related to the paper "Effect of metal ions on the binding reaction of (-)-epigallocatechin gallate to ß-lactoglobulin" (Zhang et al., 2017) [1]. Data was obtained by circular dichroism (CD) spectroscopy to investigate potential ß-lactoglobulin (ß-Lg) conformational changes with different concentrations of EGCg and Cu2+ or Al3+ added to ß-Lg. 500 µL of the 25 µM ß-Lg solution containing EGCg (25 µM) or metal ions (0-500 µM) were measured, and the spectra were recorded. CD spectroscopy data present in this article indicated that the ß-Lg-Cu, ß-Lg-Al and ß-Lg-EGCg interaction resulted in unfolding of the secondary structure of ß-Lg.

14.
Zhongguo Zhong Yao Za Zhi ; 41(2): 177-181, 2016 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-28861959

RESUMO

Traditional identification method is an effective approach to evaluate the quality for Chinese herbal medicine (CHM). Color is one of the important indicators for quality evaluation due to high correlation with quality. Therefore, a new theory of quality control for CHM based on color grading was discussed in this article. The scientific nature of this theory was illustrated by investigating the relation between CHM color, medicinal properties and active compound contents. The effect of origins, collecting time, processing, and storage on the CHM color was also analyzed. To overcome the drawback of the traditional identification method, the novel objective color evaluation methods such as spectrocolorimeter and machine vision technology were reviewed, including the application, advantages and disadvantages in Chinese medicine field, and the significance of color sense digitalization was illustrated finally.


Assuntos
Medicamentos de Ervas Chinesas/química , Tecnologia Farmacêutica/métodos , Cor , Medicina Tradicional Chinesa , Controle de Qualidade
15.
Immunol Invest ; 44(5): 482-96, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26107747

RESUMO

Streptococcus pneumoniae is an important pathogen accounting for a large number of deaths worldwide. Due to drawbacks of the current polysaccharide-based vaccine, the most promising way to generate an improved vaccine may be to utilize protection-eliciting pneumococcal proteins. Pneumococcal surface adhesin A (PsaA) and pneumococcal surface protein A (PspA) are two vaccine candidates which have been evaluated against S. pneumoniae infection in animal models or human clinical trials with encouraging results. In this study, the efficacy of the fusion protein PsaA-PspA, which includes PsaA part and PspA part, in inducing immunoprotective effects against fatal pneumococcal challenge was evaluated in an animal model. PspA part of PsaA-PspA fusion protein contains both family1 N-terminal region and family 2 N-terminal clade-defining region of PspA. Immunization with the PsaA-PspA fusion protein induced high levels of antibodies against both PsaA and PspA, which could bind to intact S. pneumoniae strains bearing different PspAs. Ex vivo stimulation of splenocytes from mice immunized with PsaA-PspA induced IL-17A secretion. Mice immunized with PsaA-PspA showed reduced S. pneumoniae levels in the blood and lungs compared with the PBS group after intranasal infection. Finally, mice immunized with PsaA-PspA fusion proteins were protected against fatal challenge with pneumococcal strains expressing different PspAs regardless of the challenge route. These results support the PsaA-PspA fusion protein as a promising vaccine strategy, as demonstrated by its ability to enhance the immune response and stimulate production of high titer antibodies against S. pneumoniae strains bearing heterologous PspAs, as well as confer protection against fatal challenge with PspA family 1 and family 2 strains.


Assuntos
Adesinas Bacterianas/imunologia , Anticorpos Antibacterianos/biossíntese , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Lipoproteínas/imunologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Streptococcus pneumoniae/imunologia , Adesinas Bacterianas/genética , Animais , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Avaliação Pré-Clínica de Medicamentos , Feminino , Interleucina-17/metabolismo , Lipoproteínas/genética , Linfócitos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/imunologia , Coelhos , Proteínas Recombinantes de Fusão/imunologia , Baço/citologia , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/patogenicidade , Vacinação , Vacinas Sintéticas/imunologia , Virulência
16.
Nat Prod Res ; 28(19): 1637-40, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24911045

RESUMO

The infructescence of Platycarya strobilacea Sieb. et Zucc is a well-known traditional medicine in China, Japan and Korea. The infructescence of P. strobilacea Sieb. et Zucc is a rich source of ellagitannins that are composed of ellagic acid (EA) and gallic acid, linked to a sugar moiety. The aim of this study was to prepare EA by acid hydrolysis of crude tannins from the infructescence of P. strobilacea Sieb. et Zucc, and establish a new technological processing method for EA. The natural antioxidant EA was prepared by using the water extraction of infructescence of P. strobilacea Sieb. et Zucc, evaporation, condensation, acid hydrolysis and prepared by the process of crystallisation. The yield percentage of EA from crude EA was more than 20% and the purity of the product was more than 98%, as identified by using HPLC. The structure was identified on the basis of spectroscopic analysis and comparison with authentic compound.


Assuntos
Medicamentos de Ervas Chinesas/química , Ácido Elágico/química , Taninos Hidrolisáveis/isolamento & purificação , Juglandaceae/química , Taninos/química , Cromatografia Líquida de Alta Pressão , Ácido Elágico/síntese química , Ácido Gálico/química , Hidrólise , Taninos Hidrolisáveis/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular
17.
Proteomics ; 13(21): 3222-32, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23970500

RESUMO

Isolated from Elephantopus scaber L., a Chinese medicinal herb that is widely used to prevent and treat cancers in China, isodeoxyelephantopin (ESI) exerted antitumor effects on several cancer cells. However, its antitumor mechanism is still not clear. In this study, we found that ESI could induce G2/M arrest and subsequently stimulate cell apoptosis in dose- and time-dependent manners. We used SILAC quantitative proteomics to identify ESI-regulated proteins in cancer cells, and found that 124 proteins were significantly altered in expression. Gene ontology and Ingenuity Pathway Analysis revealed that these proteins were mainly involved in the regulation of oxidative stress and inflammation response. Functional studies demonstrated that ESI induced G2/M arrest and apoptosis by inducing ROS generation, and that antioxidant N-acetyl-l-cysteine could block the ESI-induced antitumor effects. Accumulated ROS resulted in DNA breakage, subsequent G2/M arrest and mitochondrial-mediated apoptosis. ESI upregulated the expression of anticancer inflammation factors IL-12a, IFN-α, and IFN-ß through ROS-dependent and independent pathways. The current work reveals that ESI exerts its antitumor effects through ROS-dependent DNA damage, mitochondrial-mediated apoptosis mechanism and antitumor inflammation factor pathway.


Assuntos
Antineoplásicos/farmacologia , Lactonas/farmacologia , Neoplasias Nasofaríngeas/metabolismo , Proteoma/efeitos dos fármacos , Proteômica/métodos , Sesquiterpenos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Citocinas/análise , Citocinas/metabolismo , Humanos , Carcinoma Nasofaríngeo , Mapas de Interação de Proteínas , Proteoma/análise , Proteoma/química
18.
PLoS One ; 8(4): e61642, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23637874

RESUMO

BACKGROUND: Resveratrol is an important stilbene that benefits human health. However, it is only distributed in a few species including grape and is very expensive. At present, grape has been an important source resveratrol. However, the details are scarce on resveratrol distribution in different Vitis species or cultivars. METHODOLOGY/PRINCIPAL FINDING: The composition and content of resveratrols were investigated by HPLC for assessing genotypic variation in berry skins and leaves of 75 grape cultivars, belonging to 3 species and 7 interspecific hybrids. Trans-resveratrol, cis-piceid and trans-piceid were detected in berry skins and leaves, but cis-resveratrol was not. Resveratrol content largely varied with genetic background as well as usage. In most cultivars, total resveratrol including the above three compounds was higher in berry skins than leaves. In berry skins of most cultivars and leaves of almost all cultivars, cis-piceid was the most abundant resveratrol; trans-resveratrol and trans-piceid were minor components. Some specific cultivars were found with extremely high levels of trans-resveratrol, cis- piceid, trans-piceid or total resveratrols in berry skins or leaves. In skins and leaves, rootstock cultivars had a higher content of total resveratrols, and the cultivated European type cultivars and their hybrids with V. labrusca had relatively low totals. There were no significant correlations of the amounts of total resveratrols or any individual resveratrol between berry skins and leaves. All 75 cultivars can be divided into four groups based on the composition of resveratrols and their concentration by principal component analysis. CONCLUSION: Resveratrol content of grape berries and leaves varied largely with their genetic background and usage. Rootstock cultivars had a higher content of total resveratrols than the other germplasm. Total resveratrols were lower in leaves than berry skins in most cultivars. Cis-piceid was the most abundant resveratrol in most cultivars, and trans-res and trans-pd were minor components.


Assuntos
Frutas/química , Folhas de Planta/química , Estilbenos/química , Vitis/química , Cromatografia Líquida de Alta Pressão , Frutas/metabolismo , Extratos Vegetais/química , Folhas de Planta/metabolismo , Análise de Componente Principal , Resveratrol , Estilbenos/metabolismo , Vitis/metabolismo
19.
Neurochem Int ; 62(7): 922-30, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23499794

RESUMO

Neonatal hypoxia-ischemia (HI) produces neurodegeneration and brain injury, and leads to behavioral and cognitive dysfunction. Hyperbaric oxygen (HBO) treatment may potentially be neuroprotective in HI injury. The aim of this study was to examine any neuroprotection by HBO treatment on long-term neurological function in the rat model of neontatal HI. Seven-day-old rats were subjected to HI or sham surgery. HBO treatment was administered (2.5 ATA for 90 min) 1h after hypoxia exposure. Sensorimotor (grip test and rota-rod) and cognitive tests (inhibitory avoidance and Morris water maze) were performed at postnatal day 28 to day 60. The extent of brain damage was determined by histological evaluation. Apoptosis, caspase-3 and apoptosis inducing factor (AIF) expression were assessed by immunohistochemistry 12, 24, and 48 h after HI. HI-treated animals had significantly worse sensorimotor and cognitive performances than those in the Sham group. HBO treatment led to significant improvements in neurobehavioral functions compared to the HI group, especially for cognitive performances. Morphological evaluation revealed a remarkable recovery of brain injury in the HBO group. Furthermore, the improvements in neurobehavioral impairments were correlated with the reduction in lesion size of the hippocampus and cerebral cortex. The proportion of apoptotic cells significantly increased with time after HI, and HBO significantly inhibited apoptotic cell death. The proportion of caspase-3 positive cells and nuclear AIF translocation increased and peaked at 24h after HI injury. HBO-treated rats showed decreased expression of these proteins compared to HI-treated animals. In conclusion, our results suggested that HBO treatment was effective in promoting long-term functional and histological recovery against neonatal HI brain injury. HBO-induced neuroprotection was associated with suppression of apoptosis by inhibiting caspase-3 and AIF-mediated pathways. Further studies evaluating its associated molecular and cellular mechanism are needed.


Assuntos
Apoptose/efeitos dos fármacos , Comportamento Animal/fisiologia , Lesões Encefálicas/terapia , Oxigenoterapia Hiperbárica , Hipóxia-Isquemia Encefálica/terapia , Animais , Animais Recém-Nascidos , Lesões Encefálicas/patologia , Caspase 3/metabolismo , Modelos Animais de Doenças , Oxigenoterapia Hiperbárica/métodos , Hipóxia-Isquemia Encefálica/metabolismo , Ratos , Ratos Sprague-Dawley
20.
Molecules ; 16(6): 4428-37, 2011 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-21623313

RESUMO

The abundant fruit hulls of tea-oil tree (Camellia oleifera) are still underutilized and wastefully discaded to pollute the environment. In order to solve this problem and better utilize the fruit hulls of C. oleifera, a microwave-assisted extraction system was used to extract their polyphenols using water as the extraction solvent. A central composite design (CCD) was used to monitor the effects of three extraction processing parameters--liquid:solid ratio (mL/g), extraction time (min) and extraction temperature (°C)--on the polyphenol yield (%). The results showed that the optimal conditions were liquid:solid ratio of 15.33:1 (mL/g), extraction time of 35 min and extraction temperature of 76 °C. Validation tests indicated that under the optimized conditions the actual yield of polyphenols was 15.05 ± 0.04% with RSD = 0.21% (n = 5), which was in good agreement with the predicted yield. Phenolic compounds in the extracts were analysed by HPLC, and gallic acid was found to be the predominant constituent. The total flavonoid content in the extracts was determined and high total flavonoid content was revealed (140.06 mg/g dry material).


Assuntos
Camellia/química , Flavonoides/química , Flavonoides/isolamento & purificação , Frutas/química , Micro-Ondas , Fenóis/química , Fenóis/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Polifenóis , Reprodutibilidade dos Testes
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