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1.
Sci Total Environ ; 912: 169077, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38056672

RESUMO

The aim of this study is to propose a desulfurized rubber powder / styrene butadiene styrene (DRP/SBS) composite modified asphalt technology by combining the advantages of DRP and SBS. This reduces the production cost of modified asphalt and improves the performance of asphalt. In this paper, orthogonal tests were used to optimize preparation process parameters of DRP/SBS composite modified asphalt. And the physicochemical properties, modification mechanism of composite modified asphalt had been thoroughly studied. Subsequently, the results showed that the optimum content of DRP and SBS modifiers are 25 % and 2 %, respectively. The suitable preparation process is to add SBS first, then DRP, while shearing at 5000 r/min for 50 min. In addition, DRP/SBS composite modified asphalt has better high-temperature performance, viscosity-temperature characteristics, aging resistance, and storage stability. Meanwhile, the storage stability of the composite modified asphalt was verified by fluorescence microscopy test. Through the Fourier transform infrared spectroscopy test, it was observed that the composite modified asphalt modification process is a compatible and stable modification of physical and chemical coexistence. Overall, the composite modification method achieves recycling of waste tires while improving pavement performance, thus promoting the sustainability of pavement.

3.
J Pharm Pharmacol ; 75(7): 931-939, 2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37177975

RESUMO

OBJECTIVES: This study focuses on investigating the potential impact of DSPE-PEG polymers on intestinal absorption and related mechanism of berberine in rats. METHODS: Effect of DSPE-PEG polymer on intestinal absorption of berberine was investigated with an in situ closed-loop method in rats. To confirm the safety of DSPE-PEG polymer, morphological observation of rat intestine and measurement of biological markers in the intestinal perfusion of rats was performed. Underling mechanism behind promoting action of DSPE-PEG polymer was explored from its impact on the P-gp function and tight junction using in vitro diffusion chamber system, Caco-2 monolayer cells and western blot. KEY FINDINGS: DSPE-PEG polymer demonstrated significant enhancement action on the berberine absorption in rats without any obvious membrane toxicity. DSPE-PEG polymer (1.0%, w/v) induced the most significant promoting effect on berberine absorption specifically in the small intestine of rats. Results of mechanistic studies revealed that DSPE-PEG polymer might not regulate intestinal P-gp function, but significantly down-regulated the expression of tight junction-related proteins, which accordingly led to loosening the tight junctions of intestinal epithelium cells, and consequently increased paracellular absorption of berberine in rats. CONCLUSIONS: DSPE-PEG polymer, as an excellent absorption enhancer, seems very promising in increasing oral bioavailability of berberine.


Assuntos
Berberina , Polímeros , Humanos , Ratos , Animais , Polímeros/farmacologia , Berberina/farmacologia , Células CACO-2 , Intestino Delgado/metabolismo , Mucosa Intestinal/metabolismo , Absorção Intestinal
4.
J Cell Physiol ; 238(4): 813-828, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36879552

RESUMO

Chronic kidney disease (CKD) is a disease with decreased, irreversible renal function. Pruritus is the most common skin symptom in patients with CKD, especially in end-stage renal disease. The underlying molecular and neural mechanism of CKD-associated pruritus (CKD-aP) remains obscure. Our data show that the level of allantoin increases in the serum of CKD-aP and CKD model mice. Allantoin could induce scratching behavior in mice and active DRG neurons. The calcium influx and action potential reduced significantly in DRG neurons of MrgprD KO or TRPV1 KO mice. U73122, an antagonist of phospholipase C, could also block calcium influx in DRG neurons induced by allantoin. Thus, our results concluded that allantoin plays an important role in CKD-aP, mediated by MrgprD and TrpV1, in CKD patients.


Assuntos
Alantoína , Prurido , Insuficiência Renal Crônica , Animais , Camundongos , Alantoína/efeitos adversos , Cálcio , Prurido/induzido quimicamente , Prurido/diagnóstico , Receptores Acoplados a Proteínas G , Insuficiência Renal Crônica/complicações
5.
Environ Sci Pollut Res Int ; 30(13): 38634-38649, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36585577

RESUMO

The large-scale application of bamboo has led to the production of enormous amounts of waste in the form of bamboo residue. In order to reuse the bamboo residue, three types of bamboo fiber (sinocalamus affinis fiber (SAF), green bamboo fiber (GBF), and phyllostachys pubescens fiber (PPF)) extracted from bamboo residues were studied. The properties of bamboo fiber modified asphalt were evaluated by ductility test, cone penetration test, rheological test, and low-field nuclear magnetic resonance (LF-NMR) test. Furthermore, the dispersion properties of bamboo fiber were analyzed by dispersion uniformity test. The results show that the mechanical and high-temperature properties of the bamboo fiber modified asphalt are obviously improved while the low-temperature crack resistance is only slightly weakened. Meanwhile, the signal intensities of SAF modified asphalt and GBF modified asphalt are basically the same before and after aging. It proved the viscosity is not changed much, which verified the good anti-aging properties of SAF modified asphalt and GBF modified asphalt. However, PPF is the best dispersed uniformly in the asphalt. The maximum allowable length and dosage of bamboo fibers is recommended as follows: SAF (9 mm, 2.0%), GBF (6 mm, 1.5%), and PPF (6 mm, 2.0%). The application of bamboo residue in asphalt not only emphasizes the recycling value of bamboo residue waste but also provides an optional natural fiber material for asphalt pavement construction, which meets the requirements of sustainable development.


Assuntos
Temperatura Baixa , Estruturas Vegetais , Poaceae
6.
Polymers (Basel) ; 14(20)2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36297928

RESUMO

The sustainable reuse of waste plastic as an alternative construction material has numerous environmental and economic advantages. New opportunities to recycle waste plastic in asphalt for road construction would mitigate landfill issues and significantly reduce global carbon emissions. With a clear aim to contribute to a more efficient reuse of waste plastic, this paper reutilized two types of waste plastic (polypropylene (PP) and polyethylene (PE)) as asphalt modifiers to improve the performance of asphalt pavement as well as to achieve the purpose of sustainable recycling waste plastic. Therefore, the optimal preparation parameters of plastic-modified asphalt were recommended by the orthogonal test. Then, the dispersion and modification mechanisms of plastic particles in plastic-modified asphalt were further studied by Fourier Transform Infrared Spectroscopy (FTIR) and Thermogravimetric Differential Scanning Calorimetry (TG-DSC). The results show that the asphalt containing PP and PE shows better overall performance at high temperatures compared with the base asphalt. Furthermore, PE-modified asphalt and PP-modified asphalt exhibited optimal properties when prepared at 3000 rpm for 30 min at 170 °C. Moreover, the results of the expansion mechanism show that the main reaction process of plastic asphalt is a physical change. Finally, PP-modified asphalt and PE-modified asphalt generally perform well and are suitable for high-temperature areas. Consequentially, the results of this research promote the recycling of waste plastic, ultimately advocating the recycling of waste materials and environmental protection of pavement construction.

7.
Environ Sci Pollut Res Int ; 29(60): 90463-90478, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35871198

RESUMO

The comprehensive utilization of waste cooking oil (WCO) and waste engine oil (WEO) is of great significance to build a sustainable society because recycling WCO and WEO to develop a rejuvenator for asphalt pavement not only aids the reduction of environmental pollution, but also brings about significant benefits to the Earth's sustainable development. With a clear aim to contribute to a more efficient reuse of the waste oils and recycled asphalt mixtures, this paper develops a high-efficiency compound rejuvenator and determines the optimal combination of its main constituents (WCO and WEO) through orthogonal tests. Furthermore, the performance of the rejuvenator is verified by means of the four-fraction test and the traditional asphalt performance tests (penetration, ductility, softening point). These tests confirm the regeneration efficiency of the compound rejuvenator, and the optimum dosage of the compound rejuvenator is found of 7%. Subsequently, the mechanism of the compound rejuvenator in aged asphalt is examined, and following the application of the compound rejuvenator, it was concluded that the reclaimed asphalt pavement (RAP) could be maximized by 45%. Consequentially, the results of this research promote the recycling of WEO, WCO, and waste asphalt pavement materials, ultimately advocating the sustainability of pavement construction.


Assuntos
Óleos , Desenvolvimento Sustentável , Culinária
8.
Front Immunol ; 12: 714832, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603289

RESUMO

Systemic lupus erythematosus (SLE) is a common autoimmune connective tissue disease with unclear etiology and pathogenesis. Mesenchymal stem cell (MSC) and MSC derived extracellular vesicles (EVs) play important roles in regulating innate and adaptive immunity, which are involved in many physiological and pathological processes and contribute to the immune homeostasis in SLE. The effects of MSCs and EVs on SLE have been drawing more and more attention during the past few years. This article reviews the immunomodulatory effects and underlying mechanisms of MSC/MSC-EVs in SLE, which provides novel insight into understanding SLE pathogenesis and guiding the biological therapy.


Assuntos
Suscetibilidade a Doenças , Vesículas Extracelulares/metabolismo , Imunomodulação , Lúpus Eritematoso Sistêmico/etiologia , Lúpus Eritematoso Sistêmico/metabolismo , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/metabolismo , Linfócitos B/imunologia , Linfócitos B/metabolismo , Comunicação Celular/imunologia , Suscetibilidade a Doenças/imunologia , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo
9.
Toxicol Res (Camb) ; 10(2): 249-263, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33884175

RESUMO

Gastrodin (GAS), the main phenolic glycoside derivative from Gastrodiaelata Blume, has several bio-activities. However, the molecular mechanisms of these protective actions currently remain unclear. This study aimed to investigate the mechanisms of GAS on lead (Pb)-induced oxidative stress and inflammation in the kidneys and primary kidney mesangial cells. Results indicated that GAS improved Pb-induced renal dysfunction and morphological changes in mice. GAS ameliorated Pb-induced inflammation in kidneys by reducing the TNF-α and IL-6 levels. GAS inhibited Pb-induced oxidative stress by regulating the glutathione, thioredoxin (Trx), and Nrf2 antioxidant systems. Furthermore, GAS supplementation increased the activation of SOD, GPx, HO-1, and NQO1 in the kidneys. GAS decreased the expression levels of HMGB1, TLR4, RAGE, MyD88, and NF-κB. These results were further confirmed in primary kidney mesangial cells. Collectively, this study demonstrated that GAS alleviated Pb-induced kidney oxidative stress and inflammation by regulating the antioxidant systems and the Nrf2 signaling pathway. Highlights Gastrodin ameliorated Pb-induced kidney injury in mice.Gastrodin inhibited oxidative stress and inflammation in kidneys.Gastrodin activated the GSH, Trx and Nrf2 antioxidant system in kidneys.Gastrodin inhibited the activities of HMGB1. RAGE, TLR4, and MyD88.

10.
World J Stem Cells ; 12(8): 879-896, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32952864

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) have been reported to possess immune regulatory effects in innate and adaptive immune reactions. MSCs can mediate intercellular communications by releasing extracellular vesicles (EVs), which deliver functional molecules to targeted cells. MSC derived EVs (MSC-EVs) confer altering effects on many immune cells, including T lymphocytes, B lymphocytes, natural killer cells, dendritic cells, and macrophages. A large number of studies have suggested that MSC-EVs participate in regulating autoimmunity related diseases. This characteristic of MSC-EVs makes them be potential biomarkers for the diagnosis and treatment of autoimmunity related diseases. AIM: To verify the potential of MSC-EVs for molecular targeted therapy of autoimmunity related diseases. METHODS: Literature search was conducted in PubMed to retrieve the articles published between 2010 and 2020 in the English language. The keywords, such as "MSCs," "EVs," "exosome," "autoimmunity," "tumor immunity," and "transplantation immunity," and Boolean operator "AND" and "NOT" coalesced admirably to be used for searching studies on the specific molecular mechanisms of MSC-EVs in many immune cell types and many autoimmunity related diseases. Studies that did not investigate the molecular mechanisms of MSC-EVs in the occurrence and development of autoimmune diseases were excluded. RESULTS: A total of 96 articles were chosen for final reference lists. After analyzing those publications, we found that it had been well documented that MSC-EVs have the ability to induce multiple immune cells, like T lymphocytes, B lymphocytes, natural killer cells, dendritic cells, and macrophages, to regulate immune responses in innate immunity and adaptive immunity. Many validated EVs-delivered molecules have been identified as key biomarkers, such as proteins, lipids, and nucleotides. Some EVs-encapsulated functional molecules can serve as promising therapeutic targets particularly for autoimmune disease. CONCLUSION: MSC-EVs play an equally important part in the differentiation, activation, and proliferation of immune cells, and they may become potential biomarkers for diagnosis and treatment of autoimmunity related diseases.

11.
Mediators Inflamm ; 2020: 9743037, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32410875

RESUMO

Accumulating data have implicated that long noncoding RNA (lncRNA) plays an important role in osteoarthritis (OA), which may function as a competitive endogenous RNA (ceRNA) of microRNAs (miRNAs). lncRNA IGHCγ1 has been demonstrated to regulate inflammation and autoimmunity. Nonetheless, the altering effect of IGHCγ1 in OA remains unclear. This study is aimed at investigating the mechanism and function of lncRNA IGHCγ1 in OA. CCK-8, EdU, and transwell assays were used to estimate macrophage proliferation and migration. Fluorescence in situ hybridization (FISH) was performed to estimate the local expression of lncRNA IGHCγ1 in macrophages. Luciferase reporter assay was adopted to validate the ceRNA role of IGHCγ1 as miRNA sponge. lncRNA IGHCγ1 was primarily localized in macrophage cytoplasm and upregulated in OA. miR-6891-3p inhibited macrophage proliferation, migration, and inflammatory response by targeting TLR4, while lncRNA IGHCγ1 promoted TLR4 expression by functioning as a ceRNA for miR-6891-3p through the NF-κB signal in macrophages. This study strongly supports that lncRNA IGHCγ1 regulates inflammatory response via regulating the miR-6891-3p/TLR4/NF-κB axis in macrophages.


Assuntos
Macrófagos/metabolismo , MicroRNAs/metabolismo , Osteoartrite/metabolismo , RNA Longo não Codificante/metabolismo , Receptor 4 Toll-Like/metabolismo , Adulto , Idoso , Apoptose/efeitos dos fármacos , Autoimunidade , Estudos de Casos e Controles , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Hibridização in Situ Fluorescente , Inflamação , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Transdução de Sinais/genética
12.
Rev Sci Instrum ; 91(1): 015007, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32012618

RESUMO

In this paper, a fiber Bragg grating (FBG) temperature measurement method for intersatellite laser link is studied. Based on the analysis of the FBG temperature measurement method, the FBG sensing demodulation system is built to calibrate its wavelength and temperature parameters. The experimental data of temperature gradient monitoring are compared with the on-orbit real-time temperature data of a satellite's solar array measured by the thermistor to verify the temperature monitoring accuracy and stability of the FBG sensing demodulation system. The FBG sensing demodulation system and the thermistor temperature measurement system are compared under the same environmental conditions during the constant temperature period, the continuous heating phase and the natural cooling phase. The results show that during the constant temperature period, the temperature fluctuation range and standard deviation of the FBG sensing demodulation system are ±0.16 °C and 0.08 °C, respectively, which is significantly better than the performance of the thermistor temperature measurement system, whose temperature fluctuation range and standard deviation are ±5.92 °C and 1.08 °C, respectively. The temperature response speed of the former is significantly faster than that of the latter during the continuous heating phase and the natural cooling phase.

13.
Food Chem Toxicol ; 134: 110824, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31539617

RESUMO

Fisetin, a natural flavonoid found in plants, fruits and vegetables, exerts anti-cancer, anti-oxidant, anti-inflammatory and anti-mitotic effects. The current study instigates the protective effect of fisetin against lead-induced synaptic dysfunction, neuroinflammation and neurodegeneration in mice, and explores its underlying mechanisms. The results indicated fisetin can significantly ameliorated behavioral impairments in Pb-treated mice. Fisetin inhibited Pb-induced the apoptotic neurodegeneration, as indicated by the decreased levels of Bax and cleaved caspase-3. Fisetin suppressed activations of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), NF-κB and subsequently inactivate pro-inflammatory factor including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). It can also decrease the accumulation of p-tau and amyloid-beta (Aß) and increased the expression of the Aß remover neprilysin (NEP) in brains of mice. Fisetin also reversed Pb-induced synaptic dysfunction by increasing the levels of synaptosomal associated protein-25 (SNAP-25), postsynaptic density-95 (PSD-95), cyclic-AMP-response element-binding protein (CREB) phosphorylation and calcium/calmodulin kinase II (CaMKII) phosphorylation. Fisetin promoted Pb-induced autophagy in the brains of mice. Moreover, fisetin can increase levels of the denosine 5'-monophosphate-activated protein kinase (AMPK) phosphorylation and SIRT1. Fisetin may be developed as a potential nutritional target for the prevention of Pb-induced neurotoxicity.


Assuntos
Adenilato Quinase/metabolismo , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Flavonoides/uso terapêutico , Inflamação/tratamento farmacológico , Chumbo/toxicidade , Sirtuína 1/metabolismo , Sinapses/efeitos dos fármacos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Flavonoides/farmacologia , Flavonóis , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fosforilação , Sinapses/fisiologia
14.
Sensors (Basel) ; 19(7)2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30934942

RESUMO

A novel Fabry⁻Perot (F⁻P) interferometer model based on the ultra-small gradient-index (GRIN) fiber probe is investigated. The signal arm of the F⁻P interferometer is organically combined with the ultra-small GRIN fiber probe to establish the theoretical model of the novel F⁻P interferometer. An interferometer experimental system for vibration measurements was built to measure the performance of the novel F⁻P interferometer system. The experimental results show that under the given conditions, the output voltage of the novel interferometer is 3.9 V at the working distance of 0.506 mm, which is significantly higher than the output voltage 0.48 V of the single-mode fiber (SMF) F⁻P interferometer at this position. In the range of 0.1⁻2 mm cavity length, the novel interferometer has a higher output voltage than an SMF F⁻P interferometer. Therefore, the novel F⁻P interferometer is available for further study of the precise measurement of micro vibrations and displacements in narrow spaces.

15.
Drug Dev Ind Pharm ; 45(2): 273-281, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30346852

RESUMO

The aim of this work is to develop curcumin-loaded hollow mesoporous silica microspheres (HMSMs@curcumin) to improve the poor oral bioavailability of curcumin. Hollow mesoporous silica microspheres (HMSMs) were synthesized in facile route using a hard template. HMSMs and HMSMs@curcumin were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption/desorption measurements, differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), and X-ray diffraction (XRD). In addition, to demonstrate the potential application of the HMSMs@curcumin, cytotoxicity, in vitro release behavior and in vivo pharmacokinetics of curcumin loaded in these HMSMs were investigated by using of Caco-2 cells and Sprague-Dawley (SD) rats, respectively. These mono-dispersed HMSMs exhibited high drug loading ratio and encapsulation efficiency due to the mesoporous shell and hollow core. The excellent characteristics of HMSMs such as mono-dispersed morphology, smooth surface, uniform, ordered and size-narrowing mesopores resulted in a good in vitro release profile of curcumin from HMSMs@curcumin. Moreover, an impressive improvement in the oral absorption of curcumin and prolonged systemic circulation time were achieved in the in vivo animal studies. In addition, the good biocompatibility of developed HMSMs with Caco-2 cells was confirmed based on the in vitro cytotoxicity assay. In conclusion, this system demonstrated a great potential for efficient delivery of curcumin in vitro and in vivo, suggesting a good prospect for its application in clinic for therapeutic drug delivery in future.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Curcumina/administração & dosagem , Dióxido de Silício/química , Administração Oral , Animais , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/farmacologia , Células CACO-2 , Varredura Diferencial de Calorimetria , Curcumina/farmacocinética , Curcumina/farmacologia , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Humanos , Masculino , Microscopia Eletrônica de Varredura , Microesferas , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
16.
Food Chem Toxicol ; 122: 87-94, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30296514

RESUMO

Paeonol is a natural flavonoid isolated from Moutan Cortex, which has been found to exhibit antioxidant, anti-apoptotic, anti-aging and anti-inflammatory bioactivities. Herein, we investigated the nephroprotective efficacy of paeonol against Pb-induced toxicity and elucidated the potential mechanisms. The results revealed that paeonol significantly ameliorated renal dysfunction and histology changes of Pb-treated mice. Paeonol inhibited oxidative stress and increased activities of antioxidant enzyme in the kidneys of Pb-treated mice. Paeonol decreased the nuclear factor-κB activation and over-production of inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Paeonol suppressed endoplasmic reticulum (ER) stress in kidneys of in the Pb treatment group and primary kidney mesangial cells. Moreover, paeonol increased the denosine 5'-monophosphate-activated protein kinase (AMPK) phosphorylation and decreased the activations of glycogen synthase kinase-3 (GSK-3), protein kinase RNA-like ER kinase (PERK), inositol-requiring protein-1 (IRE1), c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). These results were further confirmed in primary kidney mesangial cells. Taken together, these findings indicate that paeonol could protect kidney form Pb-induced injury by inhibiting oxidative stress, ER stress and inflammation via the AMPK and GSK-3 pathway. Paeonol might be a potential therapeutic agent to inhibit ER stress-associated inflammation in lead-stimulated kidneys.


Assuntos
Acetofenonas/farmacologia , Adenilato Quinase/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Mesângio Glomerular/efeitos dos fármacos , Mesângio Glomerular/enzimologia , Chumbo/toxicidade , Animais , Células Cultivadas , Medicamentos de Ervas Chinesas/química , Ativação Enzimática , Mesângio Glomerular/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Inflamação/prevenção & controle , Mediadores da Inflamação/metabolismo , Interleucina-6/biossíntese , MAP Quinase Quinase 4/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Paeonia/química , Proteínas Serina-Treonina Quinases/metabolismo , Fator de Necrose Tumoral alfa/biossíntese , eIF-2 Quinase/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
17.
J Agric Food Chem ; 66(30): 7975-7982, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29975840

RESUMO

Dihydromyricetin (DHM), a natural flavonoid derived from the medicinal and edible plant Ampelopsis grossedentata, exhibits antioxidant, antiapoptosis, antitumor, and anti-inflammatory bioactivities. This study evaluated the effects of DHM on Pb-induced neurotoxicity and explored the underlying mechanisms. DHM significantly ameliorated behavioral impairments of Pb-induced mice. It decreased the levels of lipid peroxidation and protein carbonyl and increased the activities of superoxide dismutase and catalase in the brains. DHM suppressed Pb-induced apoptosis, as indicated by the decreased levels of Bax and cleaved caspase-3. DHM also decreased inflammatory cytokines in the brains of Pb-treated mice. DHM decreased amyloid-beta (Aß) level and nuclear factor-κB nuclear translocation. Moreover, DHM induced the adenosine 5'-monophosphate-activated protein kinase (AMPK) phosphorylation and inhibited the activation of p38, Toll-like receptor 4, myeloid differentiation factor 88, and glycogen synthase kinase-3. Collectively, this is the first report indicating that DHM could improve Pb-induced cognitive functional impairment by preventing oxidative stress, apoptosis, and inflammation and that the protective effect was mediated partly through the AMPK pathway.


Assuntos
Ampelopsis/química , Disfunção Cognitiva/tratamento farmacológico , Flavonóis/administração & dosagem , Chumbo/toxicidade , Extratos Vegetais/administração & dosagem , Proteínas Quinases/metabolismo , Quinases Proteína-Quinases Ativadas por AMP , Animais , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/imunologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Citocinas/genética , Citocinas/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/metabolismo , Camundongos , NF-kappa B/genética , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Quinases/genética , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
18.
Int J Pharm ; 544(1): 46-54, 2018 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-29654898

RESUMO

This study aims to evaluate the effects of Gelucire44/14 on the in vitro transport, in situ intestinal absorption, as well as in vivo antidiabetic efficacy of berberine (BBR). In the in vitro study, Gelucire44/14 (0.1%, v/v) increased the absorptive transport of BBR across the intestinal membrane of a rat and reduced the relative transport in the secretory direction, thus demonstrating its potential inhibitory effect on intestinal P-glycoprotein (P-gp). In the in situ absorption study, Gelucire44/14 (0.1%, v/v) increased BBR absorption, and this enhancing effect was more significant in the ileum than in the colon of a rat. Oral delivery of BBR with Gelucire44/14 (0.1%, v/v) to diabetic mice, compared with the BBR group, induced a significant hypoglycemic effect on day 7 and day 12 after administration. This result was well correlated with the results of the in vitro study, indicating the important contribution of the P-gp inhibitory effect of Gelucire44/14 to the improvement of the antidiabetic efficacy in vivo. In addition, Gelucire44/14 (0.1%, v/v) neither increased the levels of protein and lactate dehydrogenase in intestinal perfusion nor changed the morphology of the rat intestinal epithelium relative to those of the negative control. This finding suggested that 0.1% (v/v) Gelucire44/14 caused no apparent membrane damage to rat intestine. In conclusion, Gelucire44/14 exhibited potential for enhancing the oral absorption of BBR, thereby improving the antidiabetic efficacy of BBR.


Assuntos
Berberina/administração & dosagem , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Absorção Intestinal/efeitos dos fármacos , Polietilenoglicóis/administração & dosagem , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Administração Oral , Animais , Berberina/química , Berberina/uso terapêutico , Glicemia/análise , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Tipo 1/sangue , Hipoglicemiantes/química , Hipoglicemiantes/uso terapêutico , Mucosa Intestinal/metabolismo , Intestinos/anatomia & histologia , Intestinos/efeitos dos fármacos , L-Lactato Desidrogenase/metabolismo , Masculino , Camundongos , Polietilenoglicóis/química , Polietilenoglicóis/uso terapêutico , Ratos Sprague-Dawley
19.
Food Chem Toxicol ; 110: 325-332, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29107025

RESUMO

A-type dimeric epigallocatechin-3-gallate (A-type-EGCG-dimer, AEd), a new proanthocyanidins dimer from persimmon fruits, has been shown to have health benefit effects. However, A-type-EGCG-dimer affects gluose metabolism in the liver and the underlying mechanism is not clarified. The present study aims to examine the protective effects of A-type-EGCG-dimer on Pb-induced hepatic insulin resistance, endoplasmic reticulum (ER) stress and apoptosis in rats. Male wistar rats exposed to 0.05% w/v Pb acetate in the drinking water with or without A-type-EGCG-dimer coadministration (200 mg/kg body weight/day, intragastrically) for three months. We found that A-type-EGCG-dimer and pioglitazone supplementation significantly deceased glucose and insulin levels in plasma as compared with the Pb group. A-type-EGCG-dimer markedly prevents Pb-induced oxidative stress, ER stress and apoptosis in livers. A-type-EGCG-dimer and pioglitazone reduced the expression levels of the GRP78, PEPCK, G6Pase, p-PERK, p-IRE1, p-JNK, ATF4, CHOP and increased p-AKT in livers of the Pb group. Moreover, A-type-EGCG-dimer reduced ROS production and restored the activities of SOD and GPx in livers. A-type-EGCG-dimer decreased Bax, cytosolic cytochrome c and cleaved caspase-3 and increased Bcl-2 in livers of Pb-exposed rats. Our results suggest that A-type-EGCG-dimer might be a potential natural candidate for the prevention of hepatic insulin resistance and apoptosis induced by Pb.


Assuntos
Catequina/análogos & derivados , Diospyros/química , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Resistência à Insulina , Chumbo/toxicidade , Doenças Metabólicas/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Glicemia/metabolismo , Catequina/administração & dosagem , Catequina/química , Citocromos c/metabolismo , Dimerização , Chaperona BiP do Retículo Endoplasmático , Humanos , Insulina/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Doenças Metabólicas/metabolismo , Doenças Metabólicas/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Ratos
20.
Nutrients ; 9(9)2017 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-28867797

RESUMO

The flavonoid-rich extract from Paulownia fortunei flowers (EPF) has been reported to prevent obesity and other lipid metabolism disease. However, the mechanism of its protective effects is not yet clear. The objective of this study was to investigate molecular factors involved in the hypoglycemic and hypolipidemic effects of EPF in obese mice fed a high-fat diet (HFD). Male h ICR (Institute of Cancer Research) mice were fed a HFD containing or not containing the EPF (50 or 100 mg/kg) for eight weeks. EPF reduced body weight gain, lipid accumulation in livers and levels of lipid, glucose and insulin in plasma as well as reduced insulin resistance as compared with the HFD group. EPF significantly decreased serum aminotransferase activity of the HFD group. We observed that EPF administration significantly increased the level of AMP-activated kinase (AMPK) phosphorylation and prevented fat deposits in livers and HepG2 cells, but these effects were blocked by compound C (an AMPK inhibitor). The protective effects of EPF were probably associated with the decrease in HMGCR, SREBP-1c and FAS expressions and the increase in CPT1 and phosphor-IRS-1 expressions. Our results suggest that EPF might be a potential natural candidate for the treatment and/or prevention of overweight and hepatic and metabolic-related alterations induced by HFD.


Assuntos
Fígado Gorduroso/prevenção & controle , Flavonoides/química , Flores/química , Hiperlipidemias/prevenção & controle , Magnoliopsida/química , Extratos Vegetais/farmacologia , Animais , Fígado Gorduroso/etiologia , Flavonoides/farmacologia , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Humanos , Hiperlipidemias/etiologia , Resistência à Insulina , Masculino , Camundongos , Camundongos Endogâmicos ICR , Obesidade/complicações , Extratos Vegetais/química , Distribuição Aleatória
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