Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.708
Filtrar
1.
Bull Environ Contam Toxicol ; 105(3): 422-427, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32740746

RESUMO

This study explored the adsorption of representative non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen (AP), ibuprofen (IB), and salicylic acid (SA) by biochars. The sorption kinetics were fitted with six commonly used kinetic models, and the isotherm data was well described by both Langmuir and Freundlich models. Biochars of longer pyrolysis time showed better performance with the Langmuir maximum sorption capacities for AP, IB, and SA of 196 mg/g, 132 mg/g, and 48.8 mg/g, respectively. Variation in temperature hardly affected the adsorption performances, while the influence of pH exhibited pronounced dependency on physicochemical properties of both NSAIDs and biochars. Eighteen ball-milled (BM) biochars were then produced under different ball-milling conditions and examined for NSAIDs removal. Compared with unmilled biochars, BM-biochars produced under optimum conditions showed higher removal efficiencies. Electrostatic interaction and pore width of biochars greatly affected the NSAIDs adsorption onto biochars.


Assuntos
Anti-Inflamatórios não Esteroides/química , Carvão Vegetal/química , Adsorção , Concentração de Íons de Hidrogênio , Cinética , Pirólise , Temperatura
2.
J Nat Med ; 74(4): 741-749, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32601830

RESUMO

Cancer cachexia is a complex and multifactorial syndrome that influences about 50-80% of cancer patients and may lead to 20% of cancer deaths and muscle atrophy is the key characteristic of the syndrome. Recent researches have shown that myostatin is a negative regulator in the growth and differentiation of skeletal muscle. Herein, C2C12 cancer cachexia model was established with C26 conditioned culture medium (CCM), then treated with magnolol to evaluate the pharmacological activity of magnolol in myotube atrophy. Our results demonstrated that magnolol inhibited the activity of myostatin promotor and the myostatin signaling pathway. In C2C12 cancer cachexia model, magnolol decreased myostatin expression, inhibited the phosphorylation of SMAD2/3 activated by C26 conditioned culture medium (CCM), and elevated the phosphorylation of FOXO3a lowered by CCM. Myosin heavy chain (MyHC), myogenin (MyoG), and myogenic differentiation (MyoD), as three common myotube markers in C2C12 myotube, were decreased by CCM, which could be effectively reversed by magnolol via activation of AKT/mTOR-regulated protein synthesis and inhibition of ubiquitin-mediated proteolysis. This study reveals that magnolol inhibits myotube atrophy induced by CCM by increasing protein synthesis and decreasing ubiquitin-mediated proteolysis, so that magnolol is a promising leading compound in treating muscle atrophy induced by cancer cachexia.


Assuntos
Anti-Inflamatórios não Esteroides/química , Produtos Biológicos/química , Compostos de Bifenilo/química , Caquexia/tratamento farmacológico , Lignanas/química , Fibras Musculares Esqueléticas/efeitos dos fármacos , Atrofia Muscular/tratamento farmacológico , Miostatina/metabolismo , Neoplasias/complicações , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Transfecção
3.
Chemosphere ; 260: 127579, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32679375

RESUMO

As important emerging contaminants, nonsteroidal anti-inflammatory drugs (NSAIDs) are the most intensively prescribed pharmaceuticals introduced to drinking water due to their incomplete removal in wastewater treatment. While concentrations of NSAIDs in drinking water are generally low, they have been attracting increasing concern as a result of their disinfection byproducts (DBPs) generated in drinking water disinfection. In this work, detection methods were set up for four representative indole-derivative NSAIDs (indomethacin, acemetacin, sulindac, and etodolac) using ultra performance liquid chromatography/electrospray ionization-triple quadruple mass spectrometry (UPLC/ESI-tqMS). ESI+ was better for detection of indomethacin and sulindac, whereas ESI- was suitable to detection of acemetacin and etodolac. With optimized MS parameters, the instrument detection and quantitation limits of the four indole derivatives were achieved to be 1.1-24.6 ng/L and 3.7-41.0 ng/L, respectively. During chlorination, indomethacin and acemetacin could undergo five major reaction types (chlorine substitution, hydrolysis, decarboxylation, C-C coupling, and C-N cleavage) to form a series of DBPs, among which 19 were proposed/identified with structures. Based on the revealed structures of DBPs, transformation pathways of indomethacin and acemetacin in chlorination were partially elucidated. Notably, individual and mixture toxicity of indomethacin and acemetacin before/after chlorination were evaluated using a well-established acute toxicity assessment and a Hep G2 cell cytotoxicity assay, respectively. Results showed that the predicted acute toxicity of a few chlorination DBPs were higher than their precursors; chlorination substantially enhanced the mixture cytotoxicity of indomethacin by over 10 times and slightly increased the mixture cytotoxicity of acemetacin.


Assuntos
Anti-Inflamatórios não Esteroides/análise , Anti-Inflamatórios não Esteroides/toxicidade , Desinfecção/métodos , Poluentes Químicos da Água/análise , Anti-Inflamatórios não Esteroides/química , Cloro/química , Cromatografia Líquida , Desinfetantes/química , Água Potável/química , Halogenação , Células Hep G2 , Humanos , Indóis/análise , Indóis/química , Indóis/toxicidade , Indometacina/análogos & derivados , Indometacina/análise , Indometacina/química , Indometacina/toxicidade , Espectrometria de Massas por Ionização por Electrospray/métodos , Poluentes Químicos da Água/química , Poluentes Químicos da Água/toxicidade , Purificação da Água/métodos
4.
AAPS PharmSciTech ; 21(5): 172, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32533366

RESUMO

Dissolution testing and solubility determinations in different biorelevant media have gained considerable interest in the pharmaceutical industry from early-stage development of new products to forecasting bioequivalence. Among all biorelevant fluids, the preparation of fed-state simulated gastric fluid (FeSSGF) and handling of samples from dissolution/solubility testing in FeSSGF is considered to be relatively challenging. Challenges include maintaining the stability of FeSSGF medium upon sampling, filtration, and mitigating analytical interference of excipients and milk components. To overcome these challenges, standard and uniform working practices are required that are not only helpful in preparation of stable FeSSGF but also serve as a harmonizing guide for the collection of dissolution/solubility samples and their subsequent processing (i.e., handling and assay). The optimization of sample preparation methodology is crucial to reduce method-related variance by ensuring specificity, robustness, and reproducibility with acceptable recovery of the analytes. The sample preparation methodology includes a combination of techniques including filtration, solvent treatment, and centrifugation to remove the interfering media-related components and excipients from the analyte. The analytes of interest were chromatographically separated from the interfering analytes to quantify the drug concentration using the new high-performance liquid chromatography methods with ultraviolet detection. The methods developed allow rapid sample preparation, acceptable specificity, reproducible recoveries (greater than 95% of label claim), and quantification of study drugs (ibuprofen and ketoconazole). The sample preparation technique and method considerations provided here for ibuprofen and ketoconazole can serve as a starting point for solubility and dissolution testing of other small molecules in FeSSGF.


Assuntos
Desenvolvimento de Medicamentos/métodos , Ácido Gástrico/metabolismo , Ibuprofeno/metabolismo , Cetoconazol/metabolismo , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/metabolismo , Antifúngicos/química , Antifúngicos/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Ibuprofeno/química , Cetoconazol/química , Reprodutibilidade dos Testes , Solubilidade , Comprimidos
5.
AAPS PharmSciTech ; 21(4): 127, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32390062

RESUMO

The aim of the present study was to evaluate the development of an intra-articular nonsteroidal anti-inflammatory drug gelatin microsphere formulation based on quality risk management and quality by design approaches. Specifically, after setting the quality target product profile and the critical quality attributes, risk assessment was performed by constructing Ishikawa fishbone diagrams based on preliminary hazard analysis. A Plackett-Burman screening experimental design was applied in order to identify the factors (previously classified by risk assessment analysis as having high risk of failure) having a statistically significant impact on the formation of gelatin microspheres. Particle size, polydispersity index, and drug loading were used as responses, while diclofenac sodium was selected as a model drug. All drug-loaded gelatin microspheres were prepared by emulsion-crosslinking process. Screening results showed that gelatin type, surfactant type and quantity, oil phase type, emulsification speed, and glutaraldehyde's concentration had a statistically significant impact on microsphere's final and intermediate critical quality attributes. A design space was then constructed based on central composite design overlaying contour plots, while verification experiments for the optimum suggested formulation (derived from a set control strategy) showed good agreement between the predicted and the experimentally observed results. In addition, the physicochemical characterization of the optimum formulation showed the formation of significant molecular interactions between the drug and the gelatin matrix, leading to the complete amorphization of diclofenac within the microsphere structure, while dissolution release experiments showed a biphasic release profile which extended the drug's release for up to 30 days, governed by a Fickian diffusion release mechanism.


Assuntos
Anti-Inflamatórios não Esteroides/química , Diclofenaco/química , Desenvolvimento de Medicamentos/normas , Gelatina/química , Microesferas , Pesquisa Qualitativa , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/metabolismo , Bovinos , Diclofenaco/administração & dosagem , Diclofenaco/metabolismo , Desenvolvimento de Medicamentos/métodos , Liberação Controlada de Fármacos , Gelatina/administração & dosagem , Gelatina/metabolismo , Injeções Intra-Articulares , Tamanho da Partícula , Gestão de Riscos , Suínos
6.
AAPS PharmSciTech ; 21(5): 145, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32430787

RESUMO

The present study demonstrates the solubility and dissolution of flufenamic acid (FLF)/ß-cyclodextrin (ß-CD)/Soluplus® supramolecular ternary inclusion complex. The binary and ternary inclusion complexes were prepared using solvent evaporation and the microwave irradiation method. The prepared inclusion complexes were evaluated for physicochemical characterization and anti-inflammatory activity using a murine paw edema mol. The phase solubility studies demonstrated 4.59-fold and 17.54-fold enhancements in FLF solubility with ß-CD alone and ß-CD:Soluplus® combination compared with pure FLF, respectively. The in vitro drug release results revealed a significant improvement (P < 0.05) in the release pattern compared with pure FLF. Maximum release was found with flufenamic acid binary and ternary complexes prepared using the microwave irradiation method, i.e., 75.23 ± 3.12% and 95.36 ± 3.23% in 60 min, respectively. The physicochemical characterization results showed complex formation and conversion of the crystalline form of FLF to an amorphous form. The SEM study revealed the presence of a more agglomerated and amorphous structure of the solid particles, which confirmed the formation of complexes. The anti-inflammatory effect of the complex was higher than pure FLF. Therefore, the FLF:ß-CD:Soluplus® inclusion complex may be a very valuable formulation with improved solubility, dissolution, and anti-inflammatory effect.


Assuntos
Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Ácido Flufenâmico/química , Ácido Flufenâmico/farmacologia , Polietilenoglicóis/química , Polivinil/química , beta-Ciclodextrinas/química , Animais , Varredura Diferencial de Calorimetria , Carragenina , Cristalização , Composição de Medicamentos , Edema/induzido quimicamente , Edema/patologia , Excipientes , Masculino , Micro-Ondas , Ratos , Ratos Wistar , Solubilidade , beta-Ciclodextrinas/farmacologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-32278291

RESUMO

A fast off-line FPSE-HPLC-PDA method has been reported that allows simultaneous clean up and determination of six non-steroidal anti-inflammatory drugs (NSAIDs) in saliva samples from healthy volunteers. Particularly, furprofen, indoprofen, ketoprofen, fenbufen, flurbiprofen, and ibuprofen were chromatographically resolved. Benzyl paraben was chosen as the internal standard (BzPB, IS). These target compounds were successfully extracted from human saliva using fabric phase sorptive extraction (FPSE) and then analysed in the liquid chromatographic system by means of a short analytical column (Symmetry C18, 75 × 4.6 mm, 3.5 µm) using acetonitrile (AcN) and phosphate buffer (PBS, 30 mM; pH = 2.5) as the mobile phases. The method, validated through the calculation of all analytical parameters in accordance of International Guidelines, was applied to real saliva sample analysis collected from informed volunteers. The proposed approach that included the use of sol-gel polytetrahydrofuran (sol-gel PTHF) sorbent immobilized on cellulose support and C18 stationary phase used in HPLC, showed high potential as a fast tool for future clinical and forensic applications. The herein reported results encourage potential future application of FPSE in the forensic field. Furthermore, the FPSE membrane was tested in dried saliva spot mode (DSS) in order to check its potential use as a sampling device, also for forensic applications.


Assuntos
Anti-Inflamatórios não Esteroides/química , Flurbiprofeno/química , Fenilpropionatos/química , Saliva/química , Anti-Inflamatórios não Esteroides/farmacocinética , Celulose/química , Cromatografia Líquida de Alta Pressão , Feminino , Flurbiprofeno/farmacocinética , Humanos , Limite de Detecção , Masculino , Estrutura Molecular , Parabenos/normas , Fenilpropionatos/farmacocinética , Microextração em Fase Sólida
8.
Phys Chem Chem Phys ; 22(19): 10838-10844, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32342080

RESUMO

Employing neutron spectroscopy, we follow the tracer diffusion of two non-steroidal anti-inflammatory drug molecules, paracetamol (PCM) and ibuprofen sodium (IBU), in a supramolecular gel and the corresponding bulk solution. Both solutes show altered diffusion behaviour in the gel phase, deviating from each other and their bulk solution. Whilst picosecond diffusion of IBU is slightly quicker in the gel, this effect is significantly increased for PCM, which is up to 70% quicker in the gel than in solution. This effect is independent of changes in the solvent diffusion reported previously. An increased residence time of PCM in solution at lower temperatures points towards the onset of nucleation and crystallisation. This work reports one of the first experiments on the novel Backscattering and Time-of-Flight option (BATS) on the IN16B spectrometer at the Institut Laue-Langevin, France, which with its range and resolution in neutron energy and momentum transfer is ideally suited to observe this type of diffusion.


Assuntos
Acetaminofen/química , Anti-Inflamatórios não Esteroides/química , Difusão , Géis/química , Ibuprofeno/química
9.
Phytomedicine ; 69: 153197, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32146298

RESUMO

BACKGOUND: Ginsenoside Rb1, the main active constituent of Panax ginseng, displays significant anti-inflammatory activity, although the mechanism has not been clearly unraveled. In this study, Rb1's mechanism of anti-inflammatory effects were investigated. METHODS: The flow cytometry and enzyme-linked immunosorbent assay (ELISA) were empolyed to detect pro-inflammatory cytokines release. The related protein and gene expression was investigated by western blotting and qRT-PCR. The dimerization of TLR4 was measured by co-immunoprecipitation and molecular docking assays. Cellular thermal shift assay was used for the determination of the binding of Rb1 and TLR4. For animal moldels, LPS- or cantharidin-induced acute kidney injury, LPS-induced septic death, and dimethyl benzene-induced ear edema were employed to investigate Rb1's anti-inflammatory activity in vivo. RESULTS: Rb1 significantly decreased inflammatory cytokines release in LPS-stimulated RAW264.7 cells and BMDMs, as well as COX-2 and iNOS amounts. Rb1 reduced LPS-associated calcium influx, ROS production, and NO generation. The NF-κB and MAPK axes participated in Rb1's anti-inflammatory effects. Molecular docking simulation indicated Rb1 bound to TLR4 to prevent TLR4 dimerization, as confirmed by co-immunoprecipitation and cellular thermal shift assay. Furthermore, MyD88 recruitment and TAK1 expression were altered by reduced TLR4 dimerization, indicating the TLR4-MyD88-NF-κB/MAPK pathways contributed to Rb1's anti-inflammatory process. In animal models, Rb1 markedly alleviated LPS- or cantharidin-induced acute kidney injury, rescued LPS-induced septic mice from death, and inhibited dimethyl benzene-induced mouse ear edema. CONCLUSION: Overall, these findings demonstrate Rb1 exhibits marked anti-inflammatory effects, suggesting Rb1 represents an optimal molecule for treating inflammatory diseases.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Ginsenosídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/química , Cantaridina/toxicidade , Ginsenosídeos/química , Células HEK293 , Humanos , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Simulação de Acoplamento Molecular , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Multimerização Proteica , Células RAW 264.7 , Ratos Sprague-Dawley , Receptor 4 Toll-Like/química
10.
Life Sci ; 253: 117588, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32220621

RESUMO

AIM: The present research work aimed to prepare and characterize nanoparticles of curcumin using polymers from different sources like natural, synthetic and semi-synthetic, and compare their activity for wound healing. Curcumin, BCS class II drug, is a polyphenol with proven wound healing activity. MATERIAL AND METHODS: The curcumin-loaded chitosan and carboxymethylcellulose (CMC) nanoparticles were prepared by ionotropic gelation method. In contrast, poly-lactic co-glycolic acid (PLGA) nanoparticles were prepared by a double emulsion solvent evapouration method. The different sources of polymers include natural (chitosan), synthetic (PLGA) and semi-synthetic CMC were used for the preparation of nanoparticles. KEY FINDINGS: The percentage entrapment efficiency of curcumin-loaded nanoparticles was found to be in the order of polymers PLGA>chitosan>CMC. The in-vitro release study of carboxymethyl cellulose -curcumin nanoparticles was found to be 74.96% for 24 h. The presence of a specific peak of curcumin in all the polymeric nanoparticles specifies drug incorporation in the polymeric matrix. The in-vivo study revealed that curcumin-loaded chitosan nanoparticles fasten the healing process of the wound due to the synergistic effect produced by using a combination of curcumin and chitosan. SIGNIFICANCE: Curcumin-loaded nanoparticles showed significant enhancement in wound healing action by lowering the dose of curcumin and effecting synergistically due to the use of chitosan.


Assuntos
Anti-Inflamatórios não Esteroides/química , Curcumina/química , Nanocápsulas/química , Cicatrização/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Carboximetilcelulose Sódica/química , Quitosana/química , Curcumina/farmacologia , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Emulsões/química , Humanos , Masculino , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ratos Wistar
11.
Science ; 368(6489): 387-394, 2020 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-32193360

RESUMO

The two tandem bromodomains of the BET (bromodomain and extraterminal domain) proteins enable chromatin binding to facilitate transcription. Drugs that inhibit both bromodomains equally have shown efficacy in certain malignant and inflammatory conditions. To explore the individual functional contributions of the first (BD1) and second (BD2) bromodomains in biology and therapy, we developed selective BD1 and BD2 inhibitors. We found that steady-state gene expression primarily requires BD1, whereas the rapid increase of gene expression induced by inflammatory stimuli requires both BD1 and BD2 of all BET proteins. BD1 inhibitors phenocopied the effects of pan-BET inhibitors in cancer models, whereas BD2 inhibitors were predominantly effective in models of inflammatory and autoimmune disease. These insights into the differential requirement of BD1 and BD2 for the maintenance and induction of gene expression may guide future BET-targeted therapies.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/farmacologia , Proteínas de Ciclo Celular/antagonistas & inibidores , Histona Acetiltransferases/antagonistas & inibidores , Fatores Imunológicos/farmacologia , Terapia de Alvo Molecular , Fatores de Transcrição/antagonistas & inibidores , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/uso terapêutico , Antineoplásicos/uso terapêutico , Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/genética , Descoberta de Drogas , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Histona Acetiltransferases/química , Histona Acetiltransferases/genética , Humanos , Doenças do Sistema Imunitário/tratamento farmacológico , Fatores Imunológicos/química , Fatores Imunológicos/uso terapêutico , Inflamação/tratamento farmacológico , Neoplasias/tratamento farmacológico , Domínios Proteicos/efeitos dos fármacos , Fatores de Transcrição/química , Fatores de Transcrição/genética
12.
Phytomedicine ; 68: 153143, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32018209

RESUMO

BACKGROUND: Rhodiola rosea L. (Crassulaceae) has been used for years in the traditional medicine of several countries as an adaptogen drug, able to preserve homeostasis in response to stress stimuli. Currently R. rosea roots and rhizome are classified as a traditional herbal medicinal product for temporary relief of symptoms of stress, such as fatigue and sensation of weakness by the European Medicines Agency. HYPOTHESIS/PURPOSE: Increasing evidences suggest the involvement of neuroinflammation in response to stress. However, whether the modulation of neuroinflammatory parameters could be involved in the anti-stress effect of R. rosea has been barely studied. Thus, the aim of this work is to investigate the possible modulation of molecular inflammatory processes elicited by a R. rosea roots and rhizome ethanolic extract in an in vitro model of corticotropin releasing hormone (CRH)-stimulated BV2 microglial cells. METHODS: BV2 cells were stimulated with CRH 100 nM and changes in cell viability, cytokines production and heat shock protein 70 (HSP70) levels were evaluated. Intracellular pathways related to inflammation, such as nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) nuclear translocation and mitogen-activated protein kinases (MAPK) activation were also analyzed. RESULTS: We found that R. rosea extract (2.7% m/m rosavin and 1% m/m salidroside) 20 µg/ml was able to counteract the neuroinflammatory effect of CRH by inhibiting NF-κB nuclear translocation with a mechanism of action involving the modulation of mitogen-activated protein kinase-activated protein kinase 2 (MKK2), extracellular signal-regulated kinase 1/2 (ERK 1/2) and c-Jun n-terminal kinase (JNK), resulting in a reduction of HSP70 expression. CONCLUSION: This work expands the knowledge of the intracellular mechanisms involved in R. rosea anti-stress activity and may be useful for the study of other adaptogen drugs.


Assuntos
Hormônio Liberador da Corticotropina/metabolismo , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Rhodiola/química , Adaptação Biológica/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Hormônio Liberador da Corticotropina/farmacologia , Glucosídeos/farmacologia , Proteínas de Choque Térmico HSP70/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Microglia/citologia , Microglia/efeitos dos fármacos , NF-kappa B/metabolismo , Fenóis/farmacologia , Extratos Vegetais/química , Raízes de Plantas/química , Plantas Medicinais/química , Rizoma/química , Estresse Fisiológico/efeitos dos fármacos
13.
PLoS One ; 15(2): e0223201, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32050259

RESUMO

The objective of this study was based on the formulation development of fast dispersible Aceclofenac tablets (100 mg) and to evaluate the influence of pharmaceutical mixtures of directly compressible Avicel PH102 with Mannitol and Ac-di-sol on the compressional, mechanical characteristics and drug release properties. Fast dispersible Aceclofenac formulations were developed by central composite design (CCD). Among them the best possible formulation was selected on the basis of micromeritic properties, appropriate tablet weight and disintegration time for further study. Tablets were directly compressed using manual hydraulic press with a compressional force ranging from 7.2 to 77.2 MN/m2. Pre and post compression studies were performed and the compressed formulations (FA-FF) were assessed for different quality tests. The Heckel and Kawakita equations were applied for determination of compressional behavior of formulations. The quality attributes suggested that formulation (FB) containing avicel PH 102 (20%), mannitol (25%) and ac-di-sol (3%) as best optimized formulation showing better mechanical strength i.e. hardness 35.40 ± 6.93N, tensile strength 0.963 MN/m2, and friability 0.68%. Furthermore, compressional analysis of FB showed lowest PY value 59.520 MN/m2 and Pk value 1.040 MN/m2 indicating plasticity of the material. Formulation FB disintegrated rapidly within 21 seconds and released 99.92% drug after 45 min in phosphate buffer pH 6.8. Results of drug release kinetics showed that all formulations followed Weibull and First-order models in three different dissolution media. Avicel PH102 based formulation mixture exhibit excellent compactional strength with rapid disintegration and quick drug release.


Assuntos
Química Farmacêutica/métodos , Diclofenaco/análogos & derivados , Composição de Medicamentos/métodos , Estresse Mecânico , Comprimidos/química , Anti-Inflamatórios não Esteroides/química , Força Compressiva , Diclofenaco/química , Dureza , Cinética , Solubilidade , Resistência à Tração
14.
Dalton Trans ; 49(7): 2323-2330, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32022053

RESUMO

A superoxide dismutase mimic (Mn1) was functionalized with three positively charged-peptides: RRRRRRRRR (Mn1-R9), RRWWWRRWRR (Mn1-RW9) or Fx-r-Fx-K (Mn1-MPP). Characterization of the physico-chemical properties of the complexes show that they share similar binding affinity for Mn2+, apparent reduction potential and intrinsic superoxide dismutase activity. However, their accumulation in cells is different (Mn1-R9 < Mn1-MPP < Mn1-RW9 < Mn1), as well as their subcellular distribution. In addition, the three functionalized-complexes display a better anti-inflammatory activity than Mn1 when assayed at 10 µM. This improvement is due to a combination of an anti-inflammatory effect of the peptidyl moiety itself, and of the SOD mimic for Mn1-RW9 and Mn1-MPP. In contrast, the enhanced anti-inflammatory activity of Mn1-R9 is solely due to the SOD mimic.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Peptídeos Penetradores de Células/farmacologia , Superóxido Dismutase/metabolismo , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/metabolismo , Peptídeos Penetradores de Células/química , Peptídeos Penetradores de Células/metabolismo , Células HT29 , Humanos , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Estrutura Molecular , Superóxido Dismutase/química , Termodinâmica
15.
Microvasc Res ; 130: 103991, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32105668

RESUMO

The development of a new drug active substance is not only time-consuming and expensive, but also a chain of operations that often fails. However, increasing the bioavailability, effectiveness, safety, or targeting the drugs used in clinic by various methods, such as nanoparticles (NPs), may be a more effective way of using them in clinic. In addition, NP formulations are becoming increasingly popular in modern medical treatments. Angiogenesis, formation of new capillaries from a pre-existing one, fundamentally occurs in physiological processes such as wound healing, embryogenesis and menstrual cycle, also has a vital role in pathology of cancer, psoriasis, diabetic retinopathy and chronic inflammation. The Hen's Egg Test on the Chorioallantoic Membrane (HET-CAM) assay is a useful, well established and animal alternative in vivo procedure for evaluation of anti-inflammatory potentials and anti-irritant properties of nano drug delivery systems. In this study, diclofenac sodium (DS) loaded PLGA NPs were prepared and characterized. The particle size (PS) of DS-loaded PLGA NPs was between 114.7 and 124.8 nm and all NPs were monodisperse with negative zeta potential values. The encapsulation efficiency was in range of 41.4-77.8%. In vitro dissolution studies of NPs showed up to 24 h of DS release after the first 3 h of burst effect. The 3 h burst effect and 24 h release kinetics studied with DDSolver were found to be predominantly driven not only by one mechanism, by a combined mechanism of Fickian and non-Fickian. Solid state structures of formulations were clarified by DSC and FT-IR analysis. PS, EE% and release rates were found to be affected by the amount of DS added to the formulations. Increasing the amount of DS added to the formulations increased PS, while the EE% decreased. The release rates were affected by PS and the formulation with the lowest PS value showed slower release. The anti-inflammatory activity of optimum formulation (NP-1) was examined using in vivo HET-CAM assay. The anti-inflammatory activity results indicated that NP-1 coded NP formulation showed significantly good anti-inflammatory potential at low dose. As a result, a low dose high anti-inflammatory effect was achieved with the NP structure of DS. To the best of our knowledge this is the first study on in vivo anti-inflammatory activities of DS loaded PLGA NPs by HET-CAM.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Membrana Corioalantoide/efeitos dos fármacos , Diclofenaco/administração & dosagem , Portadores de Fármacos , Inflamação/prevenção & controle , Nanopartículas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Animais , Anti-Inflamatórios não Esteroides/química , Embrião de Galinha , Membrana Corioalantoide/patologia , Diclofenaco/química , Composição de Medicamentos , Liberação Controlada de Fármacos , Inflamação/patologia , Cinética , Tamanho da Partícula , Solubilidade
16.
Acta Crystallogr C Struct Chem ; 76(Pt 1): 69-74, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31919309

RESUMO

The title benzothiazine-3-carboxamide, C17H16N2O4S, crystallized in two enantiomorphic crystal forms with the space groups P32 and P31 despite the absence of a classic stereogenic atom. The molecular structures are mirror images of each other. Only one sulfonyl O atom takes part in intramolecular hydrogen bonding as a proton acceptor and this atom is different in the two enantiomorphic structures. As a result, the S atom becomes a pseudo-stereogenic centre. This fact is worth taking into account due to the different biological activities of the enantiomorphic forms. One form possesses a high analgesic activity, while the other form revealed a high anti-inflammatory activity.


Assuntos
Anti-Inflamatórios não Esteroides/química , Piroxicam/análogos & derivados , Cristalografia por Raios X , Ligação de Hidrogênio , Estrutura Molecular , Estereoisomerismo
17.
Phytochemistry ; 171: 112231, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31901473

RESUMO

Daphne giraldii Nitsche., a member of the genus Daphne (Thymelaeaceae), is a deciduous shrub with mild toxicity. Its rhizome bark, generally called 'Zushima' in Chinese, has many medicinal folkloric uses and good therapeutic effects. Previous studies investigating the chemical constituents and pharmacological activities of D. giraldii have focused on several major classes of compounds, such as coumarins, lignans and flavonoids, especially the interesting enantiomeric flavans. Extracts and pure compounds of D. giraldii were found to possess anti-inflammatory, anti-nociceptive, cytotoxicity, antimalarial, immunomodulating, sedative and hypnotic effects. They have also been reported to influence the cardiovascular functions and blood activities. This comprehensive review will describe the advances in the phytochemistry, pharmacology, medicinal uses and clinical applications of D. giraldii and its formulations covering the literature published from 1970 to 2018. Almost half of the reviewed studies were originally published in non-English languages (mainly in Chinese). Collectively, the aim of this article is to open new avenues for further in-depth pharmacological studies on D. giraldii.


Assuntos
Compostos Fitoquímicos/farmacologia , Thymelaeaceae/química , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Anti-Inflamatórios não Esteroides/farmacologia , Fármacos Antiobesidade/química , Fármacos Antiobesidade/isolamento & purificação , Fármacos Antiobesidade/farmacologia , Antimaláricos/química , Antimaláricos/isolamento & purificação , Antimaláricos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Humanos , Hipnóticos e Sedativos/química , Hipnóticos e Sedativos/isolamento & purificação , Hipnóticos e Sedativos/farmacologia , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação
18.
PLoS One ; 15(1): e0227637, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31929574

RESUMO

Leptin resistance and co-existing insulin resistance is considered as hallmark of diet-induced obesity. Here, we investigated therapeutic potential of hesperidin to improve leptin and insulin resistance using high fat diet (HFD)-induced obese experimental animal model. We also performed in silico studies to validate therapeutic effectiveness of hesperidin by performing protein-ligand docking and molecular dynamics simulation studies. Group 1 was identified as control group receiving vehicle only. Group 2 was marked as non-treated group receiving 60% HFD. While, other groups were treated daily with orlistat (120 mg/kg/d), hesperidin (55 mg/kg/d), combination of hesperidin (55 mg/kg/d) + orlistat (120 mg/kg/d). Hesperidin alone (P<0.001) and particularly in combination with orlistat (P<0.001), resulted in controlling the levels of HFD-altered biomarkers including random and fasting state of glycemia, leptin and insulin resistance. Similarly, hesperidin also improved the serum and tissue levels of leptin, interleukin-6 and tumor necrosis factor-alpha more significantly (P<0.05) when compared with that of orlistat. These results were found to be in accordance with the results of histopathological examination of pancreas, liver and adipose tissues. In-silico studies also proved that hesperidin binds to leptin receptor with higher affinity as compared to that of orlistat and induces the favorable variations in geometrical conformation of leptin receptor to promote its association with leptin which may lead to the cascades of reactions culminating the lipolysis of fats that may ultimately lead to cure obesity. The results of this study may be a significant expectation among the forthcoming treatment strategies for leptin and insulin resistance.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Fármacos Antiobesidade/farmacologia , Hesperidina/farmacologia , Inflamação/tratamento farmacológico , Resistência à Insulina , Obesidade/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/química , Fármacos Antiobesidade/química , Dieta Hiperlipídica , Modelos Animais de Doenças , Quimioterapia Combinada , Hesperidina/química , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/metabolismo , Hiperlipidemias/patologia , Inflamação/metabolismo , Inflamação/patologia , Leptina/metabolismo , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Obesidade/metabolismo , Obesidade/patologia , Orlistate/química , Orlistate/farmacologia , Ratos Wistar
19.
Biophys Chem ; 258: 106318, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31918024

RESUMO

Among numerous compounds found in marine organisms, astaxathin has received considerable research interest due to beneficial impact on health such as anti-inflammatory, antioxidant and neuroprotective activity. Recently new functionalities of this xanthophyll have been revealed indicating important applications in nutrition and pharmacy. However, astaxanthin, as the bioactive, has limited value without a protecting carrier that provides controlled release in a human body. Fabrication of liposomes as efficient drug delivery systems is promising strategy that may overcome these problems. However, the development of new delivery systems requires comprehensive understanding of physicochemical properties of carotenoids and their carriers as well as the interactions between them. The aim of this study was to investigate the mixed lipid-sterol monolayer in the presence of astaxanthin in terms of thermodynamic, morphological and viscoelastic behaviour. The results have been discussed in relation to pure lipid-sterol films. In addition we determined the surface charge density of the liposomes built of these components. The results are helpful in better understanding the role of interfacial viscoelasticity in the quality of liposomal drug delivery forms.


Assuntos
Lipídeos de Membrana/química , Termodinâmica , Anti-Inflamatórios não Esteroides/química , Antioxidantes/química , Sistemas de Liberação de Medicamentos , Eletricidade , Humanos , Lipossomos/química , Fármacos Neuroprotetores/química , Viscosidade , Xantofilas/química
20.
Phytomedicine ; 67: 153160, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31901889

RESUMO

BACKGROUND: Increasing evidence indicated that the cannabinoid receptors were involved in the pathogenesis of organ fibrogenesis. PURPOSE: The purpose of this study was to discover novel cannabinoid receptor 2 (CB2) agonist and assess the potential of CB2 activation in treating systemic sclerosis. METHODS: A gaussia princeps luciferase-based split luciferase complementation assay (SLCA) was developed for detection of the interaction between CB2 and ß-arrestin2. A library of 366 natural products was then screened as potential CB2 agonist using SLCA approach. Several GPCR functional assays, including HTRF-based cAMP assay and calcium mobilization were also utilized to evaluated CB2 activation. Bleomycin-induced experimental systemic sclerosis was used to assess the in vivo anti-fibrotic effects. Dermal thickness and collagen content were evaluated via H&E and sirius red staining. RESULTS: Celastrol was identified as a new agonist of CB2 by using SLCA. Furthermore, celastrol triggers several CB2-mediated downstream signaling pathways, including calcium mobilization, inhibition of cAMP accumulation, and receptor desensitization in a dose-dependent manner, and it has a moderate selectivity on CB1. In addition, celastrol exhibited the anti-inflammatory properties on lipopolysaccharide (LPS) treated murine Raw 264.7 macrophages and primary macrophages. Finally, we found that celastrol exerts anti-fibrotic effects in the bleomycin-induced systemic sclerosis mouse model accompanied by reduced inflammatory conditions. CONCLUSION: Taken together, celastrol is identified a novel selective CB2 agonist using a new developed arrestin-based SLCA, and CB2 activation by celastrol reduces the inflammatory response, and prevents the development of dermal fibrosis in bleomycin-induced systemic sclerosis mouse model.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Receptor CB2 de Canabinoide/agonistas , Escleroderma Sistêmico/tratamento farmacológico , Triterpenos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Arrestina/metabolismo , Bleomicina/toxicidade , Cálcio/metabolismo , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Fibrose , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Células RAW 264.7 , Escleroderma Sistêmico/induzido quimicamente , Escleroderma Sistêmico/metabolismo , Escleroderma Sistêmico/patologia , Triterpenos/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA