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1.
Chem Pharm Bull (Tokyo) ; 70(1): 52-56, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34980734

RESUMO

Lecithin reverse wormlike micelles (LRWs) have been studied recently for dermal application dosage use but the effects of the physicochemical properties of oils on the formation and rheological properties of LRWs have not been investigated. We studied the effect of oil on the formation of LRWs using 5 types of liquid paraffin (LP) with kinematic viscosities ranging from 4.00 to 88.0 mm2/s. Partial phase diagrams of lecithin/water/LP systems indicated that LPs with low molecular weights could form LRWs with only a small amount of water, but LPs with high molecular weights could not form LRWs, regardless of the water concentration. The solubility of lecithin in LPs was higher for low molecular weight LPs, thus possibly affecting the formation of LRWs. The zero-shear viscosity and relaxation time of LRWs initially increased with increasing water concentration, and then decreased. The water concentration providing the maximum value was dependent on the molecular weight of the LP, whereas the maximum amount and length of the LRWs were independent of the water concentration. Our results indicate that the molecular weight of LP affects the ease of formation and the viscoelasticity of LRWs.


Assuntos
Lecitinas/química , Parafina/química , Físico-Química , Micelas , Reologia
2.
Molecules ; 26(11)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071647

RESUMO

BACKGROUND: Filtration of osmotic solution affects selective penetration during osmotic dehydration (OD), and after drying is finished, this can influence the chemical composition of the material, which is also modified by OD. METHODS: Osmotic dehydration was carried out in filtrated and non-filtrated concentrated chokeberry juice with the addition of mint infusion. Then, this underwent convective drying, vacuum-microwave drying and combined convective pre-drying, followed by vacuum-microwave finishing drying. Drying kinetics were presented and mathematical models were selected. The specific energy consumption for each drying method was calculated and the energy efficiency was determined. RESULTS AND DISCUSSION: The study revealed that filtration of osmotic solution did not have significant effect on drying kinetics; however, it affected selective penetration during OD. The highest specific energy consumption was obtained for the samples treated by convective drying (CD) (around 170 kJ·g-1 fresh weight (fw)) and the lowest for the samples treated by vacuum-microwave drying (VMD) (around 30 kJ·g-1 fw), which is due to the differences in the time of drying and when these methods are applied. CONCLUSIONS: Filtration of the osmotic solution can be used to obtain the desired material after drying and the VMD method is the most appropriate considering both phenolic acid content and the energy aspect of drying.


Assuntos
Dessecação/métodos , Malus/efeitos dos fármacos , Mentha/metabolismo , Osmose , Extratos Vegetais/química , Antioxidantes/química , Ácidos Cafeicos/química , Físico-Química/métodos , Ácido Clorogênico/química , Cromatografia Líquida , Cinamatos/química , Cor , Depsídeos/química , Metabolismo Energético , Filtração , Manipulação de Alimentos , Frutas/química , Hidroxibenzoatos/análise , Cinética , Micro-Ondas , Modelos Teóricos , Fenol , Espectrometria de Massas em Tandem , Temperatura , Ácido Rosmarínico
3.
Biomed Pharmacother ; 137: 111367, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33588265

RESUMO

BACKGROUND: Metabolic syndrome (MS) is a major global health concern comprising a cluster of co-occurring conditions that increase the risk of heart disease, stroke and type 2 diabetes. MS is usually diagnosed using a combination of physiochemical indexes (such as BMI, abdominal circumference and blood pressure) but largely ignores clinical symptoms when investigating prevention and treatment of the disease. Exploring predictors of MS using multiple diagnostic indicators may improve early diagnosis and treatment of MS. Traditional Chinese medicine (TCM) attaches importance to the etiology of disease symptoms and indications using four diagnostic methods, which have long been used to treat metabolic disease. Therefore, in this study, we aimed to develop predictive indicators for MS using both physiochemical indexes and TCM methods. METHODS: Clinical information (including both physiochemical and TCM indexes) was obtained from a cohort of 586 individuals across 4 hospitals in China, comprising 136 healthy controls and 450 MS cases. Using this cohort, we compared three classic machine learning methods: decision tree (DT), support vector machine (SVM) and random forest (RF) towards MS diagnosis using physiochemical and TCM indexes, with the best model selected by comparing the accuracy, specificity and sensitivity of the three models. In parallel, the best proportional partition of the training data to the test data was confirmed by observing the changes in evaluation indexes using each model. Next, three subsets containing different categories of variables (including both TCM and physicochemical indexes combined - termed the "fused indexes", only physicochemical indexes, and TCM indexes only) were compared and analyzed using the best performing model and optimum training to test data proportion. Next, the best subset was selected through comprehensive comparative analysis, and then the important prediction variables were selected according to their weight. RESULTS: When comparing the three models, we found that the RF model had the highest average accuracy (average 0.942, 95%CI [0.925, 0.958]) and sensitivity (average 0.993, 95%CI [0.990, 0.996]). Besides, when the training set accounted for 80% of the cohort data, the specificity got the best value and the accuracy and sensitivity were also very high in RF model. In view of the performance of the three different subsets, the prediction accuracy and sensitivity of models analyzing the fused indexes and only physicochemical indexes remained at a high level. Further, the mean value of specificity of the model using fused indexes was 0.916, which was significantly higher than the model with only physicochemical indexes (average 0.822) and the model with only TCM indexes (average 0.403). Based on the RF model and data allocation ratio (8:2), we further extracted the top 20 most significant variables from the fused indexes, which included 14 physicochemical indexes and 6 TCM indexes including wiry pulse, chest tightness, spontaneous perspiration, greasy tongue coating etc. CONCLUSION: Compared with SVM and DT models, the RF model showed the best performance, especially when the ratio of the training set to test set is 8:2. Compared with single predictive indexes, the model constructed by combining physiochemical indexes with TCM indexes (i.e. the fused indexes) exhibited better predictive ability. In addition to common physicochemical indexes, some TCM indexes, such as wiry pulse, chest tightness, spontaneous perspiration, greasy tongue coating, can also improve diagnosis of MS.


Assuntos
Síndrome Metabólica/diagnóstico , Síndrome Metabólica/fisiopatologia , Modelos Estatísticos , Adulto , Idoso , Físico-Química , China , Estudos de Coortes , Árvores de Decisões , Feminino , Humanos , Aprendizado de Máquina , Masculino , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Máquina de Vetores de Suporte
4.
Chem Biodivers ; 17(10): e2000367, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32955163

RESUMO

In the current study, a functional polysaccharide fraction (HFP) was obtained from Hizikia fusiforme by ultrasound-assisted enzymatic extraction, and its structural characterization and hypoglycemic activity and potential molecular mechanism were investigated. The results indicated that HFP with high uronic acid was a heterogeneous polysaccharide composed of six monosaccharides. Congo red test explained that HFP had no triple helix conformation. AFM analysis revealed that HFP was spherical particle with flame-like aggregates and multiple strands closely arranged. Rheological analysis showed that HFP exhibited shear-thinning flow behavior. HFP significantly ameliorated diabetes-related symptoms and serum profiles and increased muscle glycogen storage in rats. HFP administration at 400 mg/kg body weight/day displayed greater advantages than metformin in controlling the levels of fasting blood glucose, triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bile acid (TBA) of diabetic rats. Intervention of HFP up-regulated markedly the expression of AMPK-α, GLUT4, PI3K and Akt in skeletal muscle of diabetic rats at the mRNA and protein levels, revealing hypoglycemic effects of HFP may be related closely to improving insulin resistance and mitochondrial function of skeletal muscle.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Sargassum/química , Animais , Glicemia/efeitos dos fármacos , Físico-Química , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Hipoglicemiantes/química , Resistência à Insulina , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Extratos Vegetais/química , Polissacarídeos/química , Ratos , Ratos Sprague-Dawley
5.
J Sep Sci ; 43(16): 3349-3358, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32506783

RESUMO

The citrus herbs have proved their important medicinal and nutritional values as medicine-food dual-purpose herbs, functional foods, or medical herbs in China. In this study, phytochemicals and antioxidant activity among ten typical citrus herbs (ethanol extracts) were investigated comprehensively. The major ingredients and their contents were analyzed by high-resolution mass spectrometry, and the differences of typical fragment ions between flavanone-7-O-rutinoside(s) and flavanone-7-O-neohesperidoside(s) were discriminated properly in negative electrospray ionization mode. Total polyphenols, total flavonoids, 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), and ferric reducing antioxidant power tests were performed, which indicated their beneficial values and antioxidant effects. The medicine-food dual-purpose herbs including Chenpi, Juluo, Daidaihua, Huajuhong, Xiangyuan, and Foshou exhibited antioxidant capacities significantly by decreasing intracellular reactive oxygen species intensity (P < 0.01), enhancing superoxide dismutase, catalase, and glutathione peroxidase activities (P < 0.01) in H2 O2 -induced RIN-m5F cells. Moreover, the functional foods Zhishi, Zhiqiao, and Qingpi showed moderate antioxidant bioactivity, while the medical herb Juhe showed weak antioxidant bioactivity, which were consistent with the multivariate analysis of their major flavonoids. The study provided a new sight for the chemical differentiation and practical application of citrus herbs as medicine-food dual-purpose herbs, functional foods, or medical herbs.


Assuntos
Antioxidantes/farmacologia , Citrus/química , Medicamentos de Ervas Chinesas/farmacologia , Extratos Vegetais/farmacologia , Animais , Antioxidantes/química , Antioxidantes/metabolismo , Benzotiazóis/antagonistas & inibidores , Compostos de Bifenilo/antagonistas & inibidores , Linhagem Celular , Técnicas de Química Analítica , Físico-Química , China , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/metabolismo , Peróxido de Hidrogênio/antagonistas & inibidores , Metabolômica , Picratos/antagonistas & inibidores , Extratos Vegetais/química , Extratos Vegetais/metabolismo , Ratos , Espectrometria de Massas por Ionização por Electrospray , Ácidos Sulfônicos/antagonistas & inibidores
6.
Phytochemistry ; 171: 112236, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31923723

RESUMO

Glycyrrhiza glabra (licorice) is a medicinal plant with valuable specialised metabolites such as triterpene sweetener glycyrrhizin. Salinity stress is the main environmental stress limiting plant growth and development. The effects of six levels of NaCl (0, 100, 200, 400, 600, and 800 mM) on growth, osmolyte content, oxidative stress markers, antioxidant enzyme activities, K+/Na+ ratio, glycyrrhizin content, and gene expression of glycyrrhizin biosynthesis (bAS, CYP88D6, and CYP72A154) were investigated in licorice rhizomes of two populations. The results showed that the salt stress progressively reduced the growth parameters and increased the proline concentrations in the rhizomes. K+/Na+ ratio showed a significant decrease under salinity as compared to the controls. Salt stress resulted in oxidative stress on the rhizomes, as indicated by increased lipid peroxidation and hydrogen peroxide concentrations and elevated the activities of antioxidant enzymes (i.e., ascorbate peroxidase and superoxide dismutase). The glycyrrhizin content increased only under 100 and 200 mM NaCl treatments. The same trend was observed in the expression of bAS, CYP88D6, and CYP72A154 genes in Fars population. Fars population was found to have more glycyrrhizin content than Khorasan population. But, growth, glycyrrhizin content, and biosynthesis genes of glycyrrhizin showed more reduction in Khorasan population as compared to those of Fars population. The results indicate that the application of 100 mM NaCl up-regulated the expression of key genes involved in the biosynthesis of triterpenoid saponins and directly enhanced the production of glycyrrhizin. Accordingly, G. glabra can be introduced as a halophyte plant.


Assuntos
Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Glycyrrhiza/efeitos dos fármacos , Ácido Glicirrízico/metabolismo , Compostos Fitoquímicos/biossíntese , Cloreto de Sódio/farmacologia , Físico-Química , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica de Plantas/genética , Glycyrrhiza/química , Glycyrrhiza/genética , Ácido Glicirrízico/química , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Compostos Fitoquímicos/química , Salinidade , Cloreto de Sódio/química
7.
Luminescence ; 35(2): 178-186, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31633294

RESUMO

One of the most promising applications of nanomaterials is that of nanobiosensors, using biomolecules such as nucleic acids as receptors. This study aimed to synthesize nickel oxide nanoparticles (NiO NPs) by an environmentally friendly green synthesis, using the extract of the herb Coriandrum sativum (coriander). The synthesized NPs were characterized using UV-Visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, X-ray photon spectroscopy, field emission scanning electron microscopy coupled with energy dispersive spectroscopy, dynamic light scattering, zeta potential and transmission electron microscopy. All results confirmed the synthesis of pure, spherical, positively charged NiO NPs of around 95 nm in diameter with prominent hydroxyl groups attached to the surface. Furthermore, interaction studies of synthesized NiO NPs with calf thymus DNA (CT DNA) were performed using UV-Visible spectroscopy, UV-thermal melting, circular dichroism, and fluorescence spectroscopy. CT DNA served as a substitute for nucleic acid biosensors. All experimental studies indicated that the NiO NPs bound electrostatically with CT DNA. These studies may facilitate exploring the potential of NiO NP-nucleic acid conjugated materials to be used as nanobiosensors for various applications, especially in pharmacological, epidemiological, and environmental diagnostic applications, and in detection.


Assuntos
DNA/química , Química Verde , Nanopartículas/química , Níquel/química , Extratos Vegetais/química , Animais , Técnicas Biossensoriais , Bovinos , Físico-Química , Coriandrum/química
8.
Drug Metab Dispos ; 47(12): 1380-1387, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31578209

RESUMO

We present a model for volume of distribution at steady state (VDss) prediction, via fraction unbound in tissues, from the Øie-equation as an extension of our and other authors' previous work. It is based on easily determined or computed physicochemical descriptors such as logD7.4 and fi (7.4) (cationic fraction ionized at pH 7.4) in addition to fraction unbound in plasma (fup). We had collected, as part of other work, an extensive dataset of VDss and fup values and used the descriptors above, gathered from the literature, for a preliminary assessment of the robustness of the method applied to 191 different compounds belonging to different charge classes and scaffolds. After this step, we addressed the use of easily computed physicochemical descriptors and experimentally derived fup on the same data set and compare the results between the two approaches and against the Øie-Tozer equation using in vivo data. This approach positions itself between fully computational models and scaling methods based on in vivo animal models or in vitro Kp (tissue:plasma) data utilizing model tissues. We consider it a useful and orthogonal complement to the two very diverse approaches mentioned yet requiring minimal in vitro experimental work. It offers a relatively inexpensive, rapid, intuitive, and simple way to predict VDss in humans, at a relatively early stage of the drug discovery. SIGNIFICANCE STATEMENT: This method allows the prediction of volume of distribution at steady state for small molecules in humans without the use of animal PK data because it utilizes only in vitro data. It is therefore amenable to use at early stages, simple, intuitive, animal-sparing, and quite accurate, and it may serve scaling efforts well. Furthermore, utilizing the same dataset, we show that the performance of a model using computed pKa and logD7.4, still using experimental fraction unbound in plasma, compares well with the model using experimentally derived values.


Assuntos
Simulação por Computador , Descoberta de Drogas/métodos , Modelos Biológicos , Preparações Farmacêuticas/sangue , Preparações Farmacêuticas/química , Animais , Físico-Química , Conjuntos de Dados como Assunto , Avaliação Pré-Clínica de Medicamentos , Humanos , Farmacocinética , Ligação Proteica
9.
Biomolecules ; 9(2)2019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30720723

RESUMO

Fruits and vegetables are a good source of potentially biologically active compounds. Their regular consumption in the human diet can help reduce the risk of developing chronic diseases such as cardiovascular diseases and cancer. Plants produce additional chemical substances when subject to abiotic stress or infected by microorganisms. The phytochemical profile of spinach leaves (Spinaciaoleracea L.), which is a vegetable with widely recognized health-promoting activity, has been affected by applying root hypoxic and re-oxygenation stress during plant growth. Leaf juice at different sampling times has been subject to liquid chromatography mass spectrometry (LC-MSn) analysis and tested on the human colorectal adenocarcinoma cell line HT29 by using the Comet assay. The cells were previously treated with H2O2 to simulate the presence of an oxidative stress (as in colon cancer condition) and the leaf juice application resulted in a significant antioxidant and protective in vitro effect. The duration of the hypoxic/re-oxygenation stress imposed on the plant reflects the antioxidant leaf juice content. After hypoxic stress (24 hours) and reoxygenation (2 hours), we show a decrease (50%) of the relative abundance of the principal identified antioxidant molecules but a higher antioxidant activity of the spinach juice on HT29 cells (20%). Data shows a complex relation between plant growing conditions and the modulation of secondary metabolites content in leaf juice that results in different chemo-protective activities in colon cancer cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Sucos de Frutas e Vegetais/análise , Oxigênio/metabolismo , Extratos Vegetais/farmacologia , Spinacia oleracea/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Físico-Química , Cromatografia Líquida , Ensaios de Seleção de Medicamentos Antitumorais , Células HT29 , Humanos , Espectrometria de Massas , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação
10.
Biometals ; 31(6): 1091-1099, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30324285

RESUMO

Iron deficiency is a significant health problem across the world. While many patients benefit from oral iron supplements, some, including those on hemodialysis require intravenous iron therapy to maintain adequate iron levels. Until recently, all iron compounds suitable for parenteral administration were colloidal iron-carbohydrate conjugates that require uptake and processing by macrophages. These compounds are associated with variable risk of anaphylaxis, oxidative stress, and inflammation, depending on their physicochemical characteristics. Ferric pyrophosphate citrate (FPC) is a novel iron compound that was approved for parenteral administration by US Food and Drug Administration in 2015. Here we report the physicochemical characteristics of FPC. FPC is a noncolloidal, highly water soluble, complex iron salt that does not contain a carbohydrate moiety. X-ray absorption spectroscopy data indicate that FPC consists of iron (III) complexed with one pyrophosphate and two citrate molecules in the solid state. This structure is preserved in solution and stable for several months, rendering it suitable for pharmaceutical applications in solid or solution state.


Assuntos
Ácido Cítrico/química , Difosfatos/química , Ferro/química , Físico-Química , Estrutura Molecular
11.
Pak J Pharm Sci ; 31(5): 2005-2009, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30150201

RESUMO

Canola oil has been used in the Pakistan for the treatment of various diseases and skin infections. Oil was extracted with n-hexane from the seeds of canola (Brassica napus L.) and was evaluated for free fatty acid value. Four microorganisms namely; Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas originals, and Klebsiella pneumonia, has known to cause some infections treatable with these oils were investigated. The results showed that all oil shown inhibitory effects against Klebsiella pneumoniae, Staphylococcus epidermidis, and Pseudomonas originals but no inhibitory effects was found against Staphylococcus aureus.


Assuntos
Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Brassica napus , Compostos Fitoquímicos/farmacologia , Óleo de Brassica napus/farmacologia , Sementes , Antibacterianos/química , Antibacterianos/isolamento & purificação , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Físico-Química/métodos , Humanos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Óleo de Brassica napus/química , Óleo de Brassica napus/isolamento & purificação , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia
12.
Georgian Med News ; (270): 115-120, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28972495

RESUMO

Medicinal muds, so called Peloids in the last decade attract attention in many countries as effective means for the treatment- preventive, and perfumery-cosmetic purposes. It has been established that the possibilities of this formation of nature are not limited to the many-year experience of the mankind. In terms of further improvement of the human social sphere, nowadays peloids are referred to as XXI century material. The aim of the research was to study the physical-chemical characteristics, such as: humidity, pH, ash content, bulk (volumetric) density and organoleptic properties of sulphide silt peloids of some Adjara region lakes, as well as to determine the content of mineral and organic compounds (humic and organic acids). The objects of the study were the sulphide silt peloids of some Adjara region lakes: Mtsvane, Gasaliani, Shratiani, Nurigeli, Ardagani and Niphi. The main good quality indicators of the sulphide silt peloids have been determined according to the methods described in the State Pharmacopoeia XI. The mineral and organic compounds in the research objects have been determined using the modern instrumental methods of analysis described in the literature. Based on the performed studies, the main physical-chemical characteristics of sulphide silt peloids of some Adjara region lakes (Mtsvane, Gasaliani, Shratiani, Nurigeli, Ardagani and Niphi) have been studied and their mineral contents (Ca-Na Feldspar, K Feldspar, Ca- Montmorillonite, Hematite, Quartz, Magnetite, Chlorite) determined. By the spectrophotometric and gravimetric methods of analysis there is established, that the sulphide silt peloids of the lakes Ardagani (1,22%), Niphi (1,72%) and Gasaliani (1,33%) are distinguished by relatively higher content of humic acids. By the Gas Chromatography-Mass Spectrometry - method of analysis, in the study objects there is established the content of complex ethers of the following organic acids: Stearic, Palmitic, Caprylic, Myristic, Valeric, Lauric, Oxalic, Phthalic and Fumaric acids.


Assuntos
Ácidos Carboxílicos/análise , Minerais/análise , Peloterapia , Sulfetos/química , Físico-Química , Ésteres/análise , República da Geórgia , Substâncias Húmicas/análise
13.
Comput Biol Chem ; 71: 1-9, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28950235

RESUMO

Due to multifactorial nature of Alzheimer's disease one target-one ligand hypothesis often looks insufficient. BACE-1 and GSK-3ß are well established therapeutic drug targets and interaction between BACE-1 and GSK-3ß pathways has also been established. Thus, designing of dual inhibitor for these two targets seems rational and may provide effective therapeutic strategies against AD. Recent studies revealed that only two scaffolds i.e. triazinone and curcumin act as a dual inhibitor against BACE-1 and GSK-3ß. Thus, this discovery set the path to screen new chemical entities from a vast chemical space (∼1060 compounds) that inhibit both the targets. However, small part of the large chemical space will only show biological activity for specific targets. Virtual screening of large libraries is impractical and computational expensive especially in case of dual inhibitor design. In the case of dual or multi target inhibitor designing, we screened the database for each target that further increases time and resources. In this study we have done physicochemical descriptor based profiling to know the biological relevant chemical space for BACE-1 and GSK-3ß inhibitors and proposed the suitable range of important physicochemical properties, occurrence of functional groups. We generated scaffolds tree of known inhibitors of BACE-1 and GSK-3ß suggesting the common structure/fragment that can be used to design dual inhibitors. This approach can filter the potential dual inhibitor candidates of BACE-1 and GSK-3ß from non inhibitors.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Físico-Química , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/química , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
14.
Comb Chem High Throughput Screen ; 20(9): 760-772, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28641513

RESUMO

BACKGROUND: Anthocephalus cadamba is used in traditional and folklore medicinal system. OBJECTIVES: In order to validate its traditional medicinal claim, the present study was designed to assess antioxidant, antigenotoxic and cytotoxic activity of fractions from Anthocephalus cadamba bark and to identify their active phytoconstituents. METHODS: The four fractions viz. hexane (HACB), chloroform (CACB), ethylacetate (EACB) and nbutanol (NACB) were fractionated from the crude methanol extract from bark of A. cadamba. All fractions were evaluated for antiradical efficacy using various in vitro antioxidant assays and for antigenotoxicity by SOS chromotest using E. coli PQ37 tester strain. Cytotoxic potential was checked using MTT assay. RESULTS: Among the four fractions, EACB and NACB exhibited promising radical quenching potential in DPPH, ABTS, superoxide anion radical scavenging and pBR322 plasmid DNA nicking assays. All the fractions were evaluated for genotoxic and antigenotoxic activity in SOS chromotest using E. coli PQ37 tester strain. Results revealed that fractions were non-genotoxic and have potential to suppress the genotoxicity induced by 4NQO (4-nitroquinoline-1-oxide) and AFB1 (aflatoxin B1). NACB was found to inhibit the growth of colon (COLO 205) cancer cells with GI50 of 54.36 µg/ml. To identify bioactive principles in the active fractions, NACB and EACB were subjected to UPLC-electrospray-ionization-quadrupole time-of-flight mass spectrometry which revealed the presence of 3ß-isodihyrocadambine-oxide, cadambine, phelasin A/B, 3ß- dihydrocadambine and 3'-O-caffeoylsweroside like compounds. CONCLUSIONS: Overall results revealed that A. cadamba is a rich source of antioxidant, antigenotoxic and cytotoxic constituents which may find their significance in various food and pharmaceutical products.


Assuntos
Antimutagênicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Casca de Planta/química , Extratos Vegetais/farmacologia , Rubiaceae/química , Antimutagênicos/química , Antimutagênicos/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Benzotiazóis/antagonistas & inibidores , Compostos de Bifenilo/antagonistas & inibidores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Físico-Química , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Escherichia coli/genética , Humanos , Picratos/antagonistas & inibidores , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Resposta SOS em Genética , Espectrometria de Massas por Ionização por Electrospray , Relação Estrutura-Atividade , Ácidos Sulfônicos/antagonistas & inibidores , Superóxidos/antagonistas & inibidores
15.
Bioorg Med Chem Lett ; 26(15): 3457-63, 2016 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-27363938

RESUMO

Rohitukine is a chromone alkaloid isolated from an Indian medicinal plant Dysoxylum binectariferum. This natural product has led to the discovery of two clinical candidates (flavopiridol and P276-00) for the treatment of cancer. Herein, for the first time we report an efficient protocol for isolation and purification of this precious natural product in a bulk-quantity from leaves (a renewable source) of D. binectariferum (>98% purity) without use of chromatography or any acid-base treatment. Despite of the fact that this scaffold has reached up to clinical stage, particularly for leukemia; however the antileukemic activity of a parent natural product has never been investigated. Furthermore, rohitukine has never been studied for cyclin-dependent kinase (Cdk) inhibition, kinase profiling and for its experimental physicochemical properties. Thus, herein, we report in vitro cytotoxicity of rohitukine in a panel of 20 cancer cell lines (including leukemia, pancreatic, prostate, breast and CNS) and 2 normal cell lines; kinase profiling, Cdk2/9 inhibition, and physicochemical properties (solubility and stability in biological medias, pKa, LogP, LogD). In cytotoxicity screening, rohitukine displayed promising activity in HL-60 and Molt-4 (leukemia) cell lines with GI50 of 10 and 12µM, respectively. It showed inhibition of Cdk2/A and Cdk9/T1 with IC50 values of 7.3 and 0.3µM, respectively. The key interactions of rohitukine with Cdk9 was also studied by molecular modeling. Rohitukine was found to be highly water soluble (Swater=10.3mg/mL) and its LogP value was -0.55. The ionization constant of rohitukine was found to be 5.83. Rohitukine was stable in various biological media's including rat plasma. The data presented herein will help in designing better anticancer agents in future.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Cromonas/farmacologia , Quinases Ciclina-Dependentes/antagonistas & inibidores , Meliaceae/química , Piperidinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Físico-Química , Cromonas/química , Cromonas/isolamento & purificação , Quinases Ciclina-Dependentes/metabolismo , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos Moleculares , Estrutura Molecular , Piperidinas/química , Piperidinas/isolamento & purificação , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/isolamento & purificação , Relação Estrutura-Atividade
16.
Osteoporos Int ; 27(2): 757-67, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26223190

RESUMO

UNLABELLED: The ultimate goal of osteoporosis treatment is prevention of fragile fracture. Local treatment targeting specific bone may decrease the incidence of osteoporotic fractures. We developed an injectable, thermosensitive simvastatin/poloxamer 407 hydrogel; a single CT-guided percutaneous intraosseous injection augmented vertebrae in ovariectomized minipigs. INTRODUCTION: The greatest hazard associated with osteoporosis is local fragility fractures. An adjunct, local treatment might be helpful to decrease the incidence of osteoporotic fracture. Studies have found that simvastatin stimulates bone formation, but the skeletal bioavailability of orally administered is low. Directly delivering simvastatin to the specific bone that is prone to fractures may reinforce the target bone and reduce the incidence of fragility fractures. METHODS: We developed an injectable, thermosensitive simvastatin/poloxamer 407 hydrogel, conducted scanning electron microscopy, rheological, and drug release analyses to evaluate the delivery system; injected it into the lumbar vertebrae of ovariectomized minipigs via minimally invasive CT-guided percutaneous vertebral injection. Three months later, BMD, microstructures, mineral apposition rates, and strength were determined by DXA, micro-CT, histology, and biomechanical test; expression of VEGF, BMP2, and osteocalcin were analyzed by immunohistochemistry and Western blots. RESULTS: Poloxamer 407 is an effective controlled delivery system for intraosseous-injected simvastatin. A single injection of the simvastatin/poloxamer 407 hydrogel significantly increased BMD, bone microstructure, and strength; the bone volume fraction and trabecular thickness increased nearly 150 %, bone strength almost doubled compared with controls (all P < 0.01); and induced higher expression of VEGF, BMP2, and osteocalcin. CONCLUSIONS: CT-guided percutaneous vertebral injection of a single simvastatin/poloxamer 407 thermosensitive hydrogel promotes bone formation in ovariectomized minipigs. The underlying mechanism appears to involve the higher expression of VEGF and BMP-2.


Assuntos
Vértebras Lombares/fisiopatologia , Osteogênese/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Poloxâmero/administração & dosagem , Sinvastatina/administração & dosagem , Absorciometria de Fóton/métodos , Animais , Densidade Óssea/efeitos dos fármacos , Proteína Morfogenética Óssea 2/metabolismo , Físico-Química , Combinação de Medicamentos , Sistemas de Liberação de Medicamentos , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Hidrogel de Polietilenoglicol-Dimetacrilato , Injeções Espinhais , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/metabolismo , Microscopia Eletrônica de Varredura , Osteoporose/diagnóstico por imagem , Osteoporose/fisiopatologia , Ovariectomia , Poloxâmero/química , Poloxâmero/farmacologia , Poloxâmero/uso terapêutico , Radiografia Intervencionista , Reologia , Sinvastatina/farmacologia , Sinvastatina/uso terapêutico , Suínos , Porco Miniatura , Tomografia Computadorizada por Raios X , Fator A de Crescimento do Endotélio Vascular/metabolismo
17.
J Colloid Interface Sci ; 457: 152-61, 2015 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-26164247

RESUMO

The phase behavior of the four-components Peceol®/lecithin/ethanol/water system has been studied in a part of the phase diagram poor in water and varying the lecithin/Peceol® ratio. Using several complementary techniques such as Karl Fischer titration, rheology, polarized microscopy and SAXS measurements several nanostructures of the complex systems were identified. W/O microemulsion (L2) as well as an inverted hexagonal (H2) liquid-crystal phase were studied. The analysis of the different phase transitions allows us to understand the effect of lecithin on the water solubilization efficiency of this clear gel and to show its pharmaceutical interest among lecithin organogels.


Assuntos
Etanol/química , Géis/química , Lecitinas/química , Ácidos Oleicos/química , Água/química , Físico-Química , Cristais Líquidos/química , Nanoestruturas/química
18.
J Hazard Mater ; 286: 152-63, 2015 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-25576783

RESUMO

In this work, the removal of uranium and thorium ions from aqueous solutions was studied by solid-liquid extraction using an advantageous extractant-impregnated resin (EIR) prepared by loading carminic acid (CA) onto Amberlite XAD-16 resin beads. Batch sorption experiments using CA/XAD-16 beads for the removal of U(VI) and Th(IV) ions were carried out as a function of several parameters, like equilibration time, metal ion concentration, etc. The equilibrium data obtained from the sorption experiments were adjusted to the Langmuir isotherm model and the calculated maximum sorption capacities in terms of monolayer sorption were in agreement with those obtained from the experiments. The experimental data on the sorption behavior of both metal ions onto the EIR beads fitted well in both Bangham and intra-particle diffusion kinetic models, indicating that the intra-particle diffusion is the rate-controlling step. The thermodynamic studies at different temperatures revealed the feasibility and the spontaneous nature of the sorption process for both uranium and thorium ions.


Assuntos
Carmim/química , Tório/química , Urânio/química , Poluentes Químicos da Água/análise , Poluentes da Água/análise , Purificação da Água/métodos , Adsorção , Físico-Química , Difusão , Concentração de Íons de Hidrogênio , Íons , Cinética , Metais/química , Polímeros/química , Termodinâmica
19.
Carbohydr Polym ; 115: 112-21, 2015 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-25439875

RESUMO

Water-, chelator-, and alkali-soluble pectins were isolated from raw and heat-processed Jalapeño peppers (green and red) and their physiochemical and rheological properties were determined. The yield, tristimulus color, degree of methyl esterification, monosaccharide composition, molecular weights distribution, and protein content depended on ripening and heat processing. The viscosity properties of pectins were independent of ripening. The water-soluble pectin was the most abundant pectin. Pectins from grilled peppers showed the lowest L* values. The alkali-soluble pectin showed the highest protein content. The content of xylose, rhamnose, and mannose in pectins was highly altered by tested factors. The degree of methyl esterification of pectins ranged from 26.8 to 91.6%. The peak Mw of the main fraction of tested pectins was sequentially reduced by ripening and heat processing. Pectins from raw peppers showed the best viscosity properties.


Assuntos
Temperatura Alta , Pectinas/química , Piperaceae/química , Reologia , Físico-Química , Pectinas/isolamento & purificação , Solubilidade , Viscosidade
20.
Ultrasonics ; 54(8): 2134-40, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25017363

RESUMO

The purpose of the paper is to address, using ultrasonic methods, the impact of temperature and pressure on the physicochemical properties of liquids on the example of diacylglycerol (DAG) oil. The paper presents measurements of sound velocity, density and volume of DAG oil sample in the pressure range from atmospheric pressure up to 0.6GPa and at temperatures ranging from 20 to 50°C. Sound speed measurements were performed in an ultrasonic setup with a DAG oil sample located in the high-pressure chamber. An ultrasonic method that uses cross-correlation method to determine the time-of-flight of the ultrasonic pulses through the liquid was employed to measure the sound velocity in DAG oil. This method is fast and reliable tool for measuring sound velocity. The DAG oil density at high pressure was determined from the monitoring of sample volume change. The adiabatic compressibility and isothermal compressibility have been calculated on the basis of experimental data. Discontinuities in isotherms of the sound speed versus pressure point to the existence of phase transitions in DAG oil. The ultrasonic method presented in this study can be applied to investigate the physicochemical parameters of other liquids not only edible oils.


Assuntos
Diglicerídeos/química , Óleos de Plantas/química , Som , Ultrassom , Físico-Química , Pressão , Temperatura
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