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2.
Biomed Pharmacother ; 83: 1265-1277, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27567586

RESUMEN

Tinospora cordifolia (Guduchi Sawras) though has been clearly demonstrated in literature for its hypolipidemic and anti-alcoholism properties but its anti-hyperlipidemia mechanistic approach is still missing. Moreover, its direct implication with alcohol induced hyperlipidemia has also not been reported till date. In order to explore the answers of these questions, phytochemicals of Tinospora cordifolia water extract "Guduchi Sawras" (GS) was analyzed using HPLC-Q-TOF-MS. On the basis of relative peak volumes 110 compounds were selected and identified in GS. Besides that, protein targets of most abundant compounds present in GS were fetched from ChEMBL and protein interaction network (PIN) was constructed. GO enrichment analysis showed that GS targets various pathways including dopamine metabolism, cAMP-dependent signaling pathway, and glycolytic process. Biological processes obtained via PIN were correlated with hyperlipidemia markers and dopamine metabolism in moderate alcohol consumers (n=25) and healthy volunteers (n=27) of age 41±3.8years. Metabolic analysis demonstrated the increased serotonin (1.9-fold) and decreased dopamine (-2.3-fold) levels in alcoholics. Further data analysis revealed a significant increase in urinary BCAAs (>2.0-fold), pantothenic acid (1.8-fold), carnitines (>2-fold) levels, and decrease in PPARα activation markers levels i.e. nicotinamide-1-oxide (-1.7-fold), and N-methylnicotinamide (-1.6-fold) in alcoholics. Biochemical analysis showed the increased AST/ALT ratio (1.91), along with triglycerides (20%), and MDA (34%) and GSH (56%) levels in alcoholics. GS treatment significantly reverted the most of the discussed metabolites levels (p<0.05) and enzymes activities (p<0.05) in alcoholics. The data depict that moderate chronic alcohol consumption lead to hyperlipidemia and oxidative burden; whereas GS treatment ameliorates hyperlipidemia by decreasing oxidative stress, activating PPARα, CREB and SREBP-1 through stimulation of dopamine D1 receptors mediated signalling molecules i.e. cAMP and protein kinase A.


Asunto(s)
Alcoholismo/metabolismo , Antioxidantes/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Extractos Vegetales/farmacología , Receptores de Dopamina D1/metabolismo , Tinospora , Adulto , Alcohólicos , Alcoholismo/tratamiento farmacológico , Antioxidantes/aislamiento & purificación , Antioxidantes/uso terapéutico , Estudios de Cohortes , Dopamina/metabolismo , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/metabolismo , Humanos , Metabolismo de los Lípidos/fisiología , Masculino , Medicina Ayurvédica , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/uso terapéutico , Receptores de Dopamina D1/agonistas , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/fisiología , Resultado del Tratamiento
3.
Bioprocess Biosyst Eng ; 36(11): 1591-9, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23494399

RESUMEN

A method is described for construction of an improved amperometric acrylamide biosensor based on covalent immobilization of hemoglobin (Hb) onto nanocomposite of carboxylated multi-walled carbon nanotubes (cMWCNT) and iron oxide nanoparticles (Fe3O4NPs) electrodeposited onto Au electrode through chitosan (CHIT) film. The Hb/cMWCNT-Fe3O4NP/CHIT/Au electrode was characterized by scanning electron microscopy, Fourier transform infra-red spectroscopy, electrochemical impedance spectroscopy, and differential pulse voltammetry at different stages of its construction. The biosensor was based on interaction between acrylamide and Hb, which led to decrease in the electroactivity of Hb, i.e., current generated during its reversible conversion [Fe(II)/Fe(III)]. The biosensor showed optimum response within 8 s at pH 5.0 and 30 °C. The linear working range for acrylamide was 3-90 nM, with a detection limit of 0.02 nM and sensitivity of 36.9 µA/nM/cm(2). The biosensor was evaluated and employed for determination of acrylamide in potato crisps.


Asunto(s)
Acrilamidas/análisis , Técnicas Biosensibles , Quitosano/química , Técnicas Electroquímicas/instrumentación , Compuestos Férricos/química , Hemoglobinas/química , Nanopartículas del Metal , Nanotubos de Carbono , Impedancia Eléctrica , Microscopía Electrónica de Rastreo , Reproducibilidad de los Resultados , Solanum tuberosum/química , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier
4.
Eur J Med Chem ; 45(5): 1772-6, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20149499

RESUMEN

A rapid preparation of compounds (1-24), with the objective of discovering novel and potent anti-inflammatory agent. All the compounds exhibited anti-inflammatory and analgesic activities at the dose 50 mg/kg p.o. The compound 1-(2',4'-Chloroacridine-9'-yl)-3-(5'-pyridine-4-yl)-(1,3,4-oxadiazol-2-yl-thiomethyl)-pyrazole-5-one 24 showed better anti-inflammatory and analgesic activities at the three graded dose of 25, 50 and 100 mg/kg p.o.


Asunto(s)
Analgésicos/uso terapéutico , Antiinflamatorios no Esteroideos/farmacología , Pirazoles/farmacología , Animales , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/química , Evaluación Preclínica de Medicamentos , Estructura Molecular , Pirazoles/síntesis química , Pirazoles/química , Ratas , Estereoisomerismo
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