RESUMEN

Deltamethrin (DLM) is a well-known pyrethroid insecticide which is widely used in the agriculture and home pest control due to restriction on the sale of organophosphate. DLM induced apoptosis is well known but its mechanism is still unclear. This study has been designed to find out its mechanism of apoptosis with the help of computational methods along with in vivo methods. The QikProp and ProTox results have shown that DLM has good oral absorption. The docking results reveal that DLM has a strong binding affinity toward the CD4, CD8, CD28 and CD45 receptors. Further, to understand the toxicity of DLM on lymphoid cells, a single dose of DLM (5 mg/kg, oral for seven days) has been administered to male Balb/c mice and cytotoxicity (MTT assay), oxidative stress indicators (glutathione, reactive oxygen species) and apoptotic markers (caspase-3 activity, DNA fragmentation) have been assessed in thymic and splenic single cell suspensions. Lowering of body weight, cellularity and loss in cell viability have been observed in DLM treated mice. The significant increase in ROS and GSH depletion in spleen and thymus, indicate the possible involvement of oxidative stress. The spleen cells appear more susceptible to the adverse effects of DLM than thymus cells. Further, for the amelioration of its effect, two structurally different bioactive herbal extracts, piperine and curcumin have been evaluated and have shown the cytoprotective effect by inhibiting the apoptogenic signaling pathways induced by DLM.

Asunto(s)

Alcaloides/farmacología , Antioxidantes/farmacología , Benzodioxoles/farmacología , Curcumina/farmacología , Insecticidas/toxicidad , Nitrilos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Piperidinas/farmacología , Alcamidas Poliinsaturadas/farmacología , Piretrinas/toxicidad , Bazo/efectos de los fármacos , Timo/efectos de los fármacos , Alcaloides/química , Animales , Antioxidantes/química , Apoptosis/efectos de los fármacos , Benzodioxoles/química , Caspasa 3/metabolismo , Supervivencia Celular/efectos de los fármacos , Curcumina/química , Citoprotección , Glutatión/metabolismo , Insecticidas/química , Insecticidas/farmacocinética , Masculino , Ratones Endogámicos BALB C , Simulación del Acoplamiento Molecular , Nitrilos/química , Nitrilos/farmacocinética , Piperidinas/química , Alcamidas Poliinsaturadas/química , Unión Proteica , Conformación Proteica , Piretrinas/química , Piretrinas/farmacocinética , Especies Reactivas de Oxígeno/metabolismo , Receptores Inmunológicos/química , Receptores Inmunológicos/metabolismo , Bazo/metabolismo , Bazo/patología , Relación Estructura-Actividad , Timo/metabolismo , Timo/patología , Factores de Tiempo

RESUMEN

Curcumin, a main component of Curcuma Longa Linn, is a plant polyphenol used as an immune-enhancer in the Indian system of traditional medicine. However, its underlying mechanism of immune-protection remains unknown. The present study is designed to delineate the role of curcumin in deltamethrin (DLM)-induced thymocyte apoptosis and altered immune functions. In silico studies revealed that curcumin has a strong binding affinity toward CD4 and CD8 receptors. DLM (25 µM) induces thymocytes apoptosis through oxidative stress and caspase-dependent pathways. Various concentrations of curcumin (1, 10 and 50 µg/ml), when added along with DLM, caused a concentration- and time-related amelioration in apoptogenic signaling pathways induced by DLM. Inhibition of DLM-induced reactive oxygen species production, replenishment of glutathione and suppression of caspase activities by curcumin may thus be responsible for the suppression of downstream cascade of events, i.e. apoptosis, phenotypic changes and altered cytokine release. Thus, this study clearly demonstrates that the mechanism of immunoprotection of curcumin in DLM-induced thymic apoptosis includes inhibition of oxidative stress and caspase-dependent pathways underlying apoptosis.

Asunto(s)

Apoptosis/inmunología , Curcumina/farmacología , Inmunidad Celular/inmunología , Inmunomodulación/inmunología , Nitrilos/toxicidad , Piretrinas/toxicidad , Timo/inmunología , Animales , Apoptosis/efectos de los fármacos , Antígenos CD4/química , Antígenos CD4/inmunología , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/inmunología , Células Cultivadas , Simulación por Computador , Curcumina/química , Relación Dosis-Respuesta a Droga , Inmunidad Celular/efectos de los fármacos , Inmunomodulación/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/inmunología , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Timo/citología , Timo/efectos de los fármacos

RESUMEN

Cancer is the one of the leading causes of death, whose incidences is increasing day by day. Various types of anticancer agents are used for its treatment, but unfortunately none of them is able to treat the cancer. Thus, the exploration of novel mechanistic pathways of existing molecules may help to develop more effective anticancer agents. Deltamethrin, at low concentration, is a safe pyrethroid insecticide that is widely used in the agriculture and home pest control. Recent in vitro and in vivo studies have shown that the deltamethrin have the potential to induce apoptogenic signaling pathways which plays an important role in the mechanism of anticancer action. Thus, deltamethrin thereof could have the potential to develop as an anticancer agent. Further both in vitro and in vivo evaluation of the therapeutic and toxic effects of this compound is needed for starting of clinical trial.

Asunto(s)

Antineoplásicos/administración & dosificación , Insecticidas/administración & dosificación , Modelos Biológicos , Neoplasias/tratamiento farmacológico , Neoplasias/fisiopatología , Nitrilos/administración & dosificación , Piretrinas/administración & dosificación , Animales , Antineoplásicos/química , Señalización del Calcio/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Medicina Basada en la Evidencia , Humanos , Insecticidas/química , Neoplasias/patología , Nitrilos/química , Piretrinas/química

RESUMEN

The present study was designed to estimate the detailed antidiabetic activity of Pterospermum acerifolium (L.) Willd flowers. In vitro alpha amylase inhibition study was carried out on 50% ethanol extract of flowers (PAFEE) and its various fractions. The active ethyl acetate fraction (PAFEF) was subfractionated into three subfractions (PAFE1, PAFE2, and PAFE3) and subjected to acute toxicity studies followed by antidiabetic screening in vivo by streptozotocin-nicotinamide induced type II diabetes. Diabetic animals treated with PAFE2 (30 mg/kg) reduced the levels of fasting blood glucose, significantly (P<0.001) compared to that of diabetic control animals. Histological studies on drug treated groups did not show remarkable positive changes in ß-cells. PAFE2 showed 32.6±1.93% glucose uptake over control and, in the presence of PI3K inhibitor wortmannin, declined to 13.7±2.51%. HPLC analysis of PAFE2 reveals the presence of quercetin and apigenin as major constituents and both are inhibiting the glycogen phosphorylase enzyme in molecular modelling studies. The study evidenced strongly that the probable glucose lowering mechanism of action of active subfraction PAFE2 is by increasing the glucose uptake in peripheral tissues and by inhibition of gluconeogenesis.

Asunto(s)

Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Células Musculares/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Animales , Apigenina/administración & dosificación , Apigenina/aislamiento & purificación , Línea Celular , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Flores/química , Glucosa/metabolismo , Humanos , Malvaceae/química , Células Musculares/metabolismo , Extractos Vegetales/química , Quercetina/administración & dosificación , Quercetina/aislamiento & purificación , Ratas

RESUMEN

Anthocyanin extracts (AEs) from Ocimum tenuiflorum (leaf), Hibiscus rosa-sinensis (petal) and Hibiscus sabdariffa (calyx) were investigated and compared for in vitro antioxidant activity and DNA damage protective property. Total phenolic content (TPC) and total anthocyanin content (TAC) of the AEs were determined and the major anthocyanins were characterised. In vitro antioxidant activities were assessed by ferric-reducing antioxidant power (FRAP) assay, 2,2-diphenyl-1-picryl hydrazyl (DPPH) radical-scavenging activity, 2-deoxy-D-ribose degradation assay and lipid peroxidation assay. The protective property of the AEs was also examined against oxidative DNA damage by H2O2 and UV using pUC19 plasmid. All the AEs particularly those from O. tenuiflorum demonstrated efficient antioxidant activity and protected DNA from damage. Strong correlation between antioxidant capacity and TPC and TAC was observed. Significant correlation between antioxidant capacity and TPC and TAC ascertained that phenolics and anthocyanins were the major contributors of antioxidant activity.

Asunto(s)

Antocianinas/aislamiento & purificación , Antocianinas/farmacología , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Daño del ADN/efectos de los fármacos , Hibiscus/química , Ocimum/química , Antocianinas/análisis , Antocianinas/química , Antioxidantes/química , Compuestos de Bifenilo/farmacología , Peróxido de Hidrógeno/farmacología , Peroxidación de Lípido , Fenoles/análisis , Picratos/farmacología , Hojas de la Planta/química , Rayos Ultravioleta/efectos adversos

RESUMEN

CONTEXT: Pterospermum acerifolium (L.) Willd (Sterculiaceae) has been traditionally used in the treatment of diabetes mellitus but no scientific data has been published supporting the claimed ethnomedical use. OBJECTIVE: The present study was designed to estimate the in silico, in vitro α-amylase inhibition potential and anti-diabetic activity of Pterospermum acerifolium bark. MATERIALS AND METHODS: In silico studies were performed between human pancreatic α-amylase (HPA) and ß-sitosterol by using autodock 4.2 software. In vitro α-amylase inhibition study was carried out with 50% ethanol extract of the bark (PABEE) and its various fractions. The active ethyl acetate fraction (PABEF) was sub-fractionated into three fractions (PABE1, PABE2 and PABE3). Two doses (15 and 30 mg/kg) based on acute toxicity studies, of the above fractions were subjected to antidiabetic screening in vivo by STZ-nicotinamide induced type II diabetic rats. RESULTS: In silico studies showed the potent inhibition of ß-sitosterol on human pancreatic amylase (HPA) with an estimated inhibition constant (Ki) of 269.35 nmol and two hydrogen bond interactions. PABEF showed marked α-amylase inhibition (69.94%) compared to other fractions. Diabetic rats treated with PABE3 (30 mg/kg) reduced the levels of fasting blood glucose, HbA1c, ALT, AST, ALP, triglycerides, total cholesterol, TBARS significantly (p < 0.01) and increased the levels of HDL-C, catalase, GSH, SOD significantly (p < 0.01) as compared to that of diabetic control animals. Histological studies on PABE3 treated group showed remarkable positive changes in ß-cells. CONCLUSION: The present study confirmed the antihyperglycemic activity along with its status on hepatic biomarkers, antihyperlipidemic and antioxidant properties of Pterospermum acerifolium bark.

Asunto(s)

Hipoglucemiantes/farmacología , Malvaceae/química , alfa-Amilasas Pancreáticas/antagonistas & inhibidores , Extractos Vegetales/farmacología , Animales , Simulación por Computador , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/fisiopatología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/fisiopatología , Relación Dosis-Respuesta a Droga , Humanos , Enlace de Hidrógeno , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/aislamiento & purificación , Masculino , Niacinamida/toxicidad , Corteza de la Planta , Extractos Vegetales/administración & dosificación , Extractos Vegetales/toxicidad , Ratas , Ratas Wistar , Sitoesteroles/metabolismo , Sitoesteroles/farmacología , Programas Informáticos , Estreptozocina/toxicidad , Pruebas de Toxicidad Aguda

RESUMEN

MAO-B and AChE are the two validated targets for Alzheimer's disease. In pursuit of a single molecule hitting both the targets, we explored a set of previously reported extremely potent MAO-B selective inhibitors, for their additional AChE inhibitory activity. We performed molecular docking studies that formed the basis for in vitro enzyme assay, and provided necessary insights into their binding mode. Most of the compounds were found active at nano molar range, and are consistent with the docking results. The identified dual acting lead molecules may provide the basis for further exploring these chemical moieties.

Asunto(s)

Acetilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/síntesis química , Inhibidores de la Colinesterasa/farmacología , Monoaminooxidasa/metabolismo , Pirazoles/síntesis química , Sitios de Unión , Inhibidores de la Colinesterasa/química , Activación Enzimática/efectos de los fármacos , Humanos , Modelos Moleculares , Estructura Molecular , Pirazoles/química , Pirazoles/farmacología

RESUMEN

Monoamine oxidase (MAO) B is a validated target for many neurodegenerative diseases. Recently we have reported a few pyrazolines as reversible and selective MAO-B inhibitors. Amongst them, we have selected the most potent analog, NP-9 (Ki=0.31 nM; selectivity index, MAO-B/A more than 100) for the current preclinical study. It selectively inhibited MAO-B activity in liver and brain. Maximum inhibition was observed at 7 mg/kg, i.p., dose, which was reversed after 8h. We did not observe any alteration in amines level on its acute administration, whereas, on its chronic administration we observed significant increase in striatal dopamine level. Other noteworthy observations were (a) it markedly potentiated the 2-phenylethylamine induced stereotype behavior, (b) it partially reversed the reserpine induced oral dyskinesia, (c) it protected the reserpine induced glutathione oxidation (in cerebrum) and (d) no hypertensive crisis was observed on tyramine co-treatment. The study provides a preclinical basis to NP-9 for MAO-B inhibition.

Asunto(s)

Aminas/metabolismo , Encéfalo/efectos de los fármacos , Dopamina/fisiología , Inhibidores de la Monoaminooxidasa/farmacología , Pirazolonas/farmacología , Conducta Estereotipada/efectos de los fármacos , Animales , Conducta Animal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Glutatión/metabolismo , Masculino , Ratones , Monoaminooxidasa/metabolismo , Fenetilaminas/farmacología , Reserpina/farmacología , Selegilina/farmacología

RESUMEN

Objective: Barleria lupulina Lindl (Acanthaceae) (B. lupulina) has been traditionally used in the treatment of rheumatoid arthritis but, no scientific data has been published supporting the claimed ethnomedical use. This study was designed to investigate the anti-arthritic potential of B. lupulina leaves and its role in immunomodulation. Methods: Methanol extract of B. lupulina (MEBL) leaves (300 and 600 mg/kg BW) was tested for its antiarthritic activity by various models namely, formalin-induced arthritis, adjuvant induced arthritis, collagen type II-induced arthritis and monosodium iodoacetate induced osteoarthritis. Immunomodulatory activity of the same was tested by measuring WBC Count, Spleen Weight, Spleen WBC Count and Delayed Type Hypersensitivity (DTH) Reaction.Results:MEBL extracts 300 mg/kg and 600 mg/ kg showed statistically significant inhibition (P<0.05 and P<0.001) of the edema formation and Myeloperoxidase (MPO) during experimental period and activities of antioxidants were restored significantly. MEBL extracts 300 mg/kg and 600 mg/kg significantly increased the Hemoglobin (Hb) level, serum albumin, total protein, calcium and phosphorus levels and reverted back the levels of WBC count and Erythrocyte Sedimentation Rate (ESR) (P<0.05 and P<0.01). Histopathological studies of ankle joints also supported this finding. Immunomodulatory study revealed an increase in the blood leukocytes count, weight of spleen, spleenic leukocytes count and increase in paw volume on delayed type hypersensitivity footpad thickness suggesting an uplift of immune status. Conclusions: The present study concluded that, MEBL holds antiarthritic and Immunomodulatory activity. Although subsequent study is required to evaluate the active constituents responsible for the activity.

RESUMEN

Glutamate transport represents a key mechanism for maintaining low level of glutamate in the extracellular milieu to restrict the excitotoxic action of glutamate released during ischemia/reperfusion (I/R) injury. Recently, it has been reported that glutamate transporter-1 (GLT-1) is a novel target for peroxisome proliferator-activated receptor-γ (PPARγ) agonist, which shows neuroprotection following oxygen glucose deprivation (OGD) in neuronal-astrocytic cocultures. Hence, the present study was undertaken to investigate the role of rosiglitazone in neuroprotection mediated by GLT-1 following focal cerebral I/R injury in rat. We found that rosiglitazone (2 mg/kg i.p) administered pre- or post-I/R injury significantly improved behavioral outcome and decreased cerebral infarct volume. However, no significant changes were observed in GLT-1 mRNA and protein expression in rosiglitazone-treated rats following 1 hr of ischemia/24 hr of reperfusion (1/24 hr I/R) injury. Interestingly, bioinformatics analysis also does not reveal any PPAR response element on the GLT-1/EAAT2 promoter region. Further rosiglitazone neither increased [(3) H]glutamate uptake in glia-enriched preparations nor caused any change in glutamine synthetase activity. On the other hand, there was a significant (P < 0.05) downregulation in tumor necrosis factor-α and interleukin-1ß gene expression, which were more pronounced in the posttreatment group. The posttreatment with rosiglitazone also significantly reduced the increase in prostaglandin E2 level in the ischemic brain. Therefore, the present findings suggest that the neuroprotective effect of rosiglitazone does not seem to be mediated by modulation of GLT-1 protein expression/activity in a focal cerebral ischemia model. However, the results do provide increasing evidence that the neuroprotective effect may be mediated by its antiinflammatory action.

Asunto(s)

Encéfalo/efectos de los fármacos , Transportador 2 de Aminoácidos Excitadores/metabolismo , Fibrinolíticos/uso terapéutico , Ataque Isquémico Transitorio/tratamiento farmacológico , Tiazolidinedionas/uso terapéutico , Animales , Encéfalo/metabolismo , Glutamato-Amoníaco Ligasa/metabolismo , Interleucina-1beta/metabolismo , Ataque Isquémico Transitorio/metabolismo , Ataque Isquémico Transitorio/fisiopatología , Masculino , Actividad Motora/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fármacos Neuroprotectores/farmacología , PPAR gamma/metabolismo , Ratas , Ratas Sprague-Dawley , Rosiglitazona , Factor de Necrosis Tumoral alfa/metabolismo

RESUMEN

INTRODUCTION: Boerhaavia diffusa Linn. (Nyctaginaceae) is widely used in traditional Indian medicines against renal afflictions including calcium oxalate (CaOx) urolithiasis and is known for antioxidant activity. OBJECTIVE: The present study was designed to investigate the ameliorating effect of aqueous extract of B. diffusa roots (BDE) in hyperoxaluric oxidative stress and renal cell injury. MATERIAL AND METHODS: In vitro antioxidant activity of BDE was estimated in terms of total phenolic content and 1,1-diphenyl-2-picryl hydrazyl free radical scavenging activity. Wistar albino rats were given 0.75% v/v ethylene glycol in drinking water to induce chronic hyperoxaluria and simultaneously BDE was given to nephrolithiasic treated rats at the dose of 100 and 200 mg/kg b.w. orally for 28 days. Urinary volume, oxalate, serum creatinine, blood urea nitrogen (BUN), malondialdehyde (MDA) and antioxidant enzyme (SOD, CAT, GST, GPx) were evaluated. RESULTS AND DISCUSSION: BDE extract was found to posses a high total phenolic content and exhibited significant free radicals scavenging activity. Oxalate excretion significantly increased in hyperoxaluric animals as compared to control which was protected in BDE-treated animals. BDE treatment significantly reduced level of MDA and improved the activity of antioxidant enzymes followed by reduction in BUN and serum creatinine. In addition, BDE reduced the number of CaOx monohydrate crystals in the urine. Histological analysis depicted that BDE treatment inhibited deposition of CaOx crystal and renal cell damage. CONCLUSION: The present study reveals that antioxidant activity of BDE significantly protects against hyperoxaluric oxidative stress and renal cell injury in urolithiasis.

Asunto(s)

Lesión Renal Aguda/tratamiento farmacológico , Hiperoxaluria/tratamiento farmacológico , Nyctaginaceae/química , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/patología , Animales , Antioxidantes/metabolismo , Compuestos de Bifenilo , Catalasa/metabolismo , Cromatografía en Capa Delgada , Glicol de Etileno , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Hiperoxaluria/inducido químicamente , Riñón/patología , Pruebas de Función Renal , Masculino , Malondialdehído/metabolismo , Ácido Oxálico/metabolismo , Picratos , Extractos Vegetales/química , Raíces de Plantas/química , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo , Agua

RESUMEN

A series of 1-substituted imidazoles 1a-d and 2a-d were synthesized and screened for antispasmodic and antidiarrheal activities. Antispasmodic activity was tested at various concentrations on isolated tissue preparations; concentration-response curves were plotted and compared with atropine. All compounds were found to inhibit contraction of the guinea pig ileum. Castor oil-induced diarrhea model in rats was used for evaluation of antidiarrheal activity. Parameters such as intestinal transit and volume of intestinal fluid were measured for antidiarrheal activity at 40 mg kg-1 dose and compared with the standard drug loperamide at 6 mg kg-1 dose. Defecation frequency in the test group was found to be significantly lower (p < 0.01) compared to the control group and comparable with that of the standard. The present study reveals that the compounds exert antidiarrheal activity through possible inhibition of intestinal movement and reduction of capillary permeability in the abdominal cavity.

Asunto(s)

Antidiarreicos/química , Antidiarreicos/uso terapéutico , Diseño de Fármacos , Imidazoles/química , Imidazoles/uso terapéutico , Parasimpatolíticos/química , Parasimpatolíticos/uso terapéutico , Animales , Antidiarreicos/farmacología , Antagonistas Colinérgicos/química , Antagonistas Colinérgicos/farmacología , Antagonistas Colinérgicos/uso terapéutico , Diarrea/inducido químicamente , Diarrea/tratamiento farmacológico , Cobayas , Íleon/efectos de los fármacos , Imidazoles/farmacología , Espectroscopía de Resonancia Magnética , Masculino , Estructura Molecular , Relajación Muscular/efectos de los fármacos , Parasimpatolíticos/farmacología , Distribución Aleatoria , Ratas , Ratas Wistar , Espectroscopía Infrarroja por Transformada de Fourier , Relación Estructura-Actividad , Temperatura de Transición

RESUMEN

LC- ESI- MS/MS simultaneous bioanalytical method was developed to determine acitretin and its metabolite isoacitretin in human plasma using acitretin-d3 used as the internal standard for both analytes. The compounds were extracted using protein precipitation coupled with liquid-liquid extraction with flash freezing technique. Negative mass transitions (m/z) of acitretin, isoacitretin and acitretin-d3 were detected in multiple reactions monitoring (MRM) mode at 325.4 → 266.3, 325.2 → 266.1 and 328.3 → 266.3, respectively, with a turbo ion spray interface. The chromatographic separation was achieved on an Ascentis-RP amide column (4.6 × 150 mm, 5 µm) with mobile phase delivered in isocratic mode. The method was validated over a concentration range of 1.025-753.217 ng/mL for acitretin and 0.394-289.234 ng/mL for isoacitretin with a limit of quantification of 1.025 and 0.394 ng/mL. The intra-day and inter-day precisions were below 8.1% for acitretin and below 13.8% for isoacitretin, while accuracy was within ±7.0 and ±10.6% respectively. For the first time, the best possible conditions for plasma stability of acitretin and isoacitretin are presented and discussed with application to clinical samples.

Asunto(s)

Acitretina/sangre , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem/métodos , Acitretina/farmacocinética , Área Bajo la Curva , Estabilidad de Medicamentos , Humanos , Análisis de los Mínimos Cuadrados , Masculino , Fotólisis , Reproducibilidad de los Resultados , Sensibilidad y Especificidad

RESUMEN

Recently glutamate transporters have emerged as a potential therapeutic target in a wide range of acute and chronic neurological disorders, owing to their novel mode of action. The modulation of GLT-1, a major glutamate transporter has been shown to exert neuroprotection in various models of ischemic injury and motoneuron degeneration. Therefore, an attempt was made to explore its neuroprotective potential in cerebral ischemia/reperfusion injury using ceftriaxone, a GLT-1 modulator. Pre-treatment with ceftriaxone (100mg/kg. i.v) for five days resulted in a significant reduction (P<0.01) in neurological deficit as well as cerebral infarct volume after 1h of ischemia followed by 24h of reperfusion injury. It also caused a significant (P<0.05) upregulation of GLT-1 mRNA, protein and glutamine synthetase (GS) activity. Furthermore, inhibition of ceftriaxone-mediated increased glutamine synthetase activity by dihydrokainate (DHK), a GLT-1 specific inhibitor, confirms the specific effect of ceftriaxone on GLT-1 activity. In addition, ceftriaxone also induced a significant (P<0.01) increase in [(3)H]-glutamate uptake, mediated by GLT-1 in glial enriched preparation, as evidenced by use of DHK and DL-threo-beta-benzyloxyaspartate (DL-TBOA). Thus, the present study provides overwhelming evidence that modulation of GLT-1 protein expression and activity confers neuroprotection in cerebral ischemia/reperfusion injury.

Asunto(s)

Isquemia Encefálica/tratamiento farmacológico , Ceftriaxona/farmacología , Transportador 2 de Aminoácidos Excitadores/biosíntesis , Fármacos Neuroprotectores/farmacología , Daño por Reperfusión/tratamiento farmacológico , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Isquemia Encefálica/complicaciones , Ceftriaxona/antagonistas & inhibidores , Ceftriaxona/uso terapéutico , Infarto Cerebral/complicaciones , Infarto Cerebral/patología , Modelos Animales de Enfermedad , Transportador 2 de Aminoácidos Excitadores/antagonistas & inhibidores , Glutamato-Amoníaco Ligasa/biosíntesis , Ácido Glutámico/metabolismo , Ácido Kaínico/análogos & derivados , Ácido Kaínico/farmacología , Masculino , Neuroglía/metabolismo , Fármacos Neuroprotectores/antagonistas & inhibidores , Fármacos Neuroprotectores/uso terapéutico , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/complicaciones , Regulación hacia Arriba/efectos de los fármacos

RESUMEN

The present study was undertaken to evaluate the gum exudates of Terminalia catappa Linn. (TC gum) as a release retarding excipient in oral controlled drug delivery system. The rheological properties of TC gum were studied and different formulation techniques were used to evaluate the comparative drug release characteristics. The viscosity was found to be dependent on concentration and pH. Temperature up to 60 degrees C did not show significant effect on viscosity. The rheological kinetics evaluated by power law, revealed the shear thinning behavior of the TC gum dispersion in water. Matrix tablets of TC gum were prepared with the model drug dextromethorphan hydrobromide (DH) by direct compression, wet granulation and solid dispersion techniques. The dissolution profiles of the matrix tablets were compared with the pure drug containing capsules using the USP Basket apparatus with 500 ml phosphate buffer of pH 6.8 as a dissolution medium. The drug release from the compressed tablets containing TC gum was comparatively sustained than pure drug containing capsules. Even though all the formulation techniques showed reduction of dissolution rate, aqueous wet granulation showed the maximum sustained release of more than 8 h. The release kinetics estimated by the power law revealed that the drug release mechanism involved in the dextromethorphan matrix is anomalous transport as indicated by the release exponent n values. Thus the study confirmed that the TC gum might be used in the controlled drug delivery system as a release-retarding polymer.

Asunto(s)

Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Gomas de Plantas/química , Gomas de Plantas/farmacocinética , Reología/métodos , Terminalia , Dextrometorfano/química , Dextrometorfano/farmacocinética , Concentración de Iones de Hidrógeno , Reología/instrumentación , Comprimidos , Viscosidad

RESUMEN

Nyctanthes arbortristis Linn is a well-documented plant. It is evident from literature and previous investigations that Nyctanthes arbortristis possesses anti-inflammatory and analgesic activity. In the present study arbortristoside-A has been isolated from the ethanolic extract of its seeds. The structure of the isolated compound was determined by chemical reactions and spectroscopic methods. Arbortristoside-A was found to possess significant and dose-dependent anti-inflammatory and antinociceptive activity. It seems arbortristoside-A inhibited the histamine, serotonin and carrageenan-induced edema suggesting its inhibiting effect on carrageenan, arachidonic acid, histamine and serotonin-induced edema suggesting its anti-inflammatory activity may be due to the inhibiting effect of prostaglandin, histamine and serotonin. The analgesic activity of arbortristoside-A may be due to the inhibition of the action of prostaglandin.

Asunto(s)

Analgésicos/farmacología , Antiinflamatorios/farmacología , Iridoides/farmacología , Analgésicos/aislamiento & purificación , Animales , Antiinflamatorios/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Glucósidos Iridoides , Iridoides/aislamiento & purificación , Ratones , Oleaceae/química , Antagonistas de Prostaglandina/farmacología , Ratas , Ratas Wistar , Semillas/química

RESUMEN

A reliable method for characterizing microbial communities on the basis of their differences in the 16S ribosomal RNA (rRNA) gene sequences in the hot arid zone sandy soils has been optimized. A desert plant (Calligonum polygonoides) was chosen to provide the rhizospheric soil samples, collected from three different agro-ecological locations. Total community DNA was efficiently extracted at small-scale level using direct lysis with hot sodium dodecyl sulphate (SDS), glass bead beating and finally subjecting the sandy soil to liquid nitrogen freeze-thaw cycles. To amplify V3 region of bacterial 16S rRNA gene, universal conserved primers were used. Second round polymerase chain reaction (PCR) was attempted to increase product concentration and to minimize the effect of inhibitory substances. To enhance the detection sensitivity of the denaturing gradient gel electrophoresis (DGGE), the effect of change in template DNA concentration was studied. The separation of bands were greatly enhanced in the fingerprints obtained after the second round of PCR representing low abundant species which were not differentiated at single optimized concentration of DNA.