RESUMEN
The leaves of Ficus johannis Boiss (F. johannis), commonly known as Fig tree, Anjir, and Teen, are used by the folk medicinal practitioners in Iran for controlling hyperglycemia in diabetic patients. This study investigated the pharmacological basis for antidiabetic effect of the ethanolic extract of F. johannis leaves using in vitro and in vivo experimental models. Qualitative screening of phytochemicals, estimation of total phenolic and flavonoid contents, and in vitro antioxidant and α-amylase inhibition assays were performed. Moreover, the High-performance liquid chromatography (HPLC) quantification, acute toxicity, glucose tolerance, and in vivo antidiabetic effect along with the evaluation of gene expressions involved in diabetes mellitus were carried out. Significant quantities of phenolic (71.208 ± 2.89 mgg-1 GAE) and flavonoid (26.38 ± 3.53 mgg-1 QE) were present. Inhibitory concentration (IC50) of the plant extract exhibited an excellent in vitro antioxidant (IC50 = 33.81 µg/mL) and α-amylase (IC50 = 12.18 µg/mL) inhibitory potential. The HPLC analysis confirmed the gallic acid (257.79 mgg-1) as main constituent of the extract followed by kaempferol (22.86 mgg-1), myricetin (0.16 mgg-1), and quercetin (3.22 mgg-1). Ethanolic extract displayed glucose tolerance in normo-glycemic rats. Streptozotocin-induced hyperglycemia declined dose dependently in the extract treated rats with improvement in lipid profile and liver and renal function biomarkers. The F. johannis-treated groups showed an increase in mRNA expressions of glucose transporter 4 (GLUT-4), glucokinase, insulin growth like factor 1 and peroxisomal proliferator activating receptor gamma in pancreas. However, the Glucose-6-phosphatase was downregulated. Present study suggests that the ethanolic extract of F. johannis leaves demonstrates a good anti-diabetic profile by improving insulin sensitivity, GLUT-4 translocation, and carbohydrate metabolism while inhibiting lipogenesis.
Asunto(s)
Diabetes Mellitus Experimental , Ficus , Hiperglucemia , Extractos Vegetales , Animales , Ratas , alfa-Amilasas , Antioxidantes/farmacología , Glucemia/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Etanol , Ficus/química , Ficus/metabolismo , Flavonoides/farmacología , Glucosa , Hiperglucemia/tratamiento farmacológico , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Fenoles , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Estreptozocina , Quinasas del Centro Germinal/efectos de los fármacos , Transportador de Glucosa de Tipo 4/efectos de los fármacos , Factor I del Crecimiento Similar a la Insulina/efectos de los fármacos , Glucosa-6-Fosfatasa/efectos de los fármacosRESUMEN
In the present study, the effect of alcoholic stem extract of Gymnema montanum (GMSt) on blood glucose, plasma insulin, and carbohydrate metabolic enzymes were studied in experimental diabetes. Diabetes mellitus was induced by a single intraperitoneal injection of STZ (60 mg/kg bw). Five days after STZ induction, diabetic rats received GMSt orally at the doses of 25, 50, 100 and 200mg/kg daily for 3 weeks. Graded doses of stem extract showed a significant reduction in blood glucose levels and improvement in plasma insulin levels. The effect was more pronounced in 100 and 200mg/kg than 50mg/kg. GMSt showed significant increase in hexokinase, Glucose-6-phosphate dehydrogenase and glycogen content in liver of diabetic rats while there was significant reduction in the levels of glucose-6-phosphatase and fructose-1,6-bisphosphatase. The present study clearly indicated significant antidiabetic effect with the stem extract of G. montanum and lends support for its traditional usage.
Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Gymnema/química , Hipoglucemiantes/administración & dosificación , Fitoterapia , Extractos Vegetales/administración & dosificación , Animales , Glucemia/efectos de los fármacos , Diabetes Mellitus Experimental/patología , Relación Dosis-Respuesta a Droga , Fructosa-Bifosfatasa/análisis , Fructosa-Bifosfatasa/efectos de los fármacos , Fructosa-Bifosfatasa/metabolismo , Glucosa-6-Fosfatasa/análisis , Glucosa-6-Fosfatasa/efectos de los fármacos , Glucosa-6-Fosfatasa/metabolismo , Glucosafosfato Deshidrogenasa/análisis , Glucosafosfato Deshidrogenasa/efectos de los fármacos , Glucosafosfato Deshidrogenasa/metabolismo , Glucógeno/análisis , Glucógeno/metabolismo , Insulina/sangre , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Hojas de la Planta/química , Tallos de la Planta/química , Plantas Medicinales , Ratas , Ratas WistarRESUMEN
The antioxidant activity of lemon balm (Melissa officinalis) essential oil (LBEO) on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals and its hypoglycaemic effect in db/db mice were investigated. LBEO scavenged 97 % of DPPH radicals at a 270-fold dilution. Mice administered LBEO (0.015 mg/d) for 6 weeks showed significantly reduced blood glucose (65 %; P < 0.05) and TAG concentrations, improved glucose tolerance, as assessed by an oral glucose tolerance test, and significantly higher serum insulin levels, compared with the control group. The hypoglycaemic mechanism of LBEO was further explored via gene and protein expression analyses using RT-PCR and Western blotting, respectively. Among all glucose metabolism-related genes studied, hepatic glucokinase and GLUT4, as well as adipocyte GLUT4, PPAR-gamma, PPAR-alpha and SREBP-1c expression, were significantly up-regulated, whereas glucose-6-phosphatase and phosphoenolpyruvate carboxykinase expression was down-regulated in the livers of the LBEO group. The results further suggest that LBEO administered at low concentrations is an efficient hypoglycaemic agent, probably due to enhanced glucose uptake and metabolism in the liver and adipose tissue and the inhibition of gluconeogenesis in the liver.
Asunto(s)
Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/enzimología , Metabolismo de los Lípidos/efectos de los fármacos , Melissa/química , Aceites Volátiles/farmacología , Aceites de Plantas/farmacología , Animales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Glucoquinasa/efectos de los fármacos , Glucoquinasa/genética , Glucoquinasa/metabolismo , Prueba de Tolerancia a la Glucosa , Proteínas Facilitadoras del Transporte de la Glucosa/efectos de los fármacos , Proteínas Facilitadoras del Transporte de la Glucosa/genética , Proteínas Facilitadoras del Transporte de la Glucosa/metabolismo , Glucosa-6-Fosfatasa/efectos de los fármacos , Glucosa-6-Fosfatasa/genética , Glucosa-6-Fosfatasa/metabolismo , Insulina/sangre , Ratones , Aceites Volátiles/química , Aceites Volátiles/uso terapéutico , Receptores Activados del Proliferador del Peroxisoma/efectos de los fármacos , Receptores Activados del Proliferador del Peroxisoma/genética , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Fosfoenolpiruvato Carboxiquinasa (GTP)/efectos de los fármacos , Fosfoenolpiruvato Carboxiquinasa (GTP)/genética , Fosfoenolpiruvato Carboxiquinasa (GTP)/metabolismo , Fitoterapia , Aceites de Plantas/química , Aceites de Plantas/uso terapéutico , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/efectos de los fármacos , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismoRESUMEN
The present study investigated the modulatory role of phenolic extract of soybean (PESB) in a rat model of nephrotoxic acute renal failure induced by cisplatin. Cisplatin (2 mg/kg/day) was administered to the rats for 5 days and the animals were pretreated with PESB (250-1000 mg/kg). Blood urea nitrogen reduced by 49.8% and 59.0%, serum creatinine by 34.7% and 62.1% and urinary N-acetyl-beta-D-glucosaminidase also decreased by 37.7% and 49.2% following treatment with 250- and 500-mg/kg doses of the extract respectively in the cisplatin-treated rats. The extract also significantly increased renal myeloperoxidase activity by 26.8% and 40.6% at these doses. PESB also decreased renal xanthine oxidase activity and serum nitrate/nitrite in the cisplatin-treated rats. In addition, PESB significantly attenuated the marked renal oxidative damage that accompanied cisplatin treatment. The extract improved liver histology and significantly increased the activities of the antioxidant enzymes measured [superoxide dismutase, catalase, glutathione-S-transferase], prevented glutathione depletion and decreased malondialdehyde level following cisplatin treatment. Furthermore, cisplatin-induced decrease in the activities of glucose-6-phosphatase and 5'-nucleotidase in these rats was attenuated only at 250 mg/kg dose of the extract. We concluded therefore that PESB via antioxidant and possibly anti-inflammatory actions offered protective benefit against cisplatin-mediated acute toxic injury to the kidney.
Asunto(s)
Lesión Renal Aguda/prevención & control , Antineoplásicos/toxicidad , Antioxidantes/farmacología , Cisplatino/toxicidad , Glycine max/química , Extractos Vegetales/farmacología , 5'-Nucleotidasa/efectos de los fármacos , 5'-Nucleotidasa/metabolismo , Acetilglucosaminidasa/orina , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/patología , Animales , Modelos Animales de Enfermedad , Glucosa-6-Fosfatasa/efectos de los fármacos , Glucosa-6-Fosfatasa/metabolismo , Riñón/efectos de los fármacos , Riñón/enzimología , Riñón/patología , Pruebas de Función Renal , Malondialdehído/metabolismo , Nitratos/sangre , Nitritos/sangre , Oxidorreductasas/efectos de los fármacos , Oxidorreductasas/metabolismo , Peroxidasa/efectos de los fármacos , Peroxidasa/metabolismo , Fenol/química , Ratas , Ratas WistarRESUMEN
In intact microsomes, quercetin 3-O-alpha-(2''-galloyl)rhamnoside (QGR) inhibits glucose-6-phosphatase (G-6-Pase) in a concentration-dependent manner. QGR increased the G-6-Pase K(m) for glucose-6-phosphate without change in the V(max). The flavonol did not change the kinetic parameters of disrupted microsomal G-6-Pase or intact or disrupted microsomal G-6-Pase pyrophosphatase (PPase) activity. This result allowed the conclusion that QGR competitively inhibits the glucose-6-phosphate (G-6-P) transporter (T1) without affecting the catalytic subunit or the phosphate/pyrophosphate transporter (T2) of the G-6-Pase system.QGR strongly inhibits the neoglucogenic capacity of rat liver slices incubated in a Krebs-Ringer bicarbonate buffer, supplemented with lactate and oleate saturated albumin. The QGR G-6-Pase inhibition might explain the decrease in the liver slice neoglucogenic capacity and, in turn, could reduce glucose levels in diabetic patients.
Asunto(s)
Bauhinia , Inhibidores Enzimáticos/farmacología , Gluconeogénesis/efectos de los fármacos , Glucosa-6-Fosfatasa/efectos de los fármacos , Fitoterapia , Extractos Vegetales/farmacología , Animales , Antiportadores/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/uso terapéutico , Glucosa-6-Fosfatasa/antagonistas & inhibidores , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/enzimología , Proteínas de Transporte de Monosacáridos/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Extractos Vegetales/uso terapéutico , Hojas de la Planta , Quercetina/administración & dosificación , Quercetina/farmacología , Quercetina/uso terapéutico , Ratas , Ratas Sprague-DawleyRESUMEN
It has recently been reported that the major green tea polyphenolic constituent, epigallocatechin 3-gallate (EGCG), mimics the cellular effects of insulin including the reductive effect on the gene expression of rate-limiting gluconeogenic enzymes in a cell culture system. We show that administration of green tea that contains EGCG caused a reduction in the level of mRNAs for gluconeogenic enzymes, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase in the mouse liver. EGCG alone was also found to down-regulate the gene expression of these enzymes but not so curcumin or quercetin. The results of this study support the idea that green tea intake may be beneficial in the prevention of diabetes mellitus.
Asunto(s)
Catequina/análogos & derivados , Gluconeogénesis/efectos de los fármacos , Hipoglucemiantes/farmacología , Hígado/efectos de los fármacos , Fitoterapia , Extractos Vegetales/farmacología , ARN Mensajero/efectos de los fármacos , Té , Animales , Catequina/administración & dosificación , Catequina/farmacología , Catequina/uso terapéutico , Cartilla de ADN , Diabetes Mellitus/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Expresión Génica/efectos de los fármacos , Glucosa-6-Fosfatasa/efectos de los fármacos , Glucosa-6-Fosfatasa/genética , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/uso terapéutico , Hígado/enzimología , Masculino , Ratones , Ratones Endogámicos C57BL , Extractos Vegetales/administración & dosificación , Extractos Vegetales/uso terapéutico , Proteínas Serina-Treonina Quinasas/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/genética , ARN Mensajero/biosíntesis , Distribución Aleatoria , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Semecarpus anacardium Linn. of the family Anacardiaceae has many applications in the Ayurvedic and Siddha systems of medicine. We have tested the antitumour activity of Semecarpus anacardium nut extract against experimental mammary carcinoma in animals. As there is a direct relationship between the proliferation of tumour cells and the activities of the glycolytic and gluconeogenic enzymes, we studied changes in the activities of enzymes involved in this metabolic pathway in the liver and kidney. The enzymes investigated were glycolytic enzymes, namely hexokinase, phosphoglucoisomerase, aldolase and the gluconeogenic enzymes, namely glucose-6-phosphatase and fructose-1,6-biphosphatase in experimental rats. A significant rise in glycolytic enzyme activities and a simultaneous fall in gluconeogenic enzyme activities were found in mammary carcinoma bearing rats. Drug administration returned these enzyme activities to their respective control activities.
Asunto(s)
Anacardiaceae , Antineoplásicos Fitogénicos/uso terapéutico , Glucosa/metabolismo , Neoplasias Mamarias Experimentales/prevención & control , Fitoterapia , Extractos Vegetales/uso terapéutico , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/farmacología , Femenino , Fructosa-Bifosfatasa/efectos de los fármacos , Fructosa-Bifosfato Aldolasa/efectos de los fármacos , Glucosa-6-Fosfatasa/efectos de los fármacos , Glucólisis/efectos de los fármacos , Hexoquinasa/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/enzimología , Hígado/efectos de los fármacos , Hígado/enzimología , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
In this study, we examined the modulatory effects of kolaviron, a biflavonoid from Garcinia kola seeds on the antioxidant defense mechanisms, cellular redox status and oxidative stress in the kidney and liver of rats pretreated with potassium bromate (KBrO(3)) intragastrically as a single dose of 300 mg kg(-1)weight for 4 weeks. Treatment of rats with KBrO(3)resulted in an insignificant difference (P> 0.05) in body weight compared to controls. However, a significant increase in kidney/body weight ratio (P< 0.001) was observed in rats treated with KBrO(3)while liver/body weight ratio was not affected. KBrO(3)depressed the activities of superoxide dismutase, glutathione peroxidase and catalase (P< 0.001) in the kidney but not in the liver. Kolaviron (200 mg kg(-1)body weight) administered three times a week for 4 weeks inhibited the decrease mediated by KBrO(3)of these enzymes in the kidney by 29, 88 and 45%, respectively. Similarly, kolaviron reduced the KBrO(3)-induced decrease in the activities of gamma -glutamyltransferase and microsomal Ca(2+)ATPase by 73 and 63% in the kidney. In addition, the extract elicited a 27 and 25% decrease in the KBrO(3)-induced increase in malondialdehyde and lipid hydroperoxide formation in the kidney. Kolaviron also attenuated the KBrO(3)-decreased activities of glucose 6-phosphatase, 5 prime prime or minute nucleotidase and alkaline phosphatase (membrane enzymes) by 72, 57 and 25% respectively. The results of the present investigation indicate the antioxidative effect of kolaviron, a natural antioxidant, on drug-induced kidney toxicity. Kolaviron may therefore intervene in the cellular redox status and depression of membrane protein activities caused by KBrO(3)and other environmental carcinogens in the kidney.
Asunto(s)
Flavonoides/farmacología , Garcinia kola , Proteínas de la Membrana/metabolismo , Extractos Vegetales/farmacología , Fosfatasa Alcalina/efectos de los fármacos , Fosfatasa Alcalina/metabolismo , Animales , Bromatos/farmacología , ATPasas Transportadoras de Calcio/efectos de los fármacos , ATPasas Transportadoras de Calcio/metabolismo , Catalasa/efectos de los fármacos , Catalasa/metabolismo , Interacciones Farmacológicas , Flavonoides/química , Glucosa-6-Fosfatasa/efectos de los fármacos , Glucosa-6-Fosfatasa/metabolismo , Glutatión/efectos de los fármacos , Glutatión/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/metabolismo , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Superóxido Dismutasa/efectos de los fármacos , Superóxido Dismutasa/metabolismoRESUMEN
The influence of Liv.100 on the hepatotoxicity of antituberculosis drugs [isoniazid (INH), rifampicin (RMP) pyrazinamide (PZA)] was studied in male albino rats. INH, RMP, and PZA were proved to be the most hepatotoxic. Rats were treated with antituberculosis drugs daily for a period of 6 weeks by intragastric administration. The combined use of antituberculosis drugs elevated the levels of cytochrome P-450 and cytochrome-b5. A significant increase was observed in the levels of NADPH-cytochrome P-450 reductase and NADH-cytochrome-b5 reductases after antitubercular drug administration. During antitubercular drug treatment a significant decrease was also observed in the activity of glucose-6-phosphatase. The extent of NADPH-induced and ascorbic acid-induced lipid peroxides were marked in antitubercular drug treatment, when compared with normal control animals. Oral Liv.100 co-administration, for the same period, modulated the alterations in the xenobiotic metabolizing system and microsomal lipid peroxidation in experimental animals. The results are discussed with reference to drug metabolizing enzymes, lipid peroxidation and the hepatoprotective nature of Liv.100.
Asunto(s)
Antituberculosos/toxicidad , Magnoliopsida , Medicina Ayurvédica , Microsomas Hepáticos/efectos de los fármacos , Fitoterapia , Extractos Vegetales/farmacología , Animales , Ácido Ascórbico/farmacología , Sistema Enzimático del Citocromo P-450/efectos de los fármacos , Reductasas del Citocromo/efectos de los fármacos , Grupo Citocromo b/efectos de los fármacos , Citocromo-B(5) Reductasa , Interacciones Farmacológicas , Glucosa-6-Fosfatasa/efectos de los fármacos , Medicina de Hierbas , India , Isoniazida/toxicidad , Peroxidación de Lípido/efectos de los fármacos , Masculino , NADPH-Ferrihemoproteína Reductasa/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Plantas Medicinales , Sustancias Protectoras/farmacología , Pirazinamida/toxicidad , Ratas , Ratas Wistar , Rifampin/toxicidadRESUMEN
The liver is an important target organ of thyroid hormone. However, only a limited number of hepatic target genes have been identified, and little is known about the pattern of their regulation by thyroid hormone. We used a quantitative fluorescent cDNA microarray to identify novel hepatic genes regulated by thyroid hormone. Fluorescent-labeled cDNA prepared from hepatic RNA of T3-treated and hypothyroid mice was hybridized to a cDNA microarray, representing 2225 different mouse genes, followed by computer analysis to compare relative changes in gene expression. Fifty five genes, 45 not previously known to be thyroid hormone-responsive genes, were found to be regulated by thyroid hormone. Among them, 14 were positively regulated by thyroid hormone, and unexpectedly, 41 were negatively regulated. The expression of 8 of these genes was confirmed by Northern blot analyses. Thyroid hormone affected gene expression for a diverse range of cellular pathways and functions, including gluconeogenesis, lipogenesis, insulin signaling, adenylate cyclase signaling, cell proliferation, and apoptosis. This is the first application of the microarray technique to study hormonal regulation of gene expression in vivo and should prove to be a powerful tool for future studies of hormone and drug action.