RESUMO
The aim of the present study was to investigate the protective effects of Trigonella foenum-graecum Linn. (fenugreek) in Streptozotocin-induced diabetic rat retina. Fenugreek (100 and 200 mg/kg body weights) treatment was carried out for 24 weeks and evaluated for inflammatory [tumor necrosis factor (TNF)-α and interleukin (IL)-1ß] and angiogenic [vascular endothelial growth factor (VEGF) and protein kinase C (PKC)-ß] molecular biomarkers. Retinal oxidative stress was evaluated by estimating antioxidant (Glutathione, Superoxide dismutase, and Catalase) parameters. Fluorescein angiography was performed to detect retinal vascular leakage. Electron microscopy was performed to determine basement membrane thickness. In the present study, significant rises in the expressions of retinal inflammatory (TNF-α and IL-1ß) and angiogenic (VEGF and PKC-ß) molecular biomarkers were observed in diabetic retinae compared with normal retinae. However, fenugreek-treated retinae showed marked inhibition in the expression of inflammatory and angiogenic molecular biomarkers. Moreover, results from the present study showed positive modulatory effects of fenugreek on retinal oxidative stress. Fluorescein angiograms and fundus photographs obtained from diabetic retinae showed retinal vascular leakage. On the other hand, fenugreek-treated retinae did not show vascular leakage. Further, thickened BM was recorded in diabetic retina compared with normal retinae. However, fenugreek-treated retinae showed relatively lesser thickening of capillary BM. In conclusion, it may be postulated that fenugreek has great potential in preventing diabetes-induced retinal degeneration in humans after regular consumption in the specified dosage.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Retinopatia Diabética/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Degeneração Retiniana/prevenção & controle , Trigonella/metabolismo , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Catalase/biossíntese , Glutationa/biossíntese , Inflamação/tratamento farmacológico , Interleucina-1beta/biossíntese , Neovascularização Patológica/tratamento farmacológico , Fitoterapia , Preparações de Plantas/uso terapêutico , Proteína Quinase C beta/biossíntese , Ratos , Ratos Wistar , Retina/patologia , Vasculite Retiniana/prevenção & controle , Estreptozocina , Superóxido Dismutase/biossíntese , Fator de Necrose Tumoral alfa/biossíntese , Fator A de Crescimento do Endotélio Vascular/biossínteseRESUMO
Nanoparticle preparations of heavy metals have attracted enormous scientific and technological interest. Biologically produced nanoparticle preparations of heavy metals are elaborately described in traditional texts and being widely prescribed. The underlying interactions of nano preparations within the physiological fluids are key feature to understand their biological impact. In this perspective, we performed an experimental assessment of the toxicity potential of a marketed metallic preparation named Vasant Kusumakar Ras (VKR), wherein different heavy metals in composite form are reduced to nanoparticle size to produce the desired effect in diabetes and its complications. VKR (50mg/kg) was administered to Albino Wistar rats rendered diabetic using streptozotocin (90mg/kg) in 2 days old neonates. Anti-hyperglycemic effect was observed with VKR along with increased levels of plasma insulin. Renal variables including total proteins and albumin along with glomerular filtration rate were found to improve biochemically. The results were supplemented by effects on different inflammatory and growth factors like TNF-α, nitric oxide, TGF-ß and VEGF. However, the results observed in kidney histopathology were not in accordance with the biochemical parameters. Inflammation observed in kidney was confirmed by immunostaining metallothionein, which was due to the accumulation of heavy metals. Furthermore, mercury accumulation in kidney further confirmed by autometallography, which activated mononuclear phagocyte system, which generated an immune response. This was further supported by increase in the extent of apoptosis in kidney tissues. In conclusion, nanoparticle preparations of heavy metals can be toxic to kidney if it is not regulated with respect to its surface chemistry and dosage.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Rim/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Metais Pesados/toxicidade , Animais , Fragmentação do DNA/efeitos dos fármacos , Taxa de Filtração Glomerular/efeitos dos fármacos , Imuno-Histoquímica , Insulina/sangue , Ayurveda , Ratos , Ratos WistarRESUMO
Chronic hyperglycemia leads to the development of microvascular complications like diabetic nephropathy. The present study investigated the potential effects of the hydroalcoholic extract of Tribulus terrestris, a plant of Zygophyllaceae family, on the renal complications in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by administering STZ (90 mg/kg) to the 2-days old neonates. After 6 weeks of induction, diabetic rats were treated with 50 mg/kg hydroalcoholic extract of T. terrestris for 8 weeks. The anti-hyperglycaemic nature was confirmed by reduction in blood glucose and improvement in insulin levels. Diabetic renal injury associated with decrease in total proteins and albumin levels was observed to be improved by T. terrestris extract. Glomerular filtration rate along with inflammatory and growth factors, adiponectin and erythropoietin were also improved by the treatment, though the findings were not significant. However, the beneficial antidiabetic effects of T. terrestris extract in plasma were not observed in kidney histopathology. This was confirmed by the quantitative estimation of unhydrolyzed fraction of saponins (major component: protodioscin) in plasma and kidney samples of normal and diabetic rats. Hence, it can be concluded that 8 weeks treatment with T. terrestris extract produces potential toxic effects in kidney, which are independent of its anti-diabetic action.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Rim/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Saponinas/toxicidade , Tribulus/química , Animais , Peso Corporal , Taxa de Filtração Glomerular , Rim/fisiopatologia , Proteínas de Transporte de Monossacarídeos/metabolismo , Ratos , Ratos Wistar , EstreptozocinaRESUMO
PURPOSE: The present study was aimed to evaluate the retinoprotective effects of Moringa oleifera (MO) in Streptozotocin-induced diabetic rats. METHODS: The study was continued for 24 weeks and evaluated for inflammatory (tumor necrosis factor [TNF]-α and interleukin [IL]-1ß, angiogenic (vascular endothelial growth factor [VEGF] and protein kinase C [PKC]-ß) and antioxidant (Glutathione, Superoxide dismutase, and Catalase) parameters. Retinal leakage was checked by Fluorescein angiography (FA) and fundus photographs were evaluated for retinal vessel caliber (arteriolar and venular). Transmission electron microscopy was done to determine basement membrane (BM) thickness. RESULTS: The results of the present study showed potential hypoglycemic and retinal antioxidant effects of MO. In the present study, a significant rise in the expression of retinal inflammatory (TNF-α and IL-1ß) and angiogenic (VEGF and PKC-ß) parameters was observed in diabetic retinae as compared to normal retinae. However, MO-treated retinae showed marked inhibition in the expression of inflammatory and angiogenic parameters. Further, in the present study, diabetic retinae showed dilated retinal vessels as compared to normal. However, MO-treated retinae showed marked prevention in the dilatation of retinal vessels. Fluorescein angiograms obtained from diabetic retinae showed leaky and diffused retinal vasculature. On the other hand, MO-treated retinae showed intact retinal vasculature. Further, results of the transmission electron microscopy study showed thickened capillary BM in the diabetic retina as compared to normal retinae. However, treatment with MO prevented thickening of capillary BM. CONCLUSION: Our result suggests that MO may be useful in preventing diabetes induced retinal dysfunction.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Retinopatia Diabética/prevenção & controle , Moringa oleifera/química , Extratos Vegetais/farmacologia , Inibidores da Angiogênese/isolamento & purificação , Inibidores da Angiogênese/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Membrana Basal/efeitos dos fármacos , Membrana Basal/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/fisiopatologia , Retinopatia Diabética/patologia , Feminino , Inflamação/etiologia , Inflamação/prevenção & controle , Masculino , Microscopia Eletrônica de Transmissão , Ratos , Ratos Wistar , Retina/efeitos dos fármacos , Retina/metabolismo , Vasos Retinianos/efeitos dos fármacos , Vasos Retinianos/metabolismo , EstreptozocinaRESUMO
CONTEXT: Tamarindus indica L. (Leguminosae) is widely used as a traditional medicine for the management of diabetes mellitus (DM) in India, in addition to its anti-inflammatory activity. The present study has been designed to understand the correlation involved between antidiabetic and anti-inflammatory action of aqueous seed extract of T. indica (TSE) in diabetic rats. OBJECTIVE: In view of the fact that fatty acid synthesis and insulin release from islets of pancreas are regulated by sterol regulatory element-binding proteins (SREBP-1c) and cytosolic calcium, respectively, the objectives of present study were to determine the influence of TSE on SREBP-1c mRNA and to investigate the intracellular islets calcium [Ca²âº](I) involvement and ß-cell mass preservation in insulin secretagogue action of TSE. MATERIALS AND METHODS: The effect of 4 weeks oral treatment (120 and 240 mg/kg) of high-performance liquid chromatography (HPLC) standardized TSE was studied in streptozotocin (STZ)-induced diabetic male Wistar rats. Reverse transcription-PCR (RT-PCR) and a spectrofluorometer were used for mRNA concentration and islets [Ca²âº](I) determination, respectively. The TUNEL assay was followed to study the pancreatic apoptosis. RESULTS: TSE (120 and 240 mg/kg) showed positive correlation with [Ca²âº](I) and insulin release. The anti-inflammatory action of TSE was significant on nitric oxide (NO) and tumor necrosis factor-α (TNF-α) in addition to a favorable effect on ß-cell neogenesis and improved mRNA concentration of SREBP-1c. DISCUSSION AND CONCLUSION: The results suggest that anti-inflammatory action of Tamarind seeds on ß-cell cells of islets and cytokines contribute toward its antidiabetic activity by way of complex mechanisms of [Ca²âº](I) handling and through SREBP-1c gene in liver.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Hiperglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Células Secretoras de Insulina/efeitos dos fármacos , Fígado/efeitos dos fármacos , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Tamarindus/química , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Apoptose/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Hipoglicemiantes/administração & dosagem , Índia , Células Secretoras de Insulina/imunologia , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Fígado/imunologia , Fígado/metabolismo , Masculino , Óxido Nítrico/metabolismo , Fitoterapia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Sementes/química , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Técnicas de Cultura de Tecidos , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
Tamarindus indica Linn. has been in use for a long time in Asian food and traditional medicine for different diseases including diabetes and obesity. However, the molecular mechanisms of these effects have not been fully understood. In view of the multidimensional activity of tamarind seeds due to their having high levels of polyphenols and flavonoids, we hypothesized that the insulin mimetic effect of aqueous tamarind seed extract (TSE) might increase glucose uptake through improvement in the expression of genes of the glucose transporter (GLUT) family and sterol regulatory element-binding proteins (SREBP) 1c messenger RNA (mRNA) in the liver. Daily oral administration of TSE to streptozotocin (STZ)-induced (90 mg/kg intraperitoneally) type 2 diabetic male Wistar rats at different doses (120 and 240 mg/kg body weight) for 4 weeks showed positive correlation with intracellular calcium and insulin release in isolated islets of Langerhans. Tamarind seed extract supplementation significantly improved the GLUT-2 protein and SREBP-1c mRNA expression in the liver and GLUT-4 protein and mRNA expression in the skeletal muscles of diabetic rats. The elevated levels of serum nitric oxide (NO), glycosylated hemoglobin level (hemoglobin (A1c)) and tumor necrosis factor α (TNF-α) decreased after TSE administration. Immunohistochemical findings revealed that TSE abrogated STZ-induced apoptosis and increased ß-cell neogenesis, indicating its effect on islets and ß-cell mass. In conclusion, it was found that the antidiabetic effect of TSE on STZ-induced diabetes resulted from complex mechanisms of ß-cell neogenesis, calcium handling, GLUT-2, GLUT-4, and SREBP-1c. These findings show the scope for formulating a new herbal drug for diabetes therapy.
Assuntos
Cálcio/metabolismo , Diabetes Mellitus Experimental/metabolismo , Transportador de Glucose Tipo 2/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Extratos Vegetais/farmacologia , Tamarindus , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Suplementos Nutricionais , Transportador de Glucose Tipo 2/genética , Transportador de Glucose Tipo 4/genética , Hemoglobinas Glicadas/metabolismo , Homeostase , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Óxido Nítrico/sangue , Fitoterapia , Extratos Vegetais/uso terapêutico , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Sementes , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Fator de Necrose Tumoral alfa/sangueRESUMO
In view of multi-dimensional activity of plant drugs beneficial to complex disorders like diabetes, the present study has been undertaken to evaluate the effect of aqueous extract of C. peltata roots on serum glucose, lipid profile, insulin, inflammatory marker namely tumour necrosis factor (TNF)-alpha and muscle glycogen in type 2 diabetic rats. Aqueous extract of C. peltata at 40 and 60 mg/kg dose significantly decreased both the fasting and postprandial blood glucose of type 2 diabetic rats; 60 mg/kg dose having more pronounced effect on hyperglycemia. An enhanced insulin levels by the aqueous extract is primary for its glucose and lipid lowering activity. The extract significantly decreased the elevated TNF-alpha in type 2 diabetic rats. The extract at 40 and 60 mg/kg dose increased the glycogen levels in skeletal muscle by 58 and 60% respectively. Improved glycogen in peripheral tissue such as skeletal muscle indicates the ability of plant drug to combat insulin resistance of type 2 diabetes.
Assuntos
Cyclea/química , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Fitoterapia , Extratos Vegetais/uso terapêutico , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Avaliação Pré-Clínica de Medicamentos , Feminino , Glibureto/uso terapêutico , Glicogênio/análise , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacologia , Insulina/sangue , Resistência à Insulina , Lipídeos/sangue , Masculino , Ayurveda , Metformina/uso terapêutico , Camundongos , Músculo Esquelético/química , Músculo Esquelético/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Plantas Medicinais/química , Distribuição Aleatória , Ratos , Ratos Wistar , Solventes , Fator de Necrose Tumoral alfa/análise , ÁguaRESUMO
One of the major etiologies in pathogenesis of type 2 diabetes especially complications is oxidative stress. Aqueous extract of Ficus religiosa at a dose of 100 and 200 mg/kg orally decreased the fasting blood glucose in streptozotocin induced type 2 diabetic rats. The drug had enzyme induction effect with respect to catalase (CAT) and glutathione peroxidase (GSH-Px) activity, however decreased the exaggerated activity of superoxide dismutase (SOD) in type 2 diabetic rats. F. religiosa modulated the enzymes of antioxidant defence system to combat oxidative stress. As a result, glutathione (GSH-reduced form) was restored and inhibited the formation of malondialdehyde. Drug at higher dose (200 mg/kg) had more pronounced effect. F. religiosa, a rasayana group of plant drug having anti-diabetic activity along with antioxidant potential was beneficial in treatment of type 2 diabetes.