ABSTRACT
Catalpol, a major bioactive component from Rehmannia glutinosa, which has been used to treat diabetes. The present study was designed to elucidate the anti-diabetic effect and mechanism of action for catalpol in db/db mice. The db/db mice were randomly divided into six groups (10/group) according to their blood glucose levels: db/db control, metformin (positive control), and four dose levels of catalpol treatment (25, 50, 100, and 200 mg·kg), and 10 db/m mice were used as the normal control. All the groups were administered orally for 8 weeks. The levels of fasting blood glucose (FBG), random blood glucose (RBG), glucose tolerance, insulin tolerance, and glycated serum protein (GSP) and the globe gene expression in liver tissues were analyzed. Our results showed that catalpol treatment obviously reduced water intake and food intake in a dose-dependent manner. Catalpol treatment also remarkably reduce fasting blood glucose (FBG) and random blood glucose (RBG) in a dose-dependent manner. The RBG-lowering effect of catalpol was better than that of metformin. Furthermore, catalpol significantly improved glucose tolerance and insulin tolerance via increasing insulin sensitivity. Catalpol treatment significantly decreased GSP level. The comparisons of gene expression in liver tissues among normal control mice, db/db mice and catalpol treated mice (200 and 100 mg·kg) indicated that there were significant increases in the expressions of 287 genes, whichwere mainly involved in lipid metabolism, response to stress, energy metabolism, and cellular processes, and significant decreases in the expressions of 520 genes, which were mainly involved in cell growth, death, immune system, and response to stress. Four genes expressed differentially were linked to glucose metabolism or insulin signaling pathways, including Irs1 (insulin receptor substrate 1), Idh2 (isocitrate dehydrogenase 2 (NADP), mitochondrial), G6pd2 (glucose-6-phosphate dehydrogenase 2), and SOCS3 (suppressor of cytokine signaling 3). In conclusion, catalpol ecerted significant hypoglycemic effect and remarkable therapeutic effect in db/db mice via modulating various gene expressions.
Subject(s)
Animals , Humans , Male , Mice , Blood Glucose , Metabolism , Diabetes Mellitus, Experimental , Drug Therapy , Genetics , Metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Drugs, Chinese Herbal , Gene Expression , Glucosephosphate Dehydrogenase , Genetics , Metabolism , Hypoglycemic Agents , Insulin , Metabolism , Insulin Receptor Substrate Proteins , Genetics , Metabolism , Iridoid Glucosides , Isocitrate Dehydrogenase , Genetics , Metabolism , Liver , Metabolism , Mice, Inbred C57BL , Rehmannia , Chemistry , Suppressor of Cytokine Signaling 3 Protein , Genetics , MetabolismABSTRACT
Catalpol, a major bioactive component from Rehmannia glutinosa, which has been used to treat diabetes. The present study was designed to elucidate the anti-diabetic effect and mechanism of action for catalpol in db/db mice. The db/db mice were randomly divided into six groups (10/group) according to their blood glucose levels: db/db control, metformin (positive control), and four dose levels of catalpol treatment (25, 50, 100, and 200 mg·kg), and 10 db/m mice were used as the normal control. All the groups were administered orally for 8 weeks. The levels of fasting blood glucose (FBG), random blood glucose (RBG), glucose tolerance, insulin tolerance, and glycated serum protein (GSP) and the globe gene expression in liver tissues were analyzed. Our results showed that catalpol treatment obviously reduced water intake and food intake in a dose-dependent manner. Catalpol treatment also remarkably reduce fasting blood glucose (FBG) and random blood glucose (RBG) in a dose-dependent manner. The RBG-lowering effect of catalpol was better than that of metformin. Furthermore, catalpol significantly improved glucose tolerance and insulin tolerance via increasing insulin sensitivity. Catalpol treatment significantly decreased GSP level. The comparisons of gene expression in liver tissues among normal control mice, db/db mice and catalpol treated mice (200 and 100 mg·kg) indicated that there were significant increases in the expressions of 287 genes, whichwere mainly involved in lipid metabolism, response to stress, energy metabolism, and cellular processes, and significant decreases in the expressions of 520 genes, which were mainly involved in cell growth, death, immune system, and response to stress. Four genes expressed differentially were linked to glucose metabolism or insulin signaling pathways, including Irs1 (insulin receptor substrate 1), Idh2 (isocitrate dehydrogenase 2 (NADP), mitochondrial), G6pd2 (glucose-6-phosphate dehydrogenase 2), and SOCS3 (suppressor of cytokine signaling 3). In conclusion, catalpol ecerted significant hypoglycemic effect and remarkable therapeutic effect in db/db mice via modulating various gene expressions.
Subject(s)
Animals , Humans , Male , Mice , Blood Glucose , Metabolism , Diabetes Mellitus, Experimental , Drug Therapy , Genetics , Metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Drugs, Chinese Herbal , Gene Expression , Glucosephosphate Dehydrogenase , Genetics , Metabolism , Hypoglycemic Agents , Insulin , Metabolism , Insulin Receptor Substrate Proteins , Genetics , Metabolism , Iridoid Glucosides , Isocitrate Dehydrogenase , Genetics , Metabolism , Liver , Metabolism , Mice, Inbred C57BL , Rehmannia , Chemistry , Suppressor of Cytokine Signaling 3 Protein , Genetics , MetabolismABSTRACT
Objective: To study the antidiabetic effects and the underlying molecular mechanisms of Lycium barbarum polysaccharide (LBP) and its DEAE cellulose elution fraction LBP-IV in diabetic rats induced by high fat diet (HFD) and streptozotocin (STZ). Methods: After ig administration of LBP-IV [50, 100, and 200 mg/(kg·d)] and LBP [100 mg/(kg·d)] once daily for consecutive 4 weeks to diabetic rats, the glucose and lipids in blood, mRNA expression of phosphoenolpyruvate carboxykinase (PEPCK), sterol regulatory element binding-protein-1c (SREBP-1c), and fatty acid synthase (FAS) in liver were determined. Results: Ig administration of LBP and LBP-IV significantly decreased the levels of blood glucose, HbA1c, TC, TG, and LDL-C, as well as the hepatic mRNA expression of PEPCK, SREBP-1c, and FAS, whereas significantly increased the oral glucose tolerance of diabetic rats. Conclusion: The findings suggest that the antidiabetic effects of LBP and LBP-IV are associated with the decreased hepatic mRNA expression of PEPCK, SREBP-1c, and FAS in HFD-STZ induced diabetic rats.
ABSTRACT
The objective of the present study was to evaluate the antidiabetic effect of Strychnos Potatorum Linn (S.P. Linn) on streptozotocin induced male diabetic rats. Method: Male albino rats (150-200 gm) were made diabetic by a single intraperitoneal injection of Streptozotocin (STZ) at a fixed dose of 40 mg/kg body weight. Animals were then given either the test drug or the standard control drug i.e. glipizide orally and the effects on fasting blood glucose level, body weight, food and water intake were recorded and compared with the standard drug. Results: The test drug S. P. Linn reduces blood sugar significantly in STZ induced diabetic male rats which is comparable to that of glipizied. Conclusion: S.P. Linn has antidiabetic action as it significantly reduces blood sugar level in male diabetic rats.
Subject(s)
Animals , Blood Glucose/metabolism , Diabetes Mellitus, Experimental/drug therapy , Glipizide/administration & dosage , Glipizide/therapeutic use , Glucose/blood , Hypoglycemic Agents/pharmacology , Male , Rats , Rats, Wistar , Strychnos/classification , Strychnos/therapeutic useABSTRACT
Aims: The present study was designed to evaluate the antidiabetic activity of the methanol stem bark extract of Terminalia superb (T. superba), a traditionally used medicinal plant in Cameroon. Place and Duration of Study: Department of Animal Biology and Physiology, Faculty of Science, University of Yaounde I, Cameroon and Laboratoire de Pharmacologie et Physiopathologie Expérimentales, Université Montpellier I, France. Between Ferbruary 2011 and September 2011. Methodology: In one set of experiments, repeated doses of T. superba extract (37.5– 300mg/kg, p.o.) were administrated once daily for 21 days to groups of diabetic rats. In another set of experiments, acute effect of the plant extract (37.5–300mg/kg) in diabetic rats was evaluated. Results: Following acute treatment, the plant extract produced a significant reduction in the blood glucose levels in diabetic rats. T. superba (75–300mg/kg) significantly decreased the blood glucose levels in glucose loaded rats. Oral administration of T. superba extract for 21 days resulted in a 31.43% and 21.42% significant reduction in blood glucose levels at the dose of 75mg/kg and 300mg/kg respectively. The plant extract significantly, reduced the plasma urea levels (20%) and induced a significant elevation in plasma insulin in treated rats. The extract did not significantly change elevated plasma cholesterol and triglycerides resulting from diabetic conditions. Conclusion: The antidiabetic effect of the methanol stem bark extract of T. superba seems to be a result of increase in glucose utilization due to stimulatory action on insulin release.
ABSTRACT
Leaf of Sasa borealis, a species of bamboo, has been reported to exhibit anti-hyperglycemic effect. However, its antidiabetic mechanism is not fully understood. In this study, we examined whether an extract of S. borealis activates AMP-activated protein kinase (AMPK) and exerts anti-hyperglycemic effects. Treatment with the S. borealis extract increased insulin signaling and phosphorylation of AMPK and stimulated the expression of its downstream targets, including PPARalpha, ACO, and CPT-1 in C2C12 cells and PPARalpha in HepG2 cells. However, inhibition of AMPK activation attenuated insulin signaling and prevented the stimulation of AMPK target genes. The S. borealis extract increased glucose uptake in C2C12 cells and suppressed expression of the gluconeogenic gene, PEPCK in HepG2 cells. The extract significantly reduced blood glucose and triglyceride levels in STZ-induced diabetic mice. The extract enhanced AMPK phosphorylation and increased Glut-4 expression in the skeletal muscle of the mice. These findings demonstrated that the S. borealis extract exerts its anti-hyperglycemic effect through activation of AMPK and enhancement of insulin signaling.