Nanobiosensors based on on-site detection approaches for rapid pesticide sensing in the agricultural arena: A systematic review of the current status and perspectives.

The extensive use of chemical pesticides has significantly boosted agricultural food crop yields. Nevertheless, their excessive and unregulated application has resulted in food contamination and pollution in environmental, aquatic, and agricultural ecosystems. Consequently, the on-site monitoring of pesticide residues in agricultural practices is paramount to safeguard global food and conservational safety. Traditional pesticide detection methods are cumbersome and ill-suited for on-site pesticide finding. The systematic review provides an in-depth analysis of the current status and perspectives of nanobiosensors (NBS) for pesticide detection in the agricultural arena. Furthermore, the study encompasses the fundamental principles of NBS, the various transduction mechanisms employed, and their incorporation into on-site detection platforms. Conversely, the assortment of transduction mechanisms, including optical, electrochemical, and piezoelectric tactics, is deliberated in detail, emphasizing its advantages and limitations in pesticide perception. Incorporating NBS into on-site detection platforms confirms a vital feature of their pertinence. The evaluation reflects the integration of NBS into lab-on-a-chip systems, handheld devices, and wireless sensor networks, permitting real-time monitoring and data-driven decision-making in agronomic settings. The potential for robotics and automation in pesticide detection is also scrutinized, highlighting their role in improving competence and accuracy. Finally, this systematic review provides a complete understanding of the current landscape of NBS for on-site pesticide sensing. Consequently, we anticipate that this review offers valuable insights that could form the foundation for creating innovative NBS applicable in various fields such as materials science, nanoscience, food technology and environmental science.

Protective Impact of Vanillic Acid on Lipid Profile and Lipid Metabolic Enzymes in Diabetic Hypertensive Rat Model Generated by a High-Fat Diet.

INTRODUCTION: Diabetes is the most common component of metabolic syndrome, including abdominal obesity, insulin resistance, hypertension, and dyslipoproteinemia. OBJECTIVE: This study aims to determine whether vanillic acid has antihyperlipidemic properties in diabetic hypertensive rats. METHODS: For this study healthy male albino Wister rats (180-220 gm) were selected. A 20-week highfat diet (HFD) was given to produce diabetic hypertension in Wister rats. Control and diabetic hypertensive rats were treated with vanillic acid. Vanillic acid effects on lipid profiles (cholesterol, triglycerides, phospholipids, free fatty acids, high-density lipoproteins (HDL)) and lipid metabolizing enzymes LPL, LCAT, and HMG CoA reductase studied by a conventional method. To understand the effect of vanillic acid control, experimental rat lipid and metabolic enzymes were studied and treated and controlled animal liver tissues were observed using the different histology staining agents. RESULTS: Vanillic acid caused considerable lipid profile reductions except for HDL and increased plasma HDL levels. After eight weeks of vanillic acid administration also boosts lipid marker enzyme activity (HMG CoA reductase, LPL, and LCAT). In addition, vanillic acid reduces the accumulation of collagen in liver tissues. CONCLUSION: These research studies suggest that vanillic acid has antihyperlipidemic effects in diabetic hypertensive rats fed an HFD.

Bacoside-A Improves Antioxidant Enzymes and Alleviates Oxidative Stress Coexist with Markers of Renal Function in a Rat Model of Type 2 Diabetes Mellitus.

Oxidative stress, imbalanced antioxidants, and dysregulated renal lipids are closely linked with diabetic nephropathy and eventual cause of end-stage renal failure. This study was performed to investigate the protective effect of bacoside-A on markers of lipid peroxidation, renal lipids, and markers of renal function in diabetic rats. Experimental diabetes was induced in Wistar rats by a single dose of streptozotocin [40 mg/kg body weight (BW)] via intraperitoneal injection. Oral administration of bacoside-A (10 mg/kg BW) and glibenclamide, a reference drug, continued for 45 days. Diabetic rats showed a significant increase in the levels of plasma glucose, renal lipids, markers of renal lipid peroxidation, and plasma biomarkers of renal function such as urea, uric acid, and creatinine. A significant decrease in the levels of plasma insulin, nonenzymatic antioxidants, and the activity of enzymatic antioxidants was seen compared with the normal controls. Bacoside-A (10 mg/kg BW) and glibenclamide (600 µg/kg BW) administered to diabetic rats resulted in a significant decrease in plasma glucose and renal lipids but a significant increase in the plasma insulin level. In addition, bacoside-A achieved a remarkable increase in the activity of enzymatic antioxidants and the levels of nonenzymatic antioxidants in the renal tissue of diabetic rats, along with significant decreases in the markers of lipid peroxidation and those of renal function, consequently substantiating the protecting effectiveness of bacoside-A in a diabetic state. These biochemical observations were supported by a histopathological study of the renal tissue. The present study suggested that bacoside-A, a triterpenoid, offers a higher renoprotective effect to counter abnormal parameters of renal function in diabetes-induced renal injury.

Citral, a Monoterpene Inhibits Adipogenesis Through Modulation of Adipogenic Transcription Factors in 3T3-L1 Cells.

Obesity is considered as a major global human health problem which significantly increases the risk for development of type 2 diabetes. Citral, a bioactive compound widely found in a variety of foods that are consumed daily. In this study, we investigated the inhibitory effect of citral against adipogenic genes in 3T3-L1 cells. The mouse fibroblast 3T3-L1 pre-adipocytes were differentiated into adipocytes using adipogenic cocktail (5 g/ml insulin, 0.5 mM isobutylmethylxanthine and 10 M dexamethasone). Differentiation of adipocytes was evaluated by assessing triglyceride accumulation assay and cell viability by MTT assay. The PI3K/AKT signaling, adipogenic specific transcription factors (PPARγ, SREBP-1c, FAS and CPD) and inflammatory genes (TNF-α, IL-6 and MCP-1) were analyzed by western blotting and reverse transcriptase PCR in differentiated 3T3-L1 cell lines. In this study, triglyceride accumulation was increased in adipogenic cocktail induced 3T3-L1 cells, whereas treatment of citral significantly decreased levels of triglyceride accumulation in concentration dependent manner. Further, MTT assay shows that there was no reduction of cell viability during the differentiation of 3T3-L1 cells. The differentiated 3T3-L1 cell significantly increases the expression of PI3K/AKT, adipogenic transcription factors (PPARγ, SREBP-1c, FAS and CPD) and inflammatory biomarkers (TNF-α, IL-6 and MCP-1). Conversely, cells were treated with citral significantly suppress the expression of PI3K/AKT, PPARγ, SREBP-1c, FAS, CPD, TNF-α, IL-6 and MCP-1 in dose dependent manner. Thus, citral exhibits beneficial effects to inhibit adipogenesis in 3T3-L1 adipocytes through the modulation of adipogenic transcription factors and inflammatory markers.

Modulatory effect of vanillic acid on antioxidant status in high fat diet-induced changes in diabetic hypertensive rats.

The worldwide incidence of diabetes has increased dramatically along with widespread lifestyle and dietary changes. Diets high in fat are strongly associated with the development of obesity and can induce insulin resistance in humans and animals. It is clear that obesity constitutes a risk factor for contributing to the development of type 2 diabetes. In the present study, we investigated the therapeutic potential action of vanillic acid on diabetes associated complications using a rat model. Rats were made diabetic hypertensive by high fat diet (HFD) for 20 weeks and were treated with vanillic acid (50mg/kg bw) for last 8 weeks. The effects of vanillic acid on glucose, plasma insulin, systolic and diastolic blood pressure, thiobarbituric acid reactive substances (TBARS), hydroperoxides as a lipid peroxidation marker, and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), vitamin C and vitamin E as an antioxidant marker, AST and ALT as a liver function marker, urea, uric acid and creatinine as a kidney function marker were investigated. Histopathology of liver and kidney was also investigated as part of the pathology of diabetes. Treatment of diabetic rats with oral administration of vanillic acid at a dose of 50mgkg/body weight for 8 weeks resulted in a significant decrease in fasting plasma glucose, insulin and blood pressure levels in comparison with diabetic control group. The antioxidant activities were significantly increased and the levels of lipid peroxidation markers were significantly decreased in diabetic hypertensive rats treated with vanillic acid. These results suggest that vanillic acid offer a modulatory effect on control of diabetic hypertension by reduction of blood glucose, insulin and blood pressure, combating oxidative stress by activation of tissue antioxidants.

RETRACTED: Combination of carvacrol and rosiglitazone ameliorates high fat diet induced changes in lipids and inflammatory markers in C57BL/6J mice.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Following concerns raised by Dr. E. Bik, the journal conducted an investigation and found evidence that there had been improper manipulation and duplication of images in Figure 4. The editors would like to thank Dr. Bik for her valuable insight in this matter. The authors have not responded to requests for an explanation of these irregularities so this article is retracted without their approval.

Renoprotective effect of myricetin restrains dyslipidemia and renal mesangial cell proliferation by the suppression of sterol regulatory element binding proteins in an experimental model of diabetic nephropathy.

Myricetin is a natural flavonoid used in various health management systems. In this present study myricetin tested to evaluate the effect on lipids and lipid metabolism enzymes in normal and streptozotocin (STZ) with cadmium (Cd) induced diabetic nephrotoxic rats. Diabetic nephrotoxic rats were significantly (P<0.05) increased the levels of urinary albumin and lipid profiles: total cholesterol (TC), triglycerides (TGs), free fatty acids (FFAs), phospholipids (PLs), low density lipoprotein (LDL), very low-density lipoproteins (VLDL), and decreased in the levels of high-density lipoproteins (HDL). In addition, the activity of lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) were decreased significantly, whereas the 3-hydroxy 3-methylglutaryl coenzyme A (HmgCoA) reductase activity was increased. The upregulation of sterol regulatory element binding protein-1a (SREBP-1a), SREBP-1c, SREBP-2, transforming growth factor-ß1 (TGF-ß1), vascular endothelial growth factor (VEGF) and downregulation peroxisome proliferator-activated receptor alpha (PPAR-α) proteins expression levels were noticed. An administration of myricetin (1.0 mg/kg body weight (b/w)) for 12 weeks was brought the above parameters towards normal level. Histopathological study of kidney samples showed that extracellular mesangial matrix expansion, glomerulosclerosis and interstitial fibrosis in diabetic nephrotoxic rats was suppressed by myricetin treatment. Further our results indicate that administration of myricetin afforded remarkable protection against STZ-Cd induced alterations in lipid metabolism and thereby reduced the diabetic nephropathy in experimental rats.

Protective effect of bioflavonoid myricetin enhances carbohydrate metabolic enzymes and insulin signaling molecules in streptozotocin-cadmium induced diabetic nephrotoxic rats.

Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. The present study was aimed to evaluate the therapeutic potential of myricetin by assaying the activities of key enzymes of carbohydrate metabolism, insulin signaling molecules and renal function markers in streptozotocin (STZ)-cadmium (Cd) induced diabetic nephrotoxic rats. After myricetin treatment schedule, blood and tissue samples were collected to determine plasma glucose, insulin, hemoglobin, glycosylated hemoglobin and renal function markers, carbohydrate metabolic enzymes in the liver and insulin signaling molecules in the pancreas and skeletal muscle. A significant increase of plasma glucose, glycosylated hemoglobin, urea, uric acid, creatinine, blood urea nitrogen (BUN), urinary albumin, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase and a significant decrease of plasma insulin, hemoglobin, hexokinase, glucose-6-phosphate dehydrogenase, glycogen and glycogen synthase with insulin signaling molecule expression were found in the STZ-Cd induced diabetic nephrotoxic rats. The administration of myricetin significantly normalizes the carbohydrate metabolic products like glucose, glycated hemoglobin, glycogen phosphorylase and gluconeogenic enzymes and renal function markers with increase insulin, glycogen, glycogen synthase and insulin signaling molecule expression like glucose transporter-2 (GLUT-2), glucose transporter-4 (GLUT-4), insulin receptor-1 (IRS-1), insulin receptor-2 (IRS-2) and protein kinase B (PKB). Based on the data, the protective effect of myricetin was confirmed by its histological annotation of the pancreas, liver and kidney tissues. These findings suggest that myricetin improved carbohydrate metabolism which subsequently enhances glucose utilization and renal function in STZ-Cd induced diabetic nephrotoxic rats.

Antihyperglycemic effect of fraxetin on hepatic key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats.

Epidemiological studies have demonstrated that the diabetes mellitus is a serious health burden for both governments and healthcare providers. The present study was hypothesized to evaluate the antihyperglycemic potential of fraxetin by determining the activities of key enzymes of carbohydrate metabolism in streptozotocin (STZ) - induced diabetic rats. Diabetes was induced in male albino Wistar rats by intraperitoneal administration of STZ (40 mg/kg b.w). Fraxetin was administered to diabetic rats intra gastrically at 20, 40, 80 mg/kg b.w for 30 days. The dose 80 mg/kg b.w, significantly reduced the levels of blood glucose and glycosylated hemoglobin (HbA1c) and increased plasma insulin level. The altered activities of the key enzymes of carbohydrate metabolism such as glucokinase, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase and hepatic enzymes (aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP)) in the liver tissues of diabetic rats were significantly reverted to near normal levels by the administration of fraxetin. Further, fraxetin administration to diabetic rats improved body weight and hepatic glycogen content demonstrated its antihyperglycemic potential. The present findings suggest that fraxetin may be useful in the treatment of diabetes even though clinical studies to evaluate this possibility may be warranted.

Protective effect of esculetin on hyperglycemia-mediated oxidative damage in the hepatic and renal tissues of experimental diabetic rats.

Diabetes mellitus is the most common serious metabolic disorder and it is considered to be one of the five leading causes of death in the world. Hyperglycemia-mediated oxidative stress plays a crucial role in diabetic complications. Hence, this study was undertaken to evaluate the protective effect of esculetin on the plasma glucose, insulin levels, tissue antioxidant defense system and lipid peroxidative status in streptozotocin-induced diabetic rats. Diabetic rats exhibited increased blood glucose with significant decrease in plasma insulin levels. Extent of oxidative stress was assessed by the elevation in the levels of lipid peroxidation markers such as thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (HP) and conjugated dienes (CD); reduction in the enzymic antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST); nonenzymic antioxidants Vitamin C, E and reduced glutathione (GSH) were observed in the liver and kidney tissues of diabetic control rats as compared to control rats. Oral supplementation of esculetin to diabetic rats for 45 days significantly brought back lipid peroxidation markers, enzymic and nonenzymic antioxidants to near normalcy. Moreover, the histological observations evidenced that esculetin effectively rescues the hepatocytes and kidney from hyperglycemia mediated oxidative damage without affecting its cellular function and structural integrity. These findings suggest that esculetin (40 mg/kg BW) treatment exerts a protective effect in diabetes by attenuating hyperglycemia-mediated oxidative stress and antioxidant competence in hepatic and renal tissues. Further, detailed studies are in progress to elucidate the molecular mechanism by which esculetin elicits its modulatory effects in insulin signaling pathway.

Antihyperglycemic, antihyperlipidemic, and renoprotective effects of Chlorella pyrenoidosa in diabetic rats exposed to cadmium.

OBJECTIVE: The objective of the present study is to evaluate the antihyperlipidemic effect of Chlorella pyrenoidosa in diabetic rats exposed to cadmium (Cd). MATERIALS AND METHODS: Group 1 and 2 rats were treated as control and C. pyrenoidosa control. Group 3 and 4 rats were given single injection of streptozotocin (40 mg/kg b.w; i.p) followed by Cd (0.6 mg/kg b.w; s.c) for 5 days per week for a total period of 90 days. In addition, group 4 rats alone were treated with C. pyrenoidosa throughout the study period of 90 days. Assessments of plasma glucose, insulin, lipid profile and renal function markers were performed in control and experimental rats along with histological examination of kidney tissues. RESULTS: Diabetic rats exposed to Cd showed increased levels of plasma glucose and decreased levels of plasma insulin accompanied by the significantly elevated levels of tissue lipids viz., total cholesterol, triglyceride, free fatty acid, and phospholipids compared with control rats. Alterations in lipoproteins (low density lipoprotein-C, very low density lipoprotein-C, and high density lipoprotein-C) levels were also observed. DISCUSSION: Elevated levels of urinary albumin, creatinine, and blood urea nitrogen confirmed the onset of renal dysfunction in unsupplemented diabetic rats exposed to Cd. CONCLUSION: C. pyrenoidosa (100 mg/kg body weight) supplemented diabetic nephropathic rats showed near normal biochemical profile and well preserved renal histology that substantiate the antihyperglycemic, antihyperlipidemic, and renoprotective effects of C. pyrenoidosa in diabetic rats exposed to Cd.

Hepatoprotective effect of morin on ethanol-induced hepatotoxicity in rats.

Morin is a flavonoid that exists in nature and is the major component of traditional medicinal herbs. Here we evaluated morin for its hepatoprotective effect against chronic ethanol-induced biochemical changes in male Wistar rats. Ethanol administration (7.9 g/kg bwt) for 60 days induced hepatic and renal damage by increasing oxidative stress and decreasing antioxidant levels. The status of lipid peroxidation (thiobarbituric reactive substances (TBARS) and hydroperoxides (HP)), antioxidant (vitamin C, vitamin E, GSH), serum hepatic markers (AST, ALT, ALP, GGT, bilirubin), and renal markers (urea, creatinine) were assessed as biochemical endpoints to determine the hepatic protective effect of morin. Oral administration of morin (100 mg/kg b.w) to alcohol-intoxicated rats for 30 days showed significant decreases in lipid peroxidation and restoration of antioxidant, hepatic, and renal markers to normal. Histopathologic observations of liver were also in correlation with biochemical parameters. The results indicate that morin might be beneficial in ameliorating alcohol-induced oxidative damage in rat liver.

Glycoprotein changes in non-insulin dependent diabetic rats: effect of N-benzoyl-D-phenylalanine and metformin.

The effect of N-benzoyl-D-phenylalanine (NBDP) and metformin on neonatal streptozotocin (nSTZ) induced diabetes has been studied on plasma and tissue glycoproteins. In some pathological conditions, such as cancer, rheumatoid arthritis and diabetes, there is an abnormal glycosylation of acute phase serum proteins. As most serum proteins are produced in the liver, we have examined glycoprotein metabolism in diabetic condition. To induce non-insulin-dependent diabetes mellitus (NIDDM) a single dose of streptozotocin (100 mg/kg body weight) was injected into two day old rats. After 10-12 weeks, rats weighing above 150 g were selected for NIDDM model. In these rat, blood glucose and plasma glycoproteins were significantly increased whereas plasma insulin was significantly decreased. There was a significant decrease in the level of sialic acid and elevated levels of hexose, hexosamine and fucose in tissues. Oral administration of NBDP and metformin to diabetic rats decreased blood glucose and plasma glycoproteins. Plasma insulin and tissue sialic acid were increased whereas tissue concentrations of hexose, hexosamine and fucose were near normal. Our study suggests that NBDP and metformin possess a significant beneficial effect on glycoproteins in addition to their antidiabetic effect.

N-Benzoyl-D-phenylalanine attenuates brain acetylcholinesterase in neonatal streptozotocin-diabetic rats.

The effect of hyperglycaemia due to experimental diabetes in male Wistar rats causes a decrease in the level of acetylcholinesterase (AChE) with significant increase in lipid peroxidative markers: thiobarbituric acid-reactive substances (TBARS) and hydroperoxides in brains of experimental animals. The decreased activity of both salt soluble and detergent soluble acetylcholinesterase observed in diabetes may be attributed to lack of insulin which causes specific alterations in the level of neurotransmitter, thus causing brain dysfunction. Administration of non-sulfonylurea drug N-benzoyl-D-phenylalanine (NBDP) could protect against direct action of lipid peroxidation on brain AChE and in this way it might be useful in the prevention of cholinergic neural dysfunction, which is one of the major complications in diabetes.

Modulation of impaired cholinesterase activity in experimental diabetes: effect of Gymnema montanum leaf extract.

We reported that a leaf extract (GLEt) obtained from an anti-diabetic plant, Gymnema montanum, an endangered species endemic to India, has anti-peroxidative and antioxidant effects on diabetic brain tissue in rats. Here we examined the effect of the extract on the activity of reduced brain and retinal acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in streptozotocin (STZ)-induced diabetic male Wistar rats. Diabetic rats received GLEt orally (200 mg/kg bwt/d) for 12 wk, and changes in blood glucose, plasma insulin, the lipid peroxidation marker thiobarbituric acid-reactive substance (TBARS), and AChE and BChE activity were measured. The results confirmed prior reports that hyperglycemia significantly enhances TBARS levels in brain and retinal tissue and decreases AChE and BChE activity. Treatment with GLEt significantly reversed the impairment in enzymatic activity in addition to reducing the level of TBARS, suggesting that GLEt protects against the adverse effect of lipid peroxidation on brain and retinal cholinesterases. We suggest that GLEt could be useful for preventing the cholinergic neural and retinal complications of hyperglycemia in diabetes.

Effect of N-benzoyl-d-phenylalanine on lipid profile in liver of neonatal streptozotocin diabetic rats.

The effect of N-benzoyl-d-phenylalanine (NBDP) and metformin combination treatment on liver lipids and lipid peroxidation markers was studied in neonatal streptozotocin (nSTZ) diabetic rats. Oral administration of NBDP (50, 100 and 200 mg/kg body weight) and metformin (500 mg/kg body weight) for 6 weeks significantly reduced the elevated blood glucose, liver cholesterol, triglycerides, free fatty acids and phospholipids. The combination treatment also caused a significant decrease in hepatic hydroxymethyl glutaryl-coenzyme A reductase, Thiobarbituric Acid Reactive Substances (TBARS) and significant increase in reduced glutathione levels. The results show that NBDP and metformin improve the hepatic lipid profile and antioxidant status in nSTZ diabetic rats. Combination treatment was more effective than either drug alone.

Effect of N-benzoyl-D-phenylalanine, a new potential oral antidiabetic agent, in neonatal streptozotocin-induced diabetes in rats.

The present investigation was undertaken to study the effect of treatment with D-phenylalanine derivative and metformin in neonatal streptozotocin (nSTZ)-induced non-insulin-dependent diabetes mellitus (NIDDM) in rats. To induce NIDDM, a single dose injection of streptozotozin (STZ) (100 mg kg(-1); ip) was given to 2-day-old rats. After 10-12 weeks, rats weighing above 150 g were selected for screening in NIDDM model. They were checked for fasting blood glucose levels to conform the status of NIDDM. D-phenylalanine derivative (50, 100 and 200 mg kg(-1)) was administered per os (po) for 6 weeks to the rats with confirmed diabetes. A group of diabetic rats was also maintained and this group received metformin as comparative drug. Significant decrease in blood glucose with significant increase in plasma insulin was observed in group receiving 100 mg of D-phenylalanine derivative plus 500 mg of metformin.

Effect of N-benzoyl-D-phenylalanine and metformin on carbohydrate metabolic enzymes in neonatal streptozotocin diabetic rats.

BACKGROUND: The effect of N-benzoyl-D-phenylalanine (NBDP) and metformin was studied on the activities of carbohydrate metabolic enzymes in neonatal streptozotocin (nSTZ) non-insulin-dependent diabetic rats. METHODS: To induce non-insulin-dependent diabetes mellitus (NIDDM), single dose injection of streptozotocin (STZ; 100 mg/kg body weight; i.p.) was given to 2-day old rats. After 10-12 weeks, rats weighing >150 g were selected for screening in NIDDM model, they were checked for fasting blood glucose concentrations to conform the status of NIDDM. NBDP (50,100 and 200 mg/kg body weight) was administered orally for 6 weeks into the confirmed diabetic rats. RESULTS: The activities of gluconeogenic enzymes were significantly increased, whereas the activities of hexokinase and glucose-6-phosphate dehydrogenase were significantly decreased in nSTZ diabetic rats. Both NBDP and metformin were able to restore the altered enzyme activities to almost control concentrations. Combination treatment was more effective than either drug alone. CONCLUSION: The administration of NBDP along with metformin to nSTZ diabetic rats normalizes blood glucose and causes marked improvement of altered carbohydrate metabolic enzymes during diabetes.