Tropisetron ameliorates early diabetic nephropathy in streptozotocin‐induced diabetic rats

It has been well established that oxidative stress and inflammation are involved in the pathogenesis of diabetic nephropathy. It has been shown that tropisetron exerts anti‐inflammatory and immunomodulatory properties. The current study was designed to investigate protective effects of tropisetron on early diabetic nephropathy in streptozotocin‐induced diabetic rats. Rats were divided into six groups: (i) untreated diabetic (streptozotocin group); (ii) untreated control; (iii) diabetic rats treated with tropisetron (3 mg/kg); (iv) normal rats treated with tropisetron (3 mg/kg); (v) diabetic rats treated with granisetron (3 mg/kg); and (vi) normal rats treated with granisetron (3 mg/kg); rats began receiving treatment at the time of diabetes induction for 2 weeks. At the termination of the experiments, bodyweight, kidney index, urinary albumin excretion, and glomerular filtration rate were measured. The levels of oxidative stress markers and tumour necrosis factor‐α were also determined. Streptozotocin‐treated animals showed significant loss of bodyweight and renal enlargement and dysfunction. Diabetic rats also exhibited an increase in malondialdehyde along with a significant decrease in glutathione, superoxide dismutase activity, and catalase activity. Furthermore, the diabetic animals demonstrated a significant rise in renal cortical, urinary tumour necrosis factor‐α, and urinary albumin excretion. Both granisetron and tropisetron decreased blood glucose in diabetic animals, but this decrease was not significant for granisetron. Treatment with tropisetron, but not granisetron, prevented increases in oxidative stress and tumour necrosis factor‐α, decreased urinary cytokine excretion and albuminuria, and improved renal morphological damage. In conclusion, the present study suggests that tropisetron may be a protective agent in early diabetic nephropathy, and its action is mediated, at least in part, by anti‐oxidative and anti‐inflammatory mechanisms that appear to be independent of the 5‐HT₃ receptor.     

Nephroprotective effect of Paeonia emodi via inhibition of advanced glycation end products and oxidative stress in streptozotocin–nicotinamide induced diabetic nephropathy

The present study aimed to evaluate the effect of alcohol (PA) and hydroalcohol (PHA) extract of Paeonia emodi Royale roots in treatment of streptozotocin–nicotinamide induced diabetic nephropathy. Diabetes mellitus was induced in male Wistar rats by streptozotocin (65 mg/kg intraperitoneally) 15 minutes after nicotinamide (230 mg/kg, intraperitoneally) administration and diabetic nephropathy was assessed by measuring serum glucose, renal parameters (urea, uric acid, creatinine, and blood urea nitrogen level) and lipid profile. The rats were treated with different doses of extracts (100 mg/kg, 200 mg/kg, and 400 mg/kg) for 45 days. Oxidative stress was assessed by measuring tissue antioxidant enzymes level along with the formation of advanced glycation end-products (AGEs) in kidney. PA and PHA (400 mg/kg) produced significant attenuation in the serum glucose level (165.08 ± 3.353 mg/dL and 154.27 ± 2.209 mg/dL, respectively) as compared to control. Elevated renal parameters, lipid levels, tissue antioxidant enzymes and AGE formation were also restored in a dose-dependent manner. These findings suggest that by amelioration of oxidative stress and formation of AGEs, PA and PHA significantly inhibited the progression diabetic nephropathy in rats.     

Cycloart-23-ene-3β, 25-diol stimulates GLP-1 (7–36) amide secretion in streptozotocin–nicotinamide induced diabetic Sprague Dawley rats: A mechanistic approach

In previous study, we have reported cycloart-23-ene-3β, 25-diol is an active antidiabetic constituent isolated from stem bark of Pongamia pinnata (Linn.) Pierre. The objective of the present investigation was to evaluate cycloart-23-ene-3β, 25-diol stimulates glucagon like peptide-1 (GLP-1) (7–36) amide secretion in streptozotocin–nicotinamide induced diabetic Sprague Dawley rats. Molecular docking studies were performed to elucidate the molecular basis for GLP-1 receptor agonistic activity. Type 2 diabetes was induced in overnight fasted Sprague Dawley rats pre-treated with nicotinamide (100 mg/kg, i.p.) followed by administration of streptozotocin (55 mg/kg, i.p.) 20 min after. The rats were divided into following groups; I- non-diabetic, II- diabetic control, III- sitagliptin (5 mg/kg, p.o.), IV- cycloart-23-ene-3β, 25-diol (1 mg/kg, p.o.). The cycloart-23-ene-3β, 25-diol and sitagliptin treatment was 8 week. Plasma glucose was estimated every week (week 0 to week 8). Body weight, food and water intake were recorded daily. Glycosylated haemoglobin, lipid profile, plasma and colonic active (GLP-1) (7–36) amide, mRNA expression of proglucagnon GLP-1, plasma and pancreatic insulin, histology of pancreata as well as biomarkers of oxidative stress (superoxidase dismutase, reduced glutathione, malondialdehyde, glutathione peroxidase, glutathione S transferase) were measured after 8th week treatment. In acute study, active GLP-1 (7–36) amide release, plasma glucose and insulin were measured during oral glucose tolerance test. The docking data clearly indicated cycloart-23-ene-3β, 25-diol bind to the GLP-1 receptor. It decreased plasma glucose level, increased plasma and pancreatic insulin level as well as increased plasma and colonic active GLP-1 (7–36) amide secretion in streptozotocin–nicotinamide induced diabetic Sprague Dawley rats.     

The effects of chronic resveratrol treatment on vascular responsiveness of streptozotocin-induced diabetic rats

Deficiency in the vasorelaxant capacity is a result of an oxidative stress in diabetic animals and seems to be an etiological factor of vascular complications of diabetes. The present study was designed to examine whether resveratrol (RSV), a polyphenolic compound which is naturally present in grape and red wine, has a protective effect on diabetic aorta. Resveratrol (5 mg/kg/d, i.p.) was administered for 42 d to streptozotocin (STZ) (60 mg/kg) induced diabetic rats. Loss of weight, hyperglycemia, and elevated levels of plasma malondialdehyde (MDA) were observed in diabetic rats. Resveratrol treatment was significantly effective for these metabolic and biochemical abnormalities. The contractile responses of the aorta were recorded. Compared with control subjects, the aorta showed significantly enhanced contractile responses to noradrenaline (NA), but not to potassium chloride (KCl), in diabetic rats. Treatment of diabetic rats with resveratrol significantly reversed the increases in responsiveness and sensitivity of aorta to noradrenaline. In diabetic aorta, the relaxation response to acetylcholine (Ach) was found to be significantly decreased compared with control subjects, and resveratrol treatment reversed this; no such change was observed in the relaxation response to sodium nitroprusside (SNP). These results indicated that resveratrol significantly improved not only glucose metabolism and oxidative injury but also impaired vascular responses in streptozotocin induced diabetic rats.     

Changes in hepatic lipogenic and oxidative enzymes and glucose homeostasis induced by an acetyl‐l‐carnitine and nicotinamide treatment in dyslipidaemic insulin‐resistant rats

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Betanin exhibits significant potential as an antihyperglycemic and attenuating the glycoprotein components in streptozotocin–nicotinamide-induced experimental rats

This study hypothesized to evaluate the effect of betanin, a chromoalkaloid on plasma and altered tissues glycoprotein components in streptozotocin–nicotinamide-induced diabetic rats. Diabetes was induced by a single intraperitoneal (i.p.) injection of streptozotocin (45?mg/kg b.w.) dissolved in 0.1 M citrate buffer (pH 4.5) 15?min after the i.p. administration of nicotinamide (110?mg/kg b.w.). Experimental rats were administered betanin at the dose of 20?mg/kg b.w. and glibenclamide (600 µg/kg b.w.) once a day for 30 days. Diabetic rats revealed significant (p?1C, hexose, hexosamine, sialic acid and fucose in the plasma; decrease in the levels of plasma insulin, Hb and sialic acid in the liver and kidney; significant (p?相似文献   

The furoxan nitric oxide donor,PRG150, evokes dose‐dependent analgesia in a rat model of painful diabetic neuropathy

Painful diabetic neuropathy (PDN) is a type of peripheral neuropathic pain that is often intractable. Elevated nitric oxide (NO) from neuronal and non‐neuronal sources in the somatosensory system is implicated in the pathobiology of peripheral neuropathic pain. However, in diabetes, nitrergic nerve degeneration to deplete NO bioactivity appears causal in the pathogenesis of irreversible autonomic neuropathy, another long term complication of diabetes. Hence, this study hypothesized that progressive NO depletion may underpin the pathobiology of PDN and that NO donors may alleviate PDN. Diabetes was induced in rats with intravenous streptozotocin (STZ) at 70 mg/kg and confirmed if blood glucose levels (BGLs) on day 10 post‐STZ were ≥15 mmol/L. Analgesic efficacy of subcutaneous (s.c.) bolus doses of the furoxan NO donor, PRG150 was assessed in the STZ‐diabetic rat model of PDN at 10‐, 14‐ and 24‐weeks post‐STZ relative to the sydnominine NO donor, SIN‐1 and its prodrug, molsidomine. PRG150 produced dose‐dependent analgesia in STZ‐diabetic rats whereas SIN‐1 and molsidomine evoked neuro‐excitatory side‐effects, but not analgesia. The 1000‐fold larger doses of PRG150 needed to produce analgesia at 14‐ and 24‐weeks (800 pmol/kg) c.f. 10‐weeks (8 fmol/kg) post‐STZ in rats, suggest that progressive NO depletion is also causal in PDN. Importantly, doses of PRG150 up to 10 000 fold higher than the analgesic dose did not produce hypotension in rats. The 50‐fold greater release of NO by SIN‐1 c.f. PRG150 in vitro, may underpin the neuro‐excitatory rather than analgesic effects of SIN‐1/molsidomine. PRG150 is worthy of further investigation as a potential novel analgesic for PDN.     

Nephroprotective effect of Paeonia emodi via inhibition of advanced glycation end products and oxidative stress in streptozotocin–nicotinamide induced diabetic nephropathy

The present study aimed to evaluate the effect of alcohol (PA) and hydroalcohol (PHA) extract of Paeonia emodi Royale roots in treatment of streptozotocin–nicotinamide induced diabetic nephropathy. Diabetes mellitus was induced in male Wistar rats by streptozotocin (65 mg/kg intraperitoneally) 15 minutes after nicotinamide (230 mg/kg, intraperitoneally) administration and diabetic nephropathy was assessed by measuring serum glucose, renal parameters (urea, uric acid, creatinine, and blood urea nitrogen level) and lipid profile. The rats were treated with different doses of extracts (100 mg/kg, 200 mg/kg, and 400 mg/kg) for 45 days. Oxidative stress was assessed by measuring tissue antioxidant enzymes level along with the formation of advanced glycation end-products (AGEs) in kidney. PA and PHA (400 mg/kg) produced significant attenuation in the serum glucose level (165.08 ± 3.353 mg/dL and 154.27 ± 2.209 mg/dL, respectively) as compared to control. Elevated renal parameters, lipid levels, tissue antioxidant enzymes and AGE formation were also restored in a dose-dependent manner. These findings suggest that by amelioration of oxidative stress and formation of AGEs, PA and PHA significantly inhibited the progression diabetic nephropathy in rats.     

C‐Aryl Glucosides with Substituents at the Distal Aryl Ring as Sodium‐Dependent Glucose Cotransporter Inhibitors for the Treatment of Diabetes Mellitus

A series of novel C‐aryl glucosides with various substituents at the distal aryl ring have been synthesized and evaluated for hypoglycemic effect in normal and diabetic mice and in type 2 diabetic rats. The results indicated that introduction of electron‐donating group at the distal aryl ring could improve glucose tolerance in normal mice, whereas introduction of electron‐withdrawing group at this position could deteriorate. The urinary glucose excretion was significantly increased after glucose (3 g/kg) administration in normal mice with the treatment of 13c . Moreover, compound 13c could reduce fed blood glucose levels in a dose‐dependent manner in type 2 diabetic rats, showed a remarkable antihyperglycemic effect with 2 weeks of treatment in diabetic mice, and might be a promising drug candidate for the treatment of diabetes mellitus.     

Gastroprotective effects of the insulin sensitizers rosiglitazone and metformin against indomethacin‐induced gastric ulcers in Type 2 diabetic rats

1. Gastric ulcers are common in Type 2 diabetic patients. Of all drugs used in the treatment of Type 2 diabetes, the insulin sensitizers thiazolidinediones (e.g. rosiglitazone) and metformin exhibit additional effects in ameliorating oxidative stress and inflammation, rendering them attractive candidates for the prevention of gastric ulcer in Type 2 diabetes. Thus, the aim of the present study was to evaluate the gastroprotective effects of rosiglitazone and metformin against indomethacin‐induced gastric ulcer in Type 2 diabetic and non‐diabetic rats. 2. Diabetes was induced by a single injection of streptozotocin (60 mg/kg, i.p., dissolved in 0.1 mol/L cold citrate buffer, pH 4.5), 15 min after administration of 120 mg/kg, i.p., nicotinamide. Three weeks after the successful induction of diabetes, rats were subjected to pyloric ligation and then injected immediately with 30 mg/kg, i.p., indomethacin. Three hours after indomethacin administration, rats were killed and gastric injury was evaluated. Ranitidine (50 mg/kg) was used as a reference drug and was administered in a single oral dose 1 h before indomethacin injection, as were rosiglitazone (3 mg/kg) and metformin (500 mg/kg). 3. Both rosiglitazone and metformin exhibited gastroprotective effects, as evidenced by significant decreases in the ulcer index, free and total acid output in gastric juice and gastric mucosal malondialdehyde concentrations, with concomitant increases in gastric juice pH (only with rosiglitazone), mucin concentrations, gastric mucosal concentrations of nitric oxide and catalase activity compared with untreated diabetic rats. Conversely, rosiglitazone and metformin had no effect on peptic activity and gastric mucosal prostaglandin E₂ content, particularly in the diabetic group, compared with the untreated groups. 4. In conclusion, rosiglitazone and metformin protect Type 2 diabetic rats against indomethacin‐induced gastric ulceration, most possibly via antisecretory actions, enhanced mucosal protection and anti‐oxidant activity. Rosiglitazone seems to be provide superior gastroprotection to metformin.     

Protective Effects of d‐Limonene on Lipid Peroxidation and Antioxidant Enzymes in Streptozotocin‐Induced Diabetic Rats

The aim of this study was to evaluate the protective effects of d ‐limonene on the levels of lipid peroxidation by‐products and antioxidant defence systems in the plasma and tissues of normal and streptozotocin (STZ)‐induced diabetes rats. The experimental diabetes was induced in rats by a single dose of STZ (40 mg/kg i.p.) injection, and treatment with d ‐limonene was continued for 45 days. After the treatment period, oxidative stress parameters such as lipid peroxidation by‐products; enzymatic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase and glutathione‐S‐transferase; non‐enzymic antioxidants including reduced glutathione, Vitamins C and E were measured in the plasma and tissues of experimental rats. An increase in the levels of lipid peroxidation by‐products and significant decrease in antioxidant enzymes were observed in untreated diabetic rats. Administration of d ‐limonene to diabetic rats for 45 days caused a significant reduction in the levels of lipid peroxidation by‐products and an increase in the activities of antioxidant enzymes, when compared with the untreated diabetic group. There was no significant difference in normal treated groups, when compared with normal rats. Biochemical observations were substantiated with the help of histopathological examinations through its antioxidant properties and thereby conferred protection against STZ‐induced diabetic rats. The result of this study indicates that d ‐limonene has antioxidant potential in addition to its antidiabetic effect in experimental diabetes.     

Morphine hyposensitivity in streptozotocin‐diabetic rats: Reversal by dietary l‐arginine treatment

Painful diabetic neuropathy (PDN) is a long‐term complication of diabetes. Defining symptoms include mechanical allodynia (pain due to light pressure or touch) and morphine hyposensitivity. In our previous work using the streptozotocin (STZ)‐diabetic rat model of PDN, morphine hyposensitivity developed in a temporal manner with efficacy abolished at 3 months post‐STZ and maintained for 6 months post‐STZ. As this time course mimicked that for the temporal development of hyposensitivity to the pain‐relieving effects of the furoxan nitric oxide (NO) donor, PRG150 (3‐methylfuroxan‐4‐carbaldehyde) in STZ‐diabetic rats, we hypothesized that progressive depletion of endogenous NO bioactivity may underpin the temporal loss of morphine sensitivity in STZ‐diabetic rats. Furthermore, we hypothesized that replenishment of NO bioactivity may restore morphine sensitivity in these animals. Diabetes was induced in male Dark Agouti rats by intravenous injection of STZ (85 mg/kg). Diabetes was confirmed on day 7 if blood glucose concentrations were ≥15 mmol/L. Mechanical allodynia was fully developed in the bilateral hindpaws by 3 weeks of STZ‐diabetes in rats and this was maintained for the study duration. Morphine hyposensitivity developed in a temporal manner with efficacy abolished by 3 months post‐STZ. Administration of dietary l ‐arginine (NO precursor) at 1 g/d to STZ‐diabetic rats according to a 15‐week prevention protocol initiated at 9 weeks post‐STZ prevented abolition of morphine efficacy. When given as an 8‐week intervention protocol in rats where morphine efficacy was abolished, dietary l ‐arginine at 1 g/d progressively rescued morphine efficacy and potency. Our findings implicate NO depletion in the development of morphine hyposensitivity in STZ‐diabetic rats.     

Effects of antidiabetic drugs in high-fat diet and streptozotocin-nicotinamide-induced type 2 diabetic mice

Based on previously established methods, we developed an easily available type 2 diabetic mouse model that exhibits obesity and insulin resistance. We investigated the effects of several antidiabetic drugs on this new model, which was induced by a high-fat diet in combination with streptozotocin and nicotinamide injection. Male ICR mice were fed a high-fat diet (45% of calories as fat) for 3weeks and then intraperitoneally administered with nicotinamide (1000mg/kg) and streptozotocin (150mg/kg). These diabetic mice exhibited hyperglycemia and glucose intolerance as a result of the loss of early-phase insulin secretion. The mice also developed significant insulin resistance, hyperlipidemia and obesity. A single dose of mitiglinide, glibenclamide, sitagliptin, insulin, metformin and voglibose significantly improved glucose tolerance during a liquid meal tolerance test. Repeated administration of sitagliptin and rosiglitazone also improved hyperglycemia and insulin resistance. These results demonstrate that a high-fat diet combined with nicotinamide and streptozotocin injection induces a diabetic mouse model that replicates the metabolic characteristics of human type 2 diabetes. This diabetic model, which exhibits impaired insulin secretion, glucose intolerance, insulin resistance, and obesity, may be suitable to evaluate antidiabetic agents for the treatment of type 2 diabetes.     

Renoprotective effect of Hypericum perforatum against diabetic nephropathy in rats: Insights in the underlying mechanisms

Oxidative stress and inflammation play a key role in the initiation and progression of diabetic nephropathy (DN). The present study aimed to investigate the possible protective effect of hypericum perforatum (HP) against DN. Rats were allocated into six groups: control, received normal saline; diabetic untreated (DM), received single dose of streptozotocin (STZ) after injection of nicotinamide (NA); gliclazide, received STZ,NA + gliclazide (10 mg/kg); DM + HP50, DM + HP100, DM + HP200, received STZ,NA and HP 50, 100, 200 mg/kg, respectively. Gliclazide and HP were administered daily via gavage for 8 weeks. Serum glucose, insulin, kidney function and histopathological picture were assessed. Furthermore, oxidative/nitrosative stress, inflammatory cytokines, apoptotic and fibrotic markers were measured. Diabetic untreated group showed increase in serum glucose, urea, creatinine with albuminurea. Renal expression of protein for nuclear factor kappa‐B (NF‐кB), renal expression of inducible nitric oxide synthase (iNOS), cyclooxygenase II (COXII), collagen IV, fibronectin were elevated. Malondialdehyde (MDA), nitric oxide (NO), tumour necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), intracellular adhesion molecule (ICAM‐1), monocellular chemoattractant protein‐1 (MCP‐1), tumour growth factor‐ β (TGF‐β), caspase‐3 and cytochrome c contents were also increased consequently with decline of serum insulin, expression of peroxisome proliferator‐activated receptor (PPARγ), renal reduced glutathione (GSH) content and superoxide dismutase (SOD) activity. Treatment with either gliclazide or HP mitigated the deleterious effects of STZ on the tested parameters. These findings indicate for the first time that HP may have a renoprotective effect against DN through reduction of oxidative/nitrosative stress, enhancement of antioxidant defense mechanisms, decline of inflammatory cytokines, antifibrotic, antiapoptotic and blood glucose lowering properties.     

Antidiabetic properties of the alcoholic extract of Sphaeranthus indicus in streptozotocin-nicotinamide diabetic rats

We have investigated the possible antihyperglycaemic effects of Sphaeranthus indicus extract in rats rendered diabetic by nicotinamide (120 mgkg(-1) i.p.) and streptozotocin (STZ) (60 mgkg(-1) i.p). Fasting plasma glucose levels, serum insulin levels, serum lipid profiles, magnesium levels, glycosylated haemoglobin, changes in body weight and liver glycogen levels were evaluated in normal and diabetic rats. Oral administration of S. indicus for 15 days resulted in significant decrease in blood glucose levels and increases in hepatic glycogen and plasma insulin levels. Fasting normal rats treated with the alcoholic extract of S. indicus showed significant improvement in oral glucose tolerance test. Glibenclamide was used as a reference standard. The findings demonstrate that the alcoholic S. indicus extract may be useful in the treatment of diabetes.     

Fisetin,a tetra hydroxy flavone recuperates antioxidant status and protects hepatocellular ultrastructure from hyperglycemia mediated oxidative stress in streptozotocin induced experimental diabetes in rats

Oxidative stress is a biological entity quoted as accountable for several pathological conditions including diabetes mellitus. Chronic hyperglycemia in diabetes is associated with oxidative stress mediated tissue damage. The present study is aimed to explore the role of fisetin, in ameliorating hyperglycemia-mediated oxidative damage to liver in streptozotocin induced diabetic rats. In addition to the levels of blood glucose, plasma insulin, glycosylated hemoglobin, the extent of oxidative stress was assessed by hepatic lipid peroxides and hydroperoxides. The levels of reduced glutathione and the activities of enzymatic antioxidants were determined in the liver tissues. The activities of serum aminotransferases and alkaline phosphatase were assayed. A portion of liver was processed for histological and ultrastructural studies. Oral administration of fisetin (10 mg/kg b.w.) to diabetic rats decreased the levels of blood glucose and glycosylated hemoglobin and increased the plasma insulin level. A reduction in lipid peroxides and hydroperoxides were observed. The diminished activities of antioxidant enzymes and reduced glutathione in diabetic rats were improved upon fisetin administration. Thus, the results of the present study indicate that fisetin treatment protects the hepatocytes by improving the antioxidant competence in hepatic tissues of diabetic rats which is further evidenced from histological and ultra structural observations.     

Evaluation of Hypoglycemic and Antioxidative Effects of Synthesized Peptide MC62

Diabetes mellitus has been considered as a major health problem in the world today. This study aimed to investigate the hypoglycemic and antioxidative effects of peptide MC62 which was synthesized by solid‐phase peptide synthesis method against diabetes induced by streptozotocin. MC62 was administered daily and injected intraperitoneally to the diabetic mice at a dose of 1 μmol/kg body weight for 20 days. The levels of fasting blood glucose and HbA1C, pancreatic islet damage, and associated changes in antioxidative activities were evaluated in streptozotocin‐induced diabetic mice used the exenatide as positive control. After the administration of MC62 together with exenatide for 20 days, the elevated fasting blood glucose and HbA1C levels were reduced, and antioxidative activities were restored. It was confirmed with the histological finding that MC62 prevented the islet from damage in diabetic mice. This indicated that MC62 can prevent mice from hyperglycemia which may be associated with oxidative stress. It also suggested that MC62 could be used as a safe alternative hypoglycemic candidate for treatment of diabetes.     

Geraniol,a natural monoterpene,ameliorates hyperglycemia by attenuating the key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats

Context: Geraniol, an acyclic monoterpene alcohol is found in medicinal plants, is used traditionally for several medical purposes including diabetes.

Objectives: The present study evaluates the antihyperglycemic potential of geraniol on key enzymes of carbohydrate metabolism in streptozotocin (STZ)-induced diabetic rats.

Materials and methods: Diabetes was induced in experimental rats, by a single intraperitoneal (i.p) injection of STZ [40?mg/kg body weight (b.w.)]. Different doses of geraniol (100, 200 and 400?mg/kg b.w.) and glyclazide (5?mg/kg b.w.) were administrated orally to diabetic rats for 45?days. Body weight, food intake, plasma glucose, insulin, blood haemoglobin (Hb), glycosylated haemoglobin (HbA_1c), hepatic glucose metabolic enzymes and glycogen were examined.

Results: The LD₅₀ value of geraniol is 3600?mg/kg b.w. at oral administration in rats. Administration of geraniol in a dose-dependent manner (100, 200, 400?mg/kg b.w.) and glyclazide (5?mg/kg b.w.) for 45?days significantly improved the levels of insulin, Hb and decreased plasma glucose, HbA_1C in diabetic-treated rats. Geraniol at its effective dose (200?mg/kg b.w.) ameliorated the altered activities of carbohydrate metabolic enzymes near normal effects compared with two other doses (100 and 400?mg/kg b.w.). Geraniol treatment to diabetic rats improved hepatic glycogen content suggesting its anti-hyperglycemic potential. Geraniol supplement was found to preserve the normal histological appearance of hepatic cells and pancreatic β-cells in diabetic rats.

Discussion and conclusions: The present findings suggest that geraniol can potentially ameliorate key enzymes of glucose metabolism in experimental diabetes even though clinical studies used to evaluate this possibility are warranted.