Efficacy of Ginger (Zingiber officinale Roscoe) Extracts in Lowering Blood Glucose in Normal and High Fat Diet-induced Diabetic Rats

Few studies have determined the effect of different ginger extracts on insulin sensitivity, very few have explored the effect of raw extract of this spice on this parameter while the effect of cooked ginger extract (the form in which the spice is commonly consumed) is yet to be ascertained. This experimental study was therefore designed to determine the effect of raw and cooked ginger extracts on insulin sensitivity in normal and high-fat diet-induced diabetic rats. Ginger rhizomes were washed, peeled, wet-milled and sieved without adding water to obtain the raw extract. The raw extract was boiled for 1 hour to obtain the cooked extract. Seventy male albino rats of weight range 120-160g were divided into seven groups (n=10) and designated thus: ND2C-non-diabetic control; ND2R-non-diabetic rats given raw ginger extract (2ml/kg body weight); ND2Co- non-diabetic rats given cooked (boiled) ginger extracts; D2C-diabetic control; D2R- diabetic rats given raw ginger extract; D2Co- diabetic rats given cooked ginger extract; and D2D-diabetic rats given metformin (anti-diabetic drug)-200mg/kg body weight. Diabetes was induced in the diabetic groups by feeding the animals with high-fat diet (HFD) for 12 weeks to mimic Type 2 diabetes. Ginger extracts and the drug were administered as a daily oral dose for 4 weeks after diabetes induction. Insulin sensitivity (Insulin Tolerance Test) was determined before and after diabetes induction and at the end of the 4 weeks extracts administration using standard analytical method. Mean data were analyzed using ANOVA at p ≤ 0.05. Baseline Insulin Sensitivity (IS-%/min) in all the groups ranged from 2.2 to 2.4. After 12 weeks feeding, the IS in the three groups fed normal diet ranged from 1.9 to 2.1 while in the four groups fed HFD Insulin Sensitivity ranged from 0.1 to 0.3. Four weeks administration of raw and cooked ginger extracts did not significantly alter IS in normal rats while in diabetic rats raw, cooked ginger extracts and metformin significantly increased IS (%/min) to 2.1, 1.2 and 1.7 respectively relative to control which was 0.1. Insulin Sensitivity was maintained within the normal level in normal rats that were given raw and cooked ginger extracts while the raw extract was more effective than the cooked extract in increasing insulin sensitivity to normal level in diabetic rats. Both raw and cooked ginger extracts improved insulin sensitivity in high-fat diet-induced diabetic rats but the raw extract was more effective, hence, ginger in both forms may be applicable in the management of Type 2 diabetes. Human trial is hereby recommended.

The increasing global prevalence of diabetes mellitus requires a holistic approach which is easy and cheap to apply for acceptability and affordability by all categories of people, hence, the use of spices to combat this social ill needs to be explored. In view of this, this study aimed at determining the effect of raw and cooked ginger juice on blood glucose in normal and streptozotocin-induced diabetic rats as a first phase of experimental study of its possible use as an anti diabetic food adjunct in human subjects. Male Albino rats (70) of weight range 143-180 g were divided into 7 groups and were treated thus: NT1S- normal control, NT1R- normal rats given 4 ml/kg body weight raw ginger juice, NT1Co- normal rats given cooked ginger juice, T1S- diabetic control, T1R- diabetic rats given raw ginger juice, T1Co- diabetic rats given cooked ginger juice and T1D- diabetic rats given glibenclamide (5 mg/kg body weight). Fasting blood glucose (FBG) was taken from overnight fasted rats before and after diabetes was induced (with 60 mg/kg body weight intra peritoneal injection) and at the end of the second and fourth weeks of ginger administration using ACCUCHEK Active Glucometer, Roche, Germany. ANOVA and Least Significant Difference were used for statistical analyses. The FBG was reduced to normal by raw and cooked ginger extracts and glibenclamide (p<0.05) in diabetic rats while it was significantly lower than normal (p< 0.05) in normal rats given ginger extracts. There was no significant difference (p< 0.05) between FBG in normal rats given raw ginger and cooked ginger extracts. It can be inferred from this study that the active hypoglycemic component of ginger was not affected by heat, hence, the consumption of ginger in raw and cooked forms in different cuisines may be an effective regimen in the management of diabetes. Also, consumption of ginger by normal subjects may not cause hypoglycemia but further study is recommended in this area.

The mechanism for the blood glucose lowering effect of different ginger extracts is yet to be clearly understood, that of raw ginger extracts has been sparsely explored while the mechanism for the cooked ginger extract, the form in which it is mostly consumed, has not been delved into. This study was therefore designed to determine the effect of raw and cooked ginger (Zingiber officinale Roscoe) extracts on glucose uptake by the muscle and adipose of normal, streptozocin-induced and high-fat diet-induced diabetic rats. Fresh ginger rhizomes were washed, peeled, milled and sieved without adding water to obtain the raw extract. A portion of this was boiled for 1 hour to give the cooked extract. Matured male albino rats (140) were divided into two major groups with 70 rats in each group. Group A was further divided into 7 sub-groups (n=10) 40 of which were rendered diabetic with intraperitoneal injection of streptozocin (60mg/kg body weight) to mimic Type 1 diabetes while in Group B Type 2 diabetes was induced with a 12 week consumption of High-Fat Diet (HFD). The remaining 30 rats in each group were left to remain non-diabetic/ normal. Ginger extracts were administered as a daily oral dose for 4 weeks after diabetes induction. The animals were the sacrificed and glucose uptake by the muscle and adipose tissue was determined using standard analytical procedure. Mean data were compared using Least Significant Difference at p≤ 0.05. It was clearly evidenced that both raw and cooked ginger extracts significantly enhanced and increased glucose uptake by the muscle and adipose tissues even in the absence of insulin, hence, mimicking insulin action. Ginger in both raw and cooked forms may therefore be beneficial in the prevention and management of diabetes mellitus. Human trial is hereby recommended.

Dyslipidemia is a risk factor of concern in public health even in a state of anomaly in blood glucose level. The effect of different ginger extracts on body lipids has been reported, few scientific studies have documented the effect of raw ginger extracts while the effect of cooked ginger extract (the form in which the spice is commonly consumed) is yet to be explored. This experimental study was therefore designed to determine the effect of raw and cooked ginger extracts on serum triglycerides and total cholesterol in diabetic rats and compare this with that of non-diabetic rats. Fresh ginger rhizomes were washed peeled, washed, wet-milled (without addition of water) and sieved to give the raw extract. A portion of of the extract was boiled for one hour and cooled to give cooked ginger extract. Seventy male albino rats of weight range 155g-195g were divided into 7 groups (n=10) with 3 groups kept as normal or non-diabetic while the remaining 4 groups were rendered diabetic by intraperitoneal administration of 60mg/kg body weight of streptozocin (STZ) to mimic Type 1 diabetes mellitus. These were repeated with another set of seventy rats but diabetes was induced in the 4 diabetic groups here with a 12 week consumption of high-fat diet (HFD) to mimic Type 2 diabetes mellitus. Serum total cholesterol and triglyceride were determined before and after diabetes induction as well as at the 2nd and 4th weeks of extracts and diabetic drugs administration using standard methods. Mean data were compared using Least Significant Difference at p≤0.05.Raw and cooked ginger extracts significantly reduced serum total cholesterol and triglyceride in both medium (2 weeks) and long (4 weeks) terms administration in non diabetic rats. In STZ-induced diabetic rats only raw ginger extract lowered these parameters significantly while the cooked extracts and glybenclamide increased these significantly. However, in HFD-induced diabetic rats, raw, cooked ginger extracts and Metformin reduced both serum total cholesterol and triglyceride significantly. Ginger in both raw and cooked forms may therefore be useful in ameliorating hyperlipidemia which commonly associates diabetic state. Human trial is hereby recommended.

Growol was traditional food that was produced by spontaneous fermentation of cassava in water for 3–5 days. . In preliminary research showed that cowpeas sprout protein had hypoglycemic properties. This research was aimed to determine the hypoglycemic properties through in vivo bioassay of composite flour that was made of growol and cowpeas sprout flour by using normal and diabetic Sprague Dawley male rats. There were two of research treatments, that were rat condition and feed treatment. The first teratments (rat condition) were normal rats and diabetic rats which was induced by alloxan injection, and the second treatments (feed) were standard feed and composite flour feed which was prepared by substitution of corn strach in standard feed with the composite flour. The blood glucose of rats were analysed on 3th, and 18 th days for the treatment and before the treatment as control (0th). The result of this research indicated that the potency of hypoglycemic were shown by decreasing of blood glucose level in diabetic rats with growol treatment. On 18th days treatment, the blood glucose of the diabetic rats with standard feed increased and they were still diabetec. While the blood glucose of diabetic rats with composite feed treatment reduced 20% on 18th days after the treatment, although they are still diabetic. The composite flour might decrease blood glucose for more than 18 days feed treatment. That was indicated that the composite flour that was made of growol and cowpeas sprout flour might be used as functional food for type 2 diabetic therapy

In recent years, ginger has become a subject of interest because of its beneficial effects on human health. The purpose of the present study was to investigate the effects of daily oral administration of ginger extract for 6 weeks on plasma glucose, lipid profile and kidney functions in alloxan -induced diabetic rats to show the ameliorating and partly curative effects in alloxan induced-diabetic rats (150 mg/kg i.p.(Intrapretonial). Rats (130-150gm) were divided into 4 groups; normal control rats, diabetic control rats, diabetic rats post -treated with ginger and diabetic rats pretreated with ginger. Ginger extract was administered orally for 6 weeks to post-treated and pre-treated rats, and they were compared with the normal and diabetic groups, respectively. Plasma glucose was reduced significantly in both post-treated and pretreated groups. The post-treatment with ginger extract reduced plasma cholesterol, triglyceride and LDL-cholesterol, but during the pre-treatment with ginger extract produced insignificant change only in plasma triglyceride level. The plasma HDLcholesterol was significantly increased in post-treated and pre-treated groups. The plasma creatinine, urea and uric acid levels were signifi cantly reduced in post-treated group; also in pre-treated group, they were reduced but urea level statistically did not change. It is concluded that the consumption of ginger produced a significant hypoglycemic effect in diabetic rats . In addition, ginger is capable of improving hyperlipidemia and the impaired kidney functions in alloxan-induced diabetic rats. Keyword: ginger, kidney function, glucose, plasma, lipids, alloxan, rats, diabetic.

Ginger (Zingiber officinale) exerts an antidiabetic effect by restoring pancreatic β-cells. The present study aimed to investigate the mechanism by which ginger extract induces the regeneration of functional β-cells in diabetic rats. Sprague-Dawley rats (n=27) were divided into three groups: normal rats given double distilled water (ddH2O) (NC, n=11), diabetic rats (injected with 60 mg/kg streptozotocin) given ddH2O (DC, n=8), and diabetic rats treated with aqueous ginger extract (DG, n=8). The effect of ginger extract intake on the differential expression of neurogenin-3 (Neurog3), V-maf musculoaponeurotic fibrosarcoma oncogene homolog B (Mafb), insulin 2 (Ins2), and glucagon (Gcg) was assessed using quantitative real-time PCR after one and eight weeks of treatment. The pancreatic insulin source was determined using immunohistochemical analysis. After one week, ginger treatment significantly up-regulated the expression of both Neurog3 and Mafb in the DG rats compared with the DC rats. However, after eight weeks, the mRNA levels of these genes dropped significantly in parallel with the up-regulation of Ins2 and Gcg expression, resulting in increased serum insulin levels, weight, and lowered fasting blood glucose levels. Immunohistochemical analysis revealed a restored β-cell mass and islet architecture in the DG group. Ginger extract exerts an antidiabetic effect by acting on pancreatic progenitors and α-cells to restore β-cell mass in streptozotocininduced diabetic rats. These findings suggest that ginger extract could be a potential stimulator of β-cell neogenesis, which provides an alternative to meet the increasing demand for exogenous insulin in patients with diabetes.

Diet and blood lipids in normal and diabetic rats

Insulin action in the brain contributes to glucose lowering during insulin treatment of diabetes

The present study aimed to assess the metabolic consequences of the chronic ingestion of two starches giving different postprandial glycaemic responses in normal and diabetic rats. The two starches chosen were mung-bean (Phaseolus aureus) starch (97% pure starch) and wheat starch presented as ground French toast. First, we studied the characteristics of these two starches. In vitro the alpha-amylase (EC 3.2.1.1) digestibilities of these starches were 40 (SE 3) and 62 (SE 4)% respectively at 30 min, whereas the contents of resistant starch were 77 (SE 4) and 22 (SE 4) g/kg respectively. In vivo the mung-bean starch produced lower postprandial glycaemic responses than the wheat starch (areas under the curve were: 91 (SE 28) and 208 (SE 33) mmol.min/l, P < 0.05) in normal rats (n 8). We then submitted twenty-eight normal and twenty-eight diabetic (neonatal streptozotocin on second day of birth) male Sprague-Dawley rats (6 weeks old) to a diet containing 570 g starch/kg as either mung-bean starch or wheat starch (n 14 rats/group). After 5 weeks on the diets food intakes and body weights were identical in each group. Liver and kidney weights were comparable when expressed as relative weight. The mung-bean-starch diet slightly decreased epididymal fat-pad weight (P < 0.14, ANOVA) and led to a marked decrease in adipocyte volume (P < 0.05). Plasma triacylglycerol and phospholipid concentrations were lower after the mung-bean-starch diet than after the wheat-starch diet in both normal and diabetic rats, whereas free fatty acid concentrations were lower only in normal rats. Similarly, non-fasting plasma glucose concentrations decreased (P < 0.05) in normal rats fed on mung-bean starch but not in diabetic ones (P < 0.14). Insulin levels tended to be lower, but not significantly, after mung-bean-starch feeding than after wheat starch. We conclude that the replacement of 570 g wheat starch/kg diet with mung-bean starch for 5 weeks resulted in (1) lowered non-fasting plasma glucose and free fatty acid levels in normal but not in diabetic rats, (2) a reduction in plasma triacylglycerol concentration and adipocyte volume in both normal and diabetic rats. Thus, the type of starch mixed into the diet may have important metabolic consequences in normal and diabetic rats.

The pharmacokinetics of zopolrestat, a carboxylic acid aldose reductase inhibitor, were examined in normal male rats dosed intravenously at 2 mg/kg and in normal and streptozotocin-diabetic male rats after oral administration at 50 mg/kg. After oral dosing, Cmax was 127 micrograms/ml for normal rats and 144 micrograms/ml for diabetic rats. AUC(0-infinity), however, was lower for diabetic rats than for normal rats and plasma half-life was longer in normal rats (8.0 vs 6.6 hr). Half-lives of zopolrestat in nerve, kidney, and lens were longer than plasma half-life and were similar for both diabetic and normal rats. Less than 2% of the dose was excreted in the urine as unchanged zopolrestat during the 48-hr period following dosing by diabetic or normal rats. Protein binding of zopolrestat was less extensive in plasma from diabetic rats than in plasma from normal rats. Similar kinetics were observed in diabetic animals receiving five daily doses of zopolrestat at 50 mg/kg/day. There was no plasma or liver accumulation of zopolrestat at steady state, consistent with the observed half-lives. However, zopolrestat did accumulate in nerve, kidney, and lens to varying degrees during multiple dosing, reflecting the longer half-lives of zopolrestat in these tissues.

Comparative pharmacokinetic investigation on baicalin and wogonoside in type 2 diabetic and normal rats after oral administration of traditional Chinese medicine Huanglian Jiedu decoction

The objective of this study is to induce experimental diabetes mellitus by Streptozotocin in normal adult Wistar rats via comparison of changes in body weight, consumption of food and water, volume of urine and levels of glucose, insulin and C-peptide in serum, between normal and diabetic rats. Intra-venous injection of 60mg/kg dose of Streptozotocin in adult wistar rats, makes pancreas swell and at last causes degeneration in Langerhans islet beta cells and induces experimental diabetes mellitus in the 2-4 days. Induction of experimental diabetes mellitus is indeed the first step in the plan of purification of pancreatic Langerhans islet cells of normal rats for transplanting under the testis subcutaneous of experimentally induced diabetic rats. Streptozotocin induces one type of diabetes which is similar to diabetes mellitus with non-ketosis hyperglycemia in some animal species. For induction of experimental diabetes in male adult rats weighted 250-300 grams (75-90 days), 60mg/kg of Streptozotocin was injected intravenously. Three days after degeneration of beta cells, diabetes was induced in all animals. The diabetic and normal animals were kept in the metabolic cages separately and their body weight, consumption of food and water, urine volume, the levels of serum glucose, insulin and C-peptide quantities in all animals were measured and then these quantities were compared. For a microscopic study of degeneration of Langerhans islet beta cells of diabetic rats, sampling from pancreas tissue of diabetic and normal rats, staining and comparison between them, were done. Induction of diabetes with Streptozotocin decreases Nicotinamide-adenine dinucleotide (NAD) in pancreas islet beta cells and causes histopathological effects in beta cells which probably intermediates induction of diabetes. In this study, we used Streptozotocin for our experiments in induction of experimental diabetes mellitus. After Induction of diabetes, consumption of food and water, volume of urine and glucose increased in the diabetic animals in comparison with normal animals, but the weight of body and the volume of insulin and C-peptide decreased in the diabetic animals. Sampling and staining of pancreas tissue of diabetic and normal rats showed that the Langerhans islet beta cells of diabetic rats have been clearly degenerated. In three days, Streptozotocin makes pancreas swell and at last causes degeneration in Langerhans islet beta cells and induces experimental diabetes. It also changes normal metabolism in diabetic rats in comparison with normal rats. Consumption of water and food, volume of urine, serum glucose increases in diabetic animals in comparison with normal rats but the levels of serum insulin, C-peptide and body weight decreases.

A High Glycemic Index Starch Diet Affects Lipid Storage–Related Enzymes in Normal and to a Lesser Extent in Diabetic Rats

We designed a study to evaluate the cardioprotective effect of two soluble epoxide hydrolase (sEH) inhibitors, 1-(1-propanoylpiperidin-4-yl)-3-(4-trifluoromethoxy)phenyl)urea (TPPU) and trans-4-{4-[3-(4-trifluoromethoxyphenyl)-ureido]cyclohexyloxy}benzoic acid (t-TUCB), in ischemia-reperfusion (IR) model. Cardioprotective effects of the sEH inhibitors were evaluated against IR-induced myocardial damage in hearts from normal, hypertensive, and diabetic rats using Langendorff's apparatus. In addition, the effect of sEH inhibitors on endothelial function was evaluated in vitro and ex vivo using isolated rat thoracic aorta. Ischemia-reperfusion (IR) increased the myocardial damage in hearts from normal rats. IR-induced myocardial damage was augmented in hearts isolated from hypertensive and diabetic rats. Myocardial damage as evident from increase in the activities of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) in heart perfusate was associated with significant decrease in the heart rate and developed tension, and increase in the resting tension in isolated heart. Both sEH inhibitors protected the heart in normal, hypertensive, and diabetic rats subjected to IR injury. The sEH inhibitor t-TUCB relaxed phenylephrine precontracted aorta from normal rats. Relaxant effect of acetylcholine (ACh) was reduced in aortas from diabetic and hypertensive rats compared to normal rats. Pretreatment of sEH inhibitors to diabetic and hypertensive rats increased relaxant effect of ACh on aortas isolated from these rats. Prophylactic treatment with sEH inhibitors decreased myocardial damage due to IR, hypertension and diabetes, and decreased endothelial dysfunction created by diabetes and hypertension. Therefore, inhibitors of sEH are useful probes to study cardiovascular pathology, and inhibition of the sEH is a potential approach in the management of IR-induced cardiac damage and endothelial dysfunction-related cardiovascular disorders.