Benznidazole biotransformation in rat heart microsomal fraction without observable ultrastructural alterations: comparison to Nifurtimox-induced cardiac effects

Benznidazole (Bz) and Nifurtimox (Nfx) have been used to treat Chagas disease. As recent studies have de-monstrated cardiotoxic effects of Nfx, we attempted to determine whether Bz behaves similarly. Bz reached the heart tissue of male rats after intragastric administration. No cytosolic Bz nitroreductases were detected, although microsomal NADPH-dependent Bz nitroreductase activity was observed, and appeared to be mediated by P450 reductase. No ultrastructurally observable deleterious effects of Bz were detected, in contrast to the overt cardiac effects previously reported for Nfx. In conclusion, when these drugs are used in chagasic patients, Bz may pose a lesser risk to heart function than Nfx when any cardiopathy is present.     

Combined treatment of heterocyclic analogues and benznidazole upon Trypanosoma cruzi in vivo

Chagas disease caused by Trypanosoma cruzi is an important cause of mortality and morbidity in Latin America but no vaccines or safe chemotherapeutic agents are available. Combined therapy is envisioned as an ideal approach since it may enhance efficacy by acting upon different cellular targets, may reduce toxicity and minimize the risk of drug resistance. Therefore, we investigated the activity of benznidazole (Bz) in combination with the diamidine prodrug DB289 and in combination with the arylimidamide DB766 upon T. cruzi infection in vivo. The oral treatment of T.cruzi-infected mice with DB289 and Benznidazole (Bz) alone reduced the number of circulating parasites compared with untreated mice by about 70% and 90%, respectively. However, the combination of these two compounds decreased the parasitemia by 99% and protected against animal mortality by 100%, but without providing a parasitological cure. When Bz (p.o) was combined with DB766 (via i.p. route), at least a 99.5% decrease in parasitemia levels was observed. DB766+Bz also provided 100% protection against mice mortality while Bz alone provided about 87% protection. This combined therapy also reduced the tissular lesions induced by T. cruzi infection: Bz alone reduced GPT and CK plasma levels by about 12% and 78% compared to untreated mice group, the combination of Bz with DB766 resulted in a reduction of GPT and CK plasma levels of 56% and 91%. Cure assessment through hemocultive and PCR approaches showed that Bz did not provide a parasitological cure, however, DB766 alone or associated with Bz cured ≥13% of surviving animals.     

Renal leptin in experimental nephrotic syndrome

Leptin is a fat derived hormone involved in the regulation of metabolism and body composition. The kidney is the principle organ responsible for elimination of circulating leptin. Our aim is to evaluate if the nephrotic kidneys participate in the metabolism of leptin by comparing the serum leptin level in renal veins and in their renal arteries and to study the relationship between leptin and lipoprotein levels in healthy and nephrotic rats. Methods: Rats were divided into two equal groups: group 1 in which experimental nephrotic syndrome was produced by injecting them intraperitoneally with a supernatant of the homogenized mixture of their own kidney (obtained by previous unilateral nephrectomy) and complete Freund’s adjuvant. Another group constituted the control group. Leptin and lipid profile were estimated in blood samples of renal veins and renal arteries. There was a highly significant increase in leptin and lipid profile levels in the nephrotic rats compared with the normal group. There was a high significant decrease in leptin in the renal venous blood compared with its level in the renal arterial blood of normal and nephrotic rats. This work has stressed the involvement of kidney and the nephrotic renal tissue in the process of leptin metabolism and lipogenesis.     

Effect of chronic exposure to aspartame on oxidative stress in brain discrete regions of albino rats

This study was aimed at investigating the chronic effect of the artificial sweetener aspartame on oxidative stress in brain regions of Wistar strain albino rats. Many controversial reports are available on the use of aspartame as it releases methanol as one of its metabolite during metabolism. The present study proposed to investigate whether chronic aspartame (75 mg/kg) administration could release methanol and induce oxidative stress in the rat brain. To mimic the human methanol metabolism, methotrexate (MTX)-treated rats were included to study the aspartame effects. Wistar strain male albino rats were administered with aspartame orally and studied along with controls and MTX-treated controls. The blood methanol level was estimated, the animal was sacrificed and the free radical changes were observed in brain discrete regions by assessing the scavenging enzymes, reduced glutathione, lipid peroxidation (LPO) and protein thiol levels. It was observed that there was a significant increase in LPO levels, superoxide dismutase (SOD) activity, GPx levels and CAT activity with a significant decrease in GSH and protein thiol. Moreover, the increases in some of these enzymes were region specific. Chronic exposure of aspartame resulted in detectable methanol in blood. Methanol per se and its metabolites may be responsible for the generation of oxidative stress in brain regions.     

Effect of tangeretin,a polymethoxylated flavone on glucose metabolism in streptozotocin-induced diabetic rats

The present study was designed to evaluate the antihyperglycemic potential of tangeretin on the activities of key enzymes of carbohydrate and glycogen metabolism in control and streptozotocin induced diabetic rats. The daily oral administration of tangeretin (100 mg/kg body weight) to diabetic rats for 30 days resulted in a significant reduction in the levels of plasma glucose, glycosylated hemoglobin (HbA1c) and increase in the levels of insulin and hemoglobin. The altered activities of the key enzymes of carbohydrate metabolism such as hexokinase, pyruvate kinase, lactate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glycogen synthase and glycogen phosphorylase in liver of diabetic rats were significantly reverted to near normal levels by the administration of tangeretin. Further, tangeretin administration to diabetic rats improved hepatic glycogen content suggesting the antihyperglycemic potential of tangeretin in diabetic rats. The effect produced by tangeretin on various parameters was comparable to that of glibenclamide – a standard oral hypoglycemic drug. Thus, these results show that tangeretin modulates the activities of hepatic enzymes via enhanced secretion of insulin and decreases the blood glucose in streptozotocin induced diabetic rats by its antioxidant potential.     

有氧运动与饮食控制对2型糖尿病大鼠肝chemerin及其受体CMKLR1的影响

目的：研究4周有氧运动与饮食控制对2型糖尿病（DM）大鼠肝chemerin及其受体趋化因子样受体1（CMKLR1）的影响及其在改善糖脂代谢中的影响。方法：50只雄性SD大鼠随机分为正常对照组（Con,n=6）和糖尿病造模组（n=44）。采用高脂高糖饲料联合小剂量链脲佐菌素（STZ）（30 mg/kg）的方法制备2型糖尿病模型大鼠。造模成功的DM大鼠随机分为4组（n=6）：糖尿病对照组（DM）、糖尿病运动组（EDM）、改喂普通饲料的糖尿病饮食控制组（NDM）和糖尿病运动+饮食控制组（ENDM）。运动组大鼠进行为期4周中等强度跑台有氧运动,每周运动6 d。采用罗氏血糖仪检测大鼠空腹血糖（FBG）,全自动生化分析仪检测大鼠血清总胆固醇（TC）、甘油三酯（TG）和低密度脂蛋白（LDL）水平,real time PCR和Western blot分别检测大鼠肝chemerin、CMKLR1的mRNA和蛋白水平。结果：DM大鼠FBG和血清TC、TG、LDL水平显著升高的同时,肝chemerin和CMKLR1的mRNA和蛋白水平显著增加;4周有氧运动和/或饮食控制显著降低EDM、NDM和ENDM组FBG和血清TC、TG、LDL的同时,显著降低这3组大鼠的肝chemerin蛋白水平,其中ENDM组降低最显著（P<0.01）;NDM和ENDM组大鼠的肝CMKLR1蛋白水平升高（P<0.01）。结论：4周有氧运动和/或饮食控制降低2型糖尿病大鼠的肝chemerin蛋白水平、增加CMKLR1蛋白水平,这可能与其改善糖尿病大鼠的糖脂代谢有关。     

Feeding conditions control the expression of genes involved in sterol metabolism in peripheral blood mononuclear cells of normoweight and diet-induced (cafeteria) obese rats

Peripheral blood mononuclear cells (PBMC) are easily obtainable cells from blood whose gene expression profiles have been proven to be highly robust in distinguishing a disease state from healthy state. Sterol metabolism is of physiological importance, and although its nutritional response in liver has been described, it is poorly studied in PBMC. To examine if PBMC sterol metabolism reflects diet-induced physiological responses, we analysed the whole genome gene expression response of PBMC and focused on sterol metabolism-related genes affected by different feeding conditions (ad libitum feeding, fasting, and refeeding) in normoweight (control) rats and in diet-induced (cafeteria) obese rats.Our results of microarray analysis show that, in control rats, 21 genes involved in sterol metabolism were regulated by the different feeding conditions, whereas in cafeteria-obese rats, only seven genes showed a changed expression. Most of the genes identified were classified into three pathways: sterol biosynthesis, cholesterol transport and uptake and sterol signaling. The expression profile of these genes was similar to that previously described for liver, decreasing in response to fasting conditions and recovering the levels found in fed animals after 6-h-refeeding. In addition, our data and the comparable expression pattern of sterol metabolism-related genes between PBMC and liver suggest similar sterol regulatory element-binding protein-mediated regulatory mechanisms in response to feeding conditions in both tissues.In conclusion, the expression of genes involved in sterol metabolism is highly controlled by feeding conditions in PBMC of control rats, but this control is impaired in cafeteria-obese animals. The pathophysiological significance of this impairment requires further investigation.     

Ameliorating effect of eugenol on hyperglycemia by attenuating the key enzymes of glucose metabolism in streptozotocin-induced diabetic rats

Epidemiological studies have demonstrated that diabetes mellitus is a serious health burden for both governments and healthcare providers. This study was hypothesized to evaluate the antihyperglycemic potential of eugenol by determine the activities of key enzymes of glucose metabolism in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced into male albino Wistar rats by intraperitoneal administration of STZ (40 mg/kg body weight (b.w.)). Eugenol was administered to diabetic rats intragastrically at 2.5, 5, and 10 mg/kg b.w. for 30 days. The dose 10 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 hexokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, and liver marker enzymes (AST, ALT, and ALP), creatine kinase and blood urea nitrogen in serum and blood of diabetic rats were significantly reverted to near normal levels by the administration of eugenol. Further, eugenol administration to diabetic rats improved body weight and hepatic glycogen content demonstrated the antihyperglycemic potential of eugenol in diabetic rats. The present findings suggest that eugenol can potentially ameliorate key enzymes of glucose metabolism in experimental diabetes, and it is sensible to broaden the scale of use of eugenol in a trial to alleviate the adverse effects of diabetes.     

Effect of coenzyme Q10 on catalase activity and other antioxidant parameters in streptozotocin-induced diabetic rats

Although coenzyme Q10 (CoQ10) is a component of the oxidative phosphorylation process in mitochondria that converts the energy in carbohydrates and fatty acids into ATP to drive cellular machinery and synthesis, its effect in type I diabetes is not clear. We have studied the effect of 4 wk of treatment with CoQ10 (10 mg/kg, ip, daily) in streptozotocin (STZ)-induced (40 mg/kg, iv in adult rats) type I diabetes rat models. Treatment with CoQ10 produced a significant decrease in elevated levels of glucose, cholesterol, triglycerides, very-low-density lipoprotein, lowdensity lipoprotein, and atherogenic index and increased high-density lipoprotein cholesterol levels in diabetic rats. CoQ10 treatment significantly decreased the area under the curve over 120 min for glucose in diabetic rats, without affecting serum insulin levels and the area under the curve over 120 min for insulin in diabetic rats. CoQ10 treatment also reduced lipid peroxidation and increased antioxidant parameters like superoxide dismutase, catalase, and glutathione in the liver homogenates of diabetic rats. CoQ10 also lowered the elevated blood pressure in diabetic rats. In conclusion, CoQ10 treatment significantly improved deranged carbohydrate and lipid metabolism of experimental chemically induced diabetes in rats. The mechanism of its beneficial effect appears to be its antioxidant property.     

Participation of leu-enkephalin in regulating carbohydrate metabolism

The experiments have been performed on 166 white male rats with a mass of 180-220 g. It has been revealed that leucine-enkephalin and its synthetic analogs prevent an increase in glucose blood levels and a decrease in glycogen liver levels caused by adrenaline and parathyroid hormone. At the same time the enkephalins inhibit the secretory activity of pancreatic beta-cells. The mechanisms of opioid peptide effect on carbohydrate metabolism are discussed.     

Antidiabetic potential of oleanolic acid from Ligustrum lucidum Ait

Ligustrum lucidum Ait. has been used in traditional Chinese medicine for over 1000 years because of its anti-tumor, antimutagenic, antidiabetic, and hepatoprotective properties. The aim of this study was to determine whether oleanolic acid (OA) is the principal active compound of L. lucidum responsible for its antidiabetic properties, and to examine its effect on the expression of thyroid hormones and insulin secretion, thus revealing the mechanism by which L. lucidum modulates insulin levels in diabetes. When rats with streptozotocin-induced diabetes were treated with OA (100 and 200 mg/kg body mass per day, for 40 days), the changes in blood glucose levels and in oral glucose tolerance tests showed that hypoglycemia was more pronounced in OA-treated groups than in the diabetic control rats, and that the levels of triglyceride, total cholesterol, and low-density lipoportein cholesterol in OA-treated rats were lower than those in the diabetic control rats, whose high-density lipoprotein cholesterol increased. OA-treated rats also gained weight, and exhibited increased serum insulin levels. In contrast, OA treatment did not effect the levels of thyroid hormone or TSH in rats with streptozotocin-induced diabetes. These results indicate that OA has hypoglycemic and hypolipidemic effects. OA treatment might stimulate insulin release, and consequently, results in the modulation of glucose levels and regulation of lipid metabolism.     

同型半胱氨酸对孕鼠糖代谢的影响与机制分析

目的:探讨同型半胱氨酸(homocysteine,HCY)摄入后对孕鼠糖代谢的影响以及生物学机制分析。方法:孕鼠妊娠10 d后,将实验动物随机分为3组,每组12只,妊娠对照组(Ctrl)腹腔注射生理盐水,同型半胱氨酸高剂量组(HCYH)和同型半胱氨酸低剂量组(HCYL)腹腔注射HCY溶液,注射浓度分别为200 mg/kg·d和100 mg/kg·d,持续20 d(即为HCY20 d)后,利用血糖含量检测试剂盒和胰岛素试剂盒分别检测孕鼠空腹血糖水平、胰岛素水平;葡萄糖检测试剂盒对孕鼠葡萄糖耐量和胰岛素抵抗进行检测;蛋白免疫印迹法检测孕鼠目的蛋白过氧化物酶体增殖物激活受体γ(PPARγ)、葡萄糖转运蛋白4(GLUT4)、蛋白激酶B(AKT)、磷酸化AKT蛋白(P-AKT)的表达。结果:与Ctrl组比较,在孕鼠注射HCY后,空腹血糖水平升高、血清中胰岛素浓度下降、HOMA-β指数下降、HOMA-IR指数升高(P<0.05);摄入葡萄糖后,孕鼠血糖随时间的变化而下降,葡萄糖曲线下面积升高(P<0.05);摄入胰岛素后,孕鼠血糖随时间的变化而升高,胰岛素曲线下面积升高(P<0.05);PPARγ、P-AKT、GLUT4蛋白表达水平下降,HCYH组降低水平更为显著(P<0.05)。结论:孕鼠HCY摄入后,生物体糖代谢紊乱,AKT磷酸化表达水平抑制,HCY可能通过降低PPARγ的表达减少AKT磷酸化,导致胰岛素受体的活化,进而激活了PI3K/AKT通路,减少了脂肪组织中的GLUT4表达,增加了对于葡萄糖的摄取能力。     

Vitamin A status and its metabolism contribute to the regulation of hepatic genes during the cycle of fasting and refeeding in rats

Vitamin A (VA) status and its metabolism affect hepatic metabolic homeostasis. We investigated if VA status and metabolism contribute to energy metabolism and expression of hepatic genes in the cycle of fasting and refeeding. Zucker lean rats with VA sufficient (VAS) or VA deficient (VAD) status were respectively grouped as: ad libitum (VAS-AD or VAD-AD), 48-h fasted (VAS-Fasted or VAD-Fasted), 48-h fasted and refed a VAS diet (VAS-Refed-VAS or VAD-Refed-VAS), or refed a VAD diet (VAS-Refed-VAD or VAD-Refed-VAD) for 6 h. Respiratory exchange ratio (RER) of rats fed the VAS or VAD diet was monitored for 6 weeks. From week four, rats fed the VAS diet had higher RER than those fed the VAD diet. VAS-Refed rats had higher plasma levels of glucose, triglyceride, insulin and leptin than VAD-Refed rats. The mRNA and protein levels of hepatic genes for fuel metabolism in the fasting and refeeding cycle were determined using real-time polymerase chain reaction and immunoblot, respectively. The mRNA levels of glucokinase (Gck), sterol regulatory element-binding protein 1c (Srebp-1c), and fatty acid synthase (Fas) were lowered in VAS-Fasted and VAD-Fasted rats, and increased in VAS-Refed-VAS, VAS-Refed-VAD and VAD-Refed-VAS, but not VAD-Refed-VAD, rats. The ACL and FAS protein levels only dropped in VAS-Fasted rats and increased in VAS-Refed-VAS rats. The GK protein level decreased only in VAS-Fasted rats, and increased in VAS-Refed-VAS, VAS-Refed-VAD and VAD-Refed-VAS (but not VAD-Refed-VAD) rats. We conclude that VA status and its metabolism in the fasting and refeeding cycle contribute to the regulation of hepatic gene expression in rats.     

Effects of the probiotic strain Lactobacillus johnsonii strain La1 on autonomic nerves and blood glucose in rats

Oral administration of Lactobacillus casei reportedly reduces blood glucose concentrations in a non-insulin-dependent diabetic KK-Ay mouse model. In order to determine if other lactobacillus strains affect glucose metabolism, we evaluated the effect of the probiotic strain Lactobacillus johnsonii La1 (LJLa1) strain on glucose metabolism in rats. Oral administration of LJLa1 via drinking water for 2 weeks inhibited the hyperglycemia induced by intracranial injection of 2-deoxy-D-glucose (2DG). We found that the hyperglucagonemic response induced by 2DG was also suppressed by LJLa1. Oral administration of LJLa1 for 2 weeks also reduced the elevation of blood glucose and glucagon levels after an oral glucose load in streptozotocin-diabetic rats. In addition, we recently observed that intraduodenal injection of LJLa1 reduced renal sympathetic nerve activity and enhanced gastric vagal nerve activity, suggesting that LJLa1 might affect glucose metabolism by changing autonomic nerve activity. Therefore, we evaluated the effect of intraduodenal administration of LJLa1 on adrenal sympathetic nerve activity (ASNA) in urethane-anesthetized rats, since the autonomic nervous system, including the adrenal sympathetic nerve, may be implicated in the control of the blood glucose levels. Indeed, we found that ASNA was suppressed by intraduodenal administration of LJLa1, suggesting that LJLa1 might improve glucose tolerance by reducing glucagon secretion via alteration of autonomic nerve activities.     

Effects of ingested fruiting bodies, submerged culture biomass, and acidic polysaccharide glucuronoxylomannan of Tremella mesenterica Retz.:Fr. on glycemic responses in normal and diabetic rats

Mushroom polysaccharides have been shown to regulate glucose metabolism. Using male Wistar rats injected with saline (normal rats), streptozotocin (STZ-NT rats), or streptozotocin plus nicotinamide (STZ+NT rats), we investigated the hypoglycemic activity of orally ingested fruiting bodies (FB), submerged culture biomass (CM), or the acidic polysaccharide glucuronoxylomannan (GXM) of Tremella mesenterica, an edible jelly mushroom. Our results demonstrated that FB ingestion significantly attenuated the elevated blood glucose levels in an oral glucose tolerance test (OGTT) in STZ-NT rats. However, in STZ+NT rats, FB, CM, and GXM ingestion significantly attenuated the increases in food and water intake, 2-h postprandial blood glucose concentrations, and blood glucose levels in OGTT. Moreover, FB and GXM ingestion significantly decreased serum concentration of fructosamine in STZ+NT rats. Our results indicated that T. mesenterica might be developed as a potential oral hypoglycemic agent or functional food for diabetic patients and for persons with high risk for diabetes mellitus.     

Antihyperglycemic effect of iridoid glucoside, isolated from the leaves of Vitex negundo in streptozotocin-induced diabetic rats with special reference to glycoprotein components

The aim of present study was to isolate an iridoid glucoside from the leaves of Vitex negundo and evaluates its effects on dearrangement in plasma and tissues glycoprotein components in streptozotocin-induced diabetic rats. The levels of blood glucose, plasma and tissues glycoproteins such as hexose, hexosamine, fucose and sialic acid were significantly increased whereas plasma insulin levels were significantly decreased in diabetic rats. On oral administration of iridoid glucoside at a concentration of 50 mg/kg b.w. once daily to diabetic rats for the period of 30 days, reversed the above-mentioned hyperglycemia-induced biochemical changes to near normal levels. The anti-hyperglycemic effect of iridoid glucoside was comparable with glibenclamide, a known hypoglycemic drug. Based on the results obtained from the present study, it may be concluded that iridoid glucoside possesses significant productive effect on glycoprotein metabolism in addition to its antidiabetic effect.     

Opposite effect of methionine-supplemented diet, a model of hyperhomocysteinemia, on plasma and liver antioxidant status in normotensive and spontaneously hypertensive rats

Hyperhomocysteinemia is often associated with an increase in blood pressure. However our previous study has shown that methionine supplementation induced an increase in blood pressure in Wistar-Kyoto (WKY) rats and a decrease in blood pressure in spontaneously hypertensive rats (SHR) with significant differences in plasma homocysteine (Hcy) metabolites levels. Previously liver antioxidant status has been shown to be decreased in SHR compared to WKY rats. It has been suggested that oxidative stress may predispose to a decrease in NO bioavailability and induce the flux of Hcy through the liver transsulfuration pathway. Thus the aim of this study was 1) to investigate the effect of methionine supplementation on NO-derived metabolites in plasma and urine 2) to investigate whether abnormalities in Hcy metabolism may be responsible for the discrepancies observed between WKY rats and SHR concerning blood pressure and 3) to investigate whether a methionine-enriched diet, differently modified plasma and liver antioxidant status in WKY rats an SHR. We conclude that the increase in blood pressure in WKY rats is related to high plasma cysteine levels and is not due to a decrease in NO bioavailability and that the decrease in blood pressure in SHR is associated with high plasma GSH levels after methionine supplementation. So GSH synthesis appears to be stimulated by liver oxidative stress and GSH is redistributed into blood in SHR. So the great GSH synthesis can be rationalized as an autocorrective response that leads to a decreased blood pressure in SHR.     

Role of non-haem iron in protecting effect of ecdysterone on development of streptozocin-induced hyperglycaemia in rats

Chronic hyperglycaemia (60 days) which developed after streptozotocine (STZ) administration (5 mg/100 g) in rats was accompanied with development of severe endothelial dysfunction as well as with disturbed non-haem iron metabolism. It was established by EPR spectroscopy method that STZ administration reduced transferrin levels in the blood as well as pools of iron associated with blood transferrin and with ferritin in the heart and aorta of rats with hyperglycaemia. Chronic ecdysterone administration (100 ng/100 g, 60 days) protects hyperglycaemia development by preventing of non-haem iron metabolism disturbance. These data suppose participation of non-haem iron in mechanisms of ecdysterone protection of streptozotocine-induced hyperglycaemia and ischemia.     

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.