糖尿病大鼠肾脏抗氧化防御系统机能的改变

目的：探讨糖尿病对肾脏抗氧化防御机能的影响。方法：观察12周糖尿病大鼠肾皮质丙二醛(MDA)及谷胱甘肽(GSH)水平,以及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)、谷胱甘肽S转移酶(GSH-ST)和过氧化氢酶(CAT)活性的变化。结果：糖尿病大鼠肾组织中SOD、CAT活性下降;GSH含量显著降低;MDA没有变化;GSH-PX活性却明显增强。结论：糖尿病大鼠肾组织抗氧化防御机能明显下降。     

Effect of alcohol on blood glucose and antioxidant enzymes in the liver and kidney of diabetic rats

Objective:

Diabetes mellitus affects every organ in the man including eyes, kidney, heart, and nervous system. Alcohol consumption is a widespread practice. As the effects of chronic alcohol consumption on diabetic state have been little studied, this study was conducted with the objective of evaluating the effect of alcohol in diabetic rats.

Materials and Methods:

For this study, the rats were divided into five groups (n = 6 in each group): normal control (NC), alcohol treatment (At), diabetic control (DC), diabetic plus alcohol treatment (D + At), diabetic plus glibenclamide treatment (D + Gli). Alcohol treatment was given to the diabetic rats for 30 days. During the period the blood glucose levels, and body weight changes were observed at regular intervals. The antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels were assayed in the liver and kidney tissues.

Results:

The blood glucose levels were significantly (P < 0.001) elevated and body weight significantly (P < 0.001) decreased in alcohol-treated diabetic rats. SOD and CAT activities were decreased and the MDA level increased significantly (P < 0.001) in alcohol-treated diabetic rats. Histopathological studies showed that alcohol damages the liver and kidney tissues in diabetic rats.

Conclusion:

These finddings concluded that the consumption of alcohol in diabetic rats worsens the condition. So the consumption of alcohol by diabetic subjects may be potentially harmful.     

L-Arginine ameliorates oxidative stress in alloxan-induced experimental diabetes mellitus

Oxidative stress occurs in diabetic patients and experimental models of diabetes. The ability of l-arginine to ameliorate the oxidative stress and metabolic changes after treatment with alloxan was investigated in rats. Adult male rats were injected intraperitoneally with 100 mg kg(-1) of alloxan to produce experimental oxidative stress characteristic of diabetes mellitus. Hyperglycaemia and hypercholesterolaemia were observed in serum after 7 days of alloxan treatment. This was associated with a depression of glutathione (GSH) concentration as well as superoxide dismutase (SOD) and catalase (CAT) activities in the liver and brain. In addition, the thiobarbituric acid-reactive substances (TBARS) were significantly elevated, indicating increased lipid peroxidation and oxidative stress in the same tissues. Administration of 100 mg kg(-1) l-arginine for 7 days either before or after alloxan injection significantly ameliorated the oxidative stress evidenced by a lower TBARS and a higher level of the endogenous GSH concentration and SOD and CAT activities than alloxan-treated rats. These effects were paralleled by marked protection and partial prophylaxis against alloxan-induced hyperglycaemia and cholesterolaemia. Thus, these results showed that exogenously administered l-arginine might improve the clinical manifestation of diabetes mellitus and decrease the oxidative stress in the liver and brain. In addition, the study supports the beneficial effect of l-arginine, which might be attributed to its direct, NO-dependent antioxidant capacity and/or NO-independent pathways.     

Succinic acid monoethyl ester prevents oxidative stress in streptozotocin-nicotinamide-induced type2 diabetic rats

Succinic acid mono ethyl ester (EMS) was recently proposed as an insulinotropic tool in the treatment of non-insulin dependent diabetes mellitus. The aim of this study was to investigate the effect of EMS on oxidative stress in a streptozotocin (STZ)-nicotinamide induced type 2 diabetic model. The EMS was injected intraperitoneally at 8 micro mol/g body weight for 30 days. Plasma glucose, plasma insulin, thiobarbituricacid reactive substances (TBARS), hydroperoxides, superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (Gpx), reduced glutathione (GSH), glutathione-S-transferase (GST), and vitamins C and E were assayed in liver and kidney. Treatment with EMS and metformin to diabetic rats resulted in a significant reduction in plasma glucose, TBARS, and hydroperoxides. In addition, the treated groups also showed a significant increase in the activities of plasma insulin, SOD, CAT, GPx, GST, GSH, vitamin C, and vitamin E in liver and kidney of STZ-nicotinamide-induced diabetic rats. Our result suggest that non glucidic nutrient, such as EMS as a potent antidiabetic, may optimalize antiperoxidative and antioxidants status by restoring the biochemical alterations found in STZ-nicotinamide-induced type 2 diabetes.     

Antidiabetic activity of Diospyros peregrina fruit: Effect on hyperglycemia, hyperlipidemia and augmented oxidative stress in experimental type 2 diabetes

Diospyros peregrina is an edible fruit of costal West-Bengal. The present investigation was undertaken to evaluate the role of aqueous extract of D. peregrina fruit in streptozotocin–nicotinamide induced type 2 diabetic rats. Oral administration of extract at the doses of 50 and 100 mg/kg body weight per day for 28 days to diabetic rats was found to possess significant dose dependant hypoglycemic and hypolipidemic activity. An increased reactive oxygen species and insufficient antioxidant activity is associated with diabetes mellitus, which is mainly responsible for diabetic pathogenesis. The role of extract on antioxidant markers of liver and kidney were estimated. The diabetic rats exhibited lower activities of superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) content in hepatic and renal tissues as compared with normal rats. The activities of SOD, CAT, and GSH were found to be increased in extract treated diabetic rats in selected tissues. The increased level of lipid peroxidation (thiobarbituric acid reactive substances and hydroperoxide) in diabetic rats was also found to be reverted back to near normal status in extract treated groups.     

Protective effect of Gymnema montanum against renal damage in experimental diabetic rats

Gymnema montanum Hook (Asclepiadaceae), is an endemic plant species of India, traditionally used for diabetes and its management. In this experiment, the ethanol extract of G. montanum (GLEt) at a dose of 200 mg/kg body weight was tested to evaluate its effect on renal damage in alloxan-induced diabetic rats and the efficacy was compared with standard hypoglycemic drug, glibenclamide (600 μg/kg body weight). The GLEt and glibenclamide were administered orally for 3 weeks and the effects on glucose, insulin, renal markers including urea, creatinine and uric acid, lipid peroxidation markers including thiobarbituric reactive substances (TBARS) and hydroperoxides and antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities in kidney were studied. In addition, the urinary protein profile was studied using SDS–PAGE. The results indicated that the GLEt significantly normalized the elevated blood glucose, renal markers and lipid peroxidation markers and increased antioxidant levels in diabetic kidney. The diabetic rats excreted large amount of proteins than untreated rats which was normalized during the treatment with GLEt. In conclusion, the GLEt was found to be more effective in reducing oxidative stress, thus confirming the ethnopharmacological use of G. montanum in protecting diabetes and its complications.     

Antihyperglycemic activity of bacosine, a triterpene from Bacopa monnieri, in alloxan-induced diabetic rats

This article describes the antihyperglycemic activity, in vivo antioxidant potential, effect on hemoglobin glycosylation, estimation of liver glycogen content, and in vitro peripheral glucose utilization of bacosine, a triterpene isolated from the ethyl acetate fraction (EAF) of the ethanolic extract of Bacopa monnieri. Bacosine produced a significant decrease in the blood glucose level when compared with the diabetic control rats both in the single administration as well as in the multiple administration study. It was observed that the compound reversed the weight loss of the diabetic rats, returning the values to near normal. Bacosine also prevented elevation of glycosylated hemoglobin in vitro with an IC?? value of 7.44 μg/mL, comparable with the one for the reference drug α-tocopherol. Administration of bacosine and glibenclamide significantly decreased the levels of malondialdehyde (MDA), and increased the levels of reduced glutathione (GSH) and the activities of superoxide dismutase (SOD) and catalase (CAT) in the liver of diabetic rats. Bacosine increased glycogen content in the liver of diabetic rats and peripheral glucose utilization in the diaphragm of diabetic rats in vitro, which is comparable with the action of insulin. Thus, bacosine might have insulin-like activity and its antihyperglycemic effect might be due to an increase in peripheral glucose consumption as well as protection against oxidative damage in alloxanized diabetes.     

Antidiabetic and antioxidant activity of the methanol extract of Diospyros peregrina fruit on Type I diabetic rats

Chronic diabetes complications are mainly associated with augmented oxidative stress. Thus the present study evaluated the hypoglycemic, as well the antioxidant effect, of the methanol extract of Diospyros peregrina Gurke. (Ebenaceae) fruits on experimental diabetic rats. Oral administration of methanol extract at 150 and 300?mg/kg body weight per day to diabetic rats was found to have profound hypoglycemic activity in term of reduction of fasting blood glucose level. The diabetic rats showed lower activities of superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) content in hepatic and renal tissues as compared with normal rats. The activities of SOD, CAT, and GSH were found to be increased in extract-treated diabetic rats in selected tissues. The increased levels of lipid peroxidation (thiobarbituric acid reactive substances and hydroperoxides) in diabetic rats were also found to be reverted back to near-normal status in extract-treated groups. It was found that the extract is more effective at the dose of 300?mg/kg body weight and this effect is almost comparable to that of standard glibenclamide.     

Bacopa monnieri modulates antioxidant responses in brain and kidney of diabetic rats

Role of oxidative stress has been reported in various diabetic complications including neuropathy, nephropathy and cardiopathy. This study was undertaken to evaluate the protective effect of Bacopa monnieri, a medicinal plant, on tissue antioxidant defense system and lipid peroxidative status in streptozotocin-induced diabetic rats. Extract of B. monnieri was administered orally, once a day for 15 days (at doses 50, 125 and 250mg/(kgbw)) to diabetic rats. Activity of antioxidant enzymes (SOD, Catalase, and GPx), levels of GSH and lipid peroxidation were estimated in kidney, cerebrum, cerebellum and midbrain of diabetic rats and compared to reference drug, Glibenclamide. Administration of plant extract to diabetic rats showed significant reversal of disturbed antioxidant status and peroxidative damage. Significant increase in SOD, CAT, GPx activity and levels of GSH was observed in extract treated diabetic rats. The present study indicates that extract of B. monnieri modulates antioxidant activity, and enhances the defense against ROS generated damage in diabetic rats.     

Effect of Coccinia indica on Blood Glucose,Insulin and Key Hepatic Enzymes in Experimental Diabetes

Administration of Coccinia indica leaf extract to normal and streptozotocin diabetic animals exhibited significant hypoglycemic and antihyperglycemic effect and reversed biochemical complications. Oral administration of 200mg/ kg of ethanol extract of Coccinia indica leaves (CLEt) to diabetic animals for 45 days resulted in a significant reduction in blood glucose, glycosylated haemoglobin and an increase in total haemoglobin and plasma insulin. Similarly, the administration of CLEt to normal animals resulted in a significant hypoglycemic effect. The activities of hepatic hexokinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase and glucose-6-phosphate dehydrogenase, a lipogenic enzyme, were measured in the liver of normal, diabetic, normal rats separately treated with CLEt and glibenclamide, and diabetic rats treated separately with CLEt and glibenclamide. The activities of the lipogenic enzyme and hexokinase were significantly decreased, whereas the activities of gluconeogenic enzymes were significantly increased in the diabetic liver. Both CLEt and glibenclamide were able to restore the altered enzyme activities to almost control levels. CLEt was more effective than glibenclamide. The results indicate that the administration of CLEt to diabetic animals normalizes blood glucose and causes marked improvement of altered carbohydrate metabolic enzymes during diabetes.     

Effect of Aloe vera leaf gel and pulp extracts on the liver in type-II diabetic rat models

The aim of this work was to investigate the effects of Aloe vera leaf pulp and gel extracts on the liver tissue of neonatal streptozotocin (n0STZ)-induced type-II diabetic rats. The diabetic rats were separated into four groups and each group was given the following samples by gavage, daily for 15 d: phosphate buffered saline (PBS; diabetic control), Aloe leaf pulp extract, Aloe leaf gel extract, glibenclamide. Liver tissues were examined histologically. The markers of oxidative stress: glutathione (GSH), non-enzymatic glycosylation (NEG) and lipid peroxidation (LPO), were determined in liver tissue. Biochemical parameters for liver function: serum alkaline phosphatase (ALP), and alanine transaminase (ALP) activities, were evaluated. All parameters were also determined in healthy (non diabetic) rats for comparison. In the diabetic control group, the degenerative changes in liver tissue were remarkable, while in the diabetic groups given Aloe pulp and gel extracts and glibenclamide, the damage to the liver tissue was decreased. The increase of GSH and the decrease of NEG and LPO in liver tissues with the treatment of Aloe gel extract, is consistent with the beneficial effect of Aloe. Serum ALP and ALT activities were also decreased in the groups given Aloe gel extract. It was concluded that Aloe gel extract has a protective effect comparable to glibenclamide against hepatotoxicity produced by diabetes if used in the treatment of type-II diabetes.     

Antihyperlipidaemic Effect of Gymnema montanum: A Study on Lipid Profile and Fatty Acid Composition in Experimental Diabetes

Abstract: In the present study, the antihyperlipidaemic efficacy of ethanol extract of Gymnema montanum leaves was investigated in alloxan‐induced diabetic rats and the effect was compared to standard hypoglycaemic drug, glibenclamide. Male adult albino Wistar rats were injected with freshly prepared solution of alloxan monohydrate (150 mg/kg body weight) to induce diabetes. After 2 weeks, the rats with moderate diabetes were administered G. montanum leaves (200 mg/kg body weight) for 21 days by gastric lavage, after which serum, liver and kidney samples were analysed for lipid profile, lipoprotein changes and fatty acid composition. While the alloxan‐induced diabetic rats showed a significant increase in the levels of cholesterol, triglycerides and free fatty acids, the levels in the animals treated with G. montanum leaves were considerably reduced and restored to near normal values. Antihyperlipidaemic effects of G. montanum leaves were found to be comparable with that of glibenclamide. Similarly, G. montanum leaves treatment resulted in reversal of alterations observed in the plasma lipoproteins (high‐density lipoprotein, low‐density lipoprotein and very high‐density lipoprotein‐cholesterol) and fatty acid composition in serum, liver and kidney of alloxan‐induced rats. Our study suggests that phytochemicals present in G. montanum may play an important role in suppressing the elevated lipid profile in diabetes and may be useful for the prevention and/or early treatment of diabetes‐associated hyperlipidaemia.     

Protective effect of Eugenia jambolana seed kernel on tissue antioxidants in streptozotocin-induced diabetic rats

Oxidative stress plays an important role in chronic complications of diabetes. In the present study the antioxidant effect of oral administration of ethanolic extract of Eugenia jambolana seed kernel on tissue antioxidant enzymes and lipid peroxidation in liver and kidney of streptozotocin-induced diabetic rats was evaluated. Administration of seed kernel to diabetic rats significantly decreased the levels of blood glucose, glycosylated hemoglobin and increased body weight gain, plasma insulin and hemoglobin. The diabetic rats showed the low activities of superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione content in liver and kidney, which were restored to near normal levels by treatment with the seed kernel extract. The increased levels of lipid peroxidation and hydroperoxides in diabetic rats were reverted back to near normal levels after the treatment with seed kernel extract. Diabetic rats treated with seed kernel extract restored almost normal architecture of liver and kidney and were confirmed by histopathological examination. The present study reveals the efficacy of Eugenia jambolana seed kernel in the amelioration of diabetes, which may be attributed to its hypoglycemic property along with its antioxidant potential. The antioxidant effect of Eugenia jambolana seed kernel was also compared with glibenclamide, a standard hypoglycemic drug.     

EUK-8 and EUK-134 reduce serum glucose and lipids and ameliorate streptozotocin-induced oxidative damage in the pancreas, liver, kidneys, and brain tissues of diabetic rats

In this study, the effects of EUK-8 and EUK-134, as two newly classified antioxidants, on the sera levels of glucose, insulin, lipids, nitric oxide (NO) and also on the extent of lipid peroxidation (measured in term of thiobarbituric acid reactive substances, TBARS), reactive oxygen species (ROS) formation and the activities of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT) as well as reduced glutathione (GSH)] in the liver, pancreas, brain and kidneys of streptozotocin (STZ)-induced diabetic rats were evaluated. Results indicated that oral daily administration of EUK-8, EUK-134 (each at 20?mg/kg), and glibenclamide (2.5?mg/kg), as the control drug, to the diabetic rats for 21 consecutive days improved the sera levels of lipids and glucose along with insulin level to varying extents. In addition, treatment of rats with EUK-8, EUK-134, and/or glibenclamide decreased the TBARS, NO, and ROS levels and increased the activities of SOD and CAT as well as the GSH content in various tissues compared to untreated diabetic rats. In conclusion, this study indicated that EUK-8 and Euk-134 compounds improved the antioxidant status by reducing lipid peroxidation and enhancing the antioxidant enzymes activities in various tissues of diabetic rats.     

Protective effect of Umbelliferone on membranous fatty acid composition in streptozotocin-induced diabetic rats

Umbelliferone (UMB), a natural antioxidant, is benzopyrone in nature, and it is present in the fruits of golden apple and bitter orange. Earlier we evaluated and reported the effect of Umbelliferone on antidiabetic, antioxidant and antihyperlipidemic properties, and this study was designed to evaluate the effect of Umbelliferone on membrane fatty acid composition and histopathology of liver and kidney of control and streptozotocin (STZ) diabetic rats. Male albino Wistar rats (180-200 g) were made diabetic by an intraperitonial administration of STZ (40 mg/kg). The control and diabetic rats were treated with Umbelliferone and glibenclamide dissolved in 10% dimethyl sulfoxide for 45 days. Diabetic rats had decreased insulin and increased glucose, and increased levels of thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes. The levels of palmitic, stearic and oleic acids increased and the levels of linolenic and arachidonic acids decreased in diabetic rats as compared with control rats. Thus, the saturated fatty acids and monounsaturated fatty acids increased and the polyunsaturated fatty acids decreased in diabetic rats. Diabetic rats had decreased liver weight and increased activities of alanine transaminase and aspartate transaminase; increased kidney weight and urine albumin, and decreased levels of urea, uric acid and creatinine in the urine. Histopathological studies of liver and kidney in diabetic rats showed fatty changes surrounding portal triad; enlargement of lining cells of tubules, fatty infiltration, large area of hemorrhage and lymphocyte infiltration. Treatment with Umbelliferone and glibenclamide reversed these changes to near normalcy. Our results showed that Umbelliferone has a protective effect on membrane fatty acid composition of liver and kidney as supported by antioxidant and antihyperlipidemic effects of Umbelliferone reported earlier as evidenced by improved histopathological changes, hepatic and nephritic markers, indicating recovery from the risk of diabetic complications.     

The sulphonylurea glibenclamide inhibits multidrug resistance protein (MRP1) activity in human lung cancer cells

1. Glibenclamide, a sulphonylurea widely used for the treatment of non-insulin-dependent diabetes mellitus, has been shown to inhibit the activities of various ATP-binding cassette (ABC) transporters. In the present study, its effects towards multidrug resistance protein 1 (MRP1), an ABC efflux pump conferring multidrug resistance and handling organic anions, were investigated. 2. Intracellular accumulation of calcein, an anionic dye substrate for MRP1, was strongly increased by glibenclamide in a dose-dependent manner in MRP1-overexpressing lung tumour GLC4/Sb30 cells through inhibition of MRP1-related calcein efflux. By contrast, glibenclamide did not alter calcein levels in parental control GLC4 cells. Another sulphonylurea, tolbutamide, was however without effect on calcein accumulation in both GLC4/Sb30 and GLC4 cells. 3. Glibenclamide used at 12.5 microM was, moreover, found to strongly enhance the sensitivity of GLC4/Sb30 cells towards vincristine, an anticancer drug handled by MRP1. 4. Efflux of carboxy-2',7'-dichlorofluorescein, an anionic dye handled by the ABC transporter MRP2 sharing numerous substrates with MRP1 and expressed at high levels in liver, was also strongly inhibited by glibenclamide in isolated rat hepatocytes. 5. In summary, glibenclamide reversed MRP1-mediated drug resistance likely through inhibiting MRP1 activity and blocked organic anion efflux from MRP2-expressing hepatocytes. Such effects associated with the known inhibitory properties of glibenclamide towards various others ABC proteins suggest that this sulphonylurea is a general inhibitor of ABC transporters.     

Antihyperlipidemic effect of Eugenia jambolana seed kernel on streptozotocin-induced diabetes in rats.

Abnormalities in lipid profile are one of the most common complications in diabetes mellitus, which is found in about 40% of diabetics. In the present study, anti-hyperlipidemic efficacy of Eugenia jambolana seed kernel (EJs-kernel) was evaluated in streptozotocin (STZ)-induced diabetic rats and the efficacy was compared with standard hypoglycemic drug, glibenclamide. The effect of oral administration of ethanolic extract of EJs-kernel (100 mg/kg body weight) was examined on the levels of cholesterol, phospholipids, triglycerides and free fatty acids in the plasma, liver and kidney tissues of STZ (55 mg/kg body weight)-induced diabetic rats. The plasma lipoproteins and tissues fatty acid composition were also monitored. STZ-induced diabetic rats, showed significant increase in the levels of cholesterol, phospholipids, triglycerides and free fatty acids which were considerably restored to near normal in EJs-kernel or glibenclamide treated animals. The plasma lipoproteins (HDL, LDL, VLDL-cholesterol) and fatty acid composition were altered in STZ-induced diabetic rats and these levels were also reverted back to near normalcy by EJs-kernel or glibenclamide treatment. It may be concluded that, EJs-kernel possesses hypolipidemic effect, which may be due to the presence of flavonoids, saponins, glycosides and triterpenoids in the extract. The hypolipidemic effect mediated by EJs-kernel may also be anticipated to have biological significance and provide a scientific rationale for the use of EJs-kernel as an anti-diabetic plant.     

Influence of 3-hydroxymethyl xylitol, a novel antidiabetic compound isolated from Casearia esculenta (Roxb.) root, on glycoprotein components in streptozotocin-diabetic rats

Casearia esculenta root (Roxb.) is widely used in traditional system of medicine to treat diabetes in India. An active compound, 3-hydroxymethyl xylitol (3-HMX), has been isolated, and its optimum dose has been determined in a short duration study and patented. In addition, the long-term effect of 3-HMX in type 2 diabetic rats on antihyperglycemic, antioxidants, antihyperlipidemic, and protein metabolism and kidney marker enzymes was investigated, and its effect was shown previously. In this study, we investigated the effect of 3-HMX on plasma and tissue glycoproteins in streptozotocin-diabetic rats. Animals were divided into five groups viz., control group, 3-HMX (40 mg/kg of body weight) treated group, diabetic group, diabetic+3-HMX (40 mg/kg of body weight), and diabetic+glibenclamide (600 μg/kg of body weight). 3-HMX was administered orally at a dose of 40 mg/kg of body weight for 45 days. The study shows significant increases in the level of sialic acid except kidney and elevated levels of hexose, hexosamine, and fucose in the liver and kidney of diabetic rats, and the treatment with 3-HMX and glibenclamide showed reversal of these parameters toward normalcy. Thus, the study indicates that 3-HMX possesses a significant beneficial effect on glycoprotein components.     

Effects of 18alpha-glycyrrhizin on the pharmacodynamics and pharmacokinetics of glibenclamide in alloxan-induced diabetic rats

This paper investigated the effects of 18alpha-glycyrrhizin (18alpha-GL) on the pharmacodynamics and pharmacokinetics of glibenclamide in experimental diabetic rats. 18alpha-GL (25 mg/kg) and/or glibenclamide (1 mg/kg) were given to alloxan-induced diabetic rats for consecutive 5 days. When the rats were co-treated with 18alpha-GL and glibenclamide, fasting plasma glucose concentration was further reduced, plasma insulin content and liver glycogen level were increased markedly as compared with glibenclamide-treated animals. Meanwhile, in co-treated group, elimination rate constant (Ke) of glibenclamide was reduced while peak plasma concentration (C(max)), area under the plasma concentration vs time curve (AUC(0-14 h)) and elimination half-life (T(1/2Ke)) were increased significantly vs glibenclamide alone administered rats. The activities of hepatic CYP3A and the markers of liver injury, plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were significantly decreased in rats treated with 18alpha-GL alone and in combination with glibenclamide. Results of immunohistochemistry showed that 18alpha-GL improved the effects of glibenclamide on the pathological morphology of pancreatic islet beta cells and the intensities of positive immunostaining for insulin. Our results revealed that 18alpha-GL led to the enhancement of the hypoglycemic effect of glibenclamide by inhibiting the activity of CYP3A; on the other hand, 18alpha-GL protected the pancreatic islet beta cells and liver from damage in diabetes which suggested that 18alpha-GL might be beneficial as an adjuvant drug of glibenclamide in a proper dose, especially to the diabetic patients associated with liver dysfunction.