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Query: UMLS:C0011849 (diabetes)
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Berberine is the major active constituent of Rhizoma coptidis. The present study was carried out to investigate the effect of berberine on diabetes in rats and its possible mechanisms. Diabetes was induced by tail vein injection with alloxan in Wistar rats. The amount of alloxan administered was 55 mg/kg. Diabetic rats were fed with a high-cholesterol diet. The fasting blood glucose, total cholesterol (TC), triglyceride (TG) and low density lipoprotein-cholesterol (LDL-c), high density lipoprotein-cholesterol (HDL-c), nitric oxide (NO) levels in serum and malondialdehyde (MDA),superoxide dismutase (SOD),glutathione peroxidase (GSH-px) contents in heart tissue were assayed by spectrophotometry. Pancreas samples collected after 3 weeks of alloxan treatment were stained with hematoxylin-eosin (HE) and examined under a light microscope, and scored. Intragastric administration of berberine (100 and 200 mg/kg) significantly decreased fasting blood glucose levels, serum content of TC, TG, LDL-c, and effectively increased HDL-c, NO level in diabetic rats. Furthermore, berberine treatment significantly blocked the increase of MDA, increased SOD and GSH-px levels in diabetic rats. Histopathological scores showed that berberine had restored the damage of pancreas tissues in rats with diabetes mellitus. The results showed berberine significantly inhibited the progression of diabetes induced by alloxan, and the inhibitory effect of berberine on diabetes might be associated with its hypoglycemic effect, modulating lipids metabolic effects and its ability to scavenge free radical.
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PMID:Effects of berberine on diabetes induced by alloxan and a high-fat/high-cholesterol diet in rats. 1675 28

Berberine has been shown to have antidiabetic properties, although its mode of action is not known. Here, we have investigated the metabolic effects of berberine in two animal models of insulin resistance and in insulin-responsive cell lines. Berberine reduced body weight and caused a significant improvement in glucose tolerance without altering food intake in db/db mice. Similarly, berberine reduced body weight and plasma triglycerides and improved insulin action in high-fat-fed Wistar rats. Berberine downregulated the expression of genes involved in lipogenesis and upregulated those involved in energy expenditure in adipose tissue and muscle. Berberine treatment resulted in increased AMP-activated protein kinase (AMPK) activity in 3T3-L1 adipocytes and L6 myotubes, increased GLUT4 translocation in L6 cells in a phosphatidylinositol 3' kinase-independent manner, and reduced lipid accumulation in 3T3-L1 adipocytes. These findings suggest that berberine displays beneficial effects in the treatment of diabetes and obesity at least in part via stimulation of AMPK activity.
Diabetes 2006 Aug
PMID:Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. 1687 88

Retinopathy is a major cause of morbidity in diabetes and remains the primary cause of new blindness. Therefore, it is necessary to find new drug to treat diabetic retinopathy. Type 2 diabetes mellitus (T2DM) rats were induced by injection (ip) with streptozotocin (STZ) 35 mg x kg(-1) and fed with a high-carbohydrate/high-fat diet 2 weeks later. From week 17 to 32, diabetic rats were given different doses of berberine 75, 150, and 300 mg x kg(-1), fenofibrate 100 mg x kg(-1) and rosiglitazone 4 mg x kg(-1), separately. Retinal structure was observed with hematoxylin-eosin staining and peroxisome proliferator-activated receptors (PPARs) alpha/delta/gamma protein expressions were detected by immunohistochemistry. The retina of control rats was thicker than that of other groups, 16 weeks treatment with berberine (150 and 300 mg x kg(-1)) and rosiglitazone 4 mg x kg(-1) thickened the diabetic retina, but no difference existed in retinal structure among groups. Both berberine (150 and 300 mg x kg(-1)) and rosiglitazone 4 mg x kg(-1) significantly decreased PPARy expression in diabetic retina; while berberine (150 and 300 mg x kg(-1)) and fenofibrate 100 mg x kg(-1) obviously increased both PPARalpha and PPARdelta expressions in diabetic retina. Berberine modulates PPARalpha/delta/gamma protein levels in diabetic retina which may contribute to ameliorate retinopathy complication induced by STZ and a high-carbohydrate/high-fat diet. It is expected that berberine might be a more beneficial drug to treat diabetic retinal complication comparing with fenofibrate and rosiglitazone.
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PMID:Effect of berberine on PPARalpha/delta/gamma expression in type 2 diabetic rat retinae. 1833 35

Diabetic nephropathy (DN), one of the most serious microvascular complications of diabetes mellitus, is a major cause of end-stage renal disease. Berberine is one of the main constituents of Coptidis rhizoma and Cortex phellodendri. In the present study, we examined effects of berberine (BBR) on renal injury in streptozotocin-induced diabetic rats, and on the changes of aldose reductase (AR) and oxidative stress in cultured rat mesangial cells exposed to high glucose. Fasting blood glucose, blood urea nitrogen, creatinine, and urine protein over 24 h were detected by using the commercially available kits. Cell proliferation, collagen synthesis, aldose reductase (AR), superoxide anion, superoxide dismutase (SOD), and malondialdehyde (MDA) were detected, respectively, by different methods. In streptozotocin-induced diabetic rats, fasting blood glucose, blood urea nitrogen, creatinine, and urine protein over 24 h were significantly decreased in rats treated with 200 mg/kg berberine for 12 weeks compared with diabetic control rats (P < 0.05). This was accompanied by a reduced AR activity and gene expression at both mRNA and protein levels. In cultured rat mesangial cells exposed to high glucose, incubation of BBR significantly decreased cell proliferation, collagen synthesis and AR activity as well as its mRNA and protein levels compared with control cells (P < 0.05). In vitro, BBR also significantly increased SOD activity and decreased superoxide anion and MDA compared with control cells (P < 0.05). These results suggested that BBR could ameliorate renal dysfunction in DN rats, which may be ascribed to inhibition of AR in mesangium, reduction of oxidative stress, and amelioration of extracellular matrix synthesis and cell proliferation. Further studies are warranted to explore the role of AR in DN and the therapeutic implications by AR inhibitors such as BBR.
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PMID:Berberine inhibits aldose reductase and oxidative stress in rat mesangial cells cultured under high glucose. 1847 86

Berberine is one of the main alkaloids of Rhizoma coptidis which has been used as a folk medicine to treat diabetes mellitus for more than 1400 years in China. To investigate the chronic effect of berberine on diabetic hyperlipidemic rats, fasted rats were intraperitoneally injected 35 mg/kg streptozotocin. Diabetic rats were admitted after 2 weeks and given a high-carbohydrate/high-fat diet to induce hyperlipidemia. The rats were divided into 7 groups at the end of week 16: normal and diabetic rats received no drug, 5 treatment groups were administered with either 75, 150, 300 mg/kg berberine, 100 mg/kg fenofibrate or 4 mg/kg rosiglitazone per day for 16 weeks, respectively. The blood glucose, hemoglobin A1c, lipid metabolic parameters and hepatic glycogen and triglyceride were measured, and histopathology and peroxisome proliferator-activated receptors (PPARs) alpha/delta/gamma expression of liver were determined by hematoxylin eosin and immunohistochemical staining. Berberine reduced diabetic rats' body weight, liver weight and liver to body weight ratio. Berberine restored the increased blood glucose, hemoglobin A1c, total cholesterol, triglyceride, low density lipoprotein-cholesterol, apolipoprotein B and the decreased high density lipoprotein-cholesterol, apolipoprotein AI levels in diabetic rats to near the control ones. Berberine alleviated the pathological progression of liver and reverted the increased hepatic glycogen and triglyceride to near the control levels. Berberine increased PPARalpha/delta expression and reduced PPARgamma expression in liver of diabetic rat to near the control ones. Berberine improved glucolipid metabolism both in blood and liver in diabetic rats possibly through modulating the metabolic related PPARalpha/delta/gamma protein expression in liver.
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PMID:Chronic effects of berberine on blood, liver glucolipid metabolism and liver PPARs expression in diabetic hyperlipidemic rats. 1852 50

Berberine has been shown to have hypoglycaemic activity in several in vitro and in vivo models, although the mechanism of action is not fully known. Berberis lyceum Royle root produces high concentrations of berberine, and in traditional medicine, the whole extract of this plant is used widely to treat diabetes. The antidiabetic activity of the ethanol root extract of Berberis lyceum was compared with pure berberine in normal and alloxan-diabetic rats using similar doses of each. The concentration of berberine in the extract was determined to be 80% dry weight with only trace amounts of other alkaloids present. The purpose of the study was to investigate the effects of berberine and a whole extract of Berberis lyceum on blood glucose and other parameters associated with diabetes, to compare the effects of the crude extract with those of pure berberine and thus validate its use as a therapeutic agent, and finally to identify any contribution of the other components of the extract to these effects. Oral administration of 50 mg/kg of Berberis extract and berberine to normal and experimental diabetic rats produced a significant (p < 0.05) reduction in blood glucose levels from days 3-7 days of treatment. Significant effects were also observed on the glucose tolerance, glycosylated haemoglobin, serum lipid profiles and body weight of experimental animals. Berberis extract and berberine demonstrated similar effects on all parameters measured, and although the extract was comparable in efficacy to berberine, it did not produce any effects additional to those shown by pure berberine. The results support the use of the extract in traditional medicine, and demonstrate that apart from being a highly cost-effective means of treating with berberine, the total extract does not appear to confer any additional benefits or disadvantages compared with the pure compound.
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PMID:Comparison of the antidiabetic activity of Berberis lyceum root extract and berberine in alloxan-induced diabetic rats. 1872 56

Berberine is a isoquinoline alkaloid extracted from Chinese herbs such as Coptidis rhizome. In the past decade, there are more than 2 000 published papers studying the clinical application, pharmacodynamic mechanism and structure-activity relationship (SAR) of berberine and its derivatives, for treating tumor, diabetes, cardiavascellum disease, hyperlipemia, inflammation, bacterium and virus infection, cerebral ischemia trauma, mental disease, Alzheimer disease, osteoporosis, and so on. These results demonstrate that berberine has wide physiologic function and has great potential for structural modification as new drug lead. However, there is no systematic review about the study of berberine and its derivatives up to now. This paper is a systematic review of the research advances of berberine and its derevatives in clinical application, pharmacodynamic mechanisms, molecular pharmacology, absorption and metabolism, and SAR studies. The current review would provide some useful information for further study on structural modification of berberine for discovering new drug leads based on its pharmacodynamic mechanisms.
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PMID:[Advances in the study of berberine and its derivatives]. 1895 68

Berberine (BBR), a hypoglycemic agent, has shown beneficial metabolic effects for anti-diabetes, but its precise mechanism was unclear. Glucagon-like peptide-1 (GLP-1) is considered to be an important incretin that can decrease hyperglycemia in the gastrointestinal tract after meals. The aim of this study was to investigate whether BBR exerts its anti-diabetic effects via modulating GCG secretion. Diabetes-like rats induced by streptozotocin received BBR (120 mg/kg per day, i.g) for 5 weeks. Two hours following the last dose, the rats were anaesthetized and received 2.5 g/kg glucose by gavage. At 15-minute and 30-minute after glucose load, blood samples, pancreas, and intestines were obtained to measure insulin and GCG using ELISA kit. The number of L cells in the ileum and beta-cells in the pancreas were identified using immunohistology. The expression of proglucagon mRNA in the ileum was measured by RT-PCR. The results indicated that BBR treatment significantly increased GCG levels in plasma and intestine (P<0.05) accompanied with the increase of proglucagon mRNA expression and the number of L-cell compared with the controls (P<0.05). Furthermore, BBR increased insulin levels in plasma and pancreas as well as beta-cell number in pancreas. The data support the hypothesis that the anti-diabetic effects of BBR may partly result from enhancing GCG secretion.
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PMID:Berberine promotes glucagon-like peptide-1 (7-36) amide secretion in streptozotocin-induced diabetic rats. 1899 45

Diabetic nephropathy, one of the microvascular complications of diabetes mellitus, is a leading cause of end-stage renal disease. Berberine is one of the main constituents of Coptidis Rhizoma and Cortex Phellodendri. In this study, we investigated the effects of berberine on fibronectin and collagen production, and explored the role of p38MAPK signaling pathway in rat glomerular mesangial cells cultured under high glucose condition. Six groups were divided according to the different experimental conditions: (1) Normal glucose group (NG); (2) Mannitol group (Mannitol); (3) High glucose group (HG); (4) SB203580 treatment group (HG + SB203580); (5) Berberine low dosage group (HG + BBR 30 microM); (6) Berberine high dosage group (HG + BBR 90 microM). Cell proliferation and collagen synthesis were measured by MTT and (3)H-proline incorporation assay, respectively. The phospho-p38MAPK, phospho-cAMP response element binding protein (CREB) and fibronectin were detected by western blot analysis. Fibronectin protein expression and collagen synthesis were significantly increased in HG-treated group compared with normal glucose group (P < 0.05). In SB203580 treatment group and two groups of berberine, protein expression of fibronectin and collagen synthesis were obviously decreased compared with HG-treated group (P < 0.05). Berberine significantly decreased protein expression of fibronectin compared with SB203580 treatment group (P < 0.05). Berberine at high dosage significantly decreased collagen synthesis compared with SB203580 treatment group (P < 0.05). Both SB203580 and berberine significantly decreased phospho-p38MAPK and phospho-CREB level compared with HG-treated group (P < 0.05). These results indicated that berberine might inhibit fibronectin and collagen synthesis partly via p38MAPK signal pathway in rat glomerular mesangial cells exposed to high glucose.
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PMID:Berberine reduces fibronectin and collagen accumulation in rat glomerular mesangial cells cultured under high glucose condition. 1914 14

Oxidative stress in diabetes coexists with a reduction in the antioxidant status, which can further increase the deleterious effects of free radicals. Berberine is one of the main alkaloids of Rhizoma coptidis which has been used to treat diabetes for more than 1400 years in China. The present study was designed to evaluate the protective effects of berberine against beta cell damage and antioxidant of pancreas in diabetic rats. Diabetic rats with hyperlipidemia were induced by intraperitoneally injection 35 mg/kg streptozotocin and a high-carbohydrate/high-fat diet. Rats were divided into 7 groups at the end of week 16: untreated control, untreated diabetic, 75, 150, 300 mg/kg berberine-treated diabetic, 100 mg/kg fenofibrate-treated, and 4 mg/kg rosiglitazone-treated. After 16 weeks treatment, serum insulin level, insulin expression in pancreas, and malonaldehyde content, superoxide dismutase activity in pancreatic homogenate were assayed. Pancreas was examined by hematoxylin/eosin staining and transmission electron microscope. Pancreas to body weight ratio, insulin level, insulin sensitivity index, malonaldehyde content and superoxide dismutase activity were altered in diabetic rats, and were near control levels treated with 150, 300 mg/kg berberine. Mitochondrial vacuolization and swelling, dilatation of the endoplasmic reticulum were observed in beta cells of diabetic rats. The pancreatic islet area atrophied and secretory granules of beta cells decreased in diabetic rats. Slight pathological changes existed in beta cells of 150, 300 mg/kg berberine-treated diabetic pancreas. These findings suggest that berberine has protective effect for diabetes through increasing insulin expression, beta cell regeneration, antioxidant enzyme activity and decreasing lipid peroxidation.
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PMID:Protective effect of berberine on beta cells in streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats. 1937 72


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