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Effect of bergenin on hepatic glucose metabolism and insulin signaling in C57BL/6J mice with high fat-diet induced type 2 diabetes

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Abstract

In this study, the therapeutic efficacy of bergenin was examined against high-fat diet (HFD) induced type 2 diabetes in C57BL/6J mice. These mice were fed continuously HFD for 16 weeks and subjected to intragastric administration of various doses (10, 20 and 40 mg/kg body weight (BW)) of bergenin daily for subsequent 8 weeks. Bergenin supplementation to HFD-fed mice lower body weight gain, plasma glucose and insulin in diabetic mice. It further restored the alterations of biochemical parameters to near normal levels in diabetic mice. As compared to other two doses of 10 mg and 20 mg, bergenin 40 mg/kg BW were showed significant protective effect on the biochemical parameter studied. Consequently, it improved insulin-dependent glucose transport in the liver through translocation and activation of glucose transporter protein 2 (GLUT 2) in phosphatidylinositol 3-kinase (PI3K)/phosphorylated protein kinase B (AKT) dependent pathway. These findings provided evidence to exhibit that bergenin could improve liver tissue hyperglycemia, insulin sensitivity increase glucose uptake and shows hepatoprotective. Hence it might be used in the management of obesity-associated type 2 diabetes mellitus.

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Mulberry leaf is a traditional medicine used to treat diabetes in the clinic. The aim of this study was to determine the mechanisms by which mulberry leaf polysaccharide (MLPII), improves hepatic glucose metabolism and insulin resistance in rats with type 2 diabetes induced by high fat and streptozotocin (STZ). MLPII was administered for 6 weeks after establishment of type 2 diabetes in Wistar rats. At the end of the experiment, oral glucose tolerance, liver glycogen content, glucose synthase (GS) activity and insulin resistance were determined. Expression patterns of proteins and genes associated with insulin signaling as well as biomarkers of oxidative stress and antioxidant enzyme activities were assayed. Compared with normal control rats, MLPII treatment significantly improved oral glucose tolerance (P<0.01) and restored the glycogen level (P<0.01) and GS activity (P<0.05) in diabetic rats. Insulin resistance was improved in MLPII-treated diabetic rats (P<0.01). Furthermore, expression levels of insulin receptor substrate 2 (IRS2), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (PKB/AKT) involved in insulin signaling were significantly increased (P<0.01), while protein-tyrosine phosphatase 1B (PTP1B) expression was markedly reduced (P<0.01). The levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) in livers of the MLPII-treated group were significantly reduced (P<0.01), while activities of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), were significantly increased (P<0.01, P<0.01, P<0.01, respectively). The results clearly indicate that MLPII treatment effectively normalizes hepatic glucose metabolism and insulin signaling by inhibiting the expression of PTP1B, activating the PI3K-AKT pathway and mitigating oxidative stress in the livers of rats with type 2 diabetes induced by high fat and STZ.
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This study was conducted to evaluate the effects of umbelliferone (UF) and 4-methylumbelliferone (mUF) on high-fat diet-induced hypertriglyceridemia and hyperglycemia in mice. The mice were assigned to normal control, high-fat control, and high-fat with UF or mUF groups. For UF or mUF groups, the high-fat diet was supplemented with UF or mUF at 0.02% (wt/wt) for 12 weeks. Both UF and mUF significantly decreased plasma triglyceride, free fatty acid and glucose levels, adipocyte size, white adipose tissue weights, and hepatic phosphatidate phosphohydrolase activity and significantly increased plasma adiponectin levels and hepatic fatty acid β-oxidation activity compared with the high-fat control group. UF and mUF improved glucose intolerance and hepatic steatosis in the high-fat fed mice. Long-term high-fat diet intake induced an increase in hepatic CYP2E1 activity and lipid peroxide and cytosolic hydrogen peroxide contents and suppressed superoxide dismutase and glutathione peroxidase activities, which were reversed by UF and mUF supplementation. These results indicate that UF and mUF similarly ameliorate hypertriglyceridemia and hyperglycemia partly by modulating hepatic lipid metabolism and the antioxidant defense system along with increasing adiponectin levels.
Article
The present study was designed to investigate the effects of the ethanol extract of Ficus racemosa (FRE) on biochemical parameters in type 2-like diabetes, induced by a combination of standardised high-fat diet and low-dose streptozotocin (25mgkg−1, i.p.) in rats. To elucidate the mode of action of FRE, its effects on a battery of targets involved in glucose homeostasis was evaluated. FRE (200 and 400mgkg−1, p.o.), in a dose-dependent manner, altered the biochemical parameters and significantly improved glucose tolerance and HDL-c levels. In different bioassays, FRE showed inhibition of PTP-1B (IC50 12.1μg/mL) and DPP-IV (42.5%). FRE exhibited 82.6% binding to PPAR-γ. Furthermore FRE exhibited stimulation of glucose uptake by skeletal muscles (hemi-diaphragm). Bergenin was quantified in bioactive-FRE by high-performance liquid chromatography (0.15%w/w). This is the first report demonstrating the effectiveness of F. racemosa stem bark in type 2 diabetes and targets involved in it.
Article
1. Levels of phosphofructokinase, glucose-6-phosphate dehydrogenase and fructose-1,6-diphosphatase activities have been compared in different yeasts belonging to glucose fermenting and non-fermenting groups grown in different conditions. 2. Phosphofructokinase was present in all the fermentative species tested. On the contrary its level was not measurable in any of the aerobic yeasts tested with the exception of Pichia species. 3. No significant variations were observed in the values of glucose-6-phosphate dehydrogenase from the two groups of yeasts. 4. The synthesis of fructose-1,6-diphosphatase was repressed in both groups, by growth in sugar carbon sources. However, a remarkable difference in the sensitivity of the fructose-1,6-diphosphatase from both groups towards inhibition by AMP was observed. The enzyme from all fermentative yeasts tested showed a strong inhibition by AMP (1 mM producing about 80% inhibition) while the enzyme from aerobic yeasts showed different responses, inhibition ranging from 10% in Rhodotorula and Sporobolomyces, to 90% in Pichia.
Article
Excess fat intake induces hyperinsulinaemia, increases nutrient uptake and lipid accumulation, amplifies ROS generation, establishes oxidative stress and morphological changes leading to tissue injury in the liver, kidney and heart of high-fat diet (HFD)-fed mice. The effect of azelaic acid (AzA), a C9 α,ω-dicarboxylic acid, against HFD-induced oxidative stress was investigated by assaying the activities and levels of antioxidants and oxidative stress markers in the liver, kidney and heart of C57BL/6J mice. Mice were segregated into two groups, one fed standard diet (NC) and the other fed high-fat diet (HFD) for 15 weeks. HFD-fed mice were subjected to intragastric administration of AzA (80 mg/kg BW)/RSG (10 mg/kg BW) during 11-15 weeks. Glucose, insulin, triglycerides, hepatic and nephritic markers were analysed in the plasma and the activity of enzymatic, non-enzymatic antioxidants and lipid peroxidation markers were examined in the plasma/erythrocytes, liver, kidney and heart of normal and experimental mice. We inferred significant decrease in enzymatic and non-enzymatic antioxidants along with significant increase in glucose, insulin, hepatic and nephritic markers, triglycerides and lipid peroxidation markers in HFD-fed mice. Administration of AzA could positively restore the levels of plasma glucose, insulin, triglycerides, hepatic and nephritic markers to near normal. AzA increased the levels of enzymatic and nonenzymatic antioxidants with significant reduction in the levels of lipid peroxidation markers. Histopathological examination of liver, kidney and heart substantiated these results. Hence, we put forward that AzA could counteract the potential injurious effects of HFD-induced oxidative stress in C57BL/6J mice.
Article
Bergenin, a major constituent of Caesalpinia digyna Rottler (Leguminosae) was isolated from its roots and was characterized by comparing its melting point and spectroscopic data (IR, (1)H, (13)C, Mass Spectra) with standard bergenin. Isolated bergenin was then evaluated for antidiabetic (Type 2) activity in streptozotocin (STZ)-nicotinamide induced diabetic rats. Bergenin was administered at doses of 2.5, 5, and 10 mg/kg; p.o. to normal rats which were subjected to oral glucose tolerance test (OGTT). Bergenin at same dose level was given to diabetic rats and fasting blood glucose level was estimated on 0th, 7th and 14th day of treatment while plasma lipids, antioxidant enzymes and liver glycogen level in diabetic rats were estimated on 14th day of treatment followed by histopathological studies of pancreas. Bergenin at 10mg/kg; p.o. was found to reduce blood glucose level significantly in OGTT (P<0.01) while it showed a significant reduction in fasting blood glucose level in diabetic rats at same dose level only on 14th day of treatment. Bergenin in all dose levels reversed plasma lipid (reduced elevated TC, LDL-C and increased HDL-C level) profile to normal values except TG. However, bergenin showed no significant effect on liver glycogen at all dose level. The decrease in lipid peroxides and increase in superoxide dismutase (SOD) and catalase (CAT) in liver illustrated the antioxidant potential of bergenin. Histopathological studies demonstrated the regenerative effect of bergenin on pancreatic β cells. Hence, bergenin isolated from C. digyna possesses significant antidiabetic, hypolipidemic and antioxidant activity in Type 2 diabetic rats.
Article
Bergenin pentacetate (2), a peracetate derivative of biologically active lead compound Bergenin (1) isolated from Bergenia stracheyi was subjected to lipase catalyzed regioselective alcoholysis to obtain 3,4,10,11-tetracetate of Bergenin (3). The free hydroxyl group of 3 was derivatised using higher carboxylic acids to obtain acyl derivatives (4-7). These compounds synthesized via chemoenzymatic route were characterized using 1H NMR, 13C NMR and mass spectral data and evaluated for DPPH radical scavenging, antimicrobial and xanthine oxidase inhibitory activities. The studies revealed that biological activity of Bergenin can be optimized by selective modification of its structure.
Article
Background: The metabolic syndrome is a constellation of common metabolic disorders that is associated with cardiovascular disease. Insulin resistance has a central role in the pathophysiology of metabolic syndrome. Recent advances: It is now commonly accepted that chronic inflammation associated with visceral obesity induces insulin resistance in the liver. Chronic inflammation is characterized by the production of abnormal adipokines and cytokines such as TNF-alpha, FFA, IL-1, IL-6, leptin and resistin. These factors inhibit insulin signalling in hepatocytes by activating SOCS proteins, several kinases such as JNK, IKK-beta and PKC and protein tyrosine phosphatases such as PTP1B and PTEN, that in turn impair insulin signalling at insulin receptor and insulin receptor substrate (IRS) level. Hepatic insulin resistance in turn causes impaired suppression of glucose production by insulin in hepatocytes leading to hyperglycemia. An important and early complication of hepatic insulin resistance is the induction of hepatic VLDL production, via changes in the rate of apoB synthesis and degradation and de novo lipogenesis, or increased FFA flux from adipose tissue into the liver. Insulin resistance also stimulates the production of CRP and PAI-1, both markers of an inflammatory state. All metabolic abnormalities related to hepatic insulin resistance have been shown to directly or indirectly promote atherosclerosis. Hyperglycemia induces a series of alterations including endothelial dysfunction, cellular proliferation, changes in extracellular matrix conformation and impairment of LDL receptor-mediated uptake decreasing the in vivo clearance of LDL. Small dense LDLs associated with high circulating VLDL have higher affinity to the intimal proteoglycans leading to the penetration of more LDL particles into the arterial wall. CRP can also accelerate atherosclerosis by increasing the expression of PAI-1 and adhesion molecules in endothelial cells, inhibition of nitric oxide formation and increasing LDL uptake into macrophages. Conclusions: Overall, growing evidence suggests that hepatic insulin resistance is sufficient to induce several components of the metabolic syndrome and promote progression to cardiovascular disease. Many unresolved questions remain however on the molecular and cellular mechanisms that trigger hepatic insulin resistance and promote the development of clinical metabolic syndrome.
Article
Insulin resistance plays a role in the pathogenesis of diabetes, including gestational diabetes. The glucose clamp is considered the gold standard for determining in vivo insulin sensitivity, both in human and in animal models. However, the clamp is laborious, time consuming and, in animals, requires anesthesia and collection of multiple blood samples. In human studies, a number of simple indexes, derived from fasting glucose and insulin levels, have been obtained and validated against the glucose clamp. However, these indexes have not been validated in rats and their accuracy in predicting altered insulin sensitivity remains to be established. In the present study, we have evaluated whether indirect estimates based on fasting glucose and insulin levels are valid predictors of insulin sensitivity in nonpregnant and 20-day-pregnant Wistar and Sprague-Dawley rats. We have analyzed the homeostasis model assessment of insulin resistance (HOMA-IR), the quantitative insulin sensitivity check index (QUICKI), and the fasting glucose-to-insulin ratio (FGIR) by comparing them with the insulin sensitivity (SI(Clamp)) values obtained during the hyperinsulinemic-isoglycemic clamp. We have performed a calibration analysis to evaluate the ability of these indexes to accurately predict insulin sensitivity as determined by the reference glucose clamp. Finally, to assess the reliability of these indexes for the identification of animals with impaired insulin sensitivity, performance of the indexes was analyzed by receiver operating characteristic (ROC) curves in Wistar and Sprague-Dawley rats. We found that HOMA-IR, QUICKI, and FGIR correlated significantly with SI(Clamp), exhibited good sensitivity and specificity, accurately predicted SI(Clamp), and yielded lower insulin sensitivity in pregnant than in nonpregnant rats. Together, our data demonstrate that these indexes provide an easy and accurate measure of insulin sensitivity during pregnancy in the rat.
Article
We studied the increased levels of hemoglobins AIa+Ib and AIc in five hospitalized diabetic patients to determine whether changes in diabetic control would cause parallel changes in the levels of these hemoglobins. Before control of diabetes the mean fasting blood sugar for all patients was 343 mg per deciliter (range, 280 to 450), and hemoglobin AIc concentration 9.8 per cent (range, 6.8 to 12.1). During optimal diabetic control the blood sugar concentration was 84 mg per deciliter (range, 70 to 100), and hemoglobin AIc concentration 5.8 per cent (range, 4.2 to 7.6). Hemoglobin AIc concentration appears to reflect the mean blood sugar concentration best over previous weeks to months. The periodic monitoring of hemoglobin AIc levels provides a useful way of documenting the degree of control of glucose metabolism in diabetic patients and provides a means whereby the relation of carbohydrate control to the development of sequelae can be assessed.
Article
The well-characterized erythrocyte glucose transporter is also expressed in brain, adipocytes, kidney, muscle, and certain transformed cells, but not in liver, intestine, or the islets of Langerhans. Using as probe a cDNA encoding the rat brain glucose transporter, we isolated from a rat liver cDNA library a clone encoding a protein 55% identical in sequence to the rat brain transporter, and with a superimpossible hydropathy plot. We expressed this protein in an E. coli mutant defective in glucose uptake; the protein was incorporated into the bacterial membrane and functioned as a glucose transporter. This new transporter is expressed in liver, intestine, kidney, and the islets of Langerhans; immunofluorescence analysis showed that it is present in the plasma membrane of the insulin-producing beta cells. Insulinoma cells express, inappropriately, the erythrocyte glucose transporter, and we suggest that this may be related to their inability to secrete insulin in response to elevations in glucose.
Article
An enzyme-linked immunosorbent assay for the measurement of insulin in human serum has been developed. The test is based on the sandwich technique with two monoclonal antibodies directed against two different epitopes of insulin using coated plastic tubes as the solid phase and horse radish peroxidase as the label. The immunoreactions are completed in one step within 2 h. The horse radish peroxidase activity bound to the tube wall is measured photometrically after an additional 1-h incubation with the substrate. The standards used cover the range from 0 to 260 mU insulin/L. Employing the Enzymun-Test System ES 22 modular batch analyzer, the detection limit was found to be 3.7 mU insulin/L. Coefficients of variation (CV's) between 1.4-7.8% for intraassay precision and 5.6-10% for interassay precision were obtained over the concentration range of 17-107 mU Insulin/L. The correlation between the procedure described here (y) and a commercially available double antibody radioimmunoassay (x) is expressed by the following equation: y = 1.07x + 1.14 mU insulin/L.
Article
cDNA clones encoding a glucose transporter-like protein have been isolated from adult human liver and kidney cDNA libraries by cross-hybridization with the human HepG2/erythrocyte glucose transporter cDNA. Analysis of the sequence of this 524-amino acid glucose transporter-like protein indicates that it has 55.5% identity with the HepG2/erythrocyte glucose transporter as well as a similar structural organization. Studies of the tissue distribution of the mRNA coding for this glucose transporter-like protein in adult human tissues indicate that the highest amounts are present in liver with lower amounts in kidney and small intestine. The amounts of glucose transporter-like mRNA in other tissues, including colon, stomach, cerebrum, skeletal muscle, and adipose tissue, were below the level of sensitivity of our assay. The single-copy gene encoding this glucose transporter-like protein has been localized to the q26.1----q26.3 region of chromosome 3.
Article
A simple colorimetric assay for catalase activity has been described using K2Cr2O7/acetic acid reagent. Kat. f values of different enzyme sources were determined by the colorimetric method and compared with the values obtained by titrimetric methods.
Article
Using an improved method of gel electrophoresis, many hitherto unknown proteins have been found in bacteriophage T4 and some of these have been identified with specific gene products. Four major components of the head are cleaved during the process of assembly, apparently after the precursor proteins have assembled into some large intermediate structure.
Article
Manual and automated methods for the determination of blood glucose have been devised using an oxidase/peroxidase system, with dl adrenaline, a non-carcinogen, as oxygen acceptor. The manual technique employs a stable single solution protein precipitant and the other reagents used are also stable. The automated methods are operated at 40/hr sample speed and washover between samples, over a very wide concentration range, is negligible.
Article
A new colorimetric method, based on the phenol sulphuric acid reaction of carbohydrates, is described for the determination of glycosylated hemoglobin. Hemolyzates were treated with 1 mol/l oxalic acid in 2 mol/l Hcl for 4 h at 100 degrees C, the protein was precipitated with trichloroacetic acid, and the free sugars and hydroxymethyl furfural in the protein free supernatant were treated with phenol and sulphuric acid to form the color. The new method is compared to the thiobarbituric acid method and the ion-exchange chromatographic method for the estimation of glycosylated hemoglobin in normals and diabetics. The increase in glycosylated hemoglobin in diabetic patients as estimated by the phenol-sulphuric acid method was more significant (P less than 0.001) than the increase observed by the thiobarbituric acid method (P less than 0.01). The correlation between the phenol-sulphuric acid method and the column method was better (r = 0.91) than the correlation between the thiobarbituric acid method and the column method (r = 0.84). No significant correlation between fasting and postprandial blood sugar level and glycosylated hemoglobin level as determined by the two colorimetric methods was observed in diabetic patients.
Article
As part of our screening of anti-AIDS agents from medicinal plants, the MeOH extract of the aerial parts of Ardisia japonica was tested, and it showed moderate in vitro anti-HIV activity. Reexamination to identify the compounds responsible for the anti-HIV activity revealed several known compounds and a new triterpenoid saponin (4) whose structure elucidation was accomplished by 1H-1H correlation spectroscopy (COSY, HOHAHA, ROESY) and 1H-13C heteronuclear correlation (HETCOR) NMR experiments. All of the isolated compounds were tested and, although none of the triterpenoid saponins was active, bergenin and norbergenin showed weak anti-HIV activity.
Article
The integration of multiple transmembrane signals is especially important during development and maintenance of the nervous system, communication between cells of the immune system, evolution of transformed cells, and metabolic control (Hunter 1997). Tyrosine phosphorylation plays a key role in many of these processes by directly controlling the activity of receptors or enzymes at early steps in signaling cascades, or by the assembly of multicomponent signaling complexes around activated receptors or their cellular substrates (Pawson 1995). In most if not all cases, initialization of the signaling cascade controlled by growth factor and cytokine receptors originates with multisite tyrosine phosphorylation catalyzed directly by kinases activated during ligand-induced dimerization of specific membrane receptors (Schlessinger 1988; Helding 1995). In many cases, tyrosine autophosphorylation sites in activated receptors directly bind signaling proteins containing Src homology-2 domains (SH2 proteins). In other cases, tyrosine autophosphorylation increases the activity of the receptor kinase, which mediates tyrosine phosphorylation of cytosolic substrates or docking proteins that recruit SH2 proteins into multipotential signaling complexes (Myers and White 1995). The network is further elaborated through other modules which mediate protein-protein or protein-lipid interactions, including PTB, PDZ, SH3, WW, and PH domains.
Article
To determine the antihepatotoxic activity of bergenin from Mallotus japonicus, carbon tetrachloride (CCl4)-induced cytotoxicity in primary cultured rat hepatocytes has been adopted as an assay system. Bergenin significantly reduced the activities of glutamic pyruvic transaminase and sorbitol dehydrogenase released from the CCl4-intoxicated hepatocytes. The antihepatotoxicity of bergenin was also evidenced by elevating the activities of glutathione S-transferase and glutathione reductase, and content of glutathione in the CCl4-intoxicated hepatocytes. From these results, it is assumed that bergenin exerted antihepatotoxicity against CCl4-induced cytotoxicity through glutathione-mediated detoxification as well as free radical suppressing activity.
Article
It is estimated that by the year 2020 there will be approximately 250 million people affected by type 2 diabetes mellitus worldwide (1). Although the primary factors causing this disease are unknown, it is clear that insulin resistance plays a major role in its development. Evidence for this comes from (a) the presence of insulin resistance 10–20 years before the onset of the disease (2, 3); (b) cross-sectional studies demonstrating that insulin resistance is a consistent finding in patients with type 2 diabetes (3–6); and (c) prospective studies demonstrating that insulin resistance is the best predictor of whether or not an individual will later become diabetic (2, 3). Here, I focus on some recent advances in our understanding of human insulin resistance that have been made using nuclear magnetic resonance spectroscopy (NMR). This technique takes advantage of the spin properties of the nuclei of certain isotopes, such as 1H, 13C, and 31P, which endow the isotopes with a magnetic component that can be used to measure the concentration of intracellular metabolites noninvasively and to assess biochemical differences between normal and diabetic subjects. Drawing on NMR studies from my laboratory and others, I first consider the control of glucose phosphorylation and transport in regulating muscle responses to insulin. I then turn to the effects of fatty acids on insulin responses, showing that commonly accepted models that attempt to explain the association of insulin resistance and obesity are incompatible with recent findings. Finally, I propose an alternative model that appears to fit these and other available data.
Article
Insulin resistance plays an important role in the pathophysiology of diabetes and is associated with obesity and other cardiovascular risk factors. The "gold standard" glucose clamp and minimal model analysis are two established methods for determining insulin sensitivity in vivo, but neither is easily implemented in large studies. Thus, it is of interest to develop a simple, accurate method for assessing insulin sensitivity that is useful for clinical investigations. We performed both hyperinsulinemic isoglycemic glucose clamp and insulin-modified frequently sampled iv glucose tolerance tests on 28 nonobese, 13 obese, and 15 type 2 diabetic subjects. We obtained correlations between indexes of insulin sensitivity from glucose clamp studies (SI(Clamp)) and minimal model analysis (SI(MM)) that were comparable to previous reports (r = 0.57). We performed a sensitivity analysis on our data and discovered that physiological steady state values [i.e. fasting insulin (I(0)) and glucose (G(0))] contain critical information about insulin sensitivity. We defined a quantitative insulin sensitivity check index (QUICKI = 1/[log(I(0)) + log(G(0))]) that has substantially better correlation with SI(Clamp) (r = 0.78) than the correlation we observed between SI(MM) and SI(Clamp). Moreover, we observed a comparable overall correlation between QUICKI and SI(Clamp) in a totally independent group of 21 obese and 14 nonobese subjects from another institution. We conclude that QUICKI is an index of insulin sensitivity obtained from a fasting blood sample that may be useful for clinical research.
Article
The hepatoprotective effects of bergenin, a major constituent of Mallotus japonicus, were evaluated against carbon tetrachloride (CCl(4))-induced liver damage in rats. Bergenin at a dose of 50, 100 or 200 mg/kg was administered orally once daily for successive 7 days and then a mixture of 0.5 ml/kg (ip) of CCl(4) in olive oil (1:1) was injected two times each at 12 and 36 h after the final administration of bergenin. The substantially elevated serum enzymatic activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase and gamma-glutamyltransferase due to CCl(4) treatment were dose dependently restored towards normalization. Meanwhile, the decreased activities of glutathione S-transferase and glutathione reductase were restored towards normalization. In addition, bergenin also significantly prevented the elevation of hepatic malondialdehyde formation and depletion of reduced glutathione content in the liver of CCl(4)-intoxicated rats in a dose dependent fashion. The results of this study clearly indicate that bergenin has a potent hepatoprotective action against CCl(4)-induced hepatic damage in rats.
Article
High-fat feeding has been shown to cause hepatic insulin resistance. The aims of this study were to investigate the biochemical steps responsible for enhanced gluconeogenesis as a result of increased dietary fat intake and the site or sites at which the antihyperglycemic agent metformin acts to inhibit this process. Male Hooded Wistar rats were fed either a standard chow diet (5% fat by weight) or a high-fat diet (60% fat by weight) for 14 days with or without metformin. Total endogenous glucose production and gluconeogenesis were determined using [6-(3)H]glucose and [U-(14)C]alanine, respectively. Gluconeogenic enzyme activity and, where appropriate, protein and mRNA levels were measured in liver tissues. The high-fat diet increased endogenous glucose production (21.9 +/- 4.4 vs. 32.2 +/- 4.8 micromol x kg(-1) x min(-1), P < 0.05) and alanine gluconeogenesis (4.5 +/- 0.9 vs. 9.6 +/- 1.9 micromol x kg(-1) x min(-1), P < 0.05). Metformin reduced both endogenous glucose production (32.2 +/- 4.8 vs. 16.1 +/- 2.1 micromol x kg(-1) x min(-1), P < 0.05) and alanine gluconeogenesis (9.6 +/- 1.9 vs. 4.7 +/- 0.8 micromol x kg(-1) x min(-1), P < 0.05) after high-fat feeding. These changes were reflected in liver fructose-1,6-bisphosphatase protein levels (4.5 +/- 0.9 vs. 9.6 +/- 1.9 arbitrary units, P < 0.05 chow vs. high-fat feeding; 9.5 +/- 1.9 vs. 4.7 +/- 0.8 arbitrary units, P < 0.05 high fat fed in the absence vs. presence of metformin) but not in changes to the activity of other gluconeogenic enzymes. There was a significant positive correlation between alanine gluconeogenesis and fructose-1,6-bisphosphatase protein levels (r = 0.56, P < 0.05). Therefore, excess supply of dietary fat stimulates alanine gluconeogenesis via an increase in fructose-1,6-bisphosphatase protein levels. Metformin predominantly inhibits alanine gluconeogenesis by preventing the fat-induced changes in fructose-1,6-bisphosphatase levels.
Article
Bergenin was isolated from the aerial parts of Fluggea virosa (Euphorbiaceae). Its structure was elucidated on the basis of chemical and spectral data. Anti-arrhythmic effects of bergenin were investigated. At concentrations of 0.2 mg/kg, 0.4 mg/kg, and 0.8 mg/kg, bergenin showed distinct therapeutic effects on BaCl2-induced arrhythmias in rats. At concentrations of 0.4 mg/kg and 0.8 mg/kg bergenin significantly countered arrhythmias induced by ligation and reperfusion of the coronary artery. At 0.8 mg/kg, bergenin elevated the atria fibrillation threshold in rabbits from 1.34 mV to 1.92 mV. Our results suggest that bergenin has good potential to treat cardiac arrhythmias.
Article
Animal studies have already shown the possibility to modulate insulin action by changing not only the amount of total fat, but also the type of fat. In these studies, saturated fat significantly increased insulin resistance, long- and short-chain omega(3) fatty acids significantly improved it, whereas the effects of monounsaturated and omega(6) polyunsaturated fatty acids ranged somewhere in between the two. A recent multicenter study (the Kanwu study) on humans has shown that shifting from a diet rich in saturated fatty acids to one rich in monounsaturated fat improved insulin sensitivity in healthy people, while a moderate omega(3) supplementation did not affect it; this second finding confirms previous results in type 2 diabetic patients with hypertriglyceridemia. There are also other aspects of the metabolic syndrome that can be influenced by the different type of dietary fat, particularly blood pressure and lipid metabolism. With respect to blood pressure, the majority of studies show that omega(3) fatty acids are able to reduce blood pressure in hypertensive patients, but not in normotensive individuals; this result has been confirmed also by the Kanwu study, where no changes in blood pressure were seen after omega(3) supplementation in healthy people. On the other hand, in this study, the change from saturated to monounsaturated fatty acids was able to significantly reduce diastolic blood pressure. As to the lipid abnormalities more frequently present in the metabolic syndrome (i.e., hypertriglyceridemia and low HDL cholesterol), the main effects are related to omega(3) fatty acids, which surely reduce triglyceride levels, but at the same time increase LDL cholesterol. In conclusion, there is so far sound evidence in humans that the quality of dietary fat is able to influence insulin resistance and some of the related metabolic abnormalities.
Article
1.1. In the venous serum of normal human adults scarcely any glucose-6-phosphatase activity can be observed.2.2. In the case of liver and kidney injuries, and then only, the serum glucose-6-phosphatase activity rises in a characteristic fashion, the maximum being no less than 2 to 20 times the normal value. The increase in activity is much less in renal diseases than in liver diseases. The enzyme is quite different from other non-specific phosphomonoesterases.3.3. The peak of the enzyme activity-time curve in experimental liver in jury occurs within 6 hours. This means that this serum enzyme is more sensitive than other serum enzymes.4.4. The glucose-6-phosphatase activity of the liver decreases to a greater or lesser extent in experimental liver injury.5.5. The serum glucose-6-phosphatase activity fails to rise in the following diseases: myocardial infarction, anemia, leukemia, myopathy and endocrine disorders.
Article
The antioxidant properties of three successive extracts of Caesalpinia digyna Rottler root and the isolated compound, bergenin, were tested using standard in vitro and in vivo models. The amount of the total phenolic compounds present was also determined. The successive methanol extract of Caesalpinia digyna root (CDM) exhibited strong scavenging effect on 2,2-diphenyl-2-picryl hydrazyl (DPPH) free radical, 2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulphonic acid) diammonium salt (ABTS) radical cation, hydrogen peroxide, nitric oxide, hydroxyl radical and inhibition of lipid peroxidation. The free radical scavenging effect of CDM was comparable with that of reference antioxidants. The CDM having the highest content of phenolic compounds and strong free radical scavenging effect when administered orally to male albino rats at 100, 200 and 400mg/kg body weight for 7 days, prior to carbontetrachloride (CCl(4)) treatment, caused a significant increase in the levels of catalase (CAT) and superoxide dismutase (SOD) and significant decrease in the levels of lipidperoxidation (LPO) in serum, liver and kidney in a dose dependent manner, when compared to CCl(4) treated control. These results clearly indicate the strong antioxidant property of Caesalpinia digyna root. The study provides a proof for the ethnomedical claims and reported biological activities. The plant has, therefore, very good therapeutic potential.
Glucose 6Phosphate Dehydrogenase: Methods of Enzymatic Analysis
  • Bergmeyer