Fuer Lu

Berberine in the treatment of type 2 diabetes mellitus: a systemic review and meta-analysis.

Objectives. To assess the efficacy and safety of berberine in the treatment of type 2 diabetes mellitus (T2DM). Methods. Randomized trials of berberine compared with lifestyle modification, placebo, and/or oral hypoglycaemics intervention on treating T2DM were included. Study population characteristics and outcome results were extracted independently by two reviewers. Meta-analyses were performed for data available. Results. Fourteen randomized trials, involving 1068 participants, were included in this study. Methodological quality was generally low. Compared with lifestyle modification with or without placebo, the cointervention of berberine and lifestyle modification showed significantly hypoglycaemic and antidyslipidemic response. Compared with oral hypoglycaemics including metformin, glipizide, or rosiglitazone, berberine did not demonstrate a significantly better glycaemic control but showed a mild antidyslipidemic effect. Compared with oral hypoglycaemic drugs, cointerventions with berberine and the same oral hypoglycaemics showed a better glycaemic control. No serious adverse effects from berberine were reported. Conclusions. Berberine appeared to be efficacious for treating hyperglycaemia and dyslipidemia in T2DM. However, the evidence of berberine for treating T2DM should be carefully interpreted due to the low methodological quality, small sample size, limited number of trials, and unidentified risks of bias.

The Effects of Berberine on Blood Lipids: A Systemic Review and Meta-Analysis of Randomized Controlled Trials

Clinical trials have reported lipid-lowering effects of berberine intake, but the findings have been inconsistent. The aim of this meta-analysis was to assess the safety of berberine and its effects on blood lipid profiles. A systemic review was designed, undertaken and reported in accordance with the PRISMA statement. Randomized controlled trials of the effects of berberine on blood lipids in adults were included. Study population characteristics and the main results, including changes in the levels of total cholesterol, triglycerides, low-density and high-density lipoprotein cholesterol, were extracted. Weighted mean differences were calculated for net changes in blood lipid concentrations using fixed-effect or random-effects models. After filtering, eleven randomized controlled trials (including a total of 874 participants) were included in this study. The methodological quality of these studies was generally low. The final analysis showed that administration of berberine produced a significant reduction in total cholesterol (mean difference - 0.61 mmol/L; 95 % confidence interval - 0.83 to - 0.39), triglycerides (mean difference - 0.50 mmol/L; 95 % confidence interval - 0.69 to - 0.31), and low-density lipoprotein cholesterol (mean difference - 0.65 mmol/L; 95 % confidence interval - 0.76 to - 0.54) levels, with a remarkable increase in high-density lipoprotein (mean difference 0.05 mmol/L; 95 % confidence interval 0.02 to 0.09). No serious adverse effects of berberine have been reported. In conclusion, berberine may have beneficial effects in the control of blood lipid levels. However, the efficacy of berberine in treating hyperlipidemia should be further evaluated by more randomized controlled trials in a larger population of patients.

Berberine reduces endoplasmic reticulum stress and improves insulin signal transduction in Hep G2 cells.

AbstractAim:Endoplasmic reticulum (ER) stress plays an important role in the pathogenesis of insulin resistance and pancreatic β-cell dysfunction. The aim of this study is to investigate whether the insulin-sensitizing action of berberine is related to reducing ER stress.Methods:ER stress in cultured Hep G2 cells was induced with tunicamycin. Cells were pretreated with berberine in combination with or without insulin. The concentration of glucose was measured by glucose oxidase method. The molecular markers of ER stress, including ORP150, PERK, and eIF2α were analyzed by Western blot or real time PCR. The activity of JNK was also evaluated. Moreover, the insulin signaling proteins such as IRS-1 and AKT were determined by Western blot.Results:The production of glucose stimulated with insulin was reduced. The expressions of ORP150 was decreased both in gene and protein levels when cells were pretreated with berberine, while the activation of JNK was blocked. The levels of phosphorylation both on PERK and eIF2α were inhibited in cells pretreated with berberine. The level of IRS-1 ser307 phosphorylation was decreased, whereas IRS-1 tyr phosphorylation was increased notablely. AKT ser473 phosphorylation was also enhanced significantly in the presence of berberine.Conclusion:The antidiabetic effect of berberine in Hep G2 cells maybe related to attenuation of ER stress and improvement of insulin signal transduction.

The anti-diabetic effects and pharmacokinetic profiles of berberine in mice treated with Jiao-Tai-Wan and its compatibility

Jiao-Tai-Wan (JTW), a classical Chinese prescription, has been clinically employed to treat diabetes mellitus in recent years. To investigate the comparative evaluations on anti-diabetic effects and pharmacokinetics of the active ingredient berberine in mice treated with JTW in various combinations of its constituent herbs. In our study, the anti-diabetic study was carried out in diabetic mice induced by intraperitoneal injection of streptozotocin. The diabetic mice were randomly assigned to three therapy groups and orally administered with different prescription proportions of Rhizoma Coptidis and Cinnamomum cassia respectively. The level of plasma glucose, lipid profile and parameters related to oxidative stress were determined. The concentrations of berberine in non-diabetic mice plasma were determined using HPLC, and main pharmacokinetic parameters were investigated. The results indicated that the compatibility effects of ingredients present in Cinnamomum cassia could affect the anti-diabetic ability and pharmacokinetics of berberine in JTW.

Berberine inhibits hepatic gluconeogenesis via the LKB1-AMPK-TORC2 signaling pathway in streptozotocin-induced diabetic rats

AIM To investigate the molecular mechanisms of berberine inhibition of hepatic gluconeogenesis in a diabetic rat model. METHODS The 40 rats were randomly divided into five groups. One group was selected as the normal group. In the remaining groups (n = 8 each), the rats were fed on a high-fat diet for 1 mo and received intravenous injection of streptozotocin for induction of the diabetic models. Berberine (156 mg/kg per day) (berberine group) or metformin (184 mg/kg per day) (metformin group) was intragastrically administered to the diabetic rats and 5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside (AICAR) (0.5 mg/kg per day) (AICAR group) was subcutaneously injected to the diabetic rats for 12 wk. The remaining eight diabetic rats served as the model group. Fasting plasma glucose and insulin levels as well as lipid profile were tested. The expressions of proteins were examined by western blotting. The nuclear translocation of CREB-regulated transcription co-activator (TORC)2 was observed by immunohistochemical staining. RESULTS Berberine improved impaired glucose tolerance and decreased plasma hyperlipidemia. Moreover, berberine decreased fasting plasma insulin and homeostasis model assessment of insulin resistance (HOMA-IR). Berberine upregulated protein expression of liver kinase (LK)B1, AMP-activated protein kinase (AMPK) and phosphorylated AMPK (p-AMPK). The level of phophorylated TORC2 (p-TORC2) protein in the cytoplasm was higher in the berberine group than in the model group, and no significant difference in total TORC2 protein level was observed. Immunohistochemical staining revealed that more TORC2 was localized in the cytoplasm of the berberine group than in the model group. Moreover, berberine treatment downregulated protein expression of the key gluconeogenic enzymes (phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) in the liver tissues. CONCLUSION Our findings revealed that berberine inhibited hepatic gluconeogenesis via the regulation of the LKB1-AMPK-TORC2 signaling pathway.

Jiao Tai Wan Attenuates Hepatic Lipid Accumulation in Type 2 Diabetes Mellitus

Jiao Tai Wan (JTW), a Chinese herbal formula containing Rhizoma Coptidis and Cortex Cinnamomi, has been used for diabetic treatment for many years. The aim of this study was to determine the main components in JTW and to investigate the effects of JTW on hepatic lipid accumulation in diabetic rats and humans. JTW extract was prepared and the main components were assayed by HPLC. An animal model of diabetes mellitus was established and JTW was administered intragastrically. In the clinical study, diabetic patients with poor glycemic control were treated with JTW. Blood glucose and lipid parameters, liver histology, hepatic triglyceride content and lipogenic gene expression were examined. Our data demonstrated that JTW significantly improved hyperglycemia, hyperlipidemia and hepatic lipid accumulation in diabetic rats. This was accompanied by the down-regulation of acetyl coenzyme A carboxylase (ACC) and fatty acid synthase (FAS) protein expressions, and the up-regulation of AMP-activated protein kinase (AMPK) and phosphorylated-ACC (pACC) protein expressions in the liver tissues. Diabetic patients also exhibited decreases in their hepatic triglyceride content. The results suggest that JTW attenuates hepatic lipid accumulation in diabetic rats and humans. These beneficial effects are possibly associated with the inhibition of lipogenic gene expression in the liver.

Soy isoflavones and glucose metabolism in menopausal women: A systematic review and meta-analysis of randomized controlled trials.

SCOPE The aim of this meta-analysis was to investigate whether soy isoflavones, a type of phytoestrogen, would affect glucose homeostasis in menopausal women. METHODS AND RESULTS Studies concerning about the relationship between soy isoflavone treatment and glucose metabolism were searched on MEDLINE and WEB OF SCIENCE (updated through April 2015) and EMBASE (1990-April 2015). Seventeen randomized controlled trials (RCTs) with a total number of 1529 menopausal women were identified for meta-analysis. Soy isoflavones were found to show great significance for the improvement of glucose metabolism, though marked heterogeneity was found between studies. The overall results showed that the average difference in fasting blood glucose values between women assigned to soy isoflavones and women in placebo groups was -0.22 mmol/L (95% CI: -0.38 to -0.07 mmol/L) under a random-effects model. In addition, the effect of soy isoflavones on insulin was also significant: -0.43 μIU/mL (95% CI: -0.71 to -0.14 μIU/mL), as was the effect on homeostasis model assessment insulin resistance (HOMA-IR): -0.52 (95% CI: -0.76 to -0.28). CONCLUSION Although the results displayed a significant tendency in favor of soy isoflavones, it appears that genistein alone played an important role in improving glucose metabolism due to its low heterogeneity.

Berberine Attenuates Intestinal Mucosal Barrier Dysfunction in Type 2 Diabetic Rats

Background: Intestinal mucosal barrier dysfunction plays an important role in the development of diabetes mellitus (DM). Berberine (BBR), a kind of isoquinoline alkaloid, is widely known to be effective for both DM and diarrhea. Here, we explored whether the anti-diabetic effect of BBR was related to the intestine mucosal barrier. Methods and Results: The rat model of T2DM was established by high glucose and fat diet feeding and intravenous injection of streptozocin. Then, those diabetic rats were treated with BBR at different concentrations for 9 weeks. The results showed, in addition to hyperglycemia and hyperlipidemia, diabetic rats were also characterized by proinflammatory intestinal changes, altered gut-derived hormones, and 2.77-fold increase in intestinal permeability. However, the treatment with BBR significantly reversed the above changes in diabetic rats, presenting as the improvement of the high glucose and triglyceride levels, the relief of the inflammatory changes of intestinal immune system, and the attenuation of the intestinal barrier damage. BBR treatment at a high concentration also decreased the intestinal permeability by 27.5% in diabetic rats. Furthermore, BBR regulated the expressions of the molecules involved in TLR4/MyD88/NF-κB signaling pathways in intestinal tissue of diabetic rats. Conclusion: The hypoglycemic effects of BBR might be related to the improvement in gut-derived hormones and the attenuation of intestinal mucosal mechanic and immune barrier damages.

Effect of Fenugreek on Hyperglycaemia and Hyperlipidemia in Diabetes and Prediabetes: a Meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE Fenugreek is a widely used herb for the treatment of diabetes mellitus (DM) but the effects in randomized controlled trials (RCTs) were controversial. Therefore, a meta-analysis was conducted to estimate the overall effects of fenugreek on hyperglycaemia and hyperlipidemia in diabetes and prediabetes. MATERIALS AND METHODS PubMed, EMBASE, web of science, Chinese Biomedical Literature database (CBM), the Cochrane library, China Doctor Dissertations Full-text Database (CDFD), Wan Fang medical database, China Proceedings of Conference Full-text Database (CPCD), China national knowledge internet (CNKI) and China Masters Theses Full-text Database (CMFD) were searched to find the available literatures. RCTs with regard to the efficacy and safety of fenugreek on prediabetes or DM were included. The data of fasting blood glucose (FBG), postprandial 2h blood glucose (2hBG), glycosylated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-c) and high density lipoprotein cholesterol (HDL-c) were extracted to appraise the net change with fixed or randomized effect model. RESULTS A total of 10 articles (12 studies) were included in the analysis. Pooled results showed fenugreek significantly decreased the levels of FBG (MD -0.84mmol/L; 95% CI -1.38 to -0.31; p=0.002), 2hBG (MD -1.30mmol/L; 95% CI -1.78 to -0.83; p<0.0001), HbA1c (MD -1.16; 95% CI -1.23 to -1.09; p<0.00001) and TC (MD -0.30mmol/L; 95% CI-0.56 to -0.03; p=0.03). In spite of the reductive trends in the TG or LDL-c levels and incremental trends of HDL-c, these results were not statistically significant or need further verification for fenugreek in the treatment of DM and prediabetes. Some studies were of low quality. No liver and kidney toxicity were found in all included studies, and the main side effects were gastrointestinal discomfort. CONCLUSIONS The results suggest fenugreek has the hypoglycaemic and TC-lowering efficacy; however, the effects on TG, LDL-c and HDL-c need further confirmations.

Hu-Lu-Ba-Wan Attenuates Diabetic Nephropathy in Type 2 Diabetic Rats through PKC-α/NADPH Oxidase Signaling Pathway

Hu-Lu-Ba-Wan (HLBW) is a Chinese herbal prescription used to treat kidney deficiency. The aim of this study was to explore the effect and mechanism of HLBW on diabetic nephropathy (DN) in type 2 diabetic rats. The rat model of DN was established by being fed a high-fat diet and intravenous injection of streptozotocin. Then, HLBW decoction was administered for 16 weeks. Blood glucose level, lipid profile, renal function, 24-hour total urinary protein, and albumin content were examined. Renal morphology and superoxide anion levels were evaluated. The activity of nicotinamide-adenine dinucleotide phosphate (NADPH) and protein kinase C-alpha (PKC-α) related genes expression in renal tissue were also determined. Our data demonstrated that HLBW significantly improved hyperglycemia, hyperlipidemia, and proteinuria in diabetic rats compared with those of control group. HLBW also alleviated glomerular expansion and fibrosis, extracellular matrix accumulation and effacement of the foot processes. Additionally, HLBW reduced superoxide anion level, NADPH oxidase activity, the protein and mRNA expressions of p47phox, and the protein expression of phosphorylated PKC-α in renal tissue. These results suggest that HLBW is effective in the treatment of DN in rats. The underlying mechanism may be related to the attenuation of renal oxidative stress via PKC-α/NADPH oxidase signaling pathway.