Jiyin Zhou

Protective effect of berberine on beta cells in streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats

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.

Resveratrol protects against hyperglycemia-induced oxidative damage to mitochondria by activating SIRT1 in rat mesangial cells

Oxidative stress and mitochondrial dysfunction are involved in the pathogenesis of diabetic nephropathy (DN). Resveratrol has potent protective effects on diabetes and diabetic complications including diabetic nephropathy. We aimed to investigate the protective effects of resveratrol on mitochondria and the underlying mechanisms by using an in vitro model of hyperglycemia. We exposed primary cultured rat mesangial cells to high glucose (30mM) for 48h. We found that pretreatment with resveratrol (10μM) 6h prior to high glucose treatment significantly reduced hyperglycemia-induced increase in reactive oxygen species (ROS) production and mitochondrial superoxide generation, as well as stimulated MnSOD activity. In addition, resveratrol pretreatment significantly reversed the decrease of mitochondrial complex III activity in glucose-treated mesangial cells, which is considered to be the major source of mitochondrial oxidative stress in glucose-treated cells. Furthermore, resveratrol pretreatment efficiently restored the hyperpolarization of ∆Ψm, increased ATP production and preserved the mtDNA content. All of these protective effects of resveratrol were successfully blocked by siRNA targeting SIRT1 and EX-527, a specific inhibitor of SIRT1 activity. Our results indicated that resveratrol efficiently reduced oxidative stress and maintained mitochondrial function related with activating SIRT1 in glucose-treated mesangial cells. It suggested that resveratrol is pharmacologically promising for treating diabetic nephropathy.

Experimental diabetes treated with trigonelline: effect on β cell and pancreatic oxidative parameters.

Oxidative stress in diabetes coexists with a reduction in the antioxidant status, which can further increase the deleterious effects of free radicals. Trigonelline is the major component of Mirabilis jalapa L., which has been used to treat diabetes in China. The present study was designed to evaluate the beneficial effects of trigonelline against hyperglycemia, hyperlipidemia, β cell damage and antioxidant of pancreas in diabetic rats. Diabetic rats were induced by intraperitoneal injection 35u2003mg/kg streptozotocin and a high‐carbohydrate/high‐fat diet. Rats were divided into four groups: normal control, diabetic control, trigonelline‐treated diabetic, and glibenclamide‐treated diabetic. After 4‐week treatment, blood glucose, serum insulin, total cholesterol (TC), and triglyceride (TG) levels, insulin content in pancreas, and oxidative stress parameters in pancreatic homogenate were assayed. Pancreas was examined by hematoxylin/eosin staining. Trigonelline significantly decreased blood glucose, TC, and TG levels of diabetic rats. Pancreas‐to‐body weight ratio, insulin level, insulin sensitivity index, insulin content in pancreas, malonaldehyde and nitric oxide contents, and superoxide dismutase, catalase, glutathione and inducible nitric oxide synthase activities were altered in diabetic rats, and were near control levels treated with trigonelline. These findings suggest that trigonelline has beneficial effect for diabetes through decreasing blood glucose and lipid levels, increasing insulin sensitivity index and insulin content, up‐regulating antioxidant enzyme activity and decreasing lipid peroxidation.

Berberine regulates peroxisome proliferator-activated receptors and positive transcription elongation factor b expression in diabetic adipocytes.

Berberine has hypoglycemic and hypolipidemic effects on diabetic rats. This study investigated the relationship between hypoglycemic and hypolipidemic effects of berberine and peroxisome proliferator-activated receptors (PPARs) and positive transcription elongation factor b (P-TEFb) (including cyclin-dependent kinase 9 (CDK9) and cyclin T1) in white adipose tissue of diabetic rats and RNA interference-treated 3T3-L1 cells. Berberine promoted differentiation and inhibited lipid accumulation of 3T3-L1 cells, further decreased PPARα/δ/γ, CDK9 and cyclin T1 mRNA and protein expression and decreased tumor necrosis factor α content in supernatants of both control and RNA interference-treated 3T3-L1 cells. After a 16-week induction with 35 mg/kg streptozotocin (i.p.) and high-carbohydrate/high-fat diet, diabetic rats were treated with 75, 150 and 300 mg/kg berberine and 100 mg/kg fenofibrate or 4 mg/kg rosiglitazone for another 16 weeks. Berberine decreased white adipose tissue to body weight ratio and adipocyte size and increased adipocyte number. Berberine upregulated PPARα/δ/γ, CDK9 and cyclin T1 mRNA and protein expression in adipose tissue, decreased tumor necrosis factor α and free fatty acid content and increased lipoprotein lipase activity in serum and adipose tissue. Berberine modulated metabolic related PPARs expression and differentiation related P-TEFb expression in adipocytes, which are associated with its hypoglycemic and hypolipidemic effects.

Neuroprotective effect of berberine is mediated by MAPK signaling pathway in experimental diabetic neuropathy in rats.

The mechanisms leading to diabetic neuropathy are complex. As an active component in several traditional Chinese medicines, berberine has a beneficial effect in the treatment of diabetes with hyperlipidemia. This study evaluated the protective effects of berberine on diabetic neuropathy induced by streptozotocin and a high-carbohydrate/high-fat diet in rats. Diabetic neuropathy was induced in rats by intraperitoneal injection of 35 mg/kg streptozotocin and a high-carbohydrate/high-fat diet. Two weeks after diabetes induction, rats were treated with berberine (100 mg/kg) and rosiglitazone (4 mg/kg) for 24 weeks. Rats were studied using evoked potentials, the Morris water maze, transmission electron microscopy, real-time PCR, and Western blotting. Blood glucose, glycated hemoglobin, lipid profile, body weight, evoked potentials, and memory were altered in diabetic rats, as was the hippocampal expression of neuritin mRNA, p38 mitogen-activated protein kinase mRNA, c-Jun N-terminal kinase (JNK) mRNA, extracellular signal-regulated kinase mRNA and the phospho-proteins of p38, JNK, and extracellular signal-regulated kinase. In diabetic rats, berberine decreased body weight and the blood levels of glucose, glycated hemoglobin, triglyceride, and total cholesterol, improved memory and affected evoked potential by decreasing latency. Berberine decreased the mRNA expression of neuritin, p38, and JNK and the protein expression of neuritin, p-p38, and p-JNK. Slight micropathological changes were observed in the hippocampus of berberine-treated diabetic rats. These findings suggest that berberine has a beneficial effect against diabetic neuropathy by improving micropathology and increasing neuritin expression via the mitogen-activated protein kinase signaling pathway.

Hypoglycemic and Hypolipidemic Effects of Ethanolic Extract of Mirabilis jalapa L. Root on Normal and Diabetic Mice.

The present study investigated the insulin sensitivity, hypoglycemic, and hypolipidemic activities of ethanolic extract of Mirabilis jalapa L. root (EEM) in normal and diabetic mice. After induction of diabetes with streptozotocin, both normal and diabetic mice were singly or repeatedly for 28 days administrated with EEM at doses of 2, 4, 8u2009g/kg, respectively. Before induction of diabetes, mice were administrated with EEM at doses of 2, 4, 8u2009g/kg for 14 days and were injected with streptozotocin and continued on EEM administration for another 28 days. Both after and before induction of diabetes, repeated administration with 4, 8u2009g/kg EEM continually lowered blood glucose level, decreased serum insulin level and improved insulin sensitivity index, and lowered serum total cholesterol, triglyceride levels and triglyceride content in liver and skeletal muscle, and increased glycogen content in these tissues; but repeated administration had no influence on those indexes of normal mice. Single administration with EEM (4, 8u2009g/kg) showed hypoglycemic effect in oral glucose tolerance test in normal and diabetic mice. Single administration with EEM had no hypoglycemic and hypolipidemic effects on normal and diabetic mice. These results suggest that EEM possesses both potential insulin sensitivity, hypoglycemic, and hypolipidemic effects on diabetes.

Effectiveness of problem-based learning in Chinese pharmacy education: a meta-analysis

BackgroundThis review provides a critical overview of problem-based learning (PBL) practices in Chinese pharmacy education. PBL has yet to be widely applied in pharmaceutical education in China. The results of those studies that have been conducted are published in Chinese and thus may not be easily accessible to international researchers. Therefore, this meta-analysis was carried out to review the effectiveness of PBL.MethodsDatabases were searched for studies in accordance with the inclusion criteria. Two reviewers independently performed the study identification and data extraction. A meta-analysis was conducted using Revman 5.3 software.ResultsSixteen randomized controlled trials were included. The meta-analysis revealed that PBL had a positive association with higher theoretical scores (SMDu2009=u20091.17, 95xa0% CI [0.77, 11.57], Pu2009<u20090.00001). The questionnaire results show that PBL methods are superior to conventional teaching methods in improving students’ learning interest, independent analysis skills, scope of knowledge, self-study, team spirit, and oral expression.ConclusionsThis meta-analysis indicates that PBL pedagogy is superior to traditional lecture-based teaching in Chinese pharmacy education. PBL methods could be an optional, supplementary method of pharmaceutical teaching in China. However, Chinese pharmacy colleges and universities should revise PBL curricula according to their own needs, which would maximize the effectiveness of PBL.

Long-Term Over-Expression of Neuropeptide Y in Hypothalamic Paraventricular Nucleus Contributes to Adipose Tissue Insulin Resistance Partly via the Y5 Receptor

Intracerebroventricular injection and overexpression of Neuropeptide Y (NPY) in the paraventricular nucleus (PVN) has been shown to induce obesity and glucose metabolism disorder in rodents; however, the underlying mechanisms are still unclear. The aim of this study was to investigate the mechanism contributing to glucose metabolic disturbance induced by NPY. Recombinant lentiviral NPY vectors were injected into the PVN of rats fed a high fat (HFD) or low-fat diet. 8 weeks later, in vivo intravenous glucose tolerance tests and euglycemic-hyperinsulinemic clamp revealed that insulin resistance of adipose tissue were induced by NPY overexpression with or without HFD. NPY increased food intake, but did not change blood glucose, glycated hemoglobin A1c (HbA1c) or lipid levels. However, NPY decreased the expression of pGSK3β, PI3K p85 and pAKTSer473 in adipose tissue of rats. In vitro, 3T3-L1 adipocytes were treated with NPY, NPY Y1 and Y5 receptor antagonists. Glucose consumption and 2-deoxy-D-[3H] glucose uptake were partly inhibited by NPY, while a decrease in PI3K-AKT pathway signaling and a decreased expression of pGSK3α and pGSK3β were observed. Nevertheless, a Y5 receptor antagonist (L-152,804) reversed the effects of NPY on glucose uptake and consumption. These data suggest that long-term over-expression of NPY in PVN contributes to the establishment of adipose tissue insulin resistance, at least partly via the Y5 Receptor.

Protective effect of total flavonoids of seabuckthorn (Hippophae rhamnoides) in simulated high-altitude polycythemia in rats.

Seabuckthorn (Hippophae rhamnoides L.) has been used to treat high altitude diseases. The effects of five-week treatment with total flavonoids of seabuckthorn (35, 70, 140 mg/kg, ig) on cobalt chloride (5.5 mg/kg, ip)- and hypobaric chamber (simulating 5,000 m)-induced high-altitude polycythemia in rats were measured. Total flavonoids decreased red blood cell number, hemoglobin, hematocrit, mean corpuscular hemoglobin levels, span of red blood cell electrophoretic mobility, aggregation index of red blood cell, plasma viscosity, whole blood viscosity, and increased deformation index of red blood cell, erythropoietin level in serum. Total flavonoids increased pH, pO2, SpO2, pCO2 levels in arterial blood, and increased Na+, HCO3−, Cl−, but decreased K+ concentrations. Total flavonoids increased mean arterial pressure, left ventricular systolic pressure, end-diastolic pressure, maximal rate of rise and decrease, decreased heart rate and protected right ventricle morphology. Changes in hemodynamic, hematologic parameters, and erythropoietin content suggest that administration of total flavonoids from seabuckthorn may be useful in the prevention of high altitude polycythaemia in rats.

Modulatory effects of quercetin on hypobaric hypoxic rats.

Quercetin is an active constituent of Hippophae rhamnoides L. and Ginkgo Biloba, which are commonly taken for high altitude sickness. The preventive effect of quercetin on hypobaric hypoxic rats was investigated. Male Wistar rats (180-220 g) were placed into six groups: normoxic group (normal control), a hypoxic group (model control), three quercetin-treated groups (5, 10, 20mg/kg, i.g.), and acetazolamide-treated group (22.5mg/kg, i.g., positive control), 10 animals in each group. Hypoxic rats were raised in a hypobaric hypoxia chamber simulating a high altitude of 5000 m for 23 h per day after a five-day pretreatment. Normoxic control rats were raised at an altitude of 300 m. After the five-day treatment, hemodynamic, arterial blood gas and electrolyte parameters, antioxidants and nitric oxide metabolism were measured. Hypobaric hypoxia enhanced the right ventricular systolic pressure, right ventricular end-diastolic pressure and left ventricular end-diastolic pressure, which were reversed by quercetin. Quercetin increased the declined pH, PO(2), Sp(O2), PCO(2) levels in arterial blood induced by hypobaric hypoxia, and increased Na(+), HCO(3)(-), Cl(-), but decreased K(+) concentrations. Quercetin increased superoxide dismutase, catalase, glutathione peroxidase activities, glutathione levels, and it decreased malondialdehyde levels in serum. Furthermore, quercetin increased nitric oxide levels and inducible nitric oxide synthase activity in serum. Rats failed to gain body weight under hypobaric hypoxia and quercetin had no effect on it. These results suggest that the activities of quercetin on cardiac function, arterial blood gas, antioxidants and nitric oxide metabolism may be related to its protective potential on hypobaric hypoxia-induced damage.