Lei Bao

Grape seed proanthocyanidin extracts alleviate oxidative stress and ER stress in skeletal muscle of low‐dose streptozotocin‐ and high‐carbohydrate/high‐fat diet‐induced diabetic rats

Although ER stress in pancreas, liver, and adipose tissue was reported to be a novel event linked to the pathogenesis of type 2 diabetes mellitus, there is much less information on this event in skeletal muscle. Some studies indicated that treatment with antioxidants had beneficial effects on ER stress and diabetes. This study focuses on the effects of a strong antioxidant, grape seed proanthocyanidin extracts (GSPE), on skeletal muscle in diabetic rats induced with low dose streptozotocin- and a high-carbohydrate/high-fat diet. After 16 wk of GSPE treatment, diabetic rats showed decreased plasma glucose levels and insulin resistance. The efficacious effect of GSPE was manifested by the amelioration of muscular damage and dysfunction, as observed by histological examination and periodic acid Schiff staining. Concurrently, calcium overload and the abnormal activities of antioxidant enzymes and ATPases in diabetic muscles were partially reversed by GSPE treatment. GSPE also increased the activity of protein kinase B (a mediator of insulins metabolic action) and partially alleviated severe ER stress. These findings suggest that GSPE may have auxiliary therapeutic potential for type 2 diabetes mellitus by decreasing oxidative stress and ER stress in skeletal muscle.

Effect of oat intake on glycaemic control and insulin sensitivity: a meta-analysis of randomised controlled trials.

The present meta-analysis of randomised controlled trials (RCT) aimed to investigate the effect of oat intake on glycaemic control and insulin sensitivity. A literature search was carried out in PubMed, ScienceDirect Online and The Cochrane Library (up to October 2013) for RCT that assessed the effect of oat intake on glucose control and insulin sensitivity. A total of fifteen articles with 673 subjects met the inclusion criteria. A random-effects model was used when the overall pooled studies exhibited significant heterogeneity. Otherwise, a fixed-effects model was used. Compared with controls, oat intake significantly reduced the concentrations of fasting insulin by - 6·29 (95 % CI - 12·32, - 0·27) pmol/l (P= 0·04) and the values of glucose AUC (GAUC; 0-120 min) by - 30·23 (95 % CI - 43·65, - 16·81) min × mmol/l (P< 0·0001). There was a slight decrease in fasting glucose concentrations, glycated Hb concentrations and homeostatic model assessment-insulin resistance values in subjects who consumed oats, but the difference was not significant. In conclusion, oat intake significantly lowers fasting insulin concentrations and GAUC values. To further investigate the effect of oat intake on fasting glucose concentrations, additional long-term and high-quality RCT with a parallel design are required.

Effects of grape seed proanthocyanidin extract on renal injury in type 2 diabetic rats

Grape seed proanthocyanidin extract (GSPE) is known to be an effective natural polyphenol capable of removing free radicals in vivo. It has been reported that GSPE has biological functions including antioxidant, anti-cancer, anti-hyperglycemic, anti-radiation, and prevention and treatment of cardiovascular diseases. This study aims to investigate the effects of GSPE on renal injury in type 2 diabetic rats induced with low-dose streptozotocin and a high-carbohydrate/high-fat diet. Rats (n=12 per group) were administered GSPE at either a low (125 mg/kg · bw), medium (250 mg/kg · bw) or high (500 mg/kg · bw) dose, while control rats and diabetes mellitus group rats received no specific treatment. After 16 weeks, GSPE slightly increased body weight and decreased food consumption, water intake and urine volume in rats. Diabetic rats treated with GSPE demonstrated decreased fasting blood glucose, serum insulin, HbA1c and systolic blood pressure (P<0.05). GSPE significantly improved renal function parameters, reduced the expression of tissue inhibitor of metalloproteinase-1 and also increased the activity of matrix metalloproteinase-9. Moreover, GSPE (particularly at a dose of 500 mg/kg · bw) increased the activity of antioxidant enzymes and reduced the levels of c-reactive proteins (P<0.01) in serum and the expression of tumor necrosis factor-α, monocyte chemoattractant protein-1 and intercellular adhesion molecule-1 (P<0.05) in the kidney. These findings suggest that GSPE ameliorates renal injury in type 2 diabetic rats through its antioxidative activity and anti-inflammatory effects.

Short- and Long-Term Effects of Wholegrain Oat Intake on Weight Management and Glucolipid Metabolism in Overweight Type-2 Diabetics: A Randomized Control Trial.

Glycemic control and weight reduction are primary goals for the management of overweight and obese type 2 diabetes mellitus (T2DM). Effective management cannot be achieved without an appropriate diet. Our study aimed to evaluate the short- and long-term effects of oat intake and develop a reasonable dietary plan for overweight T2DM patients. A randomized control trial, registered under ClinicalTrials.gov (Identification code: NCT01495052), was carried out among adult T2DM patients. A subgroup of 298 overweight subjects was selected and received a 30-day centralized intervention and 1-year free-living follow-up. Participants were randomly allocated to one of the following four groups. The usual care group (n = 60) received no intervention; the healthy diet group (n = 79) received a low-fat and high-fiber diet (“healthy diet”); the 50 g-oats group (n = 80) and 100 g-oats group (n = 79) received the “healthy diet” with the same amount of cereals replaced by 50 g and 100 g oats respectively. Anthropometric, blood glycemic and lipid variables were measured. For the 30-day intervention, significant differences in the changes of FPG (fasting plasma glucose), PPG (postprandial plasma glucose), HbA1c (glycosylated hemoglobin), HOMA-IR (homeostasis model assessment of insulin resistance), TC (total cholesterol), TG (total triglycerides), and LDL-c (low-density lipoprotein cholesterol) were observed among the four groups. Compared to the healthy diet group, the 50 g-oats group had a bigger reduction in PPG (mean difference (MD): −1.04 mmol/L; 95% CI: −2.03, −0.05) and TC (MD: −0.24 mmol/L; 95% CI: −0.47, −0.01); the 100 g-oats group had a bigger reduction in PPG (MD: −1.48 mmol/L; 95% CI: −2.57, −0.39), HOMA-IR (MD: −1.77 mU·mol/L2; 95% CI: −3.49, −0.05), TC (MD: −0.33 mmol/L; 95% CI: −0.56, −0.10) and LDL-c (MD: −0.22 mmol/L; 95% CI: −0.41, −0.03). In the 1-year follow-up, greater effects in reducing weight (MD: −0.89 kg; 95% CI: −1.56, −0.22), HbA1c (MD: −0.64%; 95% CI: −1.19, −0.09) and TG (MD: −0.70 mmol/L; 95% CI: −1.11, −0.29) were observed in the 100 g-oats group. In conclusion, short- and long-term oat intake had significant effects on controlling hyperglycemia, lowering blood lipid and reducing weight. Our study provided some supportive evidence for recommending oat as a good whole grain selection for overweight diabetics.

Grape seed procyanidin B2 ameliorates mitochondrial dysfunction and inhibits apoptosis via the AMP-activated protein kinase–silent mating type information regulation 2 homologue 1–PPARγ co-activator-1α axis in rat mesangial cells under high-dose glucosamine

Grape seed procyanidin B2 (GSPB2), an antioxidative and anti-inflammatory polyphenol in grape seed, has been found to have protective effects on diabetic nephropathy. Based on its favourable biological activities, in the present study, we aimed to investigate whether GSPB2 could inhibit apoptosis in rat mesangial cells treated with glucosamine (GlcN) under high-dose conditions. The results showed that the administration of GSPB2 (10 μg/ml) significantly increased the viability of mesangial cells treated with GlcN at a dose of 15 mM. We found that GSPB2 inhibited apoptosis in mesangial cells using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphates (dUTP) nick-end labelling staining and flow cytometry technique (P< 0·05 for both). GSPB2 treatment also suppressed oxidative stress by elevating the activity of glutathione peroxidase (P< 0·05) and superoxide dismutase (P< 0·01), as well as prevented cellular damage. GSPB2 enhanced the mRNA expression of nuclear respiratory factor 1, mitochondrial transcription factor A and mitochondrial DNA copy number in mesangial cells as determined by real-time PCR (P< 0·05 for each). Finally, GSPB2 treatment activated the protein expression of PPARγ co-activator-1α (PGC-1α), silent mating type information regulation 2 homologue 1 (SIRT1) and AMP-activated protein kinase (AMPK) in mesangial cells. These findings suggest that GSPB2 markedly ameliorates mitochondrial dysfunction and inhibits apoptosis in rat mesangial cells treated with high-dose GlcN. This protective effect could be, at least in part, due to the activation of the AMPK-SIRT1-PGC-1α axis.

Anti-Fatigue Effects of Small Molecule Oligopeptides Isolated from Panax ginseng C. A. Meyer in Mice

Panax ginseng C. A. Meyer (ginseng) is an edible and medicinal Chinese herb, which is often used in Asian countries for physical fitness. Ginseng is reported to have a wide range of biological activity and pharmaceutical properties. There were more studies on ginsenosides and polysaccharides, but fewer studies on ginseng oligopeptides (GOP), which are small molecule oligopeptides isolated from ginseng. The present study was designed to evaluate the anti-fatigue effects of GOP in mice and explore the possible underlying mechanism. Mice were randomly divided into four experimental sets for the detection of different indicators. Each set of mice were then divided into four groups. The control group was administered distilled water, and three GOP intervention groups were administered 125, 250, and 500 mg/kg of body weight, respectively, of GOP by gavage each day. After 30 days of GOP treatment, it was observed that GOP could significantly increase the forced swimming time, enhance lactate dehydrogenase (LDH) activity and hepatic glycogen levels, and retard the accumulation of serum urea nitrogen (SUN) and blood lactic acid (BLA) in mice. GOP also markedly ameliorated fatigue-induced alterations of inoxidative stress biomarkers and antioxidant enzymes. Notably, GOP increased the mRNA expression of mitochondrial biogenesis factors and mitochondrial DNA content in skeletal muscles of mice. These results suggest that GOP possess anti-fatigue effects, which may be attributed to the inhibition of oxidative stress and the improvement of mitochondrial function in skeletal muscles. GOP could be a novel natural agent for relieving exercise fatigue.

Quercetin protects RAW264.7 macrophages from glucosamine-induced apoptosis and lipid accumulation via the endoplasmic reticulum stress pathway

It is increasingly recognized that macrophages are a key cell in the development of atherosclerosis. Glucosamine, the product of the hexosamine biosynthetic pathway in diabetes mellitus, can disturb lipid metabolism, induce apoptosis and accelerate atherosclerosis via endoplasmic reticulum (ER) stress in various types of cells. Previous studies have indicated that quercetin possesses antidiabetic, anti‑oxidative, anti‑inflammatory and anti‑apoptotic activities as a flavonoid. Studies have also demonstrated its novel pharmacological properties for inhibiting ER stress. The present study focussed on the effects of quercetin on cell injury and ER stress in glucosamine‑induced macrophages. RAW264.7 macrophages were cultured with 15 mM glucosamine, following which the levels of apoptosis, intracellular total and free cholesterol, and apoptosis‑ and ER stress‑associated proteins were measured in the macrophages treated with or without quercetin. Additionally, the ratio of cholestryl ester/total cholesterol was calculated to observe the formation of foam cells. The results demonstrated that apoptosis and abnormal lipid accumulation in the RAW264.7 cells, which was induced by glucosamine, were significantly reversed by quercetin. In addition, quercetin treatment suppressed the increase of C/EBP homologous protein, and inhibited the activation of JNK and caspase‑12, which was induced by glucosamine. Quercetin also increased the expression level of full length activating transcriptional factor 6 and decreased the expression of glucose regulated protein 78. Of note, the beneficial effects of quercetin on the glucosamine‑induced RAW264.7 cells were reversed by treatment with tunicamycin. These findings suggest that quercetin may have properties to prevent glucosamine‑induced apoptosis and lipid accumulation via the ER stress pathway in RAW264.7 macrophages.

Dietary Nucleotides Supplementation and Liver Injury in Alcohol-Treated Rats: A Metabolomics Investigation

Background: Previous studies suggested that nucleotides were beneficial for liver function, lipid metabolism and so on. The present study aimed to investigate the metabolic response of dietary nucleotides supplementation in alcohol-induced liver injury rats. Methods: Five groups of male Wistar rats were used: normal control group (basal diet, equivalent distilled water), alcohol control group (basal diet, 50% alcohol (v/v)), dextrose control group (basal diet, isocaloric amount of dextrose), and 0.04% and 0.16% nucleotides groups (basal diet supplemented with 0.4 g and 1.6 g nucleotides kg−1 respectively, 50% alcohol (v/v)). The liver injury was measured through traditional liver enzymes, expression of oxidative stress markers and histopathological examination. Ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry (UPLC-Q-TOF-MS) was applied to identify liver metabolite profiles. Results: Nucleotides supplementation prevented the progression of hepatocyte steatosis. The levels of total proteins, globulin, alanine aminotransferase, aspartate aminotransferase, total cholesterol triglyceride, as well as the oxidative stress markers altered by alcohol, were improved by nucleotides supplementation. Elevated levels of liver bile acids (glycocholic acid, chenodeoxyglycocholic acid, and taurodeoxycholic acid), as well as lipids (stearic acid, palmitic acid, oleic acid, phosphatidylcholine, and lysophosphatidylethanolamine) in alcohol-treated rats were reversed by nucleotides supplementation. In addition, supplementation with nucleotides could increase the levels of amino acids, including valyl-Leucine, l-leucine, alanyl-leucine and l-phenylalanine. Conclusion: These data indicate potential biomarkers and confirm the benefit of dietary nucleotides on alcoholic liver injury.

The Effects of Intensive Nutrition Education on Late Middle-Aged Adults with Type 2 Diabetes

Objective: Many patients with type 2 diabetes find it difficult to maintain good glycemic control. Undesirable glycemic control occurs greatly due to deficiencies of nutritional knowledge and difficulty in obtaining dietary prescriptions. The late middle-aged and elder individuals are the main populations that are affected by type 2 diabetes. The main purpose of this study was to investigate whether intensive nutrition education would make benefits for late middle-aged patients with type 2 diabetes. Method: 196 patients between 50 to 65 years old meeting type 2 diabetes criteria and eligible for the program were included in a single-blinded, 30-day centralized management of an education program in China. Participants in the program were randomly divided into a usual nutrition education group or an intensive nutrition education group. The usual nutrition education group was used as a control group and received only basic health advice and principles of diabetic diets at the beginning and the end of the study. Participants in the intensive nutrition education group were arranged to receive intensive nutritional lectures about diabetes for 30 days. The primary outcomes were the changes in weight, body mass index (BMI), fasting plasma glucose (FPG), 2-h postprandial plasma glucose (PG), glycosylated hemoglobin (HbA1c), total glycerin (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c). Results: After 30 days of intervention, FPG, PG, and HbA1c in the treatment group decreased significantly than the control group (p < 0.05). HbA1c reduced significantly by 0.6% in the intervention group. No significant differences in the change of blood lipids were observed between groups. However, TG, TC, and HDL-c made improvements compared with the baseline in the experimental group. Both groups had a reduction in weight and BMI within groups, especially in intensive nutrition education group. However, there was no statistical significance between groups. Conclusions: Intensive nutrition education has significant effects on blood glucose control in late middle-aged adults with type 2 diabetes. Intensive education can cultivate good diet habits and increase physical activity, which are important for diabetes patients in the short and long terms. These findings may contribute to improving education methodology and nutrition therapy in patients with type 2 diabetes.

Grape seed proanthocyanidin extracts prevent high glucose-induced endothelia dysfunction via PKC and NF-κB inhibition

In our study, it has been detected in vivo and in vitro that GSPE reversed high glucose-induced the increase of ICAM-1 and VCAM-1. It is shown that by western blotting detection, GSPE significantly inhibited the activation of NF-κB induced by high glucose while there was significant decrease of the expression of PKC with GSPE intervention. By adding the NF-κB blocker PDTC and the PKC inhibitor peptide 19–31(10−6 M), no significant difference was found in the levels of VCAM-1 and ICAM-1 among GSPE group, the PKC inhibitor peptide 19–31-added GSPE group and the PDTC-added GSPE group. So the conclusion could be drawn that PKC inhibition must be involved in GSPE decreasing the level of ICAM-1 and VCAM-1.We proved for the first time that GSPE prevented high glucose-induced the increase of ICAM-1 and VCAM-1 by PKC and NF-κB inhibition. These findings show a novel mechanism of the action GSPE preventing endothelial dysfunction, which may have clinical application values. Graphical Abstract Structural analyses have elucidated the reaction mechanisms of enzymes with potential bioindustrial and/or bioremedial uses.