Hypoglycemic Effects of Oat Oligopeptides in High-Calorie Diet/STZ-Induced Diabetic Rats.

The study was aimed to determine whether treatment with oat oligopeptides (OOPs) could modulate hyperglycemia related to type 2 diabetes mellitus (T2DM) in Sprague⁻Dawley (SD) rats. Diabetic SD rats modeling by a joint effect of high-calorie diet for 45 days and twice intraperitoneal injection of 30 mg/kg streptozotocin at one-week interval were observed with or without OOPs administration (0.25, 0.50, 1.00, and 2.00 g/kg Body Weight) for 12 weeks. Fasting blood glucose (FBG), oral glucose test tolerance (OGTT), serum insulin, level of antioxidant, and hepatic enzymes were measured. In addition, frequency of micturition was recorded in this study for the first time. It was observed that the administration of OOPs (2.00 g/kg Body Weight) resulted in a significant decrease (p < 0.05) in FBG since 6th week and a significant decrease (p < 0.05) in the OGTT-AUC on 6th and 10th week. In addition, the administration of OOPs (2.00 g/kg Body Weight) reduced HOMA-IR index and 24-h urine volume significantly (p < 0.05) whereas increased SOD activity significantly (p < 0.05). These results suggested that OOPs may have a hypoglycemic effect in diabetic rats.

Small Molecule Oligopeptides Isolated from Walnut (Juglans regia L.) and Their Anti-Fatigue Effects in Mice.

Walnut (Juglans regia L.) is unique for its extensive biological activities and pharmaceutical properties. There are few studies on walnut oligopeptides (WOPs), which are small molecule peptides extracted from walnuts. This study aimed to evaluate the anti-fatigue effects of WOPs on ICR mice and explore the possible underlying mechanism. Mice were randomly divided into four experimental sets and each set of mice were then randomly divided into four groups. The vehicle group was administered distilled water, and the three WOP intervention groups were orally administered WOP solution at a dose of 110, 220, and 440 mg/kg of body weight, respectively. After 30 days of WOP intervention, the anti-fatigue activity of WOPs were evaluated using the weight-loaded swimming test and by measuring the change of biochemical parameters, glycogen storage and energy metabolism enzymes, anti-oxidative capacity and mitochondrial function. It was observed that WOPs could significantly prolong the swimming time, decrease the accumulation of lactate dehydrogenase (LDH), creatine kinase (CK), blood urea nitrogen (BUN) and blood lactic acid (BLA), and increased the glycogen storage of liver and gastrocnemius muscle. WOPs also markedly inhibited fatigue induced oxidative stress by increasing the activity of superoxide dismutase (SOD), glutathione peroxidase (GPX) and decreasing the content malondialdehyde (MDA). Notably, WOPs improved the activity of pyruvate kinase (PK), succinate dehydrogenase (SDH), Na+-K+-ATPase, and enhanced the mRNA expression of mitochondrial biogenesis factors and mitochondrial DNA content in skeletal muscles of mice. These results suggest that WOPs have beneficial anti-fatigue effects, which may be attributed to their positive effects on increasing glycogen storage, improving energy metabolism, inhibiting oxidative stress, enhancing mitochondrial function in skeletal muscle, and ameliorating the cell damage and the muscular injury.

Ginseng (Panax ginseng Meyer) Oligopeptides Protect Against Binge Drinking-Induced Liver Damage through Inhibiting Oxidative Stress and Inflammation in Rats.

Panax ginseng C.A. Meyer (ginseng) is an edible and traditional medicinal herb, which is reported to have a wide range of biological activity and pharmaceutical properties. There were more studies on ginsenoside and polysaccharides, but fewer on ginseng oligopeptides (GOPs), which are small molecule oligopeptides extracted from ginseng. The present study was designed to investigate the effects and underlying mechanism of ginseng oligopeptide (GOPs) on binge drinking-induced alcohol damage in rats. Sprague Dawley rats were randomly assigned to six groups (n = 10), rats in normal control group and alcohol model group was administered distilled water; rats in four GOPs intervention groups (at a dose of 0.0625, 0.125, 0.25, 0.5 g/kg of body weight, respectively) were administered GOPs once a day for 30 days. Experiment rats were intragastrically administered ethanol at a one-time dose of 7 g/kg of body weight after 30 days. The liver injury was measured through traditional liver enzymes, inflammatory cytokines, expression of oxidative stress markers, and histopathological examination. We found that the GOPs treatment could significantly improve serum alanine aminotransferase and aspartate aminotransferase, plasma lipopolysaccharide, and inflammatory cytokine levels, as well as the oxidative stress markers that were altered by alcohol. Moreover, GOPs treatment inhibited the protein expression of toll-like receptor 4, and repressed the inhibitor kappa Bα and nuclear factor-κB p65 in the liver. These findings suggested that GOPs have a significant protective effect on binge drinking-induced liver injury, and the mechanism possibly mediated by the partial inhibition of lipopolysaccharide-toll-like receptor 4-nuclear factor-κB p65 signaling in the liver.

Beneficial Effects of Small Molecule Oligopeptides Isolated from Panax ginseng Meyer on Pancreatic Beta-Cell Dysfunction and Death in Diabetic Rats.

To determine whether treatment with ginseng oligopeptides (GOPs) could modulate hyperglycemia related to type 2 diabetes mellitus (T2DM) in rats induced by high-fat diet and low doses of alloxan, type 2 diabetes was induced in male Sprague-Dawley (SD) rats by injecting them once with 105 mg/kg alloxan and feeding them high-carbohydrate/high-fat diet with or without GOP administration (0.125, 0.5, and 2.0 g/kg Body Weight) for 7, 24, and 52 weeks. Oral glucose test tolerance (OGTT), plasma glucose, serum insulin, level of antioxidant, and beta cell function were measured. Morphological observation and immunohistochemistry study of insulin of islets was performed by light microscopy. The insulin level and the expression of NF-κB and Bcl-2 family in pancreatic islets were also detected by Western blot analysis. In addition, survival time and survival rate were observed. After the treatment, the abnormal OGTT were partially reversed by GOPs treatment in diabetic rats. The efficacy of GOPs was manifested in the amelioration of pancreatic damage, as determined by microscopy analysis. Moreover, GOPs treatment increased the normal insulin content and decreased the expression of the NF-κB-signaling pathway. Compared with those in the control model, the survival time and rate were significantly longer. It is suggested that GOPs exhibit auxiliary therapeutic potential for diabetes.

Dietary nucleotides protect against alcoholic liver injury by attenuating inflammation and regulating gut microbiota in rats.

Nucleotides have been reported to be effective in attenuating liver damage and regulating gut microbiota. However, the protective effect of nucleotides against alcoholic liver injury remains unknown. The present study aims to investigate whether nucleotides ameliorate alcoholic liver injury and explores the possible mechanism. Male Wistar rats were given alcohol, equivalent distilled water or an isocaloric amount of dextrose intragastrically twice daily for up to 6 weeks respectively. Two subgroups of alcohol-treated rats were fed with a nucleotide-supplemented AIN-93G rodent diet. Serum enzymes, inflammatory cytokines and microbiota composition of the caecum content were evaluated. We found that nucleotides could significantly decrease serum alanine aminotransferase and aspartate aminotransferase, plasma lipopolysaccharide and inflammatory cytokine levels. Sequencing of 16S rRNA genes revealed that nucleotide-treated rats showed a higher abundance of Firmicutes and a lower abundance of Bacteroidetes than alcohol-treated rats. Moreover, nucleotide treatment inhibited the protein expression of toll-like receptor 4, CD14 and repressed the phosphorylation of inhibitor kappa Bα and nuclear factor-κB p65 in the liver. These results suggested that nucleotides suppressed the inflammatory response and regulated gut microbiota in alcoholic liver injury. The partial inhibition of lipopolysaccharide - toll-like receptor 4-nuclear factor-κB p65 signaling in the liver may be attributed to this mechanism.

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.