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.

Ginseng oligopeptides protect against irradiation-induced immune dysfunction and intestinal injury.

Intestinal injury and immune dysfunction are commonly encountered after irradiation therapy. While the curative abilities of ginseng root have been reported in prior studies, there is little known regarding its role in immunoregulation of intestinal repairability in cancer patients treated with irradiation. Our current study aims to closely examine the protective effects of ginseng-derived small molecule oligopeptides (Panax ginseng C. A. Mey.) (GOP) against irradiation-induced immune dysfunction and subsequent intestinal injury, using in vitro and in vivo models. Expectedly, irradiation treatment resulted in increased intestinal permeability along with mucosal injury in both Caco-2 cells and mice, probably due to disruption of the intestinal epithelial barrier, leading to high plasma lipopolysaccharide (LPS) and pro-inflammatory cytokines levels. However, when the cells were treated with GOP, this led to diminished concentration of plasma LPS and cytokines (IL-1 and TNF-α), suggesting its dampening effect on inflammatory and oxidative stress, and potential role in restoring normal baseline intestinal permeability. Moreover, the Caco-2 cells treated with GOP showed high trans-epithelial electrical resistance (TEER) and low FITC-dextran paracellular permeability when compared to the control group. This could be explained by the higher levels of tight junction proteins (ZO-1 and Occludin) expression along with reduced expression of the apoptosis-related proteins (Bax and Caspase-3) noticed in the GOP-treated cells, highlighting its role in preserving intestinal permeability, through prevention of their degradation while maintaining normal levels of expression. Further confirmatory in vivo data showed that GOP-treated mice exhibited high concentrations of lymphocytes (CD3+, CD4+, CD8+) in the intestine, to rescue the irradiation-induced damage and restore baseline intestinal integrity. Therefore, we propose that GOP can be used as an adjuvant therapy to attenuate irradiation-induced immune dysfunction and intestinal injury in cancer patients.

Ginseng (Panax ginseng Meyer) oligopeptides regulate innate and adaptive immune responses in mice via increased macrophage phagocytosis capacity, NK cell activity and Th cells secretion.

Traditionally used as a restorative medicine, ginseng (Panax ginseng Meyer) has been the most widely used and acclaimed herb in Chinese communities for thousands of years. To investigate the immune-modulating activity of ginseng oligopeptides (GOP), 420 healthy female BALB/c mice were intragastrically administered distilled water (control), whey protein (0.15 g per kg body weight (BW)), and GOP 0.0375, 0.075, 0.15, 0.3 and 0.6 g per kg BW for 30 days. Blood samples from mice were collected from the ophthalmic venous plexus and then sacrificed by cervical dislocation. Seven assays were conducted to determine the immunomodulatory effects of GOP on innate and adaptive immune responses, followed by flow cytometry to investigate spleen T lymphocyte sub-populations, multiplex sandwich immunoassays to investigate serum cytokine and immunoglobulin levels, and ELISA to investigate intestinally secreted immunoglobulin to study the mechanism of GOP affecting the immune system. Our results showed that GOP was able to enhance innate and adaptive immune responses in mice by improving cell-mediated and humoral immunity, macrophage phagocytosis capacity and NK cell activity. Notably, the use of GOP revealed a better immune-modulating activity compared to whey protein. We conclude that the immune-modulating activity might be due to the increased macrophage phagocytosis capacity and NK cell activity, and the enhancement of T and Th cells, as well as IL-2, IL-6 and IL-12 secretion and IgA, IgG1 and IgG2b production. These results indicate that GOP could be considered a good candidate that may improve immune functions if used as a dietary supplement, with a dosage that ranges from 0.3 to 0.6 g per kg BW.

Suppression of TNF-α and free radicals reduces systematic inflammatory and metabolic disorders: Radioprotective effects of ginseng oligopeptides on intestinal barrier function and antioxidant defense.

Irradiation therapy is markedly associated with intestinal injure and oxidant stress. This study aimed to investigate the effects of ginseng (Panax ginseng C.A. Mey.) oligopeptides (GOP) on irradiation-induced intestinal injury and antioxidant defense in mice. BALB/c mice (8 weeks old) were randomly divided into six groups: vehicle control, irradiation control (IR), IR+whey protein [0.30 g/kg body weight (BW)], IR+GOP 0.15 g/kg BW, IR+GOP 0.30 g/kg BW and IR+GOP 0.60 g/kg BW. Postirradiation 30-day survival trial, white blood cells count and bone marrow hematopoietic system damage were performed to identify the injury degree induced by irradiation. Then, histopathology analysis was observed and intestinal permeability in vivo was quantified with fluorescein isothiocyanate-dextran. The enzyme-linked immunosorbent assay was used to determine antioxidant ability, plasma inflammatory cytokines, diamine oxidase (DAO) and endotoxin (LPS) levels. The immunohistochemistry assay was used to analyze the expression levels of tight junction proteins. We found that GOP-treated mice exhibited lower concentrations of plasma LPS and DAO and decreased instructors of inflammatory and oxidative stress which were linked to the lower intestinal permeability and higher tight junction proteins expression. The blockage of GOP was linked with the reduction of TNF-α and free radicals. The 15-day pretreatment of GOP could exhibit radioprotective effects, and another 15-day posttreatment benefited the quick repair of irradiation-induced injury. We confirm that GOP would exhibit effective therapeutic value on attenuating irradiation-induced hematopoietic, gastrointestinal and oxidative injury in cancer patients.

Marine collagen peptides prepared from chum salmon (Oncorhynchus keta) skin extend the life span and inhibit spontaneous tumor incidence in Sprague-Dawley Rats.

To observe the effects of marine collagen peptides (MCPs) prepared from chum salmon (Oncorhynchus keta) skin on life span and spontaneous tumor incidence, Sprague-Dawley rats were fed diets supplemented with MCP at concentrations of 0%, 2.25%, 4.5%, and 9% (wt/wt) from the age of 4 weeks until natural death. There were 40 rats in each group (male:female ratio = 1:1). The results showed that the MCP did not significantly influence body weight or food consumption of rats of either sex throughout the life span; it did dose-dependently inhibit the age-related decrease in the activities of antioxidant enzymes and the age-related increase in the levels of lipid peroxidation product in both sexes. MCP notably increased the mean life span, the life span of the last 30% of the survivors, and the maximal life span; it decreased overall spontaneous tumor incidence of both sexes with significance in the 4.5% and 9% MCP-treated male groups and 9% MCP-treated female group. Compared to the control group, the incidence of death from tumors was decreased in MCP groups in comparison with the control group of both sexes. Therefore, we concluded that MCPs dose-dependently increase life span and decrease spontaneous tumor incidence in Sprague-Dawley rats. Moreover, the antioxidative property of MCPs may be responsible for the increased life span and protection against tumor development.

Variation in the expression of orexin and orexin receptors in the rat hypothalamus during the estrous cycle, pregnancy, parturition, and lactation.

The widespread distribution of mRNA encoding orexin- 1 (OX1R) and -2 receptors (OX2R) in the central nervous system suggests that orexin may be involved in multiple functional pathways. Central administration of orexin stimulates feeding and also affects ovarian steroid-dependent luteinizing hormone secretion, suggesting involvement of orexin in the regulation of reproductive function. To investigate a possible role for orexin in reproductive function, we examined variations in prepro-OX, OX1R, and OX2R mRNA levels in the female rat hypothalamus during the estrous cycle, pregnancy, parturition, and lactation using competitive reverse transcription-polymerase chain reaction. During the estrous cycle, only OX1R mRNA expression during late proestrus was significantly higher than that at metestrus. The prepro-OX and OX1R mRNA levels on d 1 of lactation were significantly higher than that during late pregnancy and lactation. Immunohistochemistry revealed the presence of orexin-A immunoreactive cells and the OX1R subtype in the lateral hypothalamic area as well as the magnocellular neurons of the paraventricular (PVN) and supraoptic (SON) nuclei, respectively, in pregnant and lactating rats. These results suggest a role for orexin in reproduction that may be involved in regulating physiological function in early lactation through important binding sites in hypothalamic PVN and SON.