Serum amyloid A aggravates endotoxin-induced ocular inflammation through the regulation of retinal microglial activation.

Serum amyloid A (SAA) are major acute-phase response proteins which actively participate in many inflammatory diseases. This study was designed to explore the function of SAA in acute ocular inflammation and the underlying mechanism. We found that SAA3 was upregulated in endotoxin-induced uveitis (EIU) mouse model, and it was primarily expressed in microglia. Recombinant SAA protein augmented intraocular inflammation in EIU, while the inhibition of Saa3 by siRNA effectively alleviated the inflammatory responses and rescued the retina from EIU-induced structural and functional damage. Further study showed that the recombinant SAA protein activated microglia, causing characteristic morphological changes and driving them further to pro-inflammatory status. The downregulation of Saa3 halted the amoeboid change of microglia, reduced the secretion of pro-inflammatory factors, and increased the expression of tissue-reparative genes. SAA3 also regulated the autophagic activity of microglial cells. Finally, we showed that the above effect of SAA on microglial cells was at least partially mediated through the expression and signaling of Toll-like receptor 4 (TLR4). Collectively, our study suggested that microglial cell-expressed SAA could be a potential target in treating acute ocular inflammation.

Correction: Fan et al. Native Collagen II Relieves Bone Impairment through Improving Inflammation and Oxidative Stress in Ageing db/db Mice. Molecules2021, 26, 4942.

The authors would like to correct spelling mistakes (undenatured type II collagen) in the title, as well as in the main manuscript including the tables and figures in the title paper [...].

Native Collagen II Relieves Bone Impairment through Improving Inflammation and Oxidative Stress in Ageing db/db Mice.

Ageing-related bone impairment due to exposure to hyperglycemic environment is scarcely researched. The aim was to confirm the improvement effects of undenatured type II collagen (UC II) on bone impairment in ageing db/db mice, and the ageing model was established by normal feeding for 48-week-old. Then, the ageing db/db mice were randomly assigned to UC II intervention, the ageing model, and the chondroitin sulfate + glucosamine hydrochloride control groups. After 12 weeks of treatment, femoral microarchitecture and biomechanical parameters were observed, biomarkers including bone metabolism, inflammatory cytokines, and oxidative stress were measured, and the gastrocnemius function and expressions of interleukin (IL) 1ß, receptor activator of nuclear factor (NF)-κB ligand (RANKL), and tartrate-resistant acid phosphatase (TRAP) were analyzed. The results showed that the mice in the UC II intervention group showed significantly superior bone and gastrocnemius properties than those in the ageing model group, including bone mineral density (287.65 ± 72.77 vs. 186.97 ± 32.2 mg/cm3), gastrocnemius index (0.46 ± 0.07 vs. 0.18 ± 0.01%), muscle fiber diameter (0.0415 ± 0.005 vs. 0.0330 ± 0.002 mm), and cross-sectional area (0.0011 ± 0.00007 vs. 0.00038 ± 0.00004 mm2). The UC II intervention elevated bone mineralization and formation and decreased bone resorption, inflammatory cytokines, and the oxidative stress. In addition, lower protein expression of IL-1ß, RANKL, and TRAP in the UC II intervention group was observed. These findings suggested that UC II improved bones impaired by T2DM during ageing, and the likely mechanism was partly due to inhibition of inflammation and oxidative stress.

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.

Radioprotective Effect of Walnut Oligopeptides Against Gamma Radiation-Induced Splenocyte Apoptosis and Intestinal Injury in Mice.

Walnut oligopeptides (WOPs) intake is associated with the augment of the antioxidant defense system and immune system. The chief object of this study is to evaluate the radioprotective effect of walnut oligopeptides extracted from walnut seed protein against 60Coγ-irradiation induced damage in mice. Female BALB/c mice were administered WOPs through drinking water for 14 days until a single dose of whole-body 60Coγ-irradiation. The 30-day survival test was carried out in the first group (8 Gy), and the other two groups (3.5 Gy) were sacrificed at 3 days and 14 days post-irradiation. Blood and organ samples of mice in the three groups were collected, the histopathological analysis and immunohistochemistry were conducted. The number of peripheral blood leukocytes, bone marrow DNA content, inflammatory cytokines, antioxidant capacity, and intestinal permeability were measured. We found that the administration of WOPs augmented antioxidant defense system, accelerated hematopoietic recovery and showed the significant trend toward higher survival rate and less weight loss compared with non-administrated control mice. In addition, WOPs administration appeared to be important to limit IR-induced splenocyte apoptosis and inflammatory cascade as well as reduce intestine epithelial barrier dysfunction and promote epithelial integrity. These results suggest that pre and post-treatment of WOPs may help to ameliorate acute damage, which is induced by ionizing radiation in mice and accelerate its recovery.

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.

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.

Exogenous Nucleotides Improve the Skin Aging of SAMP8 Mice by Modulating Autophagy through MAPKs and AMPK Pathways.

The skin, serving as the body's primary defense against external elements, plays a crucial role in protecting the body from infections and injuries, as well as maintaining overall homeostasis. Skin aging, a common manifestation of the aging process, involves the gradual deterioration of its normal structure and repair mechanisms. Addressing the issue of skin aging is increasingly imperative. Multiple pieces of evidence indicate the potential anti-aging effects of exogenous nucleotides (NTs) through their ability to inhibit oxidative stress and inflammation. This study aims to investigate whether exogenous NTs can slow down skin aging and elucidate the underlying mechanisms. To achieve this objective, senescence-accelerated mouse prone-8 (SAMP8) mice were utilized and randomly allocated into Aging, NTs-low, NTs-middle, and NTs-high groups, while senescence-accelerated mouse resistant 1 (SAMR1) mice were employed as the control group. After 9 months of NT intervention, dorsal skin samples were collected to analyze the pathology and assess the presence and expression of substances related to the aging process. The findings indicated that a high-dose NT treatment led to a significant increase in the thickness of the epithelium and dermal layers, as well as Hyp content (p < 0.05). Additionally, it was observed that low-dose NT intervention resulted in improved aging, as evidenced by a significant decrease in p16 expression (p < 0.05). Importantly, the administration of high doses of NTs could improve, in some ways, mitochondrial function, which is known to reduce oxidative stress and promote ATP and NAD+ production significantly. These observed effects may be linked to NT-induced autophagy, as evidenced by the decreased expression of p62 and increased expression of LC3BI/II in the intervention groups. Furthermore, NTs were found to upregulate pAMPK and PGC-1α expression while inhibiting the phosphorylation of p38MAPK, JNK, and ERK, suggesting that autophagy may be regulated through the AMPK and MAPK pathways. Therefore, the potential induction of autophagy by NTs may offer benefits in addressing skin aging through the activation of the AMPK pathway and the inhibition of the MAPK pathway.

The Protective Effect of Walnut Oligopeptides against Indomethacin-Induced Gastric Ulcer in Rats.

The aim of this study was to investigate the potential protective effects of walnut oligopeptides (WOPs) on indomethacin-induced gastric ulcers in rats. The rats were divided into the following groups: normal group, model group, omeprazole group (0.02 g/kg), and WOPs groups (0.22, 0.44, and 0.88 g/kg, respectively). After receiving gavage once per day for 30 consecutive days, the rats were injected intraperitoneally with indomethacin 48 mg/kg to induce gastric ulcers. Then, the serum inflammatory cytokines and gastric prostaglandin E2 (PGE2), oxidative stress-related indicators, and the RNA expression of COX-1 and COX-2 were measured. The results revealed that WOPs confer significant gastroprotection on gastric ulcers caused by indomethacin, regulating inflammatory cytokines, oxidative stress, and prostaglandins synthesis, and enhancing the expression of COX-1 and COX-2 in gastric tissue, thus exerting its protective effect on gastric mucosa. The gastroprotective mechanism may be related to the involvement of the arachidonic acid metabolism and upregulation of tryptophan, phenylalanine, tyrosine, and alpha-Linolenic acid metabolism synthesis in vivo.

Walnut (Juglans regia L.) Oligopeptides Alleviate Alcohol-Induced Acute Liver Injury through the Inhibition of Inflammation and Oxidative Stress in Rats.

The study was aimed at investigating the effects of walnut oligopeptides (WOPs) on alcohol-induced acute liver injury and its underlying mechanisms. Male Sprague Dawley (SD) rats were randomly assigned to six groups: normal control, alcohol control, whey protein (440 mg/kg.bw), and three WOPs (220 mg/kg.bw, 440 mg/kg.bw, 880 mg/kg.bw) groups. After 30 days of gavage, ethanol with a volume fraction of 50%, administered at a dose of 7 g/kg.bw., caused acute liver injury. A righting reflex experiment and a blood ethanol concentration evaluation were then performed. Serum biochemical parameters, inflammatory cytokines, liver alcohol metabolism enzymes, oxidative stress biomarkers, liver nuclear factor-κB (NF-κB p65), and cytochrome P4502E1 expression were determined. The results revealed that the intervention of 440 mg/kg and 880 mg/kg WOPs could alleviate the degree of intoxication, decrease blood ethanol concentration, alleviate alcohol-induced hepatic steatosis, enhance the activity of hepatic ethanol metabolizing enzymes and antioxidant capacity, reduce lipid oxidation products and pro-inflammatory factor contents, and inhibit the expression of NF-κBp65 in the livers of rats. The outcomes of the study suggest that WOPs have beneficial effects on liver damage caused by acute ethanol binge drinking, with the high-dose WOPs (880 mg/kg.bw) exerting the most pronounced hepatoprotective effect.

Exogenous Nucleotides Ameliorate Ageing-Related Intestinal Inflammation in Senescence-Accelerated Mouse Prone-8 (SAMP8) Mice.

As one of the most important barriers in the body, the intestinal barrier is a key factor in maintaining human health. Ageing of the intestine is a degenerative process that is closely associated with a variety of poor health conditions in the elderly. Inflammation and the immune system are anti-ageing targets that can regulate the function of the intestine. Nucleotides (NTs) are involved in important physiological and biochemical reactions in the body, but there are few studies about their effect on the ageing intestine. This paper examines the role of exogenous NTs in the ageing intestine. For this purpose, we used senescence-accelerated mouse prone-8 (SAMP8) mice and senescence-accelerated mouse resistant 1 (SAMR1) mice for the experiment, and randomly divided the mice into NTs-free, Normal Control, NTs-low, NTs-medium, NTs-high, and SAMR1 groups. After 9 months of intervention, we collected the colon tissue of mice for testing. In our study, exogenous NTs could increase bodyweight of mice during ageing and improve the morphological structure of the intestine, and we found that NTs could promote the secretion of intestinal protective factors, such as TFF3 and TE. Furthermore, supplementation with NTs suppressed intestinal inflammation and improved intestinal immunity, possibly by activating the p38 signaling pathway. These results suggest that exogenous NTs are able to maintain the health condition of the ageing intestine.

Exogenous Nucleotides Ameliorate Age-Related Decline in Testosterone in Male Senescence-Accelerated Mouse Prone-8 (SAMP8) Mice by Modulating the Local Renin-Angiotensin System Antioxidant Pathway.

In older men, an age-related decline in testosterone is closely associated with various adverse health outcomes. With the progression of aging, hyperactivation of the local renin-angiotensin system (RAS) and oxidative stress increase in the testis. The regulation of RAS antioxidants may be a target to delay testicular aging and maintain testosterone levels. Exogenous nucleotides (NTs) have anti-aging potential in several systems, but there are no studies of their effects on the reproductive system. In our study, we examined the effects of exogenous NTs on testosterone synthesis and explored possible mechanisms of action. Therefore, senescence-accelerated mouse prone-8 (SAMP8) mice and senescence-accelerated mouse resistant 1 (SAMR1) were used in the experiment, and they were randomly divided into an NTs free group (NTs-F), a normal control group (control), a low-dose NTs group (NTs-L), a middle-dose NTs (NTs-M), a high-dose NTs group (NTs-H) and SAMR1 groups, and the testis of the mice were collected for testing after 9 months of intervention. The results showed that exogenous NTs could increase the testicular organ index in mice during aging, and delayed the age-associated decline in testosterone levels in SAMP8 male mice, possibly by modulating the local RAS antioxidant pathway and reducing oxidative stress to protect the testis. The present study provides new research clues for the development of preventive and therapeutic strategies for related diseases.

Walnut Oligopeptide Delayed Improved Aging-Related Learning and Memory Impairment in SAMP8 Mice.

Aging-related learning and memory decline are hallmarks of aging and pose a significant health burden. The effects of walnut oligopeptides (WOPs) on learning and memory were evaluated in this study. Sixty SAMP8 mice were randomly divided into four groups (15 mice/group), including one SAMP8 age-control group and three WOP-treated groups. SAMR1 mice (n = 15) that show a normal senescence rate were used as controls. The SAMP8 and SAMR1 controls were administered ordinary sterilized water, while the WOP-intervention groups were administered 110, 220, and 440 mg/kg·bw of WOPs in water, respectively. The whole intervention period was six months. The remaining 15 SAMP8 (4-month-old) mice were used as the young control group. The results showed that WOPs significantly improved the decline in aging-related learning/memory ability. WOPs significantly increased the expression of BDNF and PSD95 and decreased the level of APP and Aß1-42 in the brain. The mechanism of action may be related to an increase in the activity of antioxidant enzymes (SOD and GSH-Px), a reduction in the expression of inflammatory factors (TNF-α and IL-1ß) in the brain and a reduction in oxidative stress injury (MDA). Furthermore, the expression of AMPK, SIRT-1, and PGC-1α was upregulated and the mitochondrial DNA content was increased in brain. These results indicated that WOPs improved aging-related learning and memory impairment. WOP supplementation may be a potential and effective method for the elderly.

Synthetic libraries of immune cells displaying a diverse repertoire of chimaeric antigen receptors as a potent cancer immunotherapy.

Cancer immunotherapies rely on one or few specific tumour-associated antigens. However, the adaptive immune system relies on a large and diverse repertoire of antibodies for antigen recognition. Here we report the development and applicability of libraries of immune cells displaying diverse repertoires of chimaeric antigen receptors (CARs) that can recognize non-self antigens and display antigen-dependent clonal expansion, with the expanded population of tumour-specific effector cells leading to long-lasting antitumour responses in mouse models of epithelial tumours. The intravenous injection of synthetic libraries of murine CARs on TET2- T cells led to robust immunological memory and the recognition of mutated or evolved tumours, owing to the maintenance of CAR diversity. Off-the-shelf libraries of 106 murine or human CAR clones displayed on genetically modified human NK-92 cancer cells completely eliminated established tumours in mice with murine xenografts and patient-derived xenografts. Synthetically generated CAR libraries may aid the discovery of new CARs and the development of immunotherapies.

Radioprotective Effect of Whey Hydrolysate Peptides against γ-Radiation-Induced Oxidative Stress in BALB/c Mice.

Radiation therapy is widely used in the treatment of tumor diseases, but it can also cause serious damage to the body, so it is necessary to find effective nutritional supplements. The main purpose of this study is to evaluate the protective effect of whey hydrolysate peptides (WHPs) against 60Coγ radiation damage in mice and explore the mechanism. BALB/c mice were given WHPs by oral gavage administration for 14 days. Then, some mice underwent a 30-day survival test after 8 Gy radiation, and other mice received 3.5 Gy radiation to analyze the changes in body weight, hematology and bone marrow DNA after three and 14 days. In addition, through further analysis of the level of oxidative stress and intestinal barrier function, the possible mechanism of the radioprotective effect of WHPs was explored. The study found WHPs can prolong survival time, restore body weight, and increase the number of peripheral blood white blood cells and bone marrow DNA content in irradiated mice. In addition, WHPs can significantly improve the antioxidant capacity, inhibit pro-inflammatory cytokines and protect the intestinal barrier. These results indicate that WHPs have a certain radioprotective effect in mice, and the main mechanism is related to reducing oxidative damage.

The Gastroprotective Effect of Small Molecule Oligopeptides Isolated from Walnut (Juglans regia L.) against Ethanol-Induced Gastric Mucosal Injury in Rats.

The study investigated the protective effect of walnut oligopeptides (WOPs) against ethanol-induced gastric injury using Sprague-Dawley (SD) rats. Rats were randomly divided into seven groups based on body weight (10/group), normal group, ethanol group, whey protein group (220 mg/kg body weight), omeprazole group (20 mg/kg body weight), and three WOPs groups (220, 440, 880 mg/kg body weight). After 30 days of treatment with WOPs, rats were given 5 ml/kg absolute ethanol by gavage to induce gastric mucosal injury. Gastric ulcer index (GUI) were determined and the following measured; gastric content pH, gastric mucin, endogenous pepsinogens (PG), prostaglandin E2 (PGE2), inflammatory cytokines, oxidative stress indicators, and the expression of apoptosis-related proteins were measured to evaluate the gastroprotective effect of WOPs. The results showed that the administration with WOPs markedly mitigated the hemorrhagic gastric lesions caused by ethanol in rats, and decreased the GUI, the gastric content pH, PG1, PG2, and NO levels, enhanced mucin and PGE2. Also, WOPs repressed gastric inflammation through the reduction of TNF-α, IL-6, IL-1ß and increase IL-10 levels, and revealed antioxidant properties with the enhancement of superoxide dismutase, glutathione, and catalase activity, while reduction of malondialdehyde. Moreover, WOPs treatment significantly down-regulated Bax, caspase-3 and nuclear factor-κB p65 (NF-κB p65) expression, while up-regulating the expression of Bcl-2 and inhibitor kappa Bα (IκBα) protein. These results indicated that WOPs have protective effects against ethanol-induced gastric mucosal injury in rats through anti-inflammatory, anti-oxidation, and anti-apoptosis mechanisms.

Jackfruit (Artocarpus heterophyllus Lam.) oligopeptides regulate immune responses via Th cell stimulation, cytokine secretion and antibody production.

This study aimed to observe the immunomodulatory effects of oligopeptides derived from jackfruit (Artocarpus heterophyllus Lam.) (JOPs). 200 female BALB/c mice in five groups were respectively given deionized water (control), whey protein (0.20 g per kg body weight (BW)) and JOPs at doses of 0.20, 0.40, and 0.80 g per kg BW by intragastric administration on a daily basis. 7 tests were conducted to determine the immunomodulatory effects of JOPs on immune organ indexes, cellular and humoral immune responses, macrophage phagocytosis, and natural killer (NK) cell activity. Spleen T lymphocyte sub-populations and serum cytokine and immunoglobulin levels were tested to study how JOPs improved the immune system. We found that JOPs could significantly enhance innate and adaptive immune responses in mice by the improvement of cell-mediated and humoral immunity, macrophage phagocytosis capacity and NK cell activity. The immunomodulatory effects may be based on increased T and Th cell percentages, serum interleukin (IL)-1α, IL-10, tumor necrosis factor (TNF)-α, production of immunoglobulin (Ig) M, IgG, and IgA, and depressed interferon (IFN)-γ secretion. These results suggest that dietary JOPs could be valuable as potential immunomodulators.

Naked Oat (Avena nuda L.) Oligopeptides:Immunomodulatory Effects on Innate and AdaptiveImmunity in Mice via Cytokine Secretion, AntibodyProduction, and Th Cells Stimulation.

The study aimed to investigate the immunomodulatory activity of oligopeptides derivedfrom oat (Avena Nuda L.) (OOPs). Healthy female BALB/c mice were randomly assigned to fivegroups, given deionized water (control) and 0.25, 0.5, 1.0, and 2.0 g/kg body weight (BW) of OOPsdaily by intragastric administration. Seven assays were performed to determine theimmunomodulatory effects of OOPs on immune organ ratios, cellular and humoral immuneresponses, macrophage phagocytosis, and natural killer (NK) cell activity. Spleen T lymphocytesubpopulations (by flow cytometry), serum cytokine and immunoglobulin levels (by multiplexsandwich immunoassays) were determined to evaluate how OOPs affected the immune system.Our results showed that OOPs could significantly improve innate and adaptive immune responsesin mice through the enhancement of cell-mediated and humoral immunity, macrophagephagocytosis capacity, and NK cell activity. We concluded that the immunomodulatory effectsmight be attributed to increased T and Th cell percentages, serum interferon (IFN)-γ, interleukin(IL)-1 α, IL-2, IL-6, IL-10, IL-12, tumor necrosis factor (TNF)- α, and granulocyte-macrophagecolony-stimulating factor (GM-CSF) secretions as well as immunoglobulin (Ig) A, IgG, and IgMproductions. These results indicate that dietary OOPs could be considered as promisingimmunomodulators with dosages ranging from 0.25 to 2.0 g/kg BW.

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.