The SWGEDWGEIW from Soybean Peptides Reduces Insulin Resistance in 3T3-L1 Adipocytes by Activating p-Akt/GLUT4 Signaling Pathway.

Diabetes mellitus, a group of metabolic disorders characterized by persistent hyperglycemia, affects millions of people worldwide and is on the rise. Dietary proteins, from a wide range of food sources, are rich in bioactive peptides with anti-diabetic properties. Notably, the protective mechanism of the single peptide SWGEDWGEIW (TSP) from soybean peptides (SBPs) on insulin resistance of adipocytes in an inflammatory state was investigated by detecting the lipolysis and glucose absorption and utilization of adipocytes. The results showed that different concentrations of TSP (5, 10, 20 µg/mL) intervention can reduce 3T3-L1 adipocytes' insulin resistance induced by inflammatory factors in a dose-dependent manner and increase glucose utilization by 34.2 ± 4.6%, 74.5 ± 5.2%, and 86.7 ± 6.1%, respectively. Thus, TSP can significantly alleviate the lipolysis of adipocytes caused by inflammatory factors. Further mechanism analysis found that inflammatory factors significantly reduced the phosphorylation (p-Akt) of Akt, two critical proteins of glucose metabolism in adipocytes, and the expression of GLUT4 protein downstream, resulting in impaired glucose utilization, while TSP intervention significantly increased the expression of these two proteins. After pretreatment of adipocytes with PI3K inhibitor (LY294002), TSP failed to reduce the inhibition of p-Akt and GLUT4 expression in adipocytes. Meanwhile, the corresponding significant decrease in glucose absorption and the increase in the fat decomposition of adipocytes indicated that TSP reduced 3T3-L1 adipocytes' insulin resistance by specifically activating the p-Akt/GLUT4 signal pathway. Therefore, TSP has the potential to prevent obesity-induced adipose inflammation and insulin resistance.

The SWGEDWGEIW from Soybean Peptides Reduce Oxidative Damage-Mediated Apoptosis in PC-12 Cells by Activating SIRT3/FOXO3a Signaling Pathway.

The goal of the investigation was to study the protective effects of the SWGEDWGEIW (the single peptide, TSP) from soybean peptides (SBP) on hydrogen peroxide (H2O2)-induced apoptosis together with mitochondrial dysfunction in PC-12 cells and their possible implications to protection mechanism. Meanwhile, the SBP was used as a control experiment. The results suggested that SBP and TSP significantly (p < 0.05) inhibited cellular oxidative damage and ROS-mediated apoptosis. In addition, SBP and TSP also enhanced multiple mitochondrial biological activities, decreased mitochondrial ROS levels, amplified mitochondrial respiration, increased cellular maximal respiration, spare respiration capacity, and ATP production. In addition, SBP and TSP significantly (p < 0.05) raised the SIRT3 protein expression and the downstream functional gene FOXO3a. In the above activity tests, the activity of TSP was slightly higher than that of SBP. Taken together, our findings suggested that SBP and TSP can be used as promising nutrients for oxidative damage reduction in neurons, and TSP is more effective than SBP. Therefore, TSP has the potential to replace SBP and reduce neuronal oxidative damage.

Soybean protein-derived peptide nutriment increases negative nitrogen balance in burn injury-induced inflammatory stress response in aged rats through the modulation of white blood cells and immune factors.

BACKGROUND: As an important nutrient, soybean protein-derived peptides (SPP) affect the immune function of animals. OBJECTIVE: This study describes the effects of nutrient supplementation with SPP on the negative nitrogen balance in the burn injury-induced inflammatory response of aged rats. DESIGN: Soybean protein isolate (SPI) was hydrolyzed to obtain SPP. A negative nitrogen-balance aged rat model and a major full-thickness 30% total body surface area (TBSA) burn-injury rat model were utilized. RESULTS: The results show that SPP can increase the speed and ability of inflammatory stress by adjusting white blood cell counts. Soybean protein-derived peptides significantly increased serum immunoglobulin M (IgM), immunoglobulin G (IgG) and immunoglobulin A (IgA) levels; significantly decreased serum interleukin-1 beta (IL-ß), tumor necrosis factor-alpha (TNF-α) and regulated upon activation normal T-cell expressed and secreted (RANTES) levels. These results give conclusive evidence that SPP has a significantly positive effect in improving the immune function on the condition of negative nitrogen balance with burn-injury, and reducing excessive inflammation. CONCLUSIONS: Nutrient supplementation of SPP can, therefore, be used as an adjuvant treatment to inhibit the development and severity of inflammatory reactions caused by burns, providing a novel therapy for the treatment and positive prognosis of burn patients.

Soybean protein-derived peptides inhibit inflammation in LPS-induced RAW264.7 macrophages via the suppression of TLR4-mediated MAPK-JNK and NF-kappa B activation.

This study aimed to determine the effect of soybean protein-derived peptides (SBP) on the inhibition of lipopolysaccharide (LPS)-induced RAW264.7 cell inflammation. The mRNA of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), Lymphocyte Antigen 96 (LY96), and nuclear factor-κB (NF-κB) were detected with RT-qPCR. The concentrations of cytokines (TNF-α, IL-6, and IL-1ß) secreted were detected by ELISA Kit. The results indicated that SBP inhibited the inflammatory stress induced by LPS in RAW264.7 cells. Western blot analysis was used to examine this anti-inflammatory molecular mechanism. The findings showed that SBP impeded the increase of toll-like receptor 4 activity by restricting LY96, while also inhibiting the mitogen-activated protein kinase-c-Jun N-terminal kinase pathway in cells, as well as LPS-induced NF-κB activation caused by the degradation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα). Consequently, the release of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß) was inhibited, preventing LPS-induced inflammation of RAW 264.7 cells. Therefore, this research highlighted the potential application of SBP in the development of anti-inflammatory foods that prevented inflammatory-immune diseases. PRACTICAL APPLICATIONS: Inflammation is the root cause of almost all pathology and is related to many human diseases, including arthritis, obesity, cancer and atherosclerosis. Therefore, the development of products that can regulate and intervene inflammation has a broad application prospect. Soybean protein and soybean peptide have many functional properties, including immunoregulation, anti-inflammatory, anti-oxidation and so on. However, there are still some shortcomings in the development of soy protein supplements, such as solubility and absorption. Compared with soybean protein, derived peptide is easy to digest, and has high solubility. As a good nutritional supplement, the nutritional support of soybean protein-derived peptides may help to reduce inflammation and improve the level of cytokines combined with drugs.

Effect of soybean peptides against hydrogen peroxide induced oxidative stress in HepG2 cells via Nrf2 signaling.

The aim of this study was to determine the effects of soybean protein hydrolysates against intracellular antioxidant activity. Soybean peptides (1000 to 2000 Da range) were extracted by soybean proteolysis and ultrafiltration and sequenced with a Nano-LC-ESI-MS/MS. In this study we found that soybean peptides inhibited the production of reactive oxygen species (ROS) induced by hydrogen peroxide (H2O2), malondialdehyde (MDA) and oxidized glutathione (GSSG) in HepG2 cells. Moreover, they also prevented the reduction of reduced glutathione (GSH) and up-regulated cellular resistance oxidase activity. In addition, soybean peptide treatment stimulated the mRNA and protein expression levels of antioxidant enzymes and nuclear factor erythroid-2-related factor 2 (Nrf2). Activated Nrf2 up-regulated antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px)) and inhibited ROS and MDA production. It was concluded that soybean peptides effectively activated the Nrf2/antioxidant response element (ARE) mediated activity.

Effect of small molecular weight soybean protein-derived peptide supplementation on attenuating burn injury-induced inflammation and accelerating wound healing in a rat model.

The populations most afflicted by burn injuries have limited abilities to support the significant specialized requirements and costs for acute and long-term burn injury care. This article describes the results of optimizing the use of readily absorbed small molecular weight soybean protein enzymolysis-derived peptide to attenuate rat burn injury-induced inflammation and accelerate wound healing. A major full-thickness 30% total body surface area burn-injury rat model was utilized and the systemic white blood cell (WBC) counts, the relative level of stimulation index of respiratory burst, and the inflammatory markers procalcitonin (PCT), tumor necrosis factor-α (TNF-α), chemokine (C-C motif) ligand 3 (CCL-3), chemokine (C-C motif) ligand 11 (CCL-11) and interleukin-10 (IL-10) were assessed. The burn injury-induced neutrophil and macrophage immune cell infiltration of the cutaneous tissues was detected by immunohistochemical analysis of the protein markers myeloperoxidase (MPO) and cluster of differentiation 68 (CD-68). The local induction of the burn injury-induced toll-like receptor 4/nuclear factor kappa-light-chain-enhancer of activated B (TLR4/NF-κB) signaling pathway in the effected cutaneous tissues was determined by the quantification of the protein expression of TLR4 and phosphorylated NF-κB/p65 using Western blots. In addition, burn wound size and healing rate were assessed biweekly for 8 weeks by imaging and measuring the burn wound surface area, and the angiogenesis protein marker of cluster of differentiation 31 (CD-31) expression in cutaneous tissues was also detected by immunohistochemical analysis. The results showed that nutrient supplementation with optimized readily absorbed small molecular weight soybean protein-derived peptide resulted in a dramatic anti-inflammatory effect as evidenced by the significant increase in the burn injury-induced systemic white blood cell counts and their relative level of stimulation index of respiratory burst, reduction in the burn injury-induced activation of NF-κB transcriptional signaling pathways, significant reduction in the local burn injury-induced cutaneous infiltration of neutrophils and macrophages at all measured time points, reduction in wound size and improved rate of burn injury wound healing with increased CD-31 protein expression. These results indicated that dietary supplementation with small molecular weight soybean-derived peptides could be used as an adjunct therapy in burn injury management to reduce inflammation and improve overall patient outcomes.