Endogenous Bioactive Peptides Research Articles

Neuropeptide inactivation regulates egg-laying behavior to influence reproductive health in Caenorhabditis elegans

Neural communication requires both fast-acting neurotransmitters and neuromodulators that function on slower timescales to communicate. Endogenous bioactive peptides, often called "neuropeptides," comprise the largest and most diverse class of neuromodulators that mediate crosstalk between the brain and peripheral tissues to regulate physiology and behaviors conserved across the animal kingdom. Neuropeptide signaling can be terminated through receptor binding and internalization or degradation by extracellular enzymes called neuropeptidases. Inactivation by neuropeptidases can shape the dynamics of signaling invivo by specifying both the duration of signaling and the anatomic path neuropeptides can travel before they are degraded. For most neuropeptides, the identity of the relevant inactivating peptidase(s) is unknown. Here, we established a screening platform in C.elegans utilizing mass spectrometry-based peptidomics to discover neuropeptidases and simultaneously profile the invivo specificity of these enzymes against each of more than 250 endogenous peptides. We identified NEP-2, a worm ortholog of the mammalian peptidase neprilysin-2, and demonstrated that it regulates specific neuropeptides, including those in the egg-laying circuit. We found that NEP-2 is required in muscle cells to regulate signals from neurons to modulate both behavior and health in the reproductive system. Taken together, our results demonstrate that peptidases, which are an important node of regulation in neuropeptide signaling, affect the dynamics of signaling to impact behavior, physiology, and aging.

Computational Modeling of the Interactions between DPP IV and Hemorphins.

Type 2 diabetes is a chronic metabolic disorder characterized by high blood glucose levels due to either insufficient insulin production or ineffective utilization of insulin by the body. The enzyme dipeptidyl peptidase IV (DPP IV) plays a crucial role in degrading incretins that stimulate insulin secretion. Therefore, the inhibition of DPP IV is an established approach for the treatment of diabetes. Hemorphins are a class of short endogenous bioactive peptides produced by the enzymatic degradation of hemoglobin chains. Numerous in vitro and in vivo physiological effects of hemorphins, including DPP IV inhibiting activity, have been documented in different systems and tissues. However, the underlying molecular binding behavior of these peptides with DPP IV remains unknown. Here, computational approaches such as protein-peptide molecular docking and extensive molecular dynamics (MD) simulations were employed to identify the binding pose and stability of peptides in the active site of DPP IV. Findings indicate that hemorphins lacking the hydrophobic residues LVV and VV at the N terminal region strongly bind to the conserved residues in the active site of DPP IV. Furthermore, interactions with these critical residues were sustained throughout the duration of multiple 500 ns MD simulations. Notably, hemorphin 7 showed higher binding affinity and sustained interactions by binding to S1 and S2 pockets of DPP IV.

Peptidome profiling of human, bovine, and donkey colostrum through label-free quantitative analysis reveals proteolysis of milk proteins.

Proteins and peptides play vital roles in different biological processes in vivo. As a dynamic hydrolysis system, milk is rich in proteins and proteases and provides a constant supply of endogenous bioactive peptides to newborn mammals. Previous studies have primarily focused on researching bioactive peptides by adding exogenous enzymes to milk samples. However, such an approach overlooks the significance of endogenous peptides and parent proteins that naturally exist in milk. Herein, we analyzed and compared parent proteins and their releasing peptides in human colostrum (HC), bovine colostrum (BC), and donkey colostrum (DC). The predominant proteins and hydrolyzed peptides in the three types of milk were identified. Among them, peptides were found to possess common bioactivities, including ACE inhibitory, antioxidant, antibacterial and immunomodulatory properties in HC, BC, and DC. Furthermore, the biological functions of these parent proteins were clarified using bioinformatics. These insights offer a novel perspective on natural bioactive peptides and the potential utilization of specific parent proteins and peptides to develop infant formulae derived from diverse milk sources.

Bioactive peptides derived from fermented foods: Preparation and biological activities

Bioactive peptides (BAPs) with potential health benefits are gaining popularity as people become more health-conscious. Fermented foods are produced through the vigorous metabolic activities of numerous microorganisms, which convert macromolecules in the food matrix into bioactive components, including BAPs. Access to endogenous BAPs in fermented foods reduces costs while simplifying isolation steps and provides a high-quality direct source of BAPs. Fermented foods-derived BAPs have been shown to have antihypertensive, antioxidant, and antibacterial activities; however, there is a lack of information on the production of BAPs through fermented foods, and a large number of BAPs resources in fermented foods have not been effectively explored. Therefore, this review introduces the current research status, preparation methods, biological functions, and digestive stability of BAPs in fermented foods, followed by a discussion of the shortcomings in current research and future directions to provide a foundation for applications of BAPs in fermented foods in the food and pharmaceutical fields.

Activity‐guided purification and identification of endogenous bioactive peptides from barley sprouts (Hordeum vulgare L.) with diabetes treatment potential

SummaryMetabolic‐associated disorders such as blood pressure and type 2 diabetes (T2D) are some of modern society's widespread problems. While there are many beneficial treatments, the quest for “safe” alternatives using natural products (e.g., cereals) is of great promise, especially plant‐based peptides containing inherently endogenous bioactivities that can provide multiple health‐promoting effects. Here, we aimed to purify and identify potential endogenous peptides of barley sprouts through an activity‐guided process with a potential T2D therapeutical effect. Barley seeds were germinated, and sprouts were fractionated through ultrafiltration followed by RP‐HPLC. All peptide fractions were examined for various bioactivities (α‐glucosidase/DPP4 inhibition, antiglycation, antioxidant and metal chelation activities). LC‐Q‐TOF‐MS/MS was employed for sequence identification of the fraction with the highest activity level. The data demonstrated that fractions with molecular weights lower than 3 kDa were the only ones with antiglycation activities. The RP‐HPLC of the 3 kDa fraction resulted in 11 fractions, including 4 having significant IC50/EC50 levels. F11 demonstrated the highest potential as T2D treatment, and the sequence identification provided the sequences SQQENELTSLIVESNNRFNNASNT. Natural bioactive peptides from easy to procure and cheap sources are promising molecules for therapeutic applications. Further in vivo and clinical testing are necessary to validate the current findings.

Pancreastatin inhibitor PSTi8 balances energy homeostasis by attenuating adipose tissue inflammation in high fat diet fed mice

Pancreastatin (PST) is an endogenous bioactive peptide. PST is generated from chromogranin A (Chga) protein which is released by chromaffin and neuroendocrine cells. PST exhibits diabetogenic effect by antagonizing the action of insulin in adipocytes. The level of PST rises during obesity, resulting in persistent low-grade inflammation in adipocytes. Pancreastatin inhibitor 8 (PSTi8), which is developed by modification of PST sequence which antagonizes the action of PST. In this study, we investigated the immunometabolic effect of PSTi8 in the diet-induced obesity (DIO) model in C57BL/6 mice. Here we found PSTi8 decreased the body weight gain, fat mass and increased the lean mass in (DIO) mice. It also showed reduction of adipocyte hypertrophy in eWAT and lipid accumulation in liver of DIO mice. Immunoprofiling of stromal vascular fraction isolated from eWAT of PTSi8 treated mice showed increased anti-inflammatory M2 macrophages, Eosinophil, T-regulatory cells and reduced pro-inflammatory M1 macrophages, CD4 and CD8 T cell population. Apart from this, PSTi8 also improved the mitochondrial function by decreasing reactive oxygen species and increasing mitochondrial membrane potential, NADPH/NADP ratio and citrate synthase activity in eWAT of DIO mice. It also increased the protein expression of pAMPK, pAKT, Arginase −1 and decreased the expression of MHC-II and iNOS in eWAT of DIO mice. In conclusion, PSTi8 exerted its beneficial effect on restoring energy expenditure by reducing adipose tissue inflammation.

A New Marker for Determining Cardiovascular Risk: Salusin Alpha.

Background and objective Prevention of atherosclerotic cardiovascular diseases (ASCVD) is possible with early recognition of individuals at risk. Salusin alpha is an endogenous bioactive peptide with anti-atherogenic properties. We aimed to reveal the relationship between salusin alpha levels and cardiovascular (CV) risk using the Systematic COronary Risk Estimation 2 (SCORE2) and Pooled Cohort Equation (PCE) algorithms. Methods A total of 137 asymptomatic outpatients were included in the study. The participants were divided into four quartile groups according to the distribution of salusin alpha levels: Q1 (n = 34), Q2 (n = 35), Q3 (n = 34), and Q4 (n = 34). The relationships of salusin alpha with cardiovascular risk scores and groups were investigated. Results The means of SCORE2 and PCE risk scores (11.24 ± 1.24 and 13.30 ± 1.71, respectively; p < 0.001 for both), baseline scores in the presence of SCORE2 and PCE optimal risk factors (4.82 ± 0.71 (p = 0.034); 4.20 ± 0.77 (p = 0.010)), and means of Δ SCORE2 and Δ PCE risk score (6.41 ± 0.67 and 9.10 ± 1.10, respectively; p < 0.001 for both) were significantly higher in the Q1 group. The SCORE2 "very high"cardiovascular (CV)risk group was significantly represented in the Q1 group (n = 17 (50%)), while the "low-moderate" risk group was more heavily represented in the Q4 group (n = 15 (44.1%)) (p < 0.001). The PCE"high"CV risk group was significantly represented in the Q1 group (n = 9 (26.5%)), while the "low" risk group was more intensely represented in the Q4 group (n = 20 (58.8%)) (p < 0.001). Salusin alpha had a significantly negative moderate correlation with SCORE2 and PCE risk scores. As a result of receiver operating characteristic (ROC) analysis, it was found that salusin alpha had significant diagnostic power in the prediction of CV risk groups determined by SCORE2 and PCE risk scores. Salusin alpha was observed to be a risk-reducing factor in SCORE2 and PCE CV risk groups (odds ratio (OR)(95% confidence interval (CI)): 0.989 (0.982-0.997) (p = 0.002) and OR (95% CI): 0.988 (0.978-0.998) (p = 0.009) respectively). Conclusion Salusin alpha has a negative correlation with SCORE2 and PCE risk scores. It has significant diagnostic power in the prediction of CV risk groups and is an independent variable that has a risk-reducing effect in the distribution of risk groups.

Research Progress on Dipeptidyl Peptidase Family: Structure, Function and Xenobiotic Metabolism.

Prolyl-specific peptidases or proteases, including Dipeptidyl Peptidase 2, 4, 6, 8, 9, 10, Fibroblast Activation Protein, prolyl endopeptidase, and prolyl carboxypeptidase, belong to the dipeptidyl peptidase family. In human physiology and anatomy, they have homology amino acid sequences and similarities in the structure; however, they have distinct functions and play different roles. Some of them also play important roles in the metabolism of drugs containing endogenous peptides, xenobiotics containing peptides, and exogenous peptides. The major functions of these peptidases in both the metabolism of human health and bioactive peptides are of significant importance in the development of effective inhibitors to control the metabolism of endogenous bioactive peptides. The structural characteristics, distribution of tissue, endogenous substrates, and biological functions were summarized in this review. Furthermore, the xenobiotics metabolism of the dipeptidyl peptidase family is illustrated. All the evidence and information summarized in this review would be very useful for researchers to extend the understanding of the proteins of these families and offer advice and assistance in physiology and pathology studies.

Latent potentials of camel's milk.

In a recent study (Zhang et al. in Eur Food Res Technol 10.1007/s00217-021-03952-2, 2022), a detailed description of the endogenous bioactive peptides in the milk of Dromedary and Bactrian camel was reported. The authors described multiple endogenous peptides that may contribute to the therapeutic benefits of camel milk thereby uncovering latent potential of camel milk.

Determination of ghrelin and desacyl ghrelin in human plasma and urine by means of LC-MS/MS for doping controls.

The hunger hormone ghrelin (G) is classified as prohibited substance in professional sport by the World Anti-Doping Agency (WADA), due to its known growth hormone releasing properties. The endogenous bioactive peptide consists of 28 amino acids with a caprylic acid attached to serine at position 3. Within this study, it was aimed to develop methods to determine G and desacyl ghrelin (DAG) in plasma and urine by means of LC-MS/MS. Two strategies were applied with a bottom-up approach for plasma and top-down analyses for urine. Both sample preparation procedures were based on solid-phase extraction for enrichment and sample clean-up. Method validation showed good results for plasma and urine with limits of detection (LODs) for G and DAG between 30 and 50 pg/ml, recoveries between 45-50%, and imprecisions (intra- and inter-day) between 3% and 24%. Plasma analysis was also valid for quantification with accuracies determined with ~100% for G and ~106% for DAG. The minimum required performance level for doping control laboratories is set to 2ng/ml in urine, and the herein established method yielded acceptable results even at 5% of this level. As proof-of-concept, plasma levels (G and DAG) of healthy volunteers were determined and ranged between 30 and 100 pg/ml for G and 100-1200 pg/ml for DAG. In contrast to earlier reported studies using ligand binding assays for urinary G and DAG, in this mass spectrometry-based study, no endogenous urinary G and DAG were found, although the LODs should enable this.

Peptidomics: A Review of Clinical Applications and Methodologies.

Improvements in both liquid chromatography (LC) and mass spectrometry (MS) instrumentation have greatly enhanced proteomic and small molecule metabolomic analysis in recent years. Less focus has been on the improved capability to detect and quantify small bioactive peptides, even though the exact sequences of the peptide species produced can have important biological consequences. Endogenous bioactive peptide hormones, for example, are generated by the targeted and regulated cleavage of peptides from their prohormone sequence. This process may include organ specific variants, as proglucagon is converted to glucagon in the pancreas but glucagon-like peptide-1 (GLP-1) in the small intestine, with glucagon raising, whereas GLP-1, as an incretin, lowering blood glucose. Therefore, peptidomics workflows must preserve the structure of the processed peptide products to prevent the misidentification of ambiguous peptide species. The poor in vivo and in vitro stability of peptides in biological matrices is a major factor that needs to be considered when developing methods to study them. The bioinformatic analysis of peptidomics data sets requires the inclusion of specific post-translational modifications, which are critical for the function of many bioactive peptides. This review aims to discuss and contrast the various extraction, analytical, and bioinformatics approaches used for human peptidomics studies in a multitude of matrices.

The alteration of gut microbiota by bioactive peptides: a review

Evidences suggest that the homeostasis of gut microbiota is among the most important factors for maintaining the physical and mental health of the host. Among the multiple factors affecting the homeostasis of gut microbiota, diet is one of the decisive factors. Bioactive peptides derived from protein hydrolyzed by protease or fermented by microorganism have many physiological activities that their parent proteins do not have. Currently, bioactive peptides attract more and more attention due to their bidirectional interaction with gut microbes. It has been reported that some bioactive peptides could alter the composition of gut microbiota by influencing the intestinal microenvironment. Meanwhile, quite a few bioactive peptides that are released by gut microbes or intestinal cells could resist the pathogenic bacteria to sustain the homeostasis of gut microbiota. In this review, some exogenous bioactive peptides derived from food and some endogenous bioactive peptides released from intestinal cells or microbes were discussed to summary their effects on the modulation of gut microbiota. This review is expected to provide new ideas for related research, and as well to promote the application of bioactive peptides in the fields of food and medicine.

Adrenomedullin 2 improves bone regeneration in type 1 diabetic rats by restoring imbalanced macrophage polarization and impaired osteogenesis

BackgroundBoth advanced glycation end products (AGEs) and AGE-mediated M1 macrophage polarization contribute to bone marrow mesenchymal stem cell (BMSC) dysfunction, leading to impaired bone regeneration in type 1 diabetes mellitus (T1DM). Adrenomedullin 2 (ADM2), an endogenous bioactive peptide belonging to the calcitonin gene-related peptide family, exhibits various biological activities associated with the inhibition of inflammation and reduction of insulin resistance. However, the effects and underlying mechanisms of ADM2 in AGE-induced macrophage M1 polarization, BMSC dysfunction, and impaired bone regeneration remain poorly understood.MethodsThe polarization of bone marrow-derived macrophages was verified using flow cytometry analysis. Alkaline phosphatase (ALP) staining, ALP activity detection, and alizarin red staining were performed to assess the osteogenesis of BMSCs. Quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, western blotting, and immunofluorescence staining were used to assess polarization markers, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, and osteogenic markers. In vivo, a distraction osteogenesis (DO) rat model with T1DM was established, and tibia samples were collected at different time points for radiological, biomechanical, and histological analyses, to verify the effects of ADM2 on bone regeneration and M2 polarization under diabetic conditions.ResultsADM2 treatment reversed AGE-induced M1 macrophage polarization towards the M2 phenotype, which was partially achieved by the peroxisome proliferator-activated receptor γ (PPARγ)-mediated inhibition of NF-κB signaling. The PPARγ inhibitor GW9662 significantly attenuated the effects of ADM2. Besides, ADM2 treatment improved the AGE-impaired osteogenic potential of BMSCs in vitro. Furthermore, ADM2 accelerated bone regeneration, as revealed by improved radiological and histological manifestations and biomechanical parameters, accompanied by improved M2 macrophage polarization in diabetic DO rats, and these effects were partially blocked by GW9662 administration.ConclusionsThese results indicate that ADM2 enhances diabetic bone regeneration during DO, by attenuating AGE-induced imbalances in macrophage polarization, partly through PPARγ/NF-κB signaling, and improving AGE-impaired osteogenic differentiation of BMSCs simultaneously. These findings reveal that ADM2 may serve as a potential bioactive factor for promoting bone regeneration under diabetic conditions, and imply that management of inflammation and osteogenesis, in parallel, may present a promising therapeutic strategy for diabetic patients during DO treatment.

Accelerated Bone Regeneration by Adrenomedullin 2 Through Improving the Coupling of Osteogenesis and Angiogenesis via β-Catenin Signaling.

Both osteogenic differentiation and the pro-angiogenic potential of bone marrow mesenchymal stem cells (BMSCs) contribute to bone regeneration during distraction osteogenesis (DO). Adrenomedullin 2 (ADM2), an endogenous bioactive peptide belonging to the calcitonin gene-related peptide family, exhibits various biological activities associated with the inhibition of inflammation and the attenuation of ischemic-hypoxic injury. However, the effects and underlying mechanisms of ADM2 in osteogenic differentiation and the pro-angiogenic potential of BMSCs, along with bone regeneration, remain poorly understood. In the present study, we found that osteogenic induction enhanced the pro-angiogenic potential of BMSCs, and ADM2 treatment further improved the osteogenic differentiation and pro-angiogenic potential of BMSCs. Moreover, the accumulation and activation of β-catenin, which is mediated by the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and the activation of protein kinase B (AKT), have been shown to contribute to the effects of ADM2 on BMSCs. In vivo, ADM2 accelerated vessel expansion and bone regeneration, as revealed by improved radiological and histological manifestations and the biomechanical parameters in a rat DO model. Based on the present results, we concluded that ADM2 accelerates bone regeneration during DO by enhancing the osteogenic differentiation and pro-angiogenic potential of BMSCs, partly through the NF-κB/β-catenin and AKT/β-catenin pathways. Moreover, these findings imply that BMSC-mediated coupling of osteogenesis and angiogenesis may be a promising therapeutic strategy for DO patients.

Inhibition of Notch1-mediated inflammation by intermedin protects against abdominal aortic aneurysm via PI3K/Akt signaling pathway.

The Notch1-mediated inflammatory response participates in the development of abdominal aortic aneurysm (AAA). The vascular endogenous bioactive peptide intermedin (IMD) plays an important role in maintaining vascular homeostasis. However, whether IMD inhibits AAA by inhibiting Notch1-mediated inflammation is unclear. In this study, we found Notch intracellular domain (NICD) and hes1 expression were higher in AAA patients’ aortas than in healthy controls. In angiotensin II (AngII)-induced AAA mouse model, IMD treatment significantly reduced AAA incidence and maximal aortic diameter. IMD inhibited AngII-enlarged aortas and -degraded elastic lamina, reduced NICD, hes1 and inflammatory factors expression, decreased infiltration of CD68 positive macrophages and the NOD-like receptor family pyrin domain containing 3 protein level. IMD inhibited lipopolysaccharide-induced macrophage migration in vitro and regulated macrophage polarization. Moreover, IMD overexpression significantly reduced CaCl2-induced AAA incidence and down-regulated NICD and hes1 expression. However, IMD deficiency showed opposite results. Mechanically, IMD treatment significantly decreased cleavage enzyme-a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) level. Pre-incubation with IMD17-47 (IMD receptors blocking peptide) and the phosphatidylinositol 3-kinase/protein kinase b (PI3K/Akt) inhibitor LY294002 reversed ADAM10 level. In conclusion, exogenous and endogenous IMD could inhibit the development of AAA by inhibiting Notch1 signaling-mediated inflammation via reducing ADAM10 through IMD receptor and PI3K/Akt pathway.

Novel risk factor for fatal arrhythmia in Brugada syndrome

Abstract Background Brugada syndrome (BrS) is a genetic disease associated with increased risk of ventricular fibrillation (VF)/ventricular tachycardia (VT). The VF/VT in BrS occurs more frequently during a night time or at a rest with parasympathetic nerve activation. Some risk factors of VF/VT occurrence in BrS have been elucidated, however, it remains controversial about risk stratification. Salusin-β is an endogenous bioactive peptide that systemically exerts rapid and profound hypotensive and bradycardic activities and parasympathomimetic hemodynamic actions in vivo. Previous reports suggested that salusin-β is suppressed following physiological parasympathetic stimulation and appears to constitute a negative feedback relationship with the parasympathetic nervous system. Purpose We hypothesized that salusin-β is associated with the occurrence of VF/VT in BrS. Methods The study population consisted of 26 BrS patients with newly implantation of implantable cardioverter defibrillator (ICD) during 2003–2008. In all patients, salusin-β was measured in supine position after 20 minute rest. The date of salusin-β sampling was set as the registration point for this study. The VF/VT was defined as any episode of fatal ventricular tachyarrhythmia or any appropriate shock. In accordance with the presence or absence of VF/VT events within 5 years, all patients were divided into VF/VT group (n=6) and non-VF/VT group (n=20).Various clinical parameters were compared between the two groups. For analysis of autonomic nervous function, heart rate variability (HRV) and pupil function were evaluated. Results The mean age was 54±17 years old. There is no differences between the two groups in clinical parameters. In analysis of HRV, the high-frequency component (0.15–0.40 Hz; HF), low frequency component (0.04–0.15 Hz; LF) and the LF/HF ratio were analyzed over 24 h. LF/HF ratio was significantly lower over 24h in VF/VT groups in comparison with non-VF/VT groups [day-time; 1.8 (1.2–5.6) vs. 5.2 (3.4–8.8), p=0.048, night-time; 1.2 (1.1–1.3) vs. 3.9 (2.5–8.7), p=0.003]. Furthermore, in analysis of pupil function, right/left miosis ratio was higher in VT/VF groups in comparison with non-VT/VF groups [right pupil; 0.39 (0.37–0.59) vs. 0.34 (0.28–0.38), p=0.035, left pupil; 0.43 (0.36–0.50) vs. 0.33 (0.28–0.40), p=0.049]. In plasma total salusin-β levels, the VF/VT groups exhibited significantly lower than non-VF/VT groups (55.2±14.6 vs. 73.2±22.2, p=0.039, Figure). Conclusions Salusin-β was associated with the occurrence of VF/VT in Brugada syndrome. Salusin-β might be useful to identify high-risk patients for the occurrence of VT/VF events in Brugada syndrome. Funding Acknowledgement Type of funding source: None

Potent Antibacterial Activity of Synthetic Peptides Designed from Salusin-β and HIV-1 Tat(49-57).

Salusin-β is an endogenous bioactive peptide that was identified in a human full-length enriched cDNA library using bioinformatics analyses. In our previous study, we found that synthetic salusin-β exhibits antibacterial activity against only Gram-positive microorganisms such as Staphylococcus aureus NBRC 12732. Salusin-β has an ability to depolarize the cytoplasmic membrane of this bacterium, and this phenomenon may be linked to the antibacterial activity of this peptide. A cell-penetrating peptide (CPP), human immunodeficiency virus (HIV)-1 transactivator of transcription (Tat) (49-57) is a short cationic peptide that can traverse cell membranes. In this report, synthetic peptide conjugates of salusin-β and HIV-1 Tat(49-57) showed potent antibacterial activities against both Gram-positive Staphylococcus aureus NBRC 12732 and Gram-negative Escherichia coli NBRC 12734. The synthetic peptides also depolarized the cytoplasmic membrane of Escherichia coli NBRC 12734 as well as Staphylococcus aureus NBRC 12732. These results suggested that HIV-1 Tat(49-57) is a protein transduction domain or CPP that changes the interaction mode between salusin-β and the cell membrane of Escherichia coli NBRC 12734. By binding to HIV-1 Tat(49-57), salusin-β showed a broad antibacterial spectrum regardless of whether the target was a Gram-positive or Gram-negative bacterium.

ACE inhibitory peptides in standard and fermented deer velvet: an in silico and in vitro investigation

BackgroundThe use of deer velvet antler (DVA) as a potent traditional medicine ingredient goes back for over 2000 years in Asia. Increasingly, though, DVA is being included as a high protein functional food ingredient in convenient, ready to consume products in Korea and China. As such, it is a potential source of endogenous bioactive peptides and of ‘cryptides’, i.e. bioactive peptides enzymatically released by endogenous proteases, by processing and/or by gastrointestinal digestion. Fermentation is an example of a processing step known to release bioactive peptides from food proteins. In this study, we aimed to identify in silico bioactive peptides and cryptides in DVA, before and after fermentation, and subsequently to validate the major predicted bioactivity by in vitro analysis.MethodsPeptides that were either free or located within proteins were identified in the DVA samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by database searching. Bioactive peptides and cryptides were identified in silico by sequence matching against a database of known bioactive peptides. Angiotensin-converting enzyme (ACE) inhibitory activity was measured by a colorimetric method.ResultsThree free bioactive peptides (LVVYPW, LVVYPWTQ and VVYPWTQ) were solely found in fermented DVA, the latter two of which are known ACE inhibitors. However matches to multiple ACE inhibitor cryptides were obtained within protein and peptide sequences of both unfermented and fermented DVA. In vitro analysis showed that the ACE inhibitory activity of DVA was more pronounced in the fermented sample, but both unfermented and fermented DVA had similar activity following release of cryptides by simulated gastrointestinal digestion.ConclusionsDVA contains multiple ACE inhibitory peptide sequences that may be released by fermentation or following oral consumption, and which may provide a health benefit through positive effects on the cardiovascular system. The study illustrates the power of in silico combined with in vitro methods for analysis of the effects of processing on bioactive peptides in complex functional ingredients like DVA.

Serum salusin-\u03b2 levels as predictors of coronary artery disease in obese Egyptian women

EnBackgroundObesity is a growing health concern that has become an epidemic all over the world. Obesity is associated with coronary artery disease (CAD). Salusin-β is an endogenous bioactive peptide that accelerates inflammatory responses in vascular endothelial cells and increases oxidative stress. The objective of this study was to explore the potential roles of salusin-β in endothelial dysfunction in CAD. Also, we aimed to evaluate the association between salusin-β with severity of CAD in obese Egyptian women.Patients and methodsThis cross-sectional study enrolled 95 obese women who were classified into two groups: 58 patients without CAD and 37 patients without CAD. All patients were investigated using a 12-lead standard ECG, echocardiography, and coronary arteriography. Salusin-β levels were measured by enzyme-linked immunosorbent assay.ResultsSalusin-β levels were significantly higher in obese patients with CAD compared with patients without CAD. Salusin-β levels were positively correlated with cardiometabolic risks and severity of coronary occlusion. Serum salusin-β levels, high-sensitivity C-reactive protein, and BMI were independently correlated with CAD and BMI. Homeostatic model assessment of insulin resistance, high-sensitivity C-reactive protein, and uric acid were the main associated variables of serum salusin-β levels among other clinical and laboratory biomarkers. The diagnostic power of serum salusin-β levels in differentiating CAD from obese patients without CAD was highly sensitive (97.2%) and the specificity was 98.3%.ConclusionThe higher levels of salusin-β levels in obesity, as well as CAD, were positively correlated with cardiometabolic risk factors and severity of coronary occlusion. Therefore, salusin-β levels seem to be a noninvasive biomarker of CAD.

Generation of bioactive prolyl‐hydroxyproline (Pro‐Hyp) by oral administration of collagen hydrolysate and degradation of endogenous collagen

SummaryHydroxyproline‐containing di‐ and tripeptides increase in human blood plasma after ingestion of collagen hydrolysate in a dose‐dependent manner. Prolyl‐hydroxyproline (Pro‐Hyp) and hydroxyprolyl‐glycine (Pro‐Gly) are the main food‐derived collagen peptides present in human blood plasma. Pro‐Hyp increases the number of fibroblasts migrating from the mouse skin and enhances the growth of fibroblasts attached to the collagen gel. Pro‐Hyp is also generated from endogenous collagen in the granulation tissue in mice skin and ear with dermatitis, while it does not increase in the normal tissues of the same animal. However, Hyp‐Gly does not increase in all tissues. These facts indicate that Pro‐Hyp is generated by the degradation of endogenous collagen to activate cells involved in tissue reconstruction. Orally administered Pro‐Hyp is deposited in animal organs even after clearance of Pro‐Hyp from blood. Thus, the endogenous bioactive peptide can be provided by ingestion of collagen hydrolysate.