Bioactive Peptides Research Articles

Research progress on bone repair biomaterials with the function of recruiting endogenous mesenchymal stem cells

To review the research progress on bone repair biomaterials with the function of recruiting endogenous mesenchymal stem cells (MSCs). An extensive review of the relevant literature on bone repair biomaterials, particularly those designed to recruit endogenous MSCs, was conducted, encompassing both domestic and international studies from recent years. The construction methods and optimization strategies for these biomaterials were summarized. Additionally, future research directions and focal points concerning this material were proposed. With the advancement of tissue engineering technology, bone repair biomaterials have increasingly emerged as an ideal solution for addressing bone defects. MSCs serve as the most critical "seed cells" in bone tissue engineering. Historically, both MSCs and their derived exosomes have been utilized in bone repair biomaterials; however, challenges such as limited sources of MSCs and exosomes, low survival rates, and various other issues have persisted. To address these challenges, researchers are combining growth factors, bioactive peptides, specific aptamers, and other substances with biomaterials to develop constructs that facilitate stem cell recruitment. By optimizing mechanical properties, promoting vascular regeneration, and regulating the microenvironment, it is possible to create effective bone repair biomaterials that enhance stem cell recruitment. In comparison to cytokines, phages, and metal ions, bioactive peptides and aptamers obtained through screening exhibit more specific and targeted recruitment functions. Future development directions for bone repair biomaterials will involve the modification of peptides and aptamers with targeted recruitment capabilities in biological materials, as well as the optimization of the mechanical properties of these materials to enhance vascular regeneration and adjust the microenvironment.

The development of bioactive peptides from dietary proteins as a dipeptidyl peptidase IV inhibitor for the management of type 2 diabetes

The development of bioactive peptides from dietary proteins as a dipeptidyl peptidase IV inhibitor for the management of type 2 diabetes

Comparative analysis of milk casein hydrolysates from cow, water buffalo, goat and sheep: effects of flavourzyme and neutrase on formation of bioactive peptides

Comparative analysis of milk casein hydrolysates from cow, water buffalo, goat and sheep: effects of flavourzyme and neutrase on formation of bioactive peptides

Principles and Biomedical Applications of Self-Assembled Peptides: Potential Treatment of Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is the most prevalent metabolic disorder worldwide. There have been tremendous efforts to find a safe and prolonged effective therapy for its treatment. Peptide hormones, from certain organisms in the human body, as the pharmaceutical agents, have shown outstanding profiles of efficacy and safety in plasma glucose regulation. Their therapeutic promises have undergone intensive investigations via examining their physicochemical and pharmacokinetic properties. Their major drawback is their short half-life in vivo. To address this challenge, researchers have recently started to apply the state-of-the-art molecular self-assembly on peptide hormones to form nanofibrillar structures, as a smart nanotherapeutic drug delivery technique, to tremendously enhance their prolonged bioactivity in vivo. This revolutionary therapeutic approach would significantly improve patient compliance. First, this review provides a comprehensive summary on the pathophysiology of T2DM, various efforts to treat this chronic disorder, and the limitations and drawbacks of these treatment approaches. Next, this review lays out detailed insights on various aspects of peptide self-assembly: adverse effects, potential applications in nanobiotechnology, thermodynamics and kinetics of the process, as well as the molecular structures of the self-assembled configurations. Furthermore, this review elucidates the recent efforts on applying reversible human-derived peptide self-assembly to generate highly organized smart nanostructured drug formulations known as nanofibrils to regulate and prolong the bioactivity of the human gut hormone peptides in vivo to treat T2DM. Finally, this review highlights the future research directions to advance the knowledge on the state-of-the-art peptide self-assembly process to apply the revolutionary smart nanotherapeutics for treatment of chronic disorders such as T2DM with highly improved patient compliance.

Exploring time-killing and biofilm inhibition potential of bioactive proteins extracted from two varieties of Pleurotus ostreatus

IntroductionDental caries, caused by oral microbial pathogens, are a global health concern, further exacerbated by the presence of methicillin-resistant Staphylococcus aureus (MRSA). Bioactive proteins and peptides (BAPs) exhibit potent antimicrobial properties, targeting multiple cellular mechanisms within pathogens, reducing the likelihood of resistance development. Given the antimicrobial potential of BAPs, this study aimed to compare the efficacy of BAPs extracted from cultivated (Pleurotus ostreatus, PoC) and wild (Pleurotus ostreatus, PoW) mushrooms against pathogens responsible for dental caries.MethodsBAPs were extracted from both PoC and PoW using a TCA-acetone method. Antimicrobial activities were tested against seven bacteria and one fungus using agar well diffusion and MIC determination. Antibiofilm activity was assessed via modified CV assay, while DPPH and erythrocyte lysis tests evaluated free radical scavenging.ResultsPoC showed superior antimicrobial efficacy, with lower MIC and MBC values, and disrupted biofilm integrity at increasing concentrations. PoW exhibited better antioxidant activity with higher DPPH scavenging, though its antimicrobial efficacy was slightly lower than PoC.DiscussionBoth PoC and PoW BAPs inhibited dental pathogens, with PoC showing stronger inhibition against MRSA and nystatin-resistant Candida albicans. This suggests BAPs may target additional cellular mechanisms beyond membranes, PBPs, and ergosterols. Despite PoW’s stronger antioxidant properties, both BAPs had comparable antibiofilm activity. These findings suggest complementary actions of BAPs from PoC and PoW both, in treating dental caries, offering broad-spectrum antimicrobial and antioxidant benefits.

DeepBP: Ensemble deep learning strategy for bioactive peptide prediction.

Bioactive peptides are important bioactive molecules composed of short-chain amino acids that play various crucial roles in the body, such as regulating physiological processes and promoting immune responses and antibacterial effects. Due to their significance, bioactive peptides have broad application potential in drug development, food science, and biotechnology. Among them, understanding their biological mechanisms will contribute to new ideas for drug discovery and disease treatment. This study employs generative adversarial capsule networks (CapsuleGAN), gated recurrent units (GRU), and convolutional neural networks (CNN) as base classifiers to achieve ensemble learning through voting methods, which not only obtains high-precision prediction results on the angiotensin-converting enzyme (ACE) inhibitory peptides dataset and the anticancer peptides (ACP) dataset but also demonstrates effective model performance. For this method, we first utilized the protein language model-evolutionary scale modeling (ESM-2)-to extract relevant features for the ACE inhibitory peptides and ACP datasets. Following feature extraction, we trained three deep learning models-CapsuleGAN, GRU, and CNN-while continuously adjusting the model parameters throughout the training process. Finally, during the voting stage, different weights were assigned to the models based on their prediction accuracy, allowing full utilization of the model's performance. Experimental results show that on the ACE inhibitory peptide dataset, the balanced accuracy is 0.926, the Matthews correlation coefficient (MCC) is 0.831, and the area under the curve is 0.966; on the ACP dataset, the accuracy (ACC) is 0.779, and the MCC is 0.558. The experimental results on both datasets are superior to existing methods, demonstrating the effectiveness of the experimental approach. In this study, CapsuleGAN, GRU, and CNN were successfully employed as base classifiers to implement ensemble learning, which not only achieved good results in the prediction of two datasets but also surpassed existing methods. The ability to predict peptides with strong ACE inhibitory activity and ACPs more accurately and quickly is significant, and this work provides valuable insights for predicting other functional peptides. The source code and dataset for this experiment are publicly available at https://github.com/Zhou-Jianren/bioactive-peptides .

Modification Effects of Microorganisms and Enzymes on Egg Components: A Review.

In eggs, there are several components: eggshell (ES), eggshell membrane (ESM), egg white (EW), and egg yolk (EY). Many modification methods exist, such as thermal treatment, high pressure, freeze-thaw cycles, ultrasonic treatment, ozonation, phosphorylation, and acylation, all aimed at improving the functional properties of EW and EY. Additionally, microorganism and enzyme modifications have proven effective in enhancing the functional properties of EW and EY. ES and ESM are unique components of eggs. The eggshell is rich in calcium carbonate, while the eggshell membrane is rich in protein. The effective utilization of ES and ESM can help promote economic income in the poultry industry and benefit the environment. Research on the modification of ES and ESM has shown that microorganisms and enzymes have the potential to improve their functional properties. After modification, egg components can be utilized in the production of egg-based and other food products for improved performance. Furthermore, enzyme modification of egg components can produce bioactive peptides, which have the potential to treat specific diseases and may even be used in the biomedical field. This review primarily focuses on the effects of microorganisms and enzymes on the modification of egg components and summarizes the roles of microbial and enzymatic modifications in this context.

Enhancing salt tolerance in soybeans through co-overexpression of bioactive peptides “Lunasin and Bowman-Birk Protease Inhibitor” and evaluating their antioxidant activity in vitro

Enhancing salt tolerance in soybeans through co-overexpression of bioactive peptides “Lunasin and Bowman-Birk Protease Inhibitor” and evaluating their antioxidant activity in vitro

Peptidomic Analysis of Potential Bioactive Peptides in Mare Milk Under Different Heat Treatment Conditions

Active peptides in mare milk have unique biological activities, but how the bioactive protein in mare’s milk changes under the influence of temperature has not been fully studied. Therefore, in this study, the differential expression of bioactive peptides potentially present in horse milk under different heat treatment conditions was investigated for the first time using peptidomic and bioinformatic techniques. We collected a total of 15 samples. In this study, we divided the samples into five groups, specifically, 65 °C, 30 min; 72 °C, 15 min; 83 °C; 10 min; 95 °C, 5 min; and an untreated group as a control, which involved four different temperature treatments, in order to understand changes in bioactive peptides and to identify the sequence of bioactive peptides. In the experiment, a total of 2341 active peptides were identified. The amino acid composition of the potential active peptides remained stable across different temperatures, but their abundance varied with temperature. In all, 23 peptides from 20 different proteins were identified, with the highest number of active peptides identified at 72 °C. Through database searches, we found that a majority of these peptides were within β-lactoglobulin and immunoglobulin domain proteins, which are known for their potential biological activities. These findings provide a theoretical foundation for the development of peptides with different bioactivities as potential functional foods.

Bioactive Peptide Hydrogel Scaffold with High Fluidity, Thermosensitivity, and Neurotropism in 3D Spatial Structure for Promoted Repair of Spinal Cord Injury.

Spinal cord injury (SCI) has been considered a clinically challenging disease that is characterized by local disturbance of the microenvironment, which inhibits post-injury neural regeneration. The simulation of a microenvironment conducive to the regeneration of spinal cord is beneficial for SCI repair. In this study, bioactive composite hydrogels are developed that mimic the regenerative microenvironment of spinal cord for enhanced SCI repair. The fabricated composite hydrogels (CRP) based on chitosan (CS), RADA16 nanofibers, and nerve-promoted peptide (PPFLMLLKGSTR) exhibit excellent injectability, superior biodegradability and biocompatibility. In addition, the CRP hydrogels can formquickly (a few minutes) by mixing three components at human body temperature, showing high potential as a biomimetic matrix for in situ repair of SCI. The in vitro studies demonstrate that the CRP hydrogels can not only promote the proliferation and migration of bone marrow mesenchymal stem cells but also induce the proliferation and differentiation of neural stem cells (NSCs) into neurons. Meanwhile, the hydrogels reveal the efficiency of protecting neurons and promoting axonal growth. Furthermore, the in vivo tests prove that the CRP hydrogels can reduce post-SCI inflammatory responses, inhibit reactive astrocyte over-proliferation, and promote the migration, proliferation, and differentiation of endogenous NSCs, which agree well with the in vitro results. The pre-clinical test demonstrates that the CRP hydrogels restore the motor function in completely transected spinal cord rats, and the SCI repair mechanism may involve the activation of the PI3K/AKT/mTOR pathway. It is believed that the strategies shown in this work will be valuable for the design and synthesis of novel hydrogels for biomedical and tissue engineering applications.

Cytotoxic Effects of Plant Secondary Metabolites and Naturally Occurring Bioactive Peptides on Breast Cancer Model Systems: Molecular Mechanisms

Breast cancer is the second leading cause of death among women, and the number of mortal cases in diagnosed patients is constantly increasing. The search for new plant compounds with antitumor effects is very important because of the side effects of conventional therapy and the development of drug resistance in cancer cells. The use of plant substances in medicine has been well known for centuries, but the exact mechanism of their action is far from being elucidated. The molecular mechanisms of cytotoxicity exerted by secondary metabolites and bioactive peptides of plant origin on breast cancer cell lines are the subject of this review.

Valorization of Fish Processing by-Products: Biological and Functional Properties of Bioactive Peptides

Abstract Purpose of Review This review explores the potential of fish by-products as a source of bioactive peptides for the food, pharmaceutical, and cosmetic industries. Focusing on their diverse bioactive and functional properties, it offers insights into their industrial utilization, contributing to a better understanding of their applications. Recent Findings Fish processing by-products, including wastewater and solid residues, serve as valuable sources of bioactive peptides exhibiting a remarkable range of biological activities, such as antioxidant, antimicrobial, and antihypertensive properties. These peptides exhibit a wide range of functional properties, such as solubility, water holding, fat binding, foaming, and emulsifying capacities. Moreover, they show significant potential for various industrial applications. Summary Bioactive peptides derived from fish by-products are attracting interest in multiple industries due to their diverse biological activities and functional properties. These peptides have emerged as a valuable and largely untapped resource, as they can be extracted from underutilized, or waste materials generated during fish processing operations. Graphical Abstract

Exploring the Functional Potential of Breast Milk Protein Hydrolysates: Antiglycation, Antioxidant, Metal Chelation, and Lipid Peroxidation Activities

The formation of advanced glycation end products (AGEs) is a pivotal factor in the development of various age-related and diabetes associated pathophysiologies, including but not limeted to arthritis, Alzheimer’s disease, atherosclerosis and cataracts. Consequently, the prospect of inhibiting AGE formation emerges as a viable strategy to prevent or halt the advancement of diabetic complications. In the scientific literature, there is still a reluctance to produce bioactive peptides demonstrating antiglycation activity from breast milk. The breast milk protein was hydrolysed using trypsin for 240 min. The antiglycation, metal chelating activity, lipid peroxidation activity, and antioxidant activity of the peptides in the hydrolysates obtained after hydrolysis of human milk with trypsin enzyme were performed. The peptide diversity obtained after hydrolysis was determined by RP-HPLC. The breast milk hydrolysate was demonstrated significant antiglycation activity (IC50: 312.8 ± 12.1 µg/mL), antioxidant activity (61.8±4.58 mM AAE/µg peptide) , metal chelation activity (24.4%/μg peptide). The hydrolysate effectively inhibited lipid peroxidation (30.5±0.12%) compared to Trolox (51.2±0.3%). These findings highlight the potential of breast milk protein hydrolysates as a source of bioactive peptides with diverse health benefits. The present study offers valuable insights into utilizing human milk peptides as novel functional food components.

High Stability and Reusability of Papain Immobilized on the Non‐Toxic Magnetic Dialdehyde Starch Nanoparticles

AbstractPapain is widely used in food, drug, and bioactive peptide production and must be immobilized onto carriers with biocompatibility. Dialdehyde starch (DAS) can be a good biocompatible cross‐linker according to its active aldehyde groups. In the present study, the magnetic nanoparticles dialdehyde starch (MDASN), synthesized by DAS and Fe3O4 magnetic nanoparticles (Fe‐MNP), are successfully used to immobilize papain to improve the enzymic activity. The structure and morphology of DAS, MDASN, and immobilized papain onto magnetic dialdehyde starch nanoparticles (papain‐MDASN) are characterized detailly. The morphology of DAS is like a flat ball, and that of Fe‐MNP and papain‐MDASN are spherical and clumpy. The particle size of Fe‐MNP and papain‐MDASN are small, resulting in a large surface electrostatic effect and partial agglomeration. Enzymic activity studies of papain‐MDASN exhibit that the immobilized papain on MDASN represents better temperature resistance, alkaline resistance, thermal stability, and reusability, and its activity recovery is up to 68.21%. Papain onto magnetic dialdehyde starch nanoparticles (MDASN) may enhance its potential application in production processes.

Enhanced Oligopeptide and Free Tryptophan Release from Chickpea and Lentil Proteins: A Comparative Study of Enzymatic Modification with Bromelain, Ficin, and Papain.

Plant-based foods offer a sustainable alternative to meet the growing protein demand. Legumes are the most promising of these, as they contain relatively high concentrations of protein, low digestible starch, and dietary fiber, as well as them possibly featuring low levels of fat. Enzymatically modified legume proteins provide us with tempting perspectives in terms of enhancing foods' biological values. However, their bioavailability and digestibility are generally less sufficient than that of proteins of animal origin, which may be improved by well-tailored enzyme modification. In this study, the efficacy of three plant-based proteases (bromelain, ficin, and papain) were evaluated at two distinct concentrations (2.5% and 10%) and three hydrolysis durations (1, 2, and 12 h) when transforming chickpea and lentil proteins. The degree of hydrolysis (DH), peptide profiles, and free amino acid content were analyzed to determine the efficiency of each enzyme. Results showed significant variations in DH, which was influenced by enzyme type, concentration, and hydrolysis duration. Papain exhibited the highest DH, particularly at a 10% concentration, reaching 27.8% efficiency in chickpea and 34.8% in lentils after 12 h. Bromelain and ficin were proven to be less effective, with ficin showing the least hydrolytic activity. SDS-PAGE analysis revealed substantial protein degradation, especially subsequent to papain treatment, pointing out that most proteins were cleaved into smaller peptides. SEC-HPLC indicated a predominant release of peptides within the 200-1000 Da range, suggesting enhanced bioavailability. Papain and bromelain treatments resulted in a significant release of oligopeptides and dipeptides. UHPLC analysis highlighted a marked post-hydrolysis increase in total free amino acids, with arginine, leucine, and lysine being the most abundant ones. Notably, tryptophan, being undetectable in untreated samples, was released in measurable amounts post-hydrolysis. These findings demonstrate papain's superior performance in protein hydrolysis and its potential in producing bioactive peptides, highlighting its applicability in food processing and the development of both nutraceuticals and functional foods.

Functional Food Candidate from Indonesian Green Algae Caulerpa racemosa (Försskal) J. Agardh by Two Extraction Methods: Metabolite Profile, Antioxidant Activity, and Cytotoxic Properties

There is an urgent need to explore natural sources like Caulerpa racemosa (Försskal) J. Agardh for bioactive compounds with strong antioxidant and therapeutic potential, providing sustainable alternatives for health and pharmaceutical innovation. This study aimed to determine the phytochemical profile and biological activities of extracts from edible green algae–known as sea grapes (C. racemosa). This present study has successfully identified secondary metabolites through untargeted metabolomic profiling by liquid chromatography-high resolution mass spectrometry (LC-HRMS) as well as a bioactive peptide. The antioxidant activity and cytotoxicity of extracts from C. racemosa and compounds were determined. A total of 103 metabolites were identified in the C. racemosa extract obtained by the maceration (ME), while 48 metabolites were detected in the soxhlet extract (SE). The sequence of the identified peptide was ELWKTF (Glu-Leu-Trp-Lys-Thr-Phe; C41H58N8O) and its abundance was identified in the α-chymotrypsin hydrolysate of C. racemosa. In the antioxidant activity test, SE and purified fraction 1 (PF1) had EC50<EC50 of control or Glutathione (GSH) in terms of 2,2-Diphenyl-1-picrylhydrazyl (DPPH) inhibition, and PF1 had EC50<EC50 of control or Trolox in terms of 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) inhibition. In general, C. racemosa contains antioxidant nutrients, metabolites, and bioactive peptides, suggesting its promising potential as a functional food and pharmaceutical.

Engineering PSMA-targeted nanoparticles co-encapsulating mitoxantrone and indocyanine green for precise combinatory therapy in prostate cancer

Prostate cancer is the 2nd most common cancer in men worldwide. Chemotherapeutic treatment of prostate cancer with mitoxantrone (MTX) has limited efficacy due to severe side effects in which cardiotoxicity and myelosuppression are the two major causes of its dose-limiting toxicity. This study aimed to obtain a poly (lactic-co-glycolic acid) (PLGA) nanoparticle that can precisely deliver MTX to the prostate cancer cells overexpressing the Prostate-specific membrane antigen (PSMA) receptor-sparing healthy tissues and co-loading Indocyanine green (ICG) as a fluorescent photothermal/photodynamic agent for precise combinatory therapy in prostate cancer. The biocompatible polymer PLGA was covalently modified with the peptide of sequence (WQPDTAHHWATL) to actively target the PSMA receptor. Factors like the peptide-to-polymer ratio or the peptide's orientation during the polymer's chemical modification were investigated to enhance the active targeting of the nanoparticles (NPs). NPs were characterised using dynamic light scattering, scanning electron microscopy, and UV–vis spectroscopy to determine their morphological and colloidal properties and optimal MTX and ICG encapsulation efficiency. Quantitative FACS analysis of LNCaP and PC-3 cells incubated with Nile Red-labelled non-targeted PLGA or PLGA-PSMA targeted NPs was assessed to identify the best formulation that bound selectively to PSMA. The orientation of the peptide conjugated to the polymer, which has the C-terminal end of the peptide sequence accessible for interaction with the cell receptor, maximises the targeting capacity of the system. Photothermal experiments using 808 nm near-infrared laser irradiation were conducted, and cytotoxicity was assessed using the resazurin viability assay. Remarkably, our results confirmed the safety and efficacy of a targeted and activatable therapy using polymeric NPs functionalised with the peptide and co-loaded with MTX and ICG. This pioneer nanosystem opens new perspectives for exploring advanced targeted delivery in prostate cancer. It offers a straightforward methodology for functionalising drug delivery systems with bioactive peptides that can be applied to different types of cancer.

Ultrasonication coupled to enzymatic hydrolysis of soybean okara proteins for producing bioactive and bioavailable peptides

This work was aimed to explore the antioxidative properties, bioavailability and the safety of bioactive peptides obtained by the enzymatic hydrolysis of ultrasound-treated (UO) and untreated (nUO) soybean okara proteins. Particularly, the peptidomic profiles of both hydrolysates were examined using an untargeted metabolomics technique for suspect screening that was specifically designed for the profiling of short-chain peptides and relied on ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) and bioinformatics.Next, both UO and nUO hydrolysates reduce Dipeptidyl peptidase-IV (DPP-IV) enzyme activity until 39.54 ± 0.26 % and 43.29 ± 0.36 % respectively and inhibit angiotensin converting enzyme (ACE) activities by 30.54 ± 0.42 % and 30.76 ± 0.02 %, respectively. Moreover, they demonstrate to exerted antioxidant properties. Particularly, they show a comparable in vitro antioxidant activity but when the oxidative stress is induced by H2O2 in Caco-2 cells, UO hydrolysate is more active in lowering the levels of reactive oxygen species (ROS) and of lipid peroxidation induced of 48% and 20% respectively.In addition, UO- and nUO-derived peptides trans-epithelial transported by human differentiated intestinal cell monolayer, were identified. Lastly, the possible hepatotoxicity of UO and nUO hydrolysates in HepG2 cells has not been observed by measuring alanine transferase (ALT) and aspartate transferase (AST) levels and cytotoxic effects.

Bioactivities, preparation, and bioavailability of food-derived proline-containing peptides

Bioactivities, preparation, and bioavailability of food-derived proline-containing peptides

Surface-induced self-assembly of peptides turns superhydrophobic surface of electrospun fibrous into superhydrophilic one

Current surface modification strategies for electrospun materials always require covalent conjugation technology, which is relatively inefficient and might damage the bioactivity and structure of peptides and proteins. Here we introduce the use of surface-induced self-assembly technology to modify electrospun materials, which is a simple but efficient noncovalent-based process. Results show that the peptide NapFFGRGD forms burr-like structures on the surface of PCL fibers, reducing the water contact angle of the fibers. Adjusting the peptide sequence and salt concentration affects the self-assembly and surface properties of modified PCL fibers. Additionally, we demonstrate the potential application of this surface modification technique for enhancing cellular responses in tissue engineering applications. The research provides valuable insights into the surface modification of PCL fibers and offers a new method for improving the biological compatibility of materials in tissue engineering.