Marine-derived Bioactive Peptides Research Articles

Marine-Derived Bioactive Proteins and Peptides: A Review of Current Knowledge on Anticancer Potentials, Clinical Trials, and Future Prospects

The rise in cancer cases has prompted searching for novel and alternative sources of natural bioactive compounds with antitumor potential. Nearly three-quarters of our planet is covered by the ocean, the habitat of numerous prokaryotic and eukaryotic organisms and sustainable alternative nutrient sources. The marine ecosystem is a rich reservoir of proteins and novel bioactive peptides with diverse biochemical and therapeutic potentials, including antioxidant, anti-inflammatory, and antiproliferative activities. Marine peptides are valuable due to their high stability, bioactivity, and low immunogenicity. This review focused on tracking the recent progress in studying marine-derived peptides for potential cancer treatment. We have highlighted that some of these peptides have progressed to clinical trials in the last 2 decades, while many candidates were discontinued due to failure to exhibit therapeutic-relevant activities. Due to the results from old clinical trials, interest in marine sources for antitumor peptides has dwindled in recent years. We presented other possible limitations in this field and proposed attractive future research prospects. In conclusion, we emphasize the need for increased scientific attention to explore marine organisms’ untapped nutraceutical and bioactive natural products, particularly in uncovering their potential anticancer properties.

Blue mussel (Mytilus edulis) hydrolysates attenuate oxidized-low density lipoproteins (ox-LDL)-induced foam cell formation, inflammation, and oxidative stress in RAW264.7 macrophages

Seafood consumption has a great demand in the world due to its array of health benefits. Marine-derived bioactive peptides and hydrolysates have been found to have multifunctional health benefits. In this study, inhibitory effects of blue mussel hydrolysates, including blue mussel Alcalase® hydrolysate (BMAH) and blue mussel-pepsin hydrolysate (BMPH), on foam cell formation in ox-LDL-induced RAW264.7 macrophages were investigated. BMAH inhibited lipid accumulation evidenced by Oil Red O staining. Its inhibitory effect was higher than that of BMPH. BMAH positively modulated levels of total cholesterol, free cholesterol, and cholesterol ester in model cells. It suppressed cholesterol influx by downregulating SR-A1 and CD36 expression, but increased cholesterol efflux by upregulating ABCA-1 and ABCG-1 expression. In addition, ox-LDL treated RAW264.7 macrophages produced inflammatory responses and oxidative stress during foam cell formation. However, BMAH treatment significantly ameliorated proinflammatory cytokines production (TNF-α, IL-6, and IL-1β) by inhibiting NF-κB nuclear translocation. Moreover, BMAH inhibited intracellular reactive oxygen species (ROS) generation by activating HO-1/Nrf2 signaling pathway in ox-LDL-treated RAW264.7 macrophages. Taken together, these results suggest that BMAH might be useful as an ingredient of functional foods to ameliorate the development of atherosclerosis.

Marine-Derived Bioactive Peptides Self-Assembled Multifunctional Materials: Antioxidant and Wound Healing.

Peptide self-assembling materials have received significant attention from researchers in recent years, emerging as a popular field in biological, environmental, medical, and other new materials studies. In this study, we utilized controllable enzymatic hydrolysis technology (animal proteases) to obtain supramolecular peptide self-assembling materials (CAPs) from the Pacific oyster (Crassostrea gigas). We conducted physicochemical analyses to explore the pro-healing mechanisms of CAPs on skin wounds in both in vitro and in vivo experiments through a topical application. The results demonstrated that CAPs exhibit a pH-responsive behavior for self-assembly and consist of peptides ranging from 550 to 2300 Da in molecular weight, with peptide chain lengths of mainly 11-16 amino acids. In vitro experiments indicated that CAPs display a procoagulant effect, free radical scavenging activity, and promote the proliferation of HaCaTs (112.74% and 127.61%). Moreover, our in vivo experiments demonstrated that CAPs possess the ability to mitigate inflammation, boost fibroblast proliferation, and promote revascularization, which accelerates the epithelialization process. Consequently, a balanced collagen I/III ratio in the repaired tissue and the promotion of hair follicle regeneration were observed. With these remarkable findings, CAPs can be regarded as a natural and secure treatment option with high efficacy for skin wound healing. The potential of CAPs to be further developed for traceless skin wound healing is an exciting area for future research and development.

Immune enhancement and antioxidant effects of low molecular-weight peptides derived from Nibea japonica muscles on immune-deficient mice induced by cyclophosphamide

Marine-derived bioactive peptides are widely studied and used as functional foods. The aim of this study was to investigate the effects of low molecular-weight (Mw) peptides (150 Da < Mw < 1 kDa) from Nibea japonica muscles, referred to as Nibea japonica peptides (NJP), on the immune function of mice immunosuppressed with cyclophosphamide (CTX). The results showed that NJP significantly increased the splenic and thymic indices and alleviated the morpho-pathological characteristics of immune organs exposed to CTX. NJP enhanced phagocytosis by peritoneal macrophages and significantly increased proliferation of T lymphocytes activated with concanavalin A (Con A). NJP not only significantly promoted cytokine secretion, including interleukin-2 (IL-2), interferon-γ (IFN-γ) and tumor necrosis factor α (TNF-α), but also increased the levels of immunoglobulin (Ig) A, IgG and IgM in a dose-dependent manner, indicating that NJP can enhance both cellular and humoral immunity. Furthermore, we found that NJP could attenuate CTX-induced oxidative stress in multiple organs, suggesting that NJP may play a role in immune regulation by strengthening the body's antioxidant capacity. Therefore, NJP could be used as a natural immunomodulator in the functional food industry.

Blue Mussel-Derived Peptides PIISVYWK and FSVVPSPK Trigger Wnt/β-Catenin Signaling-Mediated Osteogenesis in Human Bone Marrow Mesenchymal Stem Cells.

Marine-derived bioactive peptides have shown potential bone health promoting effects. Although various marine-derived bioactive peptides have potential nutraceutical or pharmaceutical properties, only a few of them are commercially available. This study presented an osteogenic mechanism of blue mussel-derived peptides PIISVYWK and FSVVPSPK as potential bone health promoting agents in human bone marrow-derived mesenchymal stem cells (hBMMSCs). Alkaline phosphatase (ALP) activity and mineralization were stimulated using PIISVYWK and FSVVPSPK as early and late markers of osteogenesis in a concentration-dependent manner. Western blot and RT-qPCR results revealed that PIISVYWK and FSVVPSPK increased osteoblast differentiation of hBMMSCs by activating canonical Wnt/β-catenin signaling-related proteins and mRNAs. Immunofluorescence images confirmed nuclear translocation of β-catenin in osteogenic differentiation. Treatment with the pharmacological inhibitor DKK-1 blocked PIISVYWK- and FSVVPSPK-induced ALP activity and mineralization, as well as mRNA expression of the canonical Wnt/β-catenin signaling pathway in hBMMSC differentiation into osteoblasts. These findings suggested that PIISVYWK and FSVVPSPK promoted the canonical Wnt/β-catenin signaling pathway in osteogenesis of hBMMSCs. Blue mussel-derived PIISVYWK and FSVVPSPK might help develop peptide-based therapeutic agents for bone-related diseases.

Fish Roe Polypeptide Exerts Hypoglycemia Activity via Regulating Insulin Secretion Mediated by Nrf2/ERK Signaling

In recent years, marine-derived bioactive peptides have gained considerable attention owing to their high biomedical and pharmaceutical potential. In this study, we investigated the hypoglycemic activity of fish roe polypeptide (FRP) in islet β-cells (INS-1) and the molecular mechanism whereby FRP exerts this effect. Insulin secretion, cell viability, cell apoptosis, intracellular reactive oxygen species (ROS), and intracellular antioxidant-related enzymes were detected. The nuclear factor erythroid 2-related factor 2 (Nrf2)/extracellular signal-regulated kinase (ERK) pathway was analyzed to reveal the mechanism underpinning FRP’s hypoglycemic effect. The results showed that FRP treatment promoted insulin secretion and cell viability, reduced apoptosis and intracellular ROS levels, and increased the activity and content of antioxidant-related enzymes. Cell signaling pathway analysis revealed that FRP was able to alleviate H2O2-induced oxidative stress by activating the Nrf2/ERK pathway. This was demonstrated by an evident decrease in cell viability and insulin secretion in the presence of the ERK blocker U0126. Altogether, these results suggest that FRP exerts its hypoglycemic effect by regulating insulin secretion, which is mediated by Nrf2/ERK signaling.

Marine Bioactive Peptides-An Overview of Generation, Structure and Application with a Focus on Food Sources.

The biggest obstacles in the application of marine peptides are two-fold, as in the case of non-marine plant and animal-derived bioactive peptides: elucidating correlation between the peptide structure and its effect and demonstrating its stability in vivo. The structures of marine bioactive peptides are highly variable and complex and dependent on the sources from which they are isolated. They can be cyclical, in the form of depsipeptides, and often contain secondary structures. Because of steric factors, marine-derived peptides can be resistant to proteolysis by gastrointestinal proteases, which presents an advantage over other peptide sources. Because of heterogeneity, amino acid sequences as well as preferred mechanisms of peptides showing specific bioactivities differ compared to their animal-derived counterparts. This review offers insights on the extreme diversity of bioactivities, effects, and structural features, analyzing 253 peptides, mainly from marine food sources. Similar to peptides in food of non-marine animal origin, a significant percentage (52.7%) of the examined sequences contain one or more proline residues, implying that proline might play a significant role in the stability of bioactive peptides. Additional problems with analyzing marine-derived bioactive peptides include their accessibility, extraction, and purification; this review considers the challenges and proposes possible solutions.

Bioactive Peptide of Marine Origin for the Prevention and Treatment of Non-Communicable Diseases.

Non-communicable diseases (NCD) are the leading cause of death and disability worldwide. The four main leading causes of NCD are cardiovascular diseases, cancers, respiratory diseases and diabetes. Recognizing the devastating impact of NCD, novel prevention and treatment strategies are extensively sought. Marine organisms are considered as an important source of bioactive peptides that can exert biological functions to prevent and treatment of NCD. Recent pharmacological investigations reported cardio protective, anticancer, antioxidative, anti-diabetic, and anti-obesity effects of marine-derived bioactive peptides. Moreover, there is available evidence supporting the utilization of marine organisms and its bioactive peptides to alleviate NCD. Marine-derived bioactive peptides are alternative sources for synthetic ingredients that can contribute to a consumer’s well-being, as a part of nutraceuticals and functional foods. This contribution focus on the bioactive peptides derived from marine organisms and elaborates its possible prevention and therapeutic roles in NCD.

Marine-Derived Bioactive Peptides for Biomedical Sectors: A Review.

Marine-based resources such as algae and other marine by-products have been recognized as rich sources of structurally diverse bioactive peptides. Evidently, their structural characteristics including unique amino acid residues are responsible for their biological activity. Several of the above-mentioned marine-origin species show multi-functional bioactivities that are useful for a new discovery and/or reinvention of biologically active ingredients, nutraceuticals and/or pharmaceuticals. Therefore, in recent years, marine-derived bioactive peptides have gained a considerable attention with high-value biomedical and/or pharmaceutical potentials. Furthermore, a wider spectrum of bioactive peptides can be produced through proteolytic-assisted hydrolysis of various marine resources under controlled physicochemical (pH and temperature of the reaction media) environment. Owing to their numerous health-related beneficial effects and therapeutic potential in the treatment and/or prevention of many diseases, such marine-derived bioactive peptides exhibit a wider spectrum of biological activities such as anti-cancerous, anti-proliferative, anti-coagulant, antibacterial, antifungal, and anti-tumor activities among many others. Based on emerging evidence of marine-derived peptide mining, the above-mentioned marine resources contain noteworthy levels of high-value protein. The present review article mainly summarizes the marine-derived bioactive peptides and emphasizing their potential applications in biomedical and/or pharmaceutical sectors of the modern world. In conclusion, recent literature has provided evidence that marine-derived bioactive peptides play a critical role in human health along with many possibilities of designing new functional nutraceuticals and/or pharmaceuticals to clarify potent mechanisms of action for a wider spectrum of diseases.

Marine-Derived Bioactive Peptides with Pharmacological Activities- A Review

Marine-Derived Bioactive Peptides with Pharmacological Activities- A Review

Marine peptides and their anti-infective activities.

Marine bioresources are a valuable source of bioactive compounds with industrial and nutraceutical potential. Numerous clinical trials evaluating novel chemotherapeutic agents derived from marine sources have revealed novel mechanisms of action. Recently, marine-derived bioactive peptides have attracted attention owing to their numerous beneficial effects. Moreover, several studies have reported that marine peptides exhibit various anti-infective activities, such as antimicrobial, antifungal, antimalarial, antiprotozoal, anti-tuberculosis, and antiviral activities. In the last several decades, studies of marine plants, animals, and microbes have revealed tremendous number of structurally diverse and bioactive secondary metabolites. However, the treatments available for many infectious diseases caused by bacteria, fungi, and viruses are limited. Thus, the identification of novel antimicrobial peptides should be continued, and all possible strategies should be explored. In this review, we will present the structures and anti-infective activity of peptides isolated from marine sources (sponges, algae, bacteria, fungi and fish) from 2006 to the present.

Marine-derived bioactive materials for neuroprotection

The marine environment is a rich source of materials with significant biological activities. Isolation and investigation of bioactive materials from marine organisms is a topic of current research interest in the food industry. Among marine-derived bioactive materials, peptides, chitosan, sulfated polysaccharides, phlorotannins, and natural pigments are potential neuroprotective agents. This review elaborates on the neuroprotective mechanisms of marine-derived bioactive materials and emphasizes prospects for use in neuroprotection as part of nutraceuticals and functional foods.

Marine-Derived Bioactive Peptides as New Anticoagulant Agents: A Review

The development of more effective antithrombotic agents with reduced side risk is necessary for the prevention of thromboembolic events. In recent years, bioactive peptides derived from food proteins have received considerable attention because of their numerous healths beneficial. Based on their amino acids sequences these peptides can exhibit various biological activities including, antihypertensive, antioxidative and antibacterial activities. Moreover, several naturally or food proteins-derived bioactive peptides that could prolong the activated partial thromboplastin time (APTT) and thrombin time (TT) have been isolated. Due to their therapeutic potential in the treatment or prevention of various diseases, bioactive peptides can be used as functional food ingredients, nutraceuticals or pharmaceuticals. Marine organisms represent a valuable source of new bioactive substances including bioactive peptides. This paper presents an overview of the bioactive anticoagulant peptides derived from fish protein sources, as well as the enzymatic proteolysis approach used for the development of these new biopeptides.

Marine Peptides for Preventing Metabolic Syndrome

Recently, there has been a growing in alternative prevents and therapies of marine organisms for metabolic syndrome. Marine-derived bioactive peptides attracted extensive interest due to their numerous health beneficial effects including antioxidant, antihypertensive, anti-diabetes, anti-obesity. The bioactive peptides may provide novel therapeutic applications for the prevention of metabolic syndrome. The facts summarized here may provide improvement of metabolic syndrome by peptides from marine organisms. However, further insightful researches on the prevention of metabolic syndrome by marine peptides in in vivo and clinical studies are needed to firmly establish their therapeutic potency.