The interest in algae-derived bioactive compounds has grown due to their potential therapeutic efficacy against a range of diseases. These compounds, derived from proteins, exhibit diverse functions and profound pharmacological effects. Recent research has highlighted the extensive health benefits of algae-derived bioactive compounds, positioning them as potential natural antioxidants in the food, pharmaceutical, and cosmetic industries. This study focuses on extracting proteins from Porphyra yezoensis using innovative physical pre-treatment methods such as stirring, ball milling, and homogenization, under various acidic and alkaline conditions. Enzymatic hydrolysis, employing commercial enzymes at optimal temperature, pH, and enzyme-substrate ratios, produced distinct fractions according to molecular weight. Pepsin demonstrated the highest hydrolysis rate, with the fraction above 10 kDa identified as the most bioactive hydrolysate. Antioxidant activity was evaluated through DPPH, ABTS, ferrous ion chelation, and reducing power assays, demonstrating high antioxidant potential and the ability to mitigate oxidative stress. The 10 kDa fraction of pepsin hydrolysate exhibited 82.6% DPPH activity, 77.5% ABTS activity, 88.4% ferrous ion chelation activity, and higher reducing power potential (0.84 absorbance at 700 nm). Further exploration of mechanisms, amino acid profiles, and potential in vivo benefits is essential to fully exploit the medicinal potential of these algae-derived hydrolysates.

Bioactive peptides from brewer\'s spent grain (BSG) and brewer\'s spent yeast (BSY), two by-products of the brewing industry, have great potential as functional food ingredients, dietary supplements or nutraceuticals to reduce the risk of numerous pathological conditions. Nevertheless, the oral administration of these peptides poses great challenges since peptides must undergo gastrointestinal digestion, intestinal absorption and hepatic metabolism, which can affect their bioavailability and, therefore, the expected outcomes. This review provides a comprehensive and critical analysis of the potential impact of the oral route on the bioactivity of BSG/BSY peptides as assessed by in vitro assays and identifies research gaps that require novel approaches/methodologies. The data collected indicate that in addition to the significant influence of gastrointestinal digestion, intestinal absorption and hepatic metabolism also have a major impact on the bioactivity of brewing peptides. The major gap identified was the insufficient evidence regarding hepatic metabolism, which points for the need of employing in vitro assays in this research field to provide such clarification. Thus, to reach the market, the impact of the oral route on the bioactivities of BSG/BSY peptides must be properly studied in vitro to allow adequate/effective administration (dosage/frequency) with a beneficial impact on the population health.

Recently, kafirins from white sorghum [Sorghum bicolor (L) Moench] grain have shown promise as a source of biopeptides with anti-skin aging effects (anti-inflammatory, antioxidant, and inhibition of photoaging-associated enzymes). This study employed response surface methodology (RSM) to optimize the extraction and enzymatic hydrolysis of kafirins (KAF) for the production of peptides with anti-skin aging properties. The optimization of conditions (reaction time and enzyme/substrate ratio) for liquefaction with α-amylase and hydrolysis of KAF with alcalase was performed using 32 complete factorial designs. Subsequently, ultrafiltered peptide extracts were obtained with molecular weights of 1-3 kDa (KAF-UF3) and lower than 1 kDa (KAF-UF1), which mainly contain hydrophobic amino acids (proline, leucine, isoleucine, phenylalanine, and valine) and peptide fractions with molecular weights of 0.69, 1.14, and 1.87 kDa. Consequently, the peptide extracts protected immortalized human keratinocytes (HaCaT cells) from ultraviolet B radiation (UVB)-induced damage by preventing the decrease and/or restoring the activity of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px)]. Furthermore, KAF-UF3 and KAF-UF1 inhibited (20-29%) elastase and collagenase overactivity in UVB-exposed murine fibroblasts (3T3 cells). Thus, KAF-UF3 and KAF-UF1 exhibited behavior similar to that observed with glutathione (GSH), suggesting their potential as functional peptide ingredients in skincare products.

Serine peptidases and metallopeptidases are the primary toxins found in Bothrops snakes venoms, which act on proteins in the tissues of victims or prey, and release of peptides formed through proteolytic activity. Various studies have indicated that these peptides, released by the proteolytic activity of heterologous enzymes, generate molecules with unidentified functions, referred to as cryptids. To address this, we purified serine peptidases from Bothrops jararaca venom using molecular exclusion chromatography and then incubated them with the endogenous substrate myoglobin. As a control, we also incubated the substrate with trypsin. The resulting proteolytic fragments were analyzed, separated, and collected via HPLC. These fractions were then tested on cell cultures, the active fractions were sequenced (ALELFR and TGHPETLEK) and synthesized. After confirming their activity, the peptides underwent sequencing and synthesis for additional cell tests, including the increase of cell viability, cycle phases, proliferation, signaling, growth kinetics, angiogenesis, and migration. The results revealed that the synthesized peptides exhibited cellular repair properties, suggesting a potential role in tissue repair in the range of 0.05-5 μ M. Additionally, the effects of fragments resulting from myoglobin degradation isolated (ALELFR and TGHPETLEK) revealed a regenerative action on tissue.

Egg white hydrolysates (EWH) and ovotransferrin-derived peptides have distinct beneficial effects on glucose metabolism. This research aims to investigate whether ovalbumin hydrolysates (OVAHs), without ovotransferrin can improve insulin signaling pathway in high-fat diet (HFD)-fed mice. Two types of ovalbumin hydrolysates were produced, either using thermoase (OVAT), or thermoase + pepsin (OVATP). Both OVAHs-supplemented groups exhibited lower body weight gain (P < 0.001) and enhanced oral glucose tolerance (P < 0.05) compared with HFD. Moreover, diet supplementation with either hydrolysate increased the insulin-stimulated activation of protein kinase B (AKT) and insulin receptor β (IRβ) (P < 0.0001) in skeletal muscle. In conclusion, OVAHs improved glucose tolerance and insulin-dependent signaling pathway in HFD-fed mice.

Obesity is acknowledged as a significant risk factor for cardiovascular disease, often accompanied by increased inflammation and diabetes. Bioactive peptides derived from marine animal proteins show promise as safe and effective anti-obesity agents by regulating adipocyte differentiation through the AMPK signaling pathway. Therefore, this study aims to investigate the anti-obesity and anti-diabetic effects of bioactive compounds derived from a Meretrix lusoria Protamex enzymatic hydrolysate (MLP) fraction (≤1 kDa) through a 6-week treatment (150 mg/kg or 300 mg/kg, administered once daily) in leptin receptor-deficient db/db mice. The MLP treatment significantly decreased the body weight, serum total cholesterol, triglycerides, and LDL-cholesterol levels while also exhibiting a beneficial effect on hepatic and serum marker parameters in db/db mice. A histological analysis revealed a reduction in hepatic steatosis and epididymal fat following MLP treatment. Furthermore, poor glucose tolerance was improved, and hepatic antioxidant enzyme activities were elevated in MLP-treated mice compared to db/db control mice. Western blot analysis showed an increased expression of the AMPK protein after MLP treatment. In addition, the expression of lipogenic genes decreased in db/db mice. These findings indicate that bioactive peptides, which are known to regulate blood glucose levels, lipid metabolism, and adipogenesis, could be beneficial functional food additives and pharmaceuticals.

Legumes, including beans, peas, chickpeas, and lentils, are cultivated worldwide and serve as important components of a balanced and nutritious diet. Each legume variety contains unique levels of protein, starch, fiber, lipids, minerals, and vitamins, with potential applications in various industries. By-products such as hulls, rich in bioactive compounds, offer promise for value-added utilization and health-focused product development. Various extraction methods are employed to enhance protein extraction rates from legume by-products, finding applications in various foods such as meat analogs, breads, and desserts. Moreover, essential fatty acids, carotenoids, tocols, and polyphenols are abundant in several residual fractions from legumes. These bioactive classes are linked to reduced incidence of cardiovascular diseases, chronic inflammation, some cancers, obesity, and type 2 diabetes, among other relevant health conditions. The present contribution provides a comprehensive review of the nutritional and bioactive composition of major legumes and their by-products. Additionally, the bioaccessibility and bioavailability aspects of legume consumption, as well as in vitro and in vivo evidence of their health effects are addressed.

Bioactive peptides derived from both exogenous and endogenous origins have been studied extensively to use their beneficial effects in humans and animals. Bioactive peptides exhibit beneficial bodily functions and contribute to a healthy gastrointestinal system by influencing barrier functions, immune responses, and gut microbiota. Gut microbiota is a diverse microbial community that significantly influences the overall well-being and homeostasis of the body. Factors such as diet, age, lifestyle, medication, and environmental circumstances can affect the composition and diversity of the gut microbiota. The disturbances or imbalances in the gut microbiota have been associated with various health problems. The interplays between bioactive peptides and gut microbiota are not fully understood, but bioactive peptides hold promise as modulators of the gut microbiota to promote gut health. Almost all the bioactive research on human health, including the development of therapeutics and nutritional interventions, uses cell culture, even though their direct biofunctional activities can only occur when absorbed in the intestine and into the blood system. This review focuses on the current understanding of bioactive peptides in gut microbiota and their impact and mechanisms on gut and human health. The novelty of this review lies in its comprehensive analysis of the multifaceted interactions between bioactive peptides and gut microbiota, integrating knowledge from diverse disciplines between microbiology and nutrition. By elucidating the underlying mechanisms and identifying current research gaps, this review offers an outlook on the potential of bioactive peptides in promoting gut health and shaping future therapeutic and nutritional interventions.

METHODS: High blood pressure (BP) is the main preventable risk factor for cardiovascular diseases (CVDs). Much research is aimed at finding natural alternatives to control or prevent hypertension (HT), since some hypertensive patients do not respond to current pharmacological treatments or show undesirable side effects.
RESULTS: Forty relevant articles have been selected from various scientific literature databases. The results reveal that angiotensin-converting enzyme (ACE) inhibition is the most reported mechanism of action of antihypertensive peptides. The active peptides have a great variety of origins. Biopeptides with a molecular weight of <3 kDa, short chain <20 amino acids, and a hydrophobic amino acid sequence at the C- and N-terminus exhibit higher antihypertensive activity. They also show good stability to enzymatic hydrolysis and gastrointestinal digestion, and no toxicity. To determine antihypertensive effectiveness, in vitro and in vivo animal studies are the most frequent developed, with few in silico studies and only one human clinical trial.
CONCLUSIONS: There is interesting potential for antihypertensive peptides as promising natural candidates for the development of functional foods, nutraceuticals and drugs for preventive or therapeutic treatment of hypertension. The aim of this review is to study the role of food-derived bioactive peptides in HT.

The extracellular matrix (ECM) represents a complex multi-component environment that has a decisive influence on the biomechanical properties of tissues and organs. Depending on the tissue, ECM components are subject to a homeostasis of synthesis and degradation, a subtle interplay that is influenced by external factors and the intrinsic aging process and is often disturbed in pathologies. Upon proteolytic cleavage of ECM proteins, small bioactive peptides termed matrikines can be formed. These bioactive peptides play a crucial role in cell signaling and contribute to the dynamic regulation of both physiological and pathological processes such as tissue remodeling and repair as well as inflammatory responses. In the skin, matrikines exert an influence for instance on cell adhesion, migration, and proliferation as well as vasodilation, angiogenesis and protein expression. Due to their manifold functions, matrikines represent promising leads for developing new therapeutic options for the treatment of skin diseases. This review article gives a comprehensive overview on matrikines in the skin, including their origin in the dermal ECM, their biological effects and therapeutic potential for the treatment of skin pathologies such as melanoma, chronic wounds and inflammatory skin diseases or for their use in anti-aging cosmeceuticals.