The Antihypertensive Effects and Potential Molecular Mechanism of Microalgal Angiotensin I-Converting Enzyme Inhibitor-Like Peptides: A Mini Review

Hypertension causes many deaths worldwide and has shown an increasing trend as a severe non-communicable disease. Conventional antihypertensive drugs inevitably cause side effects, and great efforts have been made to exploit healthier and more-available substitutes. Microalgae have shown great potential in this regard and have been applied in the food and pharmaceutical industries. Some compounds in microalgae have been proven to have antihypertensive effects. Among these natural compounds, peptides from microalgae are promising angiotensin-converting enzyme (ACE) inhibitors because an increasing number of peptides show hypertensive effects and ACE inhibitory-like activity. In addition to acting as ACE inhibitors for the treatment of hypertension, these peptides have other probiotic properties, such as antioxidant and anti-inflammatory properties, that are important for the prevention and treatment of hypertension. Numerous studies have revealed the important bioactivities of ACE inhibitors and their mechanisms. This review discusses the antihypertensive effects, structure-activity relationships, molecular docking studies, interaction mechanisms, and other probiotic properties of microalgal ACE inhibitory peptides according to the current research related to microalgae as potential antihypertensive drugs. Possible research directions are proposed. This review contributes to a more comprehensive understanding of microalgal antihypertensive peptides.     

Food Derived Bioactive Peptides and Intestinal Barrier Function

A wide range of food-derived bioactive peptides have been shown to exert health-promoting actions and are therefore considered functional foods or nutraceuticals. Some of these actions are related to the maintenance, reinforcement or repairment of the intestinal barrier function (IBF) whose role is to selectively allow the absorption of water, nutrients and ions while preventing the influx of microorganisms from the intestinal lumen. Alterations in the IBF have been related to many disorders, such as inflammatory bowel disease or metabolic syndrome. Components of IBF are the intestinal epithelium, the mucus layer, secretory immunoglobulin A and cells of the innate and adaptive immune systems. Here we review the effects of food derived bioactive peptides on these IBF components. In vitro and in vivo effects, both in healthy and disease states, have been reviewed. Although limited, the available information indicates a potential for food-derived peptides to modify IBF and to contribute to disease treatment, but further research is needed to better isolate responsible peptides, and to help define their mode of action.     

Bioactive peptides derived from milk proteins

Milk proteins are known for having a wide range of nutritional, functional and biological properties that make them important ingredients in functional or health promoting foods. These properties are partly attributed to bioactive peptides coded in the different milk proteins. Bioactive peptides are inactive within the protein sequence but may be released by the action of native proteolitic enzymes from milk, enzymes from lactic acid bacteria or from exogenous sources or may be produced during gastrointestinal digestion or processing of foods. Peptides derived from caseins and whey proteins were shown to present several bioactive properties such as opioid, antihypertensive, antimicrobial, immunodulatory, mineral carrier and antithrombotic. This overview presents a perspective of the importance of dairy proteins in the production of bioactive peptides and their biological activities, as well as the main analytical tecniques that have been used for the isolation and identification of these peptides.     

Rational Design of a Highly Specific Prolyl Endopeptidase To Activate the Antihypertensive Effect of Peptides

Enzymatic hydrolysis of food-derived proteins to produce bioactive peptides could activate food functions such as antihypertension. However, the diversity of enzymatic hydrolysis products can reduce bioactive peptides’ efficacy. Highly specific proteases can homogenize the hydrolysis products to reduce the production of impotent peptides. In this study, we successfully obtained M. xanthus prolyl endopeptidase mutant Y451M by constraint/free molecular dynamics simulations and binding energy calculations. The specificity of Y451M for proline was increased by 286 % compared to WT, while its activity was almost unchanged. Milk-derived substrates processed with Y451M showed an antihypertensive effect that was 567 % higher than without enzymes. The ability to activate food antihypertension increased 152 % and the use of enzyme by 192 % compared with WT. Specific proteases are thus valuable tools in the processing of complex substrates to obtain bioactive peptides.     

Bioactive Peptides as Potential Nutraceuticals for Diabetes Therapy: A Comprehensive Review

Diabetes mellitus is a major public health concern associated with high mortality and reduced life expectancy. The alarming rise in the prevalence of diabetes is linked to several factors including sedentary lifestyle and unhealthy diet. Nutritional intervention and increased physical activity could significantly contribute to bringing this under control. Food-derived bioactive peptides and protein hydrolysates have been associated with a number health benefits. Several peptides with antidiabetic potential have been identified that could decrease blood glucose level, improve insulin uptake and inhibit key enzymes involved in the development and progression of diabetes. Dietary proteins, from a wide range of food, are rich sources of antidiabetic peptides. Thus, there are a number of benefits in studying peptides obtained from food sources to develop nutraceuticals. A deeper understanding of the underlying molecular mechanisms of these peptides will assist in the development of new peptide-based therapeutics. Despite this, a comprehensive analysis of the antidiabetic properties of bioactive peptides derived from various food sources is still lacking. Here, we review the recent literature on food-derived bioactive peptides possessing antidiabetic activity. The focus is on the effectiveness of these peptides as evidenced by in vitro and in vivo studies. Finally, we discuss future prospects of peptide-based drugs for the treatment of diabetes.     

Antihypertensive Properties of Plant-Based Prebiotics

Hypertension is one of the major risk factors for cardiovascular disease. Although various drugs for its treatment have been synthesized, the occurring side effects have generated the need for natural interventions for the treatment and prevention of hypertension. Dietary intervention such as the administration of prebiotics has been seen as a highly acceptable approach. Prebiotics are indigestible food ingredients that bypass digestion and reach the lower gut as substrates for indigenous microflora. Most of the prebiotics used as food adjuncts, such as inulin, fructooligosaccharides, dietary fiber and gums, are derived from plants. Experimental evidence from recent studies has suggested that prebiotics are capable of reducing and preventing hypertension. This paper will discuss some of the mechanisms involved, the evidence generated from both in-vitro experiments and in-vivo trials and some controversial findings that are raised.     

Bioactive Peptides: Synthesis,Sources, Applications,and Proposed Mechanisms of Action

Bioactive peptides are a group of biological molecules that are normally buried in the structure of parent proteins and become active after the cleavage of the proteins. Another group of peptides is actively produced and found in many microorganisms and the body of organisms. Today, many groups of bioactive peptides have been marketed chemically or recombinantly. This article reviews the various production methods and sources of these important/ubiquitous and useful biomolecules. Their applications, such as antimicrobial, antihypertensive, antioxidant activities, blood-lipid-lowering effect, opioid role, antiobesity, ability to bind minerals, antidiabetic, and antiaging effects, will be explored. The types of pathways proposed for bioactive applications will be in the next part of the article, and at the end, the future perspectives of bioactive peptides will be reviewed. Reading this article is recommended for researchers interested in various fields of physiology, microbiology, biochemistry, and nanotechnology and food industry professionals.     

Screening of Novel Bioactive Peptides from Goat Casein: In Silico to In Vitro Validation

Food-derived bioactive peptides are of great interest to science and industry due to evolving drivers of food product innovation, including health and wellness. This study aims to draw attention through a critical study on how bioinformatics analysis is employed in the identification of bioactive peptides in the laboratory. An in silico analysis (PeptideRanker, BIOPEP, AHTpin, and mAHTPred) of a list of peptides from goat casein hydrolysate was performed to predict which sequences could potentially be bioactive. To validate the predictions, the in vitro antihypertensive potential of the five peptides with the highest potential was first measured. Then, for three of these, gastrointestinal digestion was simulated in vitro, followed by the analysis of the resulting ACE inhibitory activity as well as antioxidant capacity. We thus observed that the use of new computational biology technologies to predict peptide sequences is an important research tool, but they should not be used alone and complementarity with various in vitro and in vivo assays is essential.     

Bioactive Carbohydrates and Peptides in Foods: An Overview of Sources,Downstream Processing Steps and Associated Bioactivities

Bioactive peptides and carbohydrates are sourced from a myriad of plant, animal and insects and have huge potential for use as food ingredients and pharmaceuticals. However, downstream processing bottlenecks hinder the potential use of these natural bioactive compounds and add cost to production processes. This review discusses the health benefits and bioactivities associated with peptides and carbohydrates of natural origin and downstream processing methodologies and novel processes which may be used to overcome these.     

Natural Products for the Prevention and Treatment of Oral Mucositis—A Review

Cancer, a major world public health problem, is associated with chemotherapy treatments whose administration leads to secondary concerns, such as oral mucositis (OM). The OM disorder is characterized by the presence of ulcers in the oral mucosa that cause pain, bleeding, and difficulty in ingesting fluids and solids, or speaking. Bioactive compounds from natural sources have arisen as an effective approach for OM. This review aims to summarize the new potential application of different natural products in the prevention and treatment of OM in comparison to conventional ones, also providing a deep insight into the most recent clinical studies. Natural products, such as Aloe vera, Glycyrrhiza glabra, Camellia sinensis, Calendula officinalis, or honeybee crops, constitute examples of sources of bioactive compounds with pharmacological interest due to their well-reported activities (e.g., antimicrobial, antiviral, anti-inflammatory, analgesic, or wound healing). These activities are associated with the bioactive compounds present in their matrix (such as flavonoids), which are associated with in vivo biological activities and minimal or absent toxicity. Finally, encapsulation has arisen as a future opportunity to preserve the chemical stability and the drug bioa vailability of bioactive compounds and, most importantly, to improve the buccal retention period and the therapeutic effects.     

Enhancing ACE-inhibition of food protein hydrolysates by selective adsorption using porous carbon materials

Bioactive peptides from food proteins such as natural ACE (angiotensin-converting enzyme)-inhibitors have attracted particular attention for their potential to prevent hypertension. ACE-inhibiting peptides were enriched from food protein hydrolysates prepared from α-lactalbumin and lysozyme by selective adsorption on microporous activated carbons. For the eluate, it was shown by liquid chromatography that the strongest inhibitor isoleucyl-tryptophan was enriched by a factor of 11.2 compared to the initial α-lactalbumin hydrolysate. Natural inhibitors derived from lysozyme hydrolysates (e.g., alanyl-tryptophan) were successfully enriched as well. Identification of the enriched peptide fraction by mass spectroscopy revealed the hydrophobic character of the enriched peptides. The molecular weight distribution of the enriched peptide fraction can be controlled by the pore size distribution of the chosen adsorbent, which was proven by size exclusion chromatography of enriched peptide fractions derived from three different model carbons differing in their pore size. The selective enrichment of natural ACE-inhibitors from the α-lactalbumin hydrolysate lead to a 6 times stronger in vitro ACE-inhibition demonstrating the high potential as ingredients for hypotensive functional foods with reduced side effects.     

Endogenous Opioid Peptides and Alternatively Spliced Mu Opioid Receptor Seven Transmembrane Carboxyl-Terminal Variants

There exist three main types of endogenous opioid peptides, enkephalins, dynorphins and β-endorphin, all of which are derived from their precursors. These endogenous opioid peptides act through opioid receptors, including mu opioid receptor (MOR), delta opioid receptor (DOR) and kappa opioid receptor (KOR), and play important roles not only in analgesia, but also many other biological processes such as reward, stress response, feeding and emotion. The MOR gene, OPRM1, undergoes extensive alternative pre-mRNA splicing, generating multiple splice variants or isoforms. One type of these splice variants, the full-length 7 transmembrane (TM) Carboxyl (C)-terminal variants, has the same receptor structures but contains different intracellular C-terminal tails. The pharmacological functions of several endogenous opioid peptides through the mouse, rat and human OPRM1 7TM C-terminal variants have been considerably investigated together with various mu opioid ligands. The current review focuses on the studies of these endogenous opioid peptides and summarizes the results from early pharmacological studies, including receptor binding affinity and G protein activation, and recent studies of β-arrestin2 recruitment and biased signaling, aiming to provide new insights into the mechanisms and functions of endogenous opioid peptides, which are mediated through the OPRM1 7TM C-terminal splice variants.     

The Anti-Inflammatory Properties of Licorice (Glycyrrhiza glabra)-Derived Compounds in Intestinal Disorders

Intestinal diseases, such as inflammatory bowel diseases (IBDs) and colorectal cancer (CRC), are a significant source of morbidity and mortality worldwide. Epidemiological data have shown that IBD patients are at an increased risk for the development of CRC. IBD-associated cancer develops against a background of chronic inflammation and oxidative stress, and their products contribute to cancer development and progression. Therefore, the discovery of novel drugs for the treatment of intestinal diseases is urgently needed. Licorice (Glycyrrhiza glabra) has been largely used for thousands of years in traditional Chinese medicine. Licorice and its derived compounds possess antiallergic, antibacterial, antiviral, anti-inflammatory, and antitumor effects. These pharmacological properties aid in the treatment of inflammatory diseases. In this review, we discuss the pharmacological potential of bioactive compounds derived from Licorice and addresses their anti-inflammatory and antioxidant properties. We also discuss how the mechanisms of action in these compounds can influence their effectiveness and lead to therapeutic effects on intestinal disorders.     

Beneficial Effects of Soybean-Derived Bioactive Peptides

Peptides present in foods are involved in nutritional functions by supplying amino acids; sensory functions related to taste or solubility, emulsification, etc.; and bioregulatory functions in various physiological activities. In particular, peptides have a wide range of physiological functions, including as anticancer agents and in lowering blood pressure and serum cholesterol levels, enhancing immunity, and promoting calcium absorption. Soy protein can be partially hydrolyzed enzymatically to physiologically active soy (or soybean) peptides (SPs), which not only exert physiological functions but also help amino acid absorption in the body and reduce bitterness by hydrolyzing hydrophobic amino acids from the C- or N-terminus of soy proteins. They also possess significant gel-forming, emulsifying, and foaming abilities. SPs are expected to be able to prevent and treat atherosclerosis by inhibiting the reabsorption of bile acids in the digestive system, thereby reducing blood cholesterol, low-density lipoprotein, and fat levels. In addition, soy contains blood pressure-lowering peptides that inhibit angiotensin-I converting enzyme activity and antithrombotic peptides that inhibit platelet aggregation, as well as anticancer, antioxidative, antimicrobial, immunoregulatory, opiate-like, hypocholesterolemic, and antihypertensive activities. In animal models, neuroprotective and cognitive capacity as well as cardiovascular activity have been reported. SPs also inhibit chronic kidney disease and tumor cell growth by regulating the expression of genes associated with apoptosis, inflammation, cell cycle arrest, invasion, and metastasis. Recently, various functions of soybeans, including their physiologically active functions, have been applied to health-oriented foods, functional foods, pharmaceuticals, and cosmetics. This review introduces some current results on the role of bioactive peptides found in soybeans related to health functions.     

Common Amino Acid Subsequences in a Universal Proteome—Relevance for Food Science

A common subsequence is a fragment of the amino acid chain that occurs in more than one protein. Common subsequences may be an object of interest for food scientists as biologically active peptides, epitopes, and/or protein markers that are used in comparative proteomics. An individual bioactive fragment, in particular the shortest fragment containing two or three amino acid residues, may occur in many protein sequences. An individual linear epitope may also be present in multiple sequences of precursor proteins. Although recent recommendations for prediction of allergenicity and cross-reactivity include not only sequence identity, but also similarities in secondary and tertiary structures surrounding the common fragment, local sequence identity may be used to screen protein sequence databases for potential allergens in silico. The main weakness of the screening process is that it overlooks allergens and cross-reactivity cases without identical fragments corresponding to linear epitopes. A single peptide may also serve as a marker of a group of allergens that belong to the same family and, possibly, reveal cross-reactivity. This review article discusses the benefits for food scientists that follow from the common subsequences concept.     

Edible Bioactive Film with Curcumin: A Potential “Functional” Packaging?

Edible packaging has been developed as a biodegradable and non-toxic alternative to traditional petroleum-based food packaging. Biopolymeric edible films, in addition to their passive protective function, may also play a bioactive role as vehicles for bioactive compounds of importance to human health. In recent years, a new generation of edible food packaging has been developed to incorporate ingredients with functional potential that have beneficial effects on consumer health. Curcumin, a bioactive compound widely used as a natural dye obtained from turmeric rhizomes (Curcuma longa L.), has a broad spectrum of beneficial properties for human health, such as anti-inflammatory, anti-hypertensive, antioxidant, anti-cancer, and other activities. To demonstrate these properties, curcumin has been explored as a bioactive agent for the development of bioactive packaging, which can be referred to as functional packaging and used in food. The aim of this review was to describe the current and potential research on the development of functional-edible-films incorporating curcumin for applications such as food packaging.     

Novel Insights on Dietary Polyphenols for Prevention in Early-Life Origins of Hypertension: A Review Focusing on Preclinical Animal Models

Polyphenols are the largest group of phytochemicals with health benefits. Early life appears to offer a critical window of opportunity for launching interventions focused on preventing hypertension, as increasing evidence supports the supposition that hypertension can originate in early life. Although polyphenols have antihypertensive actions, knowledge of the potential beneficial action of the early use of polyphenols to avert the development of hypertension is limited. Thus, in this review, we first provide a brief summary of the chemistry and biological function of polyphenols. Then, we present the current epidemiological and experimental evidence supporting the early-life origins of hypertension. We also document animal data on the use of specific polyphenols as an early-life intervention to protect offspring against hypertension in adulthood and discuss underlying mechanisms. Continued research into the use of polyphenols to prevent hypertension from starting early in life will have far-reaching implications for future health.     

The Improvement of Hypertension by Probiotics: Effects on Cholesterol, Diabetes, Renin, and Phytoestrogens

Probiotics are live organisms that are primarily used to improve gastrointestinal disorders such as diarrhea, irritable bowel syndrome, constipation, lactose intolerance, and to inhibit the excessive proliferation of pathogenic intestinal bacteria. However, recent studies have suggested that probiotics could have beneficial effects beyond gastrointestinal health, as they were found to improve certain metabolic disorders such as hypertension. Hypertension is caused by various factors and the predominant causes include an increase in cholesterol levels, incidence of diabetes, inconsistent modulation of renin and imbalanced sexual hormones. This review discusses the antihypertensive roles of probiotics via the improvement and/or treatment of lipid profiles, modulation of insulin resistance and sensitivity, the modulation of renin levels and also the conversion of bioactive phytoestrogens as an alternative replacement of sexual hormones such as estrogen and progesterone.     

Assessment of the bioactive lipid profiles of oil extracted from Tunisian table olive cultivars (Barouni,Besbassi, and Marsaline cvs.)

Bioactive compounds are components extracted from biological matrices that may offer physiological health benefits and have nutritive value. The present study characterized bioactive lipid components such as fatty acids, phytosterols, policosanol, and triterpenes from table olives. The table olives were processed according to the green Spanish-style method. The obtained results indicate that phytosterol fraction constitutes the major portion of the total unsaponifiable matter. The analysis of phytosterols showed the presence of 11 compounds, β-sitosterol the predominant one. The policosanol composition indicated that hexacosanol, tetracosanol, octacosanol, and docosanol were the main compounds, accounting for over 85% of total policosanols. Pentacyclic triterpenes (cycloartenol and 24-methylene cycloartenol) were found at a higher level (over 85%) compared to tetracyclic triterpenes (β-amyrin, δ-amyrin). These findings reveal that processed table olives contain an interesting amount of various bioactive compounds compared to marine and other floral biological matrices. Thus, processed table olives represent an interesting natural functional food that presents high stability and bioavailability of their natural bioactive ingredients. Practical Applications: Nowadays, with health food gaining popularity among consumers, the demand for natural bioactive compounds and functional food is expanding considerably all over the world. This study focuses on analyzing bioactive lipid components from processed table olives. Fruits were processed according to the green Spanish-style method. The salt content of the brine was adjusted to the minimum sodium chloride value required by the Codex Alimentarius Comission, which is 5%, taking into consideration people suffering from hypertension. This concentration is considered the minimum amount of salt necessary to exhibit antibacterial activities. Considering the results obtained, processed table olives present one of the most valuable potential resources for bioactive lipid compounds and have a considerable ability to preserve the stability of their lipid components. Thus, the food industry in Mediterranean countries can promote processed table olives as conventional functional food with no need for any enrichment or fortification.