Oral bioavailability of bioactive compounds; modulating factors, in vitro analysis methods, and enhancing strategies.

Foods are complex biosystems made up of a wide variety of compounds. Some of them, such as nutrients and bioactive compounds (bioactives), contribute to supporting body functions and bring important health benefits; others, such as food additives, are involved in processing techniques and contribute to improving sensory attributes and ensuring food safety. Also, there are antinutrients in foods that affect food bioefficiency and contaminants that increase the risk of toxicity. The bioefficiency of food is evaluated with bioavailability which represents the amount of nutrients or bioactives from the consumed food reaching the organs and tissues where they exert their biological activity. Oral bioavailability is the result of some physicochemical and biological processes in which food is involved such as liberation, absorption, distribution, metabolism, and elimination (LADME). In this paper, a general presentation of the factors influencing oral bioavailability of nutrients and bioactives as well as the in vitro techniques for evaluating bioaccessibility and is provided. In this context, a critical analysis of the effects of physiological factors related to the characteristics of the gastrointestinal tract (GIT) on oral bioavailability is discussed, such as pH, chemical composition, volumes of gastrointestinal (GI) fluids, transit time, enzymatic activity, mechanical processes, and so on, and the pharmacokinetics factors including BAC and solubility of bioactives, their transport across the cell membrane, their biodistribution and metabolism. The impact of matrix and food processing on the BAC of bioactives is also explained. The researchers' recent concerns for improving oral bioavailability of nutrients and food bioactives using both traditional techniques, for example, thermal treatments, mechanical processes, soaking, germination and fermentation, as well as food nanotechnologies, such as loading of bioactives in different colloidal delivery systems (CDSs), is also highlighted.

Impact of solid-state fermentation on factors and mechanisms influencing the bioactive compounds of grains and processing by-products.

Cereal and legume grains and their processing by-products are rich sources of bioactives such as phenolics with considerable health potential, but these bioactives suffer from low bioaccessibility and bioavailability, resulting in limited use. Several studies have demonstrated that solid-state fermentation (SSF) with food-grade microorganisms is effective in releasing bound phenolic compounds in cereal and legume products. In this review, we discuss the effect of SSF on cereal and legume grains and their by-products by examining the role of specific microorganisms, their hydrolytic enzymes, fermentability of agri-food substrates, and the potential health benefits of SSF-enhanced bioactive compounds. SSF with fungi (Aspergillus spp. and Rhizopus spp.), bacteria (Bacillus subtilis and lactic acid bacteria (LAB) spp.) and yeast (Saccharomyces cerevisiae) significantly increased the bioactive phenolics and antioxidant capacities in cereal and legume grains and by-products, mainly through carbohydrate-cleaving enzymes. Increased bioactive phenolic and peptide contents of SSF-bioprocessed cereal and legume grains have been implicated for improved antioxidant, anti-inflammatory, anti-carcinogenic, anti-diabetic, and angiotensin-converting-enzyme (ACE) inhibitory effects in fermented agri-food products, but these remain as preliminary results. Future research should focus on the microbial mechanisms, suitability of substrates, and the physiological health benefits of SSF-treated grains and by-products.

Health effects of 100% fruit and vegetable juices: evidence from human subject intervention studies.

The health effects of 100% fruit and vegetable juices (FVJ) represent a controversial topic. FVJ contain notable amounts of free sugars, but also vitamins, minerals, and secondary compounds with proven biological activities like (poly)phenols and carotenoids. The review aimed to shed light on the potential impact of 100% FVJ on human subject health, comprehensively assessing the role each type of juice may have in specific health outcomes for a particular target population, as reported in dietary interventions. The effects of a wide range of FVJ (orange, grapefruit, mandarin, lemon, apple, white, red, and Concord grapes, pomegranate, cranberry, chokeberry, blueberry, other minor berries, sweet and tart cherry, plum, tomato, carrot, beetroot, and watermelon, among others) were evaluated on a series of outcomes (anthropometric parameters, body composition, blood pressure and vascular function, lipid profile, glucose homeostasis, biomarkers of inflammation and oxidative stress, cognitive function, exercise performance, gut microbiota composition and bacterial infections), providing a thorough picture of the contribution of each FVJ to a health outcome. Some juices demonstrated their ability to exert potential preventive effects on some outcomes while others on other health outcomes, emphasising how the differential composition in bioactive compounds defines juice effects. Research gaps and future prospects were discussed. Although 100% FVJ appear to have beneficial effects on some cardiometabolic health outcomes, cognition and exercise performance, or neutral effects on anthropometric parameters and body composition, further efforts are needed to better understand the impact of 100% FVJ on human subject health.

Research advances of in vivo biological fate of food bioactives delivered by colloidal systems.

Food bioactives exhibit various health-promoting effects and are widely used in functional foods to maintain human health. After oral intake, bioactives undergo complex biological processes before reaching the target organs to exert their biological effects. However, several factors may reduce their bioavailability. Colloidal systems have attracted special attention due to their great potential to improve bioavailability and bioefficiency. Herein, we focus on the importance of in vivo studies of the biological fates of bioactives delivered by colloidal systems. Increasing evidence demonstrates that the construction, composition, and physicochemical properties of the delivery systems significantly influence the in vivo biological fates of bioactives. These results demonstrate the great potential to control the in vivo behavior of food bioactives by designing specific delivery systems. We also compare in vivo and in vitro models used for biological studies of the fate of food bioactives delivered by colloidal systems. Meanwhile, the significance of the gut microbiota, targeted delivery, and personalized nutrition should be carefully considered. This review provides new insight for further studies of food bioactives delivered by colloidal systems, as well as scientific guidance for the reasonable design of personalized nutrition.

The Potential of Dietary Bioactive Compounds against SARS-CoV-2 and COVID-19-Induced Endothelial Dysfunction.

COVID-19 is an endothelial disease. All the major comorbidities that increase the risk for severe SARS-CoV-2 infection and severe COVID-19 including old age, obesity, diabetes, hypertension, respiratory disease, compromised immune system, coronary artery disease or heart failure are associated with dysfunctional endothelium. Genetics and environmental factors (epigenetics) are major risk factors for endothelial dysfunction. Individuals with metabolic syndrome are at increased risk for severe SARS-CoV-2 infection and poor COVID-19 outcomes and higher risk of mortality. Old age is a non-modifiable risk factor. All other risk factors are modifiable. This review also identifies dietary risk factors for endothelial dysfunction. Potential dietary preventions that address endothelial dysfunction and its sequelae may have an important role in preventing SARS-CoV-2 infection severity and are key factors for future research to address. This review presents some dietary bioactives with demonstrated efficacy against dysfunctional endothelial cells. This review also covers dietary bioactives with efficacy against SARS-CoV-2 infection. Dietary bioactive compounds that prevent endothelial dysfunction and its sequelae, especially in the gastrointestinal tract, will result in more effective prevention of SARS-CoV-2 variant infection severity and are key factors for future food research to address.

The ACE2/Ang (1-7)/MasR axis as an emerging target for antihypertensive peptides.

Food protein-derived bioactive peptides, particularly antihypertensive peptides, are important constituents of functional foods or nutraceuticals. Most antihypertensive are identified as the inhibitors of angiotensin converting enzyme (ACE), a key enzyme responsible for the generation of angiotensin II (Ang II), which is a vasoconstricting peptide. Hence, ACE has long been used as a universal target to identify antihypertensive peptides. Angiotensin converting enzyme 2 (ACE2), is a homolog of ACE but uses Ang II as its key substrate to produce angiotensin (1-7), exerting vasodilatory activity via the mas receptor (MasR). Therefore, ACE2 functions in the opposite way as ACE and is an emerging novel target for cardiovascular therapy. The potential of food protein-derived bioactive peptides in targeting ACE2 has been rarely explored. While, recently we found that IRW, an egg white ovotransferrin-derived antihypertensive peptide, reduced blood pressure in spontaneously hypertensive rats via the ACE2/Ang (1-7)/MasR axis, indicating a new mechanism of food protein-derived bioactive peptides in reducing blood pressure. The objectives of this review are to summarize the functions of the ACE2/Ang (1-7)/MasR axis and to examine its potential roles in the actions of food protein-derived antihypertensive peptides. The interaction between antihypertensive peptides and the ACE2/Ang (1-7)/MasR axis will also be discussed.

Plant-food-derived bioactives: Key health benefits and current nanosystems as a strategy to enhance their bioavailability.

Natural products interest is gradually increasing worldwide. Plant-food-derived bioactives have a long history of use as a good source of ingredients for valuable medical usages. Plant-based foods consist of micro and macronutrients, and bioactive components, with health-promoting benefits. The handling of complex mixtures of plants has been methodically switched by therapies using a single isolated substance. The delivery of bioactive molecules in nanosystems is enhancing their bioavailability, it is much safer and cost-effective. However, there are many challenges in combining bioactive substances in nanocarrier materials. A discussion related with nanocarriers will be done in this review.

Inhibition of Pancreatic α-amylase by Resveratrol Derivatives: Biological Activity and Molecular Modelling Evidence for Cooperativity between Viniferin Enantiomers.

To improve the current understanding of the role of stilbenoids in the management of diabetes, the inhibition of the pancreatic α-amylase by resveratrol derivatives was investigated. To approach in a systematic way, the mechanistic and structural aspects of the interaction, potential bioactive agents were prepared as single molecules, that were used for the biological evaluation of the determinants of inhibitory binding. Some dimeric stilbenoids-in particular, viniferin isomers- were found to be better than the reference drug acarbose in inhibiting the pancreatic α-amylase. Racemic mixtures of viniferins were more effective inhibitors than the respective isolated pure enantiomers at an equivalent total concentration, and displayed cooperative effects not observed with the individual enantiomers. The molecular docking analysis provided a thermodynamics-based rationale for the measured inhibitory ability and for the observed synergistic effects. Indeed, the binding of additional ligands on the surface of the alpha-amylase was found to decrease the dissociation constant of inhibitors bound to the active site of the enzyme, thus providing a mechanistic rationale for the observed inhibitory synergies.

Therapeutic Perspectives of Molecules from Urtica dioica Extracts for Cancer Treatment.

A large range of chronic and degenerative diseases can be prevented through the use of food products and food bioactives. This study reports the health benefits and biological activities of the Urtica dioica (U. dioica) edible plant, with particular focus on its cancer chemopreventive potential. Numerous studies have attempted to investigate the most efficient anti-cancer therapy with few side effects and high toxicity on cancer cells to overcome the chemoresistance of cancer cells and the adverse effects of current therapies. In this regard, natural products from edible plants have been assessed as sources of anti-cancer agents. In this article, we review current knowledge from studies that have examined the cytotoxic, anti-tumor and anti-metastatic effects of U. dioica plant on several human cancers. Special attention has been dedicated to the treatment of breast cancer, the most prevalent cancer among women and one of the main causes of death worldwide. The anti-proliferative and apoptotic effects of U. dioica have been demonstrated on different human cancers, investigating the properties of U. dioica at cellular and molecular levels. The potent cytotoxicity and anti-cancer activity of the U. dioica extracts are due to its bioactive natural products content, including polyphenols which reportedly possess anti-oxidant, anti-mutagenic and anti-proliferative properties. The efficacy of this edible plant to prevent or mitigate human cancers has been demonstrated in laboratory conditions as well as in experimental animal models, paving the way to the development of nutraceuticals for new anti-cancer therapies.

Deep eutectic solvents: Preparation, properties, and food applications.

Deep Eutectic Solvents (DESs) emerge as innovative 21st-century solvents, supplanting traditional ones like ethanol and n-hexane. Renowned for their non-toxic, biodegradable, and water-miscible nature with reduced volatility, DESs are mostly synthesized through heating and stirring method. Physicochemical properties such as polarity, viscosity, density and surface tension of DESs influenced their application. This review paper gives the overview of application of eco-benign DESs in fruits, vegetables, cereals, pulses, spices, herbs, plantation crops, oil seed crops, medicinal and aromatic plants, seaweed, and milk for the extraction of bioactive compounds. Also, it gives insight of determination of pesticides, insecticides, hazardous and toxic compounds, removal of heavy metals, detection of illegal milk additive, purification of antibiotics and preparation of packaging film. Methodologies for separating bioactive compounds from DESs extracts are systematically examined. Further, safety regulations of DESs are briefly discussed and reviewed literature reveals prevalent utilization of DES-based bioactive compound rich extracts in cosmetics, indicating untapped potential of their application in the food industry.

Recent advances in encapsulation of resveratrol for enhanced delivery.

Due to its numerous biological activities, such as antioxidant, anti-inflammatory, antitumor, anti-atherosclerosis, anti-aging, anti-osteoporosis, anti-obesity, estrogenic, neuroprotective and cardioprotective effects, resveratrol has attracted a lot of attention in the food and pharmaceutical industries as a promising bioactive. However, low solubility in aqueous media, limited bioavailability, and low stability of resveratrol in hostile environments limit its applications. The necessity for a summary of recent developments is highlighted by the growing body of research on resveratrol encapsulation as a means of overcoming the mentioned application constraints. This review highlights the present developments in resveratrol delivery techniques, including spray drying, liposomes, emulsions, and nanoencapsulation. Bioaccessibility, bioavailability, stability, and release of resveratrol from encapsulating matrices are discussed. Future research should focus on encapsulation approaches with high loading capacity, targeted delivery, and controlled release. In light of the growing interest in resveratrol and the increasing complexity of resveratrol-based formulations, review of current encapsulation methods is crucial to address existing limitations and pave the way for the development of next-generation delivery systems. This review discusses how the delivery systems with different structures and release mechanisms can unlock the full potential and benefits of resveratrol by enhancing its bioavailability and stability.

Insights into the early-life chemical exposome of Nigerian infants and potential correlations with the developing gut microbiome.

Early-life exposure to natural and synthetic chemicals can impact acute and chronic health conditions. Here, a suspect screening workflow anchored on high-resolution mass spectrometry was applied to elucidate xenobiotics in breast milk and matching stool samples collected from Nigerian mother-infant pairs (n = 11) at three time points. Potential correlations between xenobiotic exposure and the developing gut microbiome, as determined by 16S rRNA gene amplicon sequencing, were subsequently explored. Overall, 12,192 and 16,461 features were acquired in the breast milk and stool samples, respectively. Following quality control and suspect screening, 562 and 864 features remained, respectively, with 149 of these features present in both matrices. Taking advantage of 242 authentic reference standards measured for confirmatory purposes of food bio-actives and toxicants, 34 features in breast milk and 68 features in stool were identified and semi-quantified. Moreover, 51 and 78 features were annotated with spectral library matching, as well as 416 and 652 by in silico fragmentation tools in breast milk and stool, respectively. The analytical workflow proved its versatility to simultaneously determine a diverse panel of chemical classes including mycotoxins, endocrine-disrupting chemicals (EDCs), antibiotics, plasticizers, perfluorinated alkylated substances (PFAS), and pesticides, although it was originally optimized for polyphenols. Spearman rank correlation of the identified features revealed significant correlations between chemicals of the same classification such as polyphenols. One-way ANOVA and differential abundance analysis of the data obtained from stool samples revealed that molecules of plant-based origin elevated as complementary foods were introduced to the infants' diets. Annotated compounds in the stool, such as tricetin, positively correlated with the genus Blautia. Moreover, vulgaxanthin negatively correlated with Escherichia-Shigella. Despite the limited sample size, this exploratory study provides high-quality exposure data of matched biospecimens obtained from mother-infant pairs in sub-Saharan Africa and shows potential correlations between the chemical exposome and the gut microbiome.

Neuroprotection of Food Bioactives in Neurodegenerative Diseases: Role of the Gut Microbiota and Innate Immune Receptors.

Gut-brain connections may be mediated by an assortment of microbial molecules, which can subsequently traverse intestinal and blood-brain barriers and impact neurological function. Pattern recognition receptors (PRRs) are important innate immune proteins in the gut. Gut microbiota act in concert with the PRRs is a novel target for regulating host-microbe signaling and immune homeostasis, which may involve the pathogenesis of neurodegenerative diseases. Natural food bioactives bestow a protective advantage on neurodegenerative diseases through immunomodulatory effects of the modified gut microbiota or alterations in the landscape of microbiota-produced metabolites via PRRs modulation. In this review, we discuss the effect of natural food bioactives on the gut microbiota and the role of PRRs in the gut-brain crosstalk. We focused on the neuroprotective mechanisms of natural bioactive compounds behind the action of the gut microbiota and PRRs. Research advances in natural food bioactives as antineurodegeneration agents were also presented.

Fruit Smoothies Enriched in a Honeysuckle Berry Extract-An Innovative Product with Health-Promoting Properties.

Smoothies are claimed to be an effective way of promoting fruit and vegetable consumption. They are a rich source of bioactive compounds and provide numerous health benefits. Strawberries and apples are among the most popular smoothie ingredients. Additionally, chokeberry presents antibacterial, antiviral and anti-inflammatory properties. Another interesting fruit with a wide range of health benefits is the honeysuckle berry. In this study, a dry extract from the mentioned fruit was combined to produce a smoothie enriched in bioactive compounds of unique health-promoting properties. The smoothies were rich in anthocyanins, flavonols, phenolic acids, flavan-3-ols and iridoids. Smoothies with higher concentrations of a polyphenol-iridoid honeysuckle berry extract (0.50%) were the products of a greater content of bioactive compounds and higher antioxidant activity compared to those with no extract or a lower amount (0.25%). However, the sensory evaluation showed that, according to customers, the least attractive smoothies are those with the greatest amounts of the honeysuckle berry extract. Therefore, the correct balance between taste and bioactivity should be sought in order to obtain an innovative product showing characteristics of functional food.

Nanostructured steady-state nanocarriers for nutrients preservation and delivery.

Food bioactives possess specific physiological benefits of preventing certain diet-related chronic diseases or maintain human health. However, the limitations of the bioactives are their poor stability, lower water solubility and unacceptable bioaccessibility. Structure damage or degradation is often found for the bioactives under certain environmental conditions like high temperature, strong light, extreme pH or high oxygen concentration during food processing, packaging, storage and absorption. Nanostructured steady-state nanocarriers have shown great potential in overcoming the drawbacks for food bioactives. Various delivery systems including solid form delivery system, liquid form delivery system and encapsulation technology have been developed. The embedded food nutrients can largely decrease the loss and degradation during food processing, packaging and storage. The design and application of stimulus and targeted delivery systems can improve the stability, bioavailability and efficacy of the food bioactives upon oral consumption due to enzymatic degradation in the gastrointestinal tract. The food nutrients encapsulated in the smart delivery system can be well protected against degradation during oral administration, thus improving the bioavailability and releazing controlled or targeted release for food nutrients. The encapsulated food bioactives show great potential in nutrition therapy for sub-health status and disease. Much effort is required to design and prepare more biocompatible nanostructured steady-state nanocarriers using food-grade protein or polysaccharides as wall materials, which can be used in food industry and maintain the human health.

Potential of Phenolic Compounds and Their Gut Microbiota-Derived Metabolites to Reduce TMA Formation: Application of an In Vitro Fermentation High-Throughput Screening Model.

Trimethylamine N-oxide (TMAO) is a pro-atherosclerotic product of dietary choline metabolism generated by a microbiome-host axis. The first step in this pathway is the enzymatic metabolism of choline to trimethylamine (TMA) by the gut microbiota. This reaction could be targeted to reduce atherosclerosis risk. We aimed to evaluate potential inhibitory effects of select dietary phenolics and their relevant gut microbial metabolites on TMA production via a human ex vivo-in vitro fermentation model. Various phenolics inhibited choline use and TMA production. The most bioactive compounds tested (caffeic acid, catechin, and epicatechin) reduced TMA-d9 formation (compared to control) by 57.5 ± 1.3 to 72.5 ± 0.4% at 8 h and preserved remaining choline-d9 concentrations by 194.1 ± 6.4 to 256.1 ± 6.3% at 8 h. These inhibitory effects were achieved without altering cell respiration or cell growth. However, inhibitory effects decreased at late fermentation times, which suggested that these compounds delay choline metabolism rather than completely inhibiting TMA formation. Overall, caffeic acid, catechin, and epicatechin were the most effective noncytotoxic inhibitors of choline use and TMA production. Thus, these compounds are proposed as lead bioactives to test in vivo.

Paradigm Shift in Phytochemicals Research: Evolution from Antioxidant Capacity to Anti-Inflammatory Effect and to Roles in Gut Health and Metabolic Syndrome.

Food bioactive components, particularly phytochemicals with antioxidant capacity, have been extensively studied over the past two decades. However, as new analytical and molecular biological tools advance, antioxidants related research has undergone significant paradigm shifts. This review is a high-level overview of the evolution of phytochemical antioxidants research. Early research used chemical models to assess the antioxidant capacity of different phytochemicals, which provided important information about the health potential, but the results were overused and misinterpreted despite the lack of biological relevance (Antioxidants v1.0). This led to findings in the anti-inflammatory properties and modulatory effects of cell signaling of phytochemicals (Antioxidants v2.0). Recent advances in the role of diet in modulating gut microbiota have suggested a new phase of food bioactives research along the phytochemicals-gut microbiota-intestinal metabolites-low-grade inflammation-metabolic syndrome axis (Antioxidants v3.0). Polyphenols and carotenoids were discussed in-depth, and future research directions were also provided.

Polyphenol Exposure, Metabolism, and Analysis: A Global Exposomics Perspective.

Polyphenols are generally known for their health benefits and estimating actual exposure levels in health-related studies can be improved by human biomonitoring. Here, the application of newly available exposomic and metabolomic technology, notably high-resolution mass spectrometry, in the context of polyphenols and their biotransformation products, is reviewed. Comprehensive workflows for investigating these important bioactives in biological fluids or microbiome-related experiments are scarce. Consequently, this new era of nontargeted analysis and omic-scale exposure assessment offers a unique chance for better assessing exposure to, as well as metabolism of, polyphenols. In clinical and nutritional trials, polyphenols can be investigated simultaneously with the plethora of other chemicals to which we are exposed, i.e., the exposome, which may interact abundantly and modulate bioactivity. This research direction aims at ultimately eluting into atrue systems biology/toxicology evaluation of health effects associated with polyphenol exposure, especially during early life, to unravel their potential for preventing chronic diseases.

Recent Developments in Solid Lipid Microparticles for Food Ingredients Delivery.

Health food has become a prominent force in the market place, influencing many food industries to focus on numerous bioactive compounds to reap benefits from its properties. Use of these compounds in food matrices has several limitations. Most of the food bio-additives are sensitive compounds that may quickly decompose in both food and within the gastrointestinal tract. Since most of these bioactives are highly or partially lipophilic molecules, they possess very low water solubility and insufficient dispersibility, leading to poor bioavailability. Thus, various methods of microencapsulation of large number of food bioactives have been studied. For encapsulation of hydrophobic compounds several lipid carriers and lipid platforms have been studied, including emulsions, microemulsions, micelles, liposomes, and lipid nano- and microparticles. Solid lipid particles (SLP) are a promising delivery system, can both deliver bioactive compounds, reduce their degradation, and permit slow and sustained release. Solid lipid particles have important advantages compared to other polymer carriers in light of their simple production technology, including scale up ability, higher loading capacity, extremely high biocompatibility, and usually low cost. This delivery system provides improved stability, solubility in various matrixes, bioavailability, and targeting properties. This article reviews recent studies on microencapsulation of selected bioactive food ingredients in solid lipid-based carriers from a point of view of production methods, characteristics of obtained particles, loading capability, stability, and release profile.

An overview of conventional and emerging techniques of roasting: Effect on food bioactive signatures.

Roasting is a food processingtechnique that employs the principle of heating to cook the product evenly and enhance the digestibility, palatability and sensory aspects of foods with desirable structural modifications of the food matrix. With the burgeoning demand for fortified roasted products along with the concern for food hygiene and the effects of harmful compounds, novel roasting techniques, and equipment to overcome the limitations of conventional operations are indispensable. Roasting techniques employing microwave, infrared hot-air, superheated steam, Revtech roaster, and Forced Convection Continuous Tumble (FCCT) roasting have been figuratively emerging to prominence for effectively roasting different foods without compromising the nutritional quality. The present review critically appraises various conventional and emerging roasting techniques, their advantages and limitations, and their effect on different food matrix components, functional properties, structural attributes, and sensory aspects for a wide range of products. It was seen that thermal processing at high temperatures for increased durations affected both the physicochemical and structural properties of food. Nevertheless, novel techniques caused minimum destructive impacts as compared to the traditional processes. However, further studies applying novel roasting techniques with a wide range of operating conditions on different types of products are crucial to establish the potential of these techniques in obtaining safe, quality foods.