Functional foods to counterbalance low-grade inflammation and oxidative stress in cardiovascular diseases: a multilayered strategy combining food and health sciences

Functional foods (FF) have been studied for various physiologically relevant conditions, especially diet-related chronic diseases, such as type-2 diabetes, hypercholesterolaemia and cardiovascular diseases (CVD). In CVD, low-grade sterile inflammation and oxidative/nitrosative stress are at stake and should be mitigated using different approaches, such as the chronic use of medications and radical changes in life/eating habits. Considering the well-known relationship between oxidative stress/ inflammation and CVDs, this paper describes how the development of FF destined to target CVDs should be considered in light of the inflammation and oxidative cascades in vivo. The main target is to counterbalance the effects of oxidation and sustained inflammation by regulating the secretion of pro- and anti-inflammatory markers and enhancing endogenous protection systems that will ultimately retard the onset and progression of CVDs. Finally, a multilayered connection between food and health science is highlighted considering the FF context.</p

Cellular antioxidant activity measurement: An alternative to chemical antioxidant methods?

Oxidative stress occurs when the production of reactive oxygen species (ROS) overpasses their degradation and buffering by endogenous antioxidants and those derived from the diet (exogenous antioxidants). In food science and nutrition, assessing antioxidant activity relies on chemical reactions—chemical test‐tube assays—and human and murine cell lines. Usually, an ROS inductor, such as hydrogen peroxide (H2O2) or peroxyl radicals (ROO• ), is used to induce oxidation. Some biomarkers related to endogenous protection (i.e., catalase, superoxide dis?mutase, and glutathione reductase), oxidation‐end products (i.e., malondialdehyde), and intracellular ROS generation can be quantitatively determined. Herein, some insights into using human cell lines and related biomarkers are described, and the downsides of using chemical antioxidant assays are explained. In conclusion, research on antioxidants should be based on using relevant human cell cultures. In contrast, chemical antioxidant assays should be limited to an initial screening as their physiological importance is negligible.</p

Next-generation analytical platforms for antioxidant capacity assessment: The urge for realistic and physiologically relevant methods

Bioactive compounds, such as carotenoids, alkaloids, and phenolics, are well known because of their alleged  health benefits when consumed regularly in a balanced healthy diet. Some well-documented bioactivities are  antioxidant, antihypertensive, antihyperglycemic, antilipidemic, anti-obesity, anti-inflammatory, and antimicrobial capacities. Trying to associate the chemical composition of distinct sources and their bioactivity using in  vitro methods, several assays have been developed, implemented, and optimised to recapitulate human physiological conditions. However, in most cases, pitfalls are apparent, and no single test tube-based assay can predict in vivo responses. The need for a more physiologically relevant cell-based method to evaluate the antioxidant  capacity of putative antioxidants is apparent. Therefore, in this Review, the current state-of-the-art in food  science and nutrition is aligned with cell biology/bioengineering approaches to propose combining in vitro  digestion and absorption to obtain a bioavailable fraction containing antioxidants. Overall, human plasma, 2-  dimensional human cell lines, such as erythrocytes, lymphocytes, hepatocytes, enterocytes and, ultimately, 3-  dimensional spheroids (organoids) could be used as biologically relevant models to assess the antioxidant activity of compounds, foods, and nutraceuticals. This versatile approach is deemed suitable, accurate, reproducible, and physiologically relevant to evaluate the protective effects of antioxidants against ROS-mediated  oxidation in vitro.  </p

Comparison of antioxidant capacity and network pharmacology of phloretin and phlorizin against neuroinflammation in traumatic brain injury

Neuroinflammation is a hallmark of traumatic brain injury (TBI)’s acute and chronic phases. Despite the medical and scientific advances in recent years, there is still no effective treatment that mitigates the oxidative and inflammatory damage that affects neurons and glial cells. Therefore, searching for compounds with a broader spectrum of action that can regulate various inflammatory signaling pathways is of clinical interest. In this study, we determined not only the in vitro antioxidant capacity of apple pomace phenolics, namely, phlorizin and its metabolite, phloretin, but we also hypothesize that the use of these bioactive molecules may have potential use in TBI. We explored the antioxidant effects of both compounds in vitro (DPPH, iron-reducing capacity (IRC), and Folin– Ciocalteu reducing capacity (FCRC)), and using network pharmacology, we investigated the proteins involved in their protective effects in TBI. Our results showed that the antioxidant properties of phloretin were superior to those of phlorizin in the DPPH (12.95 vs. 3.52 mg ascorbic acid equivalent (AAE)/L), FCRC (86.73 vs. 73.69 mg gallic acid equivalent (GAE)/L), and iron-reducing capacity (1.15 vs. 0.88 mg GAE/L) assays. Next, we examined the molecular signature of both compounds and found 11 proteins in common to be regulated by them and involved in TBI. Meta-analysis and GO functional enrichment demonstrated their implication in matrix metalloproteinases, p53 signaling, and cell secretion/transport. Using MCODE and Pearson’s correlation analysis, a subcluster was generated. We identified ESR1 (estrogen receptor alpha) as a critical cellular hub being regulated by both compounds and with potential therapeutic use in TBI. In conclusion, our study suggests that because of their vast antioxidant effects, probably acting on estrogen receptors, phloretin and phlorizin may be repurposed for TBI treatment due to their ease of obtaining and low cost. </p

Macroporous resin purification of phenolics from Irish apple pomace: Chemical characterization, and cellular antioxidant and anti-inflammatory activities

Apple pomace (AP) is a highly prevalent waste product worldwide in the fruit processing sector. This study compared the chemical profile, antioxidant, and anti-inflammatory activities of crude (CE) and an extract purified using XAD-7 resin (PE). The purification process increased the total phenolic content, flavonoids, and tannins by 3.35, 40.31, and 8.87-fold, respectively. The main phenolic compounds identified in PE were phlorizin (20.54 mg/g), chlorogenic acid (10.01 mg/g), and hyperoside (2.77 mg/g). No difference was found between CE and PE in protecting human plasma against oxidation. In human erythrocytes, both CE and PE decreased the reactive oxygen species (ROS) generation and decreased lipoperoxidation. However, PE had stronger anti-inflammatory effects than CE by promoting HO-1 gene expression, suppressing NO production, and inhibiting IL-1β, IL-6, and IL-10 mRNA expression in lipopolysaccharide-challenged RAW.264.7 macrophages. Therefore, purifying apple pomace crude extract is a promising approach to boosting valuable antioxidants and anti-inflammatory phenolics.</p

Seed phytochemical profiling of three olive cultivars, antioxidant capacity, enzymatic inhibition, and effects on human neuroblastoma cells (SH-SY5Y)

This work evaluated the phytochemical composition of olive seed extracts from different cultivars (‘Cobrançosa’, ‘Galega’, and ’Picual’) and their antioxidant capacity. In addition, it also appraised their potential antineurodegenerative properties on the basis of their ability to inhibit enzymes associated with neurodegenerative diseases: acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase (TYR). To achieve this goal, the phenolic composition of the extracts was deter-mined through high-performance liquid chromatography coupled with photodiode-array detection and electrospray ionization/ion trap mass spectrometry (HPLC-DAD-ESI/MSn ).The antioxidant capacity was assessed by two different methods (ABTS•+ and DPPH•), and the antineurodegenerative potential by the capacity of these extracts to inhibit the aforementioned related enzymes. The results showed that seed extracts presented a high content of phenolic compounds and a remarkable ability to scavenge ABTS•+ and DPPH•. Tyrosol, rutin, luteolin-7-glucoside, nüzhenide, oleuropein, and ligstroside were the main phenolic compounds identified in the extracts. ‘Galega’ was the most promising cultivar due to its high concentration of phenolic compounds, high antioxidant capacity, and remarkable inhibition of AChE, BChE, and TYR. It can be concluded that olive seed extracts may provide a sustainable source of bioactive compounds for medical and industrial applications.</p

A mosaic-structured framework applied in the healthy food design: insights from integrated in silico and in vitro approaches

Agrifood system technologies have enabled the development of novel foods with enhanced nutritional composition. Herein, we provide an overview of food model/prototype development by placing natural compounds (NCs) as an inspiration source through the combination of multidisciplinary approaches and food technologies. To design healthy foods, we propose that these interlinked technologies derived from applied fields, such as nutrition, chemical synthesis, pharmacology and food technology should be combined with biological system analyses. Food molecule development is a slow process with mandatory steps based on desired bioactive properties, which is challenged by food matrix diversity and the difficulty of reconstituting its biosynthetic pathways. Overcoming these challenges should be the primary trend in food science, leading to more sustainable processes and health benefits.</p

Atherosclerosis fate in the era of tailored functional foods: Evidence-based guidelines elicited from structure- and ligand-based approaches

Background: Atherosclerosis is the primary cause of cardiovascular diseases (CVDs), contributing to more than 33% of the annual deaths globally. Westernized dietary patterns, a high prevalence (50%) of overweight and obesity, and an increased incidence of glucose intolerance and type-2 diabetes are related to atherosclerosis. However, increased demand for functional foods has boosted the production of different foods to improve people’s life quality and decrease the CVDs’ risk. Nonetheless, functional foods targeting CVDs are scarce in the marketplace.  Scope and approach: To perform a multidisciplinary and cross-sectoral approach by linking atherosclerosis bio-markers, potential bioactive compounds (e.g., phenolics), and food technology, besides scientific limitations, we propose a practical step-by-step guide to designing functional foods. First, a comprehensive and up-to-date overview of atherosclerosis is provided, focusing on the inflammation markers to counteract its onset and proression. Then, a structure-based–(SBDD) or ligand-based drug design (LBDD) approach is presented, and illustrated by the incorporation of vescalagin, a phenolic compound from jaboticaba seed, into a functional food to mitigate atherosclerosis. Key findings and conclusions: Tailored functional foods added with phenolic compounds can be designed through computational approaches predicting their bioactivity. Together with chemical analyses, mathematical models can explore a vast array of molecular mechanisms, allowing the discovery of novel bioactive compound sources. Altogether, food science/technology, nutrition, and structure- and ligand-based approaches should be combined to support the design of tailor-made functional foods/nutraceuticals to contribute to public health interventions related to atherosclerosis and other cardiometabolic diseases</p

Jabuticaba (myrciaria jaboticaba) peel as a sustainable source of anthocyanins and ellagitannins delivered by phospholipid vesicles for alleviating oxidative stress in human keratinocytes

The Brazilian berry scientifically known as jabuticaba is a fruit covered by a dark purple peel that is still rich in bioactives, especially polyphenols. Considering that, this work was aimed at obtaining an extract from the peel of jabuticaba fruits, identifying its main components, loading it in phospholipid vesicles specifically tailored for skin delivery and evaluating their biological efficacy. The extract was obtained by pressurized hot water extraction (PHWE), which is considered an easy and low dissipative method, and it was rich in polyphenolic compounds, especially flavonoids (ortho-diphenols and condensed tannins), anthocyanins (cyanidin 3-O-glucoside and delphinidin 3-O-glucoside) and gallic acid, which were responsible for the high antioxidant activity detected using different colorimetric methods (DPPH, FRAP, CUPRAC and metal chelation). To improve the stability and extract effectiveness, it was incorporated into ultradeformable phospholipid vesicles (transfersomes) that were modified by adding two different polymers (hydroxyethyl cellulose and sodium hyaluronate), thus obtaining HEcellulose transfersomes and hyaluronan-transfersomes. Transfersomes without polymers were the smallest, as the addition of the polymer led to the formation of larger vesicles that were more stable in storage. The incorporation of the extract in the vesicles promoted their beneficial activities as they were capable, to a greater extent than the solution used as reference, of counteracting the toxic effect of hydrogen peroxide and even of speeding up the healing of a wound performed in a cell monolayer, especially when vesicles were enriched with polymers. Given that, polymer enriched vesicles may represent a good strategy to produce cosmetical and cosmeceutical products with beneficial properties for skin

Comprehensive applications of metabolomics on tea science and technology: opportunities, hurdles, and perspectives

With the development of metabolomics analytical techniques, relevant studies have increased in recent decades. The procedures of metabolomics analysis mainly include sample preparation, data acquisition and pre-processing, multivariate statistical analysis, as well as maker compounds’ identification. In the present review, we summarized the published articles of tea metabolomics regarding different analytical tools, such as mass spectrometry, nuclear magnetic resonance, ultraviolet–visible spectrometry, and Fourier transform infrared spectrometry. The metabolite variation of fresh tea leaves with different treatments, such as biotic/abiotic stress, horticultural measures, and nutritional supplies was reviewed. Furthermore, the changes of chemical composition of processed tea samples under different processing technologies were also profiled. Since the identification of critical or marker metabolites is a complicated task, we also discussed the procedure of metabolite identification to clarify the importance of omics data analysis. The present review provides a workflow diagram for tea metabolomics research and also the perspectives of related studies in the future</p