Integration of multi-omics analysis reveals metabolic alterations of B lymphocytes in systemic lupus erythematosus.

OBJECTIVE: To link changes in the B-cell transcriptome from systemic lupus erythematosus (SLE) patients with those in their macroenvironment, including cellular and fluidic components. METHODS: Analysis was performed on 363 patients and 508 controls, encompassing transcriptomics, metabolomics, and clinical data. B-cell and whole-blood transcriptomes were analysed using DESeq and GSEA. Plasma and urine metabolomics peak changes were quantified and annotated using Ceu Mass Mediator database. Common sources of variation were identified using MOFA integration analysis. RESULTS: Cellular macroenvironment was enriched in cytokines, stress responses, lipidic synthesis/mobility pathways and nucleotide degradation. B cells shared these pathways, except nucleotide degradation diverted to nucleotide salvage pathway, and distinct glycosylation, LPA receptors and Schlafen proteins. CONCLUSIONS: B cells showed metabolic changes shared with their macroenvironment and unique changes directly or indirectly induced by IFN-α signalling. This study underscores the importance of understanding the interplay between B cells and their macroenvironment in SLE pathology.

Identification of Bioactive Compounds of Asparagus officinalis L.: Permutation Test Allows Differentiation among "Triguero" and Hybrid Green Varieties.

In this study, we determined the phytochemical profile of the Spanish "triguero" asparagus landrace "verde-morado" (Asparagus officinalis L.), a wild traditional landrace, and the improved "triguero" HT-801, together with two commercial green asparagus varieties. For comparison, we used reverse-phase high-performance liquid chromatography coupled with diode array electrospray time-of-flight mass spectrometry (RP-HPLC-DAD-ESI-TOF/MS) followed by a permutation test applied using a resampling methodology valid under a relaxed set of assumptions, such as i.i.d. errors (not necessarily normal) that are exchangeable under the null hypothesis. As a result, we postulate that "triguero" varieties (the improved HT-801 followed by its parent "verde-morado") have a significantly different phytochemical profile from that of the other two commercial hybrid green varieties. In particular, we found compounds specific to the "triguero" varieties, such as feruloylhexosylhexose isomers, or isorhamnetin-3-O-glucoside, which was found only in the "triguero" variety HT-801. Although studies relating the phytochemical content of "triguero" asparagus varieties to its health-promoting effects are required, this characteristic phytochemical profile can be used for differentiating and revalorizating these asparagus cultivars.

Metabolic Disturbances in Urinary and Plasma Samples from Seven Different Systemic Autoimmune Diseases Detected by HPLC-ESI-QTOF-MS.

Systemic autoimmune diseases (SADs) are characterized by dysfunctioning of the immune system, which causes damage in several tissues and organs. Among these pathologies are systemic lupus erythematosus (SLE), systemic sclerosis or scleroderma, Sjögren's syndrome, rheumatoid arthritis, primary antiphospholipid syndrome (PAPS), mixed connective tissue disease (MCTD), and undifferentiated connective tissue disease (UCTD). Early diagnosis is difficult due to similarity in symptoms, signs, and clinical test results. Hence, our aim was to search for differentiating metabolites of these diseases in plasma and urine samples. We performed metabolomic profiling by liquid chromatography-mass spectrometry (LC-MS) of samples from 228 SADs patients and 55 healthy volunteers. Multivariate PLS models were applied to investigate classification accuracies and identify metabolites differentiating SADs and healthy controls. Furthermore, we specifically investigated UCTD against the other SADs. PLS models were able to classify most SADs vs healthy controls (area under the roc curve (AUC) > 0.7), with the exception of MCTD and PAPS. Differentiating metabolites consisted predominantly of unsaturated fatty acids, acylglycines, acylcarnitines, and amino acids. In accordance with the difficulties in defining UCTD, the UCTD metabolome did not differentiate well from the other SADs. However, most UCTD cases were classified as SLE, suggesting that metabolomics may provide a tool to reassess UCTD diagnosis into other conditions for more well-informed therapeutic strategies.

New technological approaches for recovering bioactive food constituents from sweet cherry (Prunus avium L.) stems.

INTRODUCTION: In recent years, an increasing interest in biological properties of sweet cherry (Prunus avium L.) stems has resulted in increased attention for advanced extraction techniques and their optimisation. OBJECTIVES: In the present study chemical profiles of P. avium stems extracts obtained by selected emerging technologies, such as pressurised liquid extraction (PLE) and supercritical fluid extraction (SFE), under different experimental conditions were compared. MATERIAL AND METHODS: All SFEs were carried out at 40°C in a dynamic mode with different solvent combinations (CO2 plus ethanol at 7 and 15%) and pressures (150 and 300 bar). The PLE experiments were performed in a static mode for all tested combinations of extraction solvent (ethanol-water from 0% to 100%) at temperatures ranging from 40 to 200°C. A complete analytical characterisation of cherry stem extracts was performed by high-performance liquid chromatography coupled to electrospray ionisation quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS). RESULTS: PLE showed to be more efficient than SFE removing a wide variety of compounds with different polarities being phenols the most abundant, whereas SFE resulted in a higher amount of fatty acids and derivatives. Chemical characterisation of the extracts was carried out by HPLC-ESI-QTOF-MS yielding in total 42 identified compounds, among which 22 compounds were identified in P. avium stems for the first time. CONCLUSION: These results point out the possibility of sweet cherry stem extracts to be incorporated in formulations manufactured by food and pharmaceutical industry. Also, these new thermal and high-pressure industrial technologies proved to be promising candidates in the valorisation of sweet cherry by-product.

Comparative Assessment of Phytochemical Profiles of Comfrey (Symphytum officinale L.) Root Extracts Obtained by Different Extraction Techniques.

In this work a comparative study on phytochemical profiles of comfrey root extracts obtained by different extraction approaches has been carried out. Chemical profiles of extracts obtained by supercritical fluid (SFE), pressurized liquid (PLE), and conventional solid/liquid extraction were compared and discussed. Phytochemical composition was assessed by high-performance liquid chromatography coupled with electrospray time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS/MS) identifying 39 compounds reported for the first time in comfrey root, mainly phenolic acids and fatty acids. The influence of different extraction parameters on phytochemical profiles of S. officinale root was investigated for all applied techniques. PLE and maceration, using alcohol-based solvents (aqueous methanol or ethanol), were shown to be more efficient in the recovery of more polar compounds. Greater numbers of phenolics were best extracted by PLE using 85% EtOH at 63 °C. The use of SFE and 100% acetone for 30 min enabled good recoveries of nonpolar compounds. SFE using 15% EtOH as a cosolvent at 150 bar produced the best recoveries of a significant number of fatty acids. The main compositional differences between extracts obtained by different extraction techniques were assigned to the solvent type. Hence, these results provided comprehensive approaches for treating comfrey root enriched in different phytochemicals, thereby enhancing its bioaccessibility.

In-Depth Characterization of Bioactive Extracts from Posidonia oceanica Waste Biomass.

Posidonia oceanica waste biomass has been valorised to produce extracts by means of different methodologies and their bioactive properties have been evaluated. Water-based extracts were produced using ultrasound-assisted and hot water methods and classified according to their ethanol-affinity (E1: ethanol soluble; E2: non-soluble). Moreover, a conventional protocol with organic solvents was applied, yielding E3 extracts. Compositional and structural characterization confirmed that while E1 and E3 extracts were mainly composed of minerals and lipids, respectively, E2 extracts were a mixture of minerals, proteins and carbohydrates. All the extracts showed remarkably high antioxidant capacity, which was not only related to phenolic compounds but also to the presence of proteins and polysaccharides. All E2 and E3 extracts inhibited the growth of several foodborne fungi, while only E3 extracts decreased substantially the infectivity of feline calicivirus and murine norovirus. These results show the potential of P. oceanica waste biomass for the production of bioactive extracts.

Water Extract of Cryphaea heteromalla (Hedw.) D. Mohr Bryophyte as a Natural Powerful Source of Biologically Active Compounds.

Bryophytes comprise of the mosses, liverworts, and hornworts. Cryphaea heteromalla, (Hedw.) D. Mohr, is a non-vascular lower plant belonging to mosses group. To the date, the most chemically characterized species belong to the liverworts, while only 3.2% and 8.8% of the species belonging to the mosses and hornworts, respectively, have been investigated. In this work, we present Folin-Ciocalteu and oxygen radical absorbance capacity (ORAC) data related to crude extracts of C. heteromalla obtained by three different extraction solvents: pure water (WT), methanol:water (80:20 v/v) (MET), and ethanol:water (80:20 v/v) (ETH). The water extract proved to be the best solvent showing the highest content of biophenols and the highest ORAC value. The C. heteromalla-WT extract was investigated by HPLC-TOF/MS (High Performance Liquid Chromatography-Time of Flight/Mass Spectrometry) allowing for the detection of 14 compounds, five of which were phenolic compounds, derivatives of benzoic, caffeic, and coumaric acids. Moreover, the C. heteromalla WT extract showed a protective effect against reactive oxygen species (ROS) generation induced by tert-butyl hydroperoxide (TBH) on the murine NIH-3T3 fibroblast cell line.

Obtaining an Extract Rich in Phenolic Compounds from Olive Pomace by Pressurized Liquid Extraction.

The olive oil industry produces large volumes of wastes, which are also potential sources of bioactive compounds by developing healthy and/or functional foods. Extraction of phenolic compounds from the residues of the olive oil is mainly carried out with solvents. However, there is currently a growing public awareness about the use of organic solvents in food processing, which has pointed out the need for the application of clean technologies such as pressurized liquid extraction (PLE). Therefore, the aim of this research was to optimize the phenolic compound extraction from olive pomace by PLE, establishing the qualitative and quantitative phenolic profile by HPLC-ESI-TOF/MS. The extraction design to recover phenolics from olive pomace demonstrates a great compositional variability of PLE extracts obtained under different experimental conditions. Indeed, quantitative results have pointed out the selectivity of PLE extraction when this technique is applied to the treatment of olive pomace. PLE-optimized conditions showed higher total phenolic compound content than conventional extraction (1659 mg/kg d.w. and 281.7 mg/kg d.w., respectively). Among these phenolics, the quantity of secoiridoids and flavonoids in the optimized PLE extract was three and four times higher than in conventional extracts. Furthermore, optimal PLE conditions allowed to obtain an enriched hydroxytyrosol extract which was not detected in the conventional one.

Extra-virgin olive oil contains a metabolo-epigenetic inhibitor of cancer stem cells.

Targeting tumor-initiating, drug-resistant populations of cancer stem cells (CSC) with phytochemicals is a novel paradigm for cancer prevention and treatment. We herein employed a phenotypic drug discovery approach coupled to mechanism-of-action profiling and target deconvolution to identify phenolic components of extra virgin olive oil (EVOO) capable of suppressing the functional traits of CSC in breast cancer (BC). In vitro screening revealed that the secoiridoid decarboxymethyl oleuropein aglycone (DOA) could selectively target subpopulations of epithelial-like, aldehyde dehydrogenase (ALDH)-positive and mesenchymal-like, CD44+CD24-/low CSC. DOA could potently block the formation of multicellular tumorspheres generated from single-founder stem-like cells in a panel of genetically diverse BC models. Pretreatment of BC populations with noncytotoxic doses of DOA dramatically reduced subsequent tumor-forming capacity in vivo. Mice orthotopically injected with CSC-enriched BC-cell populations pretreated with DOA remained tumor-free for several months. Phenotype microarray-based screening pointed to a synergistic interaction of DOA with the mTOR inhibitor rapamycin and the DNA methyltransferase (DNMT) inhibitor 5-azacytidine. In silico computational studies indicated that DOA binds and inhibits the ATP-binding kinase domain site of mTOR and the S-adenosyl-l-methionine (SAM) cofactor-binding pocket of DNMTs. FRET-based Z-LYTE™ and AlphaScreen-based in vitro assays confirmed the ability of DOA to function as an ATP-competitive mTOR inhibitor and to block the SAM-dependent methylation activity of DNMTs. Our systematic in vitro, in vivo and in silico approaches establish the phenol-conjugated oleoside DOA as a dual mTOR/DNMT inhibitor naturally occurring in EVOO that functionally suppresses CSC-like states responsible for maintaining tumor-initiating cell properties within BC populations.

Optimization of drying process and pressurized liquid extraction for recovery of bioactive compounds from avocado peel by-product.

The aim of the present study was to optimize the extraction of phenolic compounds in avocado peel using pressurized liquid extraction (PLE) with GRAS solvents. Response surface methodology (RSM) based on Central Composite Design 22 model was used in order to optimize PLE conditions. Moreover, the effect of air drying temperature on the total polyphenol content (TPC) and individual phenolic compounds concentration were evaluated. The quantification of individual compounds was performed by HPLC-DAD-ESI-TOF-MS. The optimized extraction conditions were 200°C as extraction temperature and 1:1 v/v as ethanol/water ratio. Regarding to the effect of drying, the highest TPC was obtained with a drying temperature of 85°C. Forty seven phenolic compounds were quantified in the obtained extracts, showing that phenolic acids found to be the more stables compounds to drying process, while procyanidins were the more thermolabiles analytes. To our knowledge, this is the first available study in which phenolic compounds extraction was optimized using PLE and such amount of phenolic compounds was quantified in avocado peel. These results confirm that PLE represents a powerful tool to obtain avocado peel extracts with high concentration in bioactive compounds suitable for its use in the food, cosmetic or pharmaceutical sector.

Cocoa and Grape Seed Byproducts as a Source of Antioxidant and Anti-Inflammatory Proanthocyanidins.

Phenolic compounds, which are secondary plant metabolites, are considered an integral part of the human diet. Physiological properties of dietary polyphenols have come to the attention in recent years. Especially, proanthocyanidins (ranging from dimers to decamers) have demonstrated potential interactions with biological systems, such as antiviral, antibacterial, molluscicidal, enzyme-inhibiting, antioxidant, and radical-scavenging properties. Agroindustry produces a considerable amount of phenolic-rich sources, and the ability of polyphenolic structures to interacts with other molecules in living organisms confers their beneficial properties. Cocoa wastes and grape seeds and skin byproducts are a source of several phenolic compounds, particularly mono-, oligo-, and polymeric proanthocyanidins. The aim of this work is to compare the phenolic composition of Theobroma cacao and Vitis vinifera grape seed extracts by high pressure liquid chromatography coupled to a quadrupole time-of-flight mass spectrometer and equipped with an electrospray ionization interface (HPLC-ESI-QTOF-MS) and its phenolic quantitation in order to evaluate the proanthocyanidin profile. The antioxidant capacity was measured by different methods, including electron transfer and hydrogen atom transfer-based mechanisms, and total phenolic and flavan-3-ol contents were carried out by Folin-Ciocalteu and Vanillin assays. In addition, to assess the anti-inflammatory capacity, the expression of MCP-1 in human umbilical vein endothelial cells was measured.

Further exploring the absorption and enterocyte metabolism of quercetin forms in the Caco-2 model using nano-LC-TOF-MS.

When using the Caco-2 intestinal model, the low uptake, intracellular presence at low levels as well as generation of trace metabolites may limit the analysis of flavonoids. To overcome these limitations, we performed a simple but sensitive methodology based on nano-LC-TOF-MS, using an on-line trapping step. The analytical method was validated for quercetin, quercetin 3-O-glucoside, and quercetin 3-O-glucuronide and the reliability for characterization using lock-mass calibration was also assessed along the linear range. Afterwards, the in vitro absorption, metabolism, and cellular occurrence were explored with the proposed methodology. The apparent permeability coefficient in the absorptive direction and the cellular accumulation were higher for quercetin aglycone, with a value of 2.61 × 10(-6) cm/s and relative amounts of 0.73 and 1.17% in the cytosolic and solid particle fraction at the end of the assay, respectively. Alternatively, the net efflux ratio was lower for quercetin than for their derivatives. Moreover, depending on the structure of the parent compound, metabolites were generated by glucuronidation, sulfation, and methylation.

Permeability Study of Polyphenols Derived from a Phenolic-Enriched Hibiscus sabdariffa Extract by UHPLC-ESI-UHR-Qq-TOF-MS.

Previous findings on the capacity of Hibiscus sabdariffa (HS) polyphenols to ameliorate metabolic disturbances justify the necessity of studies oriented to find the potential metabolites responsible for such an effect. The present study examined the intestinal epithelial membrane permeability of polyphenols present in a phenolic-enriched Hibiscus sabdariffa extract (PEHS), free and encapsulated, using the Caco-2 cell line. Additionally, selected polyphenols (quercetin, quercetin-3-glucoside, quercetin-3-glucuronide, and N-feruloyltyramine) were also studied in the same absorption model. The powerful analytical platform used ultra-high-performance liquid chromatography coupled with ultra-high-resolution quadrupole time-of-flight mass spectrometry (UHPLC-ESI-UHR-Qq-TOF-MS), and enabled the characterization of seven new compounds in PEHS. In the permeation study, only a few compounds were able to cross the cell monolayer and the permeability was lower when the extract was in an encapsulated form. Pure compounds showed a moderate absorption in all cases. Nevertheless, these preliminary results may need further research to understand the complete absorption mechanism of Hibiscus polyphenols.

Rosmarinus officinalis leaves as a natural source of bioactive compounds.

In an extensive search for bioactive compounds from plant sources, the composition of different extracts of rosemary leaves collected from different geographical zones of Serbia was studied. The qualitative and quantitative characterization of 20 rosemary (Rosmarinus officinalis) samples, obtained by microwave-assisted extraction (MAE), was determined by high performance liquid chromatography coupled to electrospray quadrupole-time of flight mass spectrometry (HPLC-ESI-QTOF-MS). The high mass accuracy and true isotopic pattern in both MS and MS/MS spectra provided by the QTOF-MS analyzer enabled the characterization of a wide range of phenolic compounds in the extracts, including flavonoids, phenolic diterpenes and abietan-type triterpenoids, among others. According to the data compiled, rosemary samples from Sokobanja presented the highest levels in flavonoids and other compounds such as carnosol, rosmaridiphenol, rosmadial, rosmarinic acid, and carnosic acid. On the other hand, higher contents in triterpenes were found in the extracts of rosemary from Glozan (Vojvodina).

Monitoring the Phenolic and Terpenic Profile of Olives, Olive Oils and By-Products throughout the Production Process.

Olive oil is a food of great importance in the Mediterranean diet and culture. However, during its production, the olive oil industry generates a large amount of waste by-products that can be an important source of bioactive compounds, such as phenolic compounds and terpenes, revalorizing them in the context of the circular economy. Therefore, it is of great interest to study the distribution and abundance of these bioactive compounds in the different by-products. This research is a screening focused on phytochemical analysis, with particular emphasis on the identification and quantification of the phenolic and terpenic fractions. Both the main products of the olive industry (olives, olive paste and produced oil) and the by-products generated throughout the oil production process (leaf, "alpeorujo", liquid and solid residues generated during decanting commonly named "borras" and washing water) were analyzed. For this purpose, different optimized extraction procedures were performed for each matrix, followed by high-performance liquid chromatography coupled with electrospray time-of-flight mass spectrometry (HPLC-ESI-TOF/MS) analysis. Although no phenolic alcohols were quantified in the leaf and the presence of secoiridoids was low, this by-product was notable for its flavonoid (720 ± 20 µg/g) and terpene (5000 ± 300 µg/g) contents. "Alpeorujo" presented a complete profile of compounds of interest, being abundant in phenolic alcohols (900 ± 100 µg/g), secoiridoids (4500 ± 500 µg/g) and terpenes (1200 ± 100 µg/g), among others. On the other hand, while the solid residue of the borras was the most abundant in phenolic alcohols (3700 ± 200 µg/g) and secoiridoids (680 ± 20 µg/g), the liquid fraction of this waste was notable for its content of elenolic acid derivatives (1700 ± 100 µg/mL) and phenolic alcohols (3000 ± 300 µg/mL). Furthermore, to our knowledge, this is the first time that the terpene content of this by-product has been monitored, demonstrating that it is an important source of these compounds, especially maslinic acid (120 ± 20 µg/g). Finally, the phytochemical content in wash water was lower than expected, and only elenolic acid derivatives were detected (6 ± 1 µg/mL). The results highlighted the potential of the olive by-products as possible alternative sources of a wide variety of olive bioactive compounds for their revalorization into value-added products.

Mass Spectrometry Characterization of Honeydew Honey: A Critical Review.

Honeydew honey is produced by bees (Apis mellifera) foraging and collecting secretions produced by certain types of aphids on various parts of plants. In addition to exhibiting organoleptic characteristics that distinguish them from nectar honey, these honeys are known for their functional properties, such as strong antioxidant and anti-inflammatory activities. Despite their importance, they remain poorly characterized in comparison with flower honeys, as most studies on this subject are not only carried out on too few samples but also still focused on traditional chemical-physical parameters, such as specific rotation, major sugars, or melissopalynological information. Since mass spectrometry has consistently been a primary tool for the characterization and authentication of honeys, this review will focus on the application of these methods to the characterization of the minor fraction of honeydew honey. More specifically, this review will attempt to highlight what progress has been made so far in identifying markers of the authenticity of the botanical and/or geographical origin of honeydew honeys by mass spectrometry-based approaches. Furthermore, strategies devoted to the determination of contaminants and toxins in honeydew honeys will be addressed. Such analyses represent a valuable tool for establishing the level of food safety associated with these products. A critical analysis of the presented studies will identify their limitations and critical issues, thereby describing the current state of research on the topic.

Suppression of sweet taste-related responses by plant-derived bioactive compounds and eating. Part I: A systematic review in humans.

The taste of food plays a crucial role in determining what and how much we eat. Thus, interventions that temporarily block sweet taste receptors offer a promising approach to addressing unhealthy behaviours associated with sugary foods. However, the relationship between reduced sweet taste response and food consumption remains unclear, with contradictory findings. Certain studies suggest that a diminished perception of sweetness leads to a sense of fullness and results in reduced food intake, while others suggest the opposite effect. To shed some light, our systematic review looked into the relationship between diminished sweet taste response and food consumption by examining the effects of bioactive compounds that experimentally inhibit sweetness in healthy individuals. This review was registered in the International Prospective Register of Systematic Reviews and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Scottish Intercollegiate Guidelines Network, and covered original papers included in Web of Science, PubMed, Scopus, Food Science Source and Food Science and technology abstracts. We identified 33 peer-reviewed English-language studies that fit the topic and met the inclusion criteria. The current literature predominantly focuses on the immediate impact of oral gymnemic acids, failing to provide preliminary evidence in support of the specific threshold hypothesis, above which food consumption decreases and below which the opposite effect occurs. Additionally, there was inconsistency in the findings regarding the short-term desire to eat following sweetness inhibition. Considering the downstream effects on energy intake and their clinical applications, further research is needed to clarify both the acute within-session effects (i.e., not wanting any more now) and the longer-term effects (i.e., deciding not to start eating) linked to oral sweet-taste-suppressing compounds.

Suppression of sweet taste-related responses by plant-derived bioactive compounds and eating. Part II: A systematic review in animals.

This article, the second in a two-part series, continues the discussion on the nature of the relationship between the level of sweet taste suppression and eating behaviour, but in animal rather human subjects. In particular, the aim was to review the scientific literature on the impact that bioactive compounds that decrease oral sweet sensations have on intake, preference and physiological status in preclinical studies. This review was registered in the International Prospective Register of Systematic Reviews and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Scottish Intercollegiate Guidelines Network and covered original papers included in Web of Science, PubMed, Scopus, Food Science Source and Food Science and technology abstracts. We identified 28 peer-reviewed English-language studies that fit the topic and met the inclusion criteria. We identified three plant species, Gymnema sylvestre, Hovenia dulcis, and Ziziphus jujuba, that possess acute sweetness-inhibitory properties. When administered orally, these plants reduced neural responses to sweet stimuli and decreased consumption. However, studies on the longer-term effects of antisweet activity remain to be conducted. Translating the valuable insights into the mechanisms underlying the relationship between sweet taste impairment and eating behaviour into practical clinical applications are discussed.

Extraction, Characterization, and Bioactivity of Phenolic Compounds-A Case on Hibiscus Genera.

Phenolic compounds have recently gained interest, as they have been related to improvements in health and disease prevention, such as inflammatory intestinal pathologies and obesity. However, their bioactivity may be limited by their instability or low concentration in food matrices and along the gastrointestinal tract once consumed. This has led to the study of technological processing with the aim of optimizing phenolic compounds' biological properties. In this sense, different extraction systems have been applied to vegetable sources for the purpose of obtaining enriched phenolic extracts such as PLE, MAE, SFE, and UAE. In addition, many in vitro and in vivo studies evaluating the potential mechanisms of these compounds have also been published. This review includes a case study of the Hibiscus genera as an interesting source of phenolic compounds. The main goal of this work is to describe: (a) phenolic compound extraction by designs of experiments (DoEs) applied to conventional and advanced systems; (b) the influence of the extraction system on the phenolic composition and, consequently, on the bioactive properties of these extracts; and (c) bioaccessibility and bioactivity evaluation of Hibiscus phenolic extracts. The results have pointed out that the most used DoEs were based on response surface methodologies (RSM), mainly the Box-Behnken design (BBD) and central composite design (CCD). The chemical composition of the optimized enriched extracts showed an abundance of flavonoids, as well as anthocyanins and phenolic acids. In vitro and in vivo studies have highlighted their potent bioactivity, with particular emphasis on obesity and related disorders. This scientific evidence establishes the Hibiscus genera as an interesting source of phytochemicals with demonstrated bioactive potential for the development of functional foods. Nevertheless, future investigations are needed to evaluate the recovery of the phenolic compounds of the Hibiscus genera with remarkable bioaccessibility and bioactivity.

Non-Digestible Carbohydrates: Green Extraction from Food By-Products and Assessment of Their Effect on Microbiota Modulation.

The nature and composition of the waste produced by food industrial processing make its abundance and accumulation an environmental problem. Since these by-products may present a high potential for revalorization and may be used to obtain added-value compounds, the main goals of the technological advancements have been targeted at reducing the environmental impact and benefiting from the retrieval of active compounds with technological and health properties. Among the added-value substances, nondigestible carbohydrates have demonstrated promise. In addition to their well-known technological properties, they have been discovered to modify the gut microbiota and enhance immune function, including the stimulation of immune cells and the control of inflammatory reactions. Furthermore, the combination of these compounds with other substances such us phenols could improve their biological effect on different noncommunicable diseases through microbiota modulation. In order to gain insight into the implementation of this combined strategy, a broader focus concerning different aspects is needed. This review is focused on the optimized green and advanced extraction system applied to obtain added-value nondigestible carbohydrates, the combined administration with phenols and their beneficial effects on microbiota modulation intended for health and/or illness prevention, with particular emphasis on noncommunicable diseases. The isolation of nondigestible carbohydrates from by-products as well as in combination with other bioactive substances could provide an affordable and sustainable source of immunomodulatory chemicals.