Globe Artichoke (Cynara scolymus L.) By-Products in Food Applications: Functional and Biological Properties.

Globe artichoke (Cynara cardunculus var. scolymus L.) is widely cultivated in the Mediterranean area and Italy is one of the largest producers. A great issue is represented by its high amount of by-product, mainly consisting of external bracts and stems, but also of residual leaves, stalks, roots, and seeds. Artichoke by-products are rich in nutrients (carbohydrates and proteins) and bioactive compounds (polyphenols and terpenes) and represent potential ingredients for foodstuffs, functional foods, and food supplements, due to their functional and biological properties. In fact, artichoke by-products' components exhibit many beneficial effects, such as dyspeptic, prebiotic, antioxidant, anti-inflammatory, antiglycative, antimicrobial, anticarcinogenic, and hypolipidemic properties. Therefore, they can be considered potential food ingredients useful in reducing the risk of developing metabolic and age-related disorders. This work summarizes the economic and environmental impact of the recovery and valorization of artichoke by-products, focusing on rheological, physical, and biological properties of the different components present in each by-product and their different food applications.

Towards Valorization of Food-Waste-Derived Pectin: Recent Advances on Their Characterization and Application.

Pectin, a natural biopolymer, can be extracted from food waste biomass, adding value to raw materials. Currently, commercial pectin is mostly extracted from citrus peels (85.5%) and apple pomace (14.0%), with a small segment from sugar beet pulp (0.5%). However, driven by high market demand (expected to reach 2.12 billion by 2030), alternative agro-industrial waste is gaining attention as potential pectin sources. This review summarizes the recent advances in characterizing pectin from both conventional and emerging food waste sources. The focus is the chemical properties that affect their applications, such as the degree of esterification, the neutral sugars' composition, the molecular weight, the galacturonic acid content, and technological-functional properties. The review also highlights recent updates in nutraceutical and food applications, considering the potential use of pectin as an encapsulating agent for intestinal targeting, a sustainable biopolymer for food packaging, and a functional and emulsifying agent in low-calorie products. It is clear from the considered literature that further studies are needed concerning the complexity of the pectin structure extracted from emerging food waste raw materials, in order to elucidate their most suitable commercial application.

Valorization of Rice Husk (Oryza sativa L.) as a Source of In Vitro Antiglycative and Antioxidant Agents.

Rice husk is a good source of polyphenols, but it has not been efficiently utilized in food applications yet. Therefore, the aim of this work is to investigate, by in vitro assays, the polyphenolic extract (RHE) capacity of this waste to counteract the protein glycation at different stages of the reaction, correlating this activity with the antiradical properties. A microwave-assisted extraction using hydro-alcoholic solvents was applied to recover husk polyphenols. Extraction parameters were optimized by the design of the experiment. The extract with the highest polyphenolic recovery was obtained at 500 W and 90 °C, using 1:35 g of dry material/mL solvent, 80% ethanol, and a 5 min extraction time. Results highlight the ability of RHE to inhibit the formation of fructosamine in the early stage of glycation with a dose-dependent activity. Furthermore, in the middle stage of the reaction, the highest RHE tested concentration (2.5 mg/mL) almost completely inhibit the monitored advanced glycation end products (AGEs), as well as showing a good trapping ability against α-dicarbonyl intermediates. A strong positive correlation with antioxidant activity is also found. The obtained results are supported by the presence of ten polyphenols detected by RP-HPLC-DAD-ESI-MSn, mainly hydroxycinnamic acids and flavonoids, already reported in the literature as antiglycative and antioxidant agents.

Effect of the simulated digestion process on the chlorogenic acid trapping activity against methylglyoxal.

Chlorogenic acids are hydroxycinnamic derivatives widespread in food or food by-products, known for their antioxidant effects and ability to interfere with the formation of advanced glycation end products (AGEs). AGEs are potential glycotoxins involved in age-related disorders, such as diabetes, cardiovascular diseases, and neurological disorders. The ability of chlorogenic acids to inhibit AGE formation under physiological conditions needs further investigation other than the in vitro assays. Therefore, in this study, the capacity of 5-caffeoylquinic acid (5-CQA) to effectively trap methylglyoxal (MGO), an AGE precursor compound also present in daily consumed food, was investigated by evaluating 5-CQA and MGO metabolic fate when subjected to digestion. Two different in vitro digestion approaches (static based on the Infogest protocol and dynamic based on a novel millifluidic gastrointestinal model) were set up and the samples collected at different steps of the static and dynamic processes were analyzed by a validated RP-HPLC-DAD method. The obtained results indicated that the gastrointestinal process strongly affected the 5-CQA capacity to trap MGO and its resulting antiglycation activity. Therefore, preliminary investigation using advanced in vitro tests, particularly dynamic approaches, should always be performed to predict the effect of the digestion process on the potential bioactives present in food, food by-products, or plant extracts.

Rice Byproduct Compounds: From Green Extraction to Antioxidant Properties.

Currently, rice (Oryza sativa L.) production and consumption is increasing worldwide, and many efforts to decrease the substantial impact of its byproducts are needed. In recent years, the interest in utilizing rice kernels, husk, bran, and germ for the recovery of different molecules, from catalysts (to produce biodiesel) to bioactive compounds, has grown. In fact, rice byproducts are rich in secondary metabolites (phenolic compounds, flavonoids, and tocopherols) with different types of bioactivity, mainly antioxidant, antimicrobial, antidiabetic, and anti-inflammatory, which make them useful as functional ingredients. In this review, we focus our attention on the recovery of antioxidant compounds from rice byproducts by using innovative green techniques that can overcome the limitations of traditional extraction processes, such as their environmental and economic impact. In addition, traditional assays and more innovative methodologies to evaluate the antioxidant activity are discussed. Finally, the possible molecular mechanisms of action of the rice byproduct antioxidant compounds (phenolic acids, flavonoids, γ-oryzanol, and vitamin E) are discussed as well. In the future, it is expected that rice byproduct antioxidants will be important food ingredients that reduce the risk of the development of several human disorders involving oxidative stress, such as metabolic diseases, inflammatory disorders, and cancer.

Natural carriers: Recent advances in their use to improve the stability and bioaccessibility of food active compounds.

In the last decades, the incorporation of bioactive compounds in food supplements aroused the attention of scientists. However, these ingredients often exhibit both low solubility and stability and their poor bioaccessibility within the gastrointestinal tract limits their effectiveness. To overcome these drawbacks, many carriers have been investigated for encapsulating nutraceuticals and enhancing their bioavailability. It is note that several different vegetable wall materials have been applied to build delivery systems. Considering their encapsulation mechanism, lipid and protein-based carriers display specific interaction patterns with bioactives, whereas polysaccharidic-based carriers can entrap them by creating porous highly stable networks. To maximize the encapsulation efficiency, mixed systems are very promising. Following the current goal of using natural and sustainable ingredients, only a limited number of studies about the isolation of new ingredients from agro-food waste are available. In this review, a comprehensive overview of the state of art in the development of innovative natural lipid-, protein- and polysaccharide-based plant carriers is presented, focusing on their application as food active compounds. Different aspects to be considered in the design of delivery systems are discussed, including the carrier structure and chemical features, the interaction between the encapsulating and the core material, and the parameters affecting bioactives entrapment.

Antiviral activity of Inonotusin A an active compound isolated from Boletus bellinii and Boletus subtomentosus.

Mushrooms produce various classes of secondary metabolites that could be used as antivirals in the future. The aim of this study was to determine the antiviral activity of methanolic extracts obtained from two edible mushrooms, Boletus bellinii (B. bellinii) and Boletus subtomentosus (B. subtomentosus), collected from the north forests of Tunisia, against Herpes Simplex Virus type 2 and Coxsackie Virus B type 3. In vitro micro-inhibition assays and cytotoxicity screening were performed on Vero cells. The tested Boletus methanolic extracts were found to be non-cytotoxic at high doses (50% cytotoxic concentration - CC50 > 1 mg/mL) and exhibited relevant viral inhibition with 50% inhibitory concentration, i.e., IC50 of 3.60 ± 0.66 µg/mL and 35.70 ± 7.42 µg/mL for B. bellinii, and 5.67 ± 1.02 µg/mL and 56.88 ± 9.56 µg/mL for B. subtomentosus, against HSV-2 and CVB-3, respectively. Interestingly, Boletus methanolic extracts showed high selectivity index (SI) values against both viruses, with the highest values against HSV-2 (SI > 800). Both viral strains were inhibited when treated with extracts during the early stages of virus replication. Inonotusin A was isolated and identified as the compound responsible for these activities. The latter is a novel antiviral agent that may have clinical utility or serve as a lead compound for further development. This study is the first attempt to investigate the antiviral activity of inonotusin A, isolated from the genus Boletus. The information from the present work should be a valuable reference for future studies on the antiviral activity of inonotusin A.

A New Polysaccharide Carrier Isolated from Camelina Cake: Structural Characterization, Rheological Behavior, and Its Influence on Purple Corn Cob Extract's Bioaccessibility.

A polysaccharide fraction obtained from camelina cake (CCP), selected as a carrier to encapsulate purple corn cob extract (MCE), was investigated. A wide population of carbohydrate polymers (with a polydispersivity index of 3.26 ± 0.07 and an average molecular weight of about 139.749 × 103 ± 4.392 × 103 g/mol) with a gel-like behavior and a thixotropic feature characterized the fraction. MCE-CCP combinations (50-50 and 25-75, w/w), selected based on CCP encapsulation efficiency, were tested for their stability and MCE polyphenols' bioaccessibility during digestion (monitored using an in vitro static procedure). During the oral and gastric phases of the digestion process, CCP gradually swelled and totally released MCE polyphenols. MCE-CCP50 had the fastest release. Moreover, anthocyanins were still detectable during the duodenal phase, in both MCE-CCP ingredients. Furthermore, CCP (5 mg/mL) exerted in vitro potential hypocholesterolemic activity via bile salts binding during digestion.

Effectiveness of crisis resolution home treatment for the management of acute psychiatric crises in Southern Switzerland: a natural experiment based on geography.

BACKGROUND: Crisis Resolution Home Treatment (CRHT) is an alternative to inpatient treatment for acute psychiatric crises management. However, evidence on CRHT effectiveness is still limited. In the Canton of Ticino (Southern Switzerland), in 2016 the regional public psychiatric hospital replaced one acute ward with a CRHT. The current study was designed within this evaluation setting to assess the effectiveness of CRHT compared to standard inpatient treatment. METHODS: CRHT was offered to patients aged 18 to 65 with an acute psychiatric crisis that would have required hospitalization. We used a natural experiment based on geography, where intervention and control groups were formed according to the place of residence. Primary endpoints were reduction of psychiatric symptoms at discharge measured using the Health of the Nation Outcome Scales, treatment duration in days, and rate and length of readmissions during a two-year follow-up period after discharge. Safety during the treatment period was measured with the number of serious adverse events (suicide/suicide attempts, major self-harm episodes, acute alcohol/drug intoxications, aggressions to caregivers or family members). We used linear, log-linear and logistic regression models with propensity scores for the main analysis. RESULTS: We enrolled 321 patients; 67 were excluded because the treatment period was too short and 17 because they were transferred before the end of the treatment. Two hundred thirty-seven patients were available for data analysis, 93 in the intervention group and 144 in the control group. No serious adverse event was observed during the treatment period in both groups. Reduction of psychiatric symptoms at discharge (p-value = 0.359), readmission rates (p-value = 0.563) and length of readmissions (p-value = 0.770) during the two-year follow-up period did not differ significantly between the two groups. Treatment duration was significantly higher in the treatment group (+ 29.6% on average, p-value = 0.002). CONCLUSIONS: CRHT was comparable to standard hospitalization in terms of psychiatric symptoms reduction, readmission rates and length of readmissions, but it was also characterized by a longer first treatment period. However, observational evidence following the study indicated that CRHT duration constantly lowered over time since its introduction in 2016 and became comparable to hospitalization, showing therefore to be an effective alternative also in terms of treatment length. TRIAL REGISTRATION: ISRCTN38472626 (17/11/2020, retrospectively registered).

Selection and Optimization of an Innovative Polysaccharide-Based Carrier to Improve Anthocyanins Stability in Purple Corn Cob Extracts.

The extraction process of alcohol-insoluble polysaccharides from exhausted Moradyn cob (Zea mays L. cv. Moradyn) (EMCP), camelina cake (Camelina sativa L. Crantz) (CCP), and common bean seeds (Phaseolus vulgaris L.) (CBP) was investigated and optimized by Response Surface Methodology. Each fraction was tested at different core/carrier ratios in the encapsulation of Moradyn cob extract (MCE), a rich source of antioxidant anthocyanins, and the obtained ingredients were screened for their encapsulation efficiency (EE%) and extraction process sustainability. The ingredients containing 50% and 75% CCP had EE% higher than 60% and 80%, respectively, and were selected for further studies. Preliminary structural analysis indicated CCP was mostly composed of neutral polysaccharides and proteins in a random-coiled conformation, which was also unchanged in the ingredients. CCP-stabilizing properties were tested, applying an innovative stress testing protocol. CCP strongly improved MCE anthocyanins solid-state stability (25 °C, 30% RH), and therefore it could be an innovative anthocyanins carrier system.

Phytochemical profiling of aqeous methanolic leaf extract of Triclisia gilletii by gas chromatography (GC/MS) and liquid chromatography (HPLC-PDA-ESI/MSn) tandem mass spectroscopy (MS): a pointer to its nephroprotection.

The phytochemical constituents in the aqueous methanolic leaf extract of Triclisia gilletii responsible for its nephroprotective potentials against ethane-1,2-diol induced nephrolithiasis as previously investigated in our laboratory were elucidated. The extract was prepared using 80% aqueous methanol in 72 h, Phytochemical contents of aqueous methanolic extract of Triclisia gilletii (TGME) was identified using both a Thermo Scientific DSQII single quadrupole gas chromatography (GC) and a Thermo Scientific liquid chromatography (LCQ Fleet system) tandem mass spectroscopy. The chromatogram acquisition, detection of mass spectral peaks and their waveform processing were performed using Xcalibur MS Software (Thermo Scientific Inc.). GC-MS analysis revealed the presence of phenols, fatty acids, vitamins and steroids. Likewise, for LC-MS analysis kaempferol and dihydrovomifoliol-O-glucoside were detected. The identified constituents have possible contributively effect on the acclaimed pharmacological potential of Triclisia gilletii against ethane-1,2-diol induced nephrolithiasis.

Home Treatment for Acute Mental Health Care: Protocol for the Financial Outputs, Risks, Efficacy, Satisfaction Index and Gatekeeping of Home Treatment (FORESIGHT) Study.

BACKGROUND: Crisis Resolution and Home Treatment (CRHT) teams represent a community-based mental health service offering a valid alternative to hospitalization. CRHT teams have been widely implemented in various mental health systems worldwide, and their goal is to provide care for people with severe acute mental disorders who would be considered for admission to acute psychiatric wards. The evaluation of several home-treatment experiences shows promising results; however, it remains unclear which specific elements and characteristics of CRHT are more effective and acceptable. OBJECTIVE: This study aims to assess the acceptability, effectiveness, and cost-effectiveness of a new CRHT intervention in Ticino, Southern Switzerland. METHODS: This study includes an interventional, nonrandomized, quasi-experimental study combined with a qualitative study and an economic evaluation to be conducted over a 48-month period. The quasi-experimental evaluation involves two groups: patients in the northern area of the region who were offered the CRHT service (ie, intervention group) and patients in the southern area of the region who received care as usual (ie, control group). Individual interviews will be conducted with patients receiving the home treatment intervention and their family members. CRHT members will also be asked to participate in a focus group. The economic evaluation will include a cost-effectiveness analysis. RESULTS: The project is funded by the Swiss National Science Foundation as part of the National Research Program NRP74 for a period of 48 months starting from January 2017. As of October 2021, data for the nonrandomized, quasi-experimental study and the qualitative study have been collected, and the results are expected to be published by the end of the year. Data are currently being collected for the economic evaluation. CONCLUSIONS: Compared to other Swiss CRHT experiences, the CRHT intervention in Ticino represents a unique case, as the introduction of the service is backed by the closing of one of its acute wards. The proposed study will address several areas where there are evidence gaps or contradictory findings relating to the home treatment of acute mental crisis. Findings from this study will allow local services to improve their effectiveness in a challenging domain of public health and contribute to improving access to more effective care for people with severe mental disorders. TRIAL REGISTRATION: ISRCTN registry ISRCTN38472626; https://www.isrctn.com/ISRCTN38472626. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/28191.

Development of an Accelerated Stability Model to Estimate Purple Corn Cob Extract Powder (Moradyn) Shelf-Life.

Moradyn is an Italian purple corn variety whose cobs represent a rich source of polyphenols. At the industrial level, they are used to produce a dried extract (MCE) by the addition of 20% Arabic gum. In order to evaluate the extract solid-state stability, an innovative accelerated stress protocol was developed following the isoconversion approach. The degradation kinetics of cyanidin-3-O-glucoside (C3G), the most suitable marker to monitor the overall MCE degradation status, was monitored under five temperature-humidity (RH) combinations. These data were used to build a mathematical model, able to estimate the C3G stability at 25 °C and 30% RH, whose predictiveness was further assessed by comparing the predicted vs. experimental C3G isoconversion time. Finally, by applying this model, the expiry date of the extract was calculated to be within 26-33 days, confirming that the addition of 20% Arabic gum is insufficient to stabilize MCE and highlighting the need of a new formula in order to prolong MCE shelf-life.

Recovery of Chlorogenic Acids from Agri-Food Wastes: Updates on Green Extraction Techniques.

The agri-food sector produces a huge amount of agri-food wastes and by-products, with a consequent great impact on environmental, economic, social, and health aspects. The reuse and recycling of by-products represents a very important issue: for this reason, the development of innovative recovery and extraction methodologies must be mandatory. In this context of a circular economy, the study of green extraction techniques also becomes a priority in substitution of traditional extraction approaches. This review is focused on the recovery of chlorogenic acids from agri-food wastes, as these compounds have an important impact on human health, exhibiting several different and important healthy properties. Novel extraction methodologies, namely microwave and ultrasound-assisted extractions, supercritical fluid extraction, and pressurized-liquid extraction, are discussed here, in comparison with conventional techniques. The great potentialities of these new innovative green and sustainable approaches are pointed out. Further investigations and optimization are mandatory before their application in industrial processes.

Advances in static in vitro digestion models after the COST action Infogest consensus protocol.

In vitro digestion models are essential to predictively evaluate the bioaccessibility and bioactivity of food molecules or natural products. Dynamic models better simulate the gastrointestinal conditions as they reproduce similar physiological environments. Despite this, static methods, also known as biochemical methods, represent a simple and useful approach for the study of different types of molecules, with a broad applicability in the nutritional, pharmaceutical, and toxicological fields. In addition, static models can be validated, avoiding the disadvantage of a difficult reproducibility of dynamic in vitro systems and inter-individual variations of in vivo experiments. A crucial point in the standardization of static models was the COST Action Infogest in 2014, which elaborated an international consensus static digestion method to harmonize experimental conditions and has general guidelines, thus allowing the comparison of studies and data. The aim of our review is to underline the impact of the Infogest consensus method and the development and evolution of in vitro static methods in the following years, with a focus on food applications.

Bioactivities and in silico study of Pergularia tomentosa L. phytochemicals as potent antimicrobial agents targeting type IIA topoisomerase, TyrRS, and Sap1 virulence proteins.

Pergularia tomentosa L. (P. tomentosa) has been largely used in Tunisian folk medicine as remedies against skin diseases, asthma, and bronchitis. The main objectives of this study were to identify phytochemical compounds that have antioxidant and antimicrobial properties from the stem, leaves, and fruit crude methanolic extracts of P. tomentosa, and to search for tyrosyl-tRNA synthetase (TyrRS), topoisomerase type IIA, and Candidapepsin-1 (SAP1) enzyme inhibitors through molecular docking study. Phytochemical quantification revealed that fruit and leaves extracts displayed the highest total flavonoids (582 mg QE/g Ex; 219 mg QE/g Ex) and tannins content (375 mg TAE/g Ex; 216 mg TAE/g Ex), also exhibiting significant scavenging activity to decrease free radicals for ABTS, DPPH, ß-carotene, and FRAP assay with IC50 values (> 1 mg/mL). Additionally, promising antimicrobial activities towards different organs have been observed against several bacteria and Candida strains. From the liquid chromatography-mass spectrometry (LC-MS) analysis, five polyphenolic compounds, namely digitoxigenin, digitonin glycoside and calactina in the leaves, kaempferol in the fruit, and calotropagenin in the stems, were identified. They were also analyzed for their drug likeliness, based on computational methods. Molecular docking study affirmed that the binding affinity of calactin and actodigin to the active site of TyrRS, topoisomerase type IIA, and SAP1 target virulence proteins was the highest among the examined dominant compounds. Therefore, this study indicated that P. tomentosa methanolic extracts displayed great potential to become a potent antimicrobial agent and might be a promising source for therapeutic and nutritional functions. These phytocompounds could be further promoted as a candidate for drug discovery and development.

Colored Corn: An Up-Date on Metabolites Extraction, Health Implication, and Potential Use.

Colored (orange, pink, red, purple, and blue) corn strongly attracted attention on its healthy properties mainly due to its anthocyanin and carotenoid composition which is also responsible for its pigmentation. The present review summarized the recent updates on the extraction and chemical characterization of the main plant secondary metabolites present in colored seeds, kernel, cob, husk, and silk. The main approaches used to stabilize the extracts have been discussed as well as their food and non-food uses. Both in vitro and in vivo (animal models) studies on the different effects (antibacterial, antimutagenic, antioxidant, and anti-inflammatory activities, effects on metabolic syndrome, diabetes, glucose and lipidic metabolism, and neuroprotection) of pigmented extracts on animal and human health have been summarized.

Decaffeinated coffee and its benefits on health: focus on systemic disorders.

The current literature has mainly focused on benefits and risks deriving from the consumption of caffeinated coffee and its implications for inflammation, cardiovascular diseases, neurodegenerative disorders, and cancer. Today, data about the role of caffeine in many disorders are controversial and the attention has increasingly focused on decaffeinated coffee and its non-caffeine compounds, which could have mainly beneficial effects. In fact, coffee phenolic compounds not only exhibit well-known antioxidant properties, but they can also antagonize some negative effects of caffeine, for example in inflammatory pathway and in glucose metabolism and homeostasis. In this review, we consider the literature of the last two decades and critically discuss the effects of decaffeinated coffee compounds on systemic disorders, mainly inflammation, cardiovascular diseases, hepatic dysfunctions, and cancer.

Pre-Concentration and Analysis of Mycotoxins in Food Samples by Capillary Electrophoresis.

Mycotoxins are considered one of the most dangerous agricultural and food contaminants. They are toxic and the development of rapid and sensitive analytical methods to detect and quantify them is a very important issue in the context of food safety and animal/human health. The need to detect mycotoxins at trace levels and to simultaneously analyze many different mycotoxin types became mandatory to protect public health. In fact, European Commission regulations specified both their limits in foodstuffs and official sample preparation protocols in addition to analytical methods to verify their presence. Capillary Electrophoresis (CE) includes different separation modes, allowing many versatile applications in food analysis and safety. In the context of mycotoxins, recent advances to improve CE sensitivity, particularly pre-concentration techniques or miniaturized systems, deserve remarkable attention, as they provide an interesting approach in the analysis of such contaminants in complex food matrices. This review summarizes the applications of CE combined with different pre-concentration approaches, which have been proposed in the literature (mainly) in the last ten years. A section is also dedicated to recent microchip-CE devices since they represent the most promising CE mode for this application.

A New Italian Purple Corn Variety (Moradyn) Byproduct Extract: Antiglycative and Hypoglycemic In Vitro Activities and Preliminary Bioaccessibility Studies.

The reuse of byproducts from agricultural and food industries represents the key factor in a circular economy, whose interest has grown in the last two decades. Thus, the extraction of bioactives from agro-industrial byproducts is a potential source of valuable molecules. The aim of this work was to investigate the in vitro capacity of byproducts from a new Italian corn variety, named Moradyn, to inhibit the accumulation of advanced glycation end products (AGEs) involved in several chronic age-related disorders. In addition, the hypoglycemic effect of Moradyn was tested by in vitro enzymatic systems. A Moradyn phytocomplex and its purified anthocyanin fraction were able to inhibit fructosamine formation and exhibited antiglycative properties when tested using BSA-sugars and BSA-methylglyoxal assays. These properties could be attributed to the polyphenols, mainly anthocyanins and flavonols, detected by RP-HPLC-DAD-ESI-MSn. Finally, a Moradyn phytocomplex was submitted to a simulated in vitro digestion process to study its bioaccessibility. Moradyn could be considered as a promising food ingredient in the context of typical type 2 diabetes risk factors and the study will continue in the optimization of the ideal formulation to preserve its bioactivities from digestion.