**2. Bio-accessibility and bioavailability of dietary polyphenols**

Polyphenols, a class of chemical compounds consisting of one or more hydroxyl groups (OH) attached directly to at least two phenyl rings lacking nitrogen-based functional group in their most basic structural expression are plant secondary natural metabolites, ubiquitous in all vascular plants arising biogenetically from either the shikimate derived phenylpropanoid and/or the polyketide pathway(s) [27–29]. Polyphenols are classified into diverse classes on the basis of their chemical structures and/or the attachment of hydroxyl groups to the aromatic rings structure while the main classes of polyphenols consist of flavonoids, phenolic acid, tannins (phenolic polymers), phenylethanoid [30], stilbenes and lignans [4, 27, 31–34].

Flavonoids are recognized as one of the largest and most abundant type of polyphenols in the diet that constitute approximately two-thirds of intake. The core structural unit of flavonoids encompasses a common carbon skeleton of diphenyl propane in which two benzene rings (A, B) are linked by a linear three-carbon chain, forming a closed pyran ring with the A benzene ring. Flavonoids (**Figure 1**) are then subdivided into several subclasses based on the central pyran ring's oxidation state that the most important of them follow as: flavonols (e.g. Quercetin, kaempferol), flavones (e.g. luteolin, apigenin), anthocyanins (e.g. cyaniding, pelargonidin), flavanones (e.g. naringenin, hesperetin), flavanols also known as flavan-3-ols (e.g. catechin, epicatechin), and isflavones (e.g. daidzein, genistein) [4, 7, 32, 35, 36].

Phenolic acids (**Figure 2**) ubiquitously found in plant materials at varying levels are divided into two sub-classes hydroxybenzoic (e.g., gallic, phydroxybenzoic, vanillic, syringic, and protocatechuic acids) that are often the component of a complex structure like lignins and hydrolyzable tannins, and hydroxycinnamic acids (e.g., p-coumaric, caffeic, ferulic, sinapic and cinnamic acids). Further, decarboxylation of benzoic acid and phenylpropanoid derivatives leads to the formation of simple phenols namely, phenol, o-cresol, 4-ethylphenol, guaiacol, 4-vinylguaiacol and eugenol [4]. Some phenolic acids are found in free form in red fruits and vegetables such as strawberries and blackberries, black radish, onions, and tea [35], but hull, bran, and seed contain phenolic acids that in bound form that are released by acid, alkali, and enzyme hydrolysis [7].

Tannins are compounds of intermediate to high molecular weight (500– 20,000 Da) [37] and are more extensively hydroxylated [35]. Depending on their structures, tannins are classified into two major groups including hydrolyzable and non-hydrolyzable tannins, also called condensed tannins or proanthocyanidins (PAs). Hydrolyzable tannins (HTs) consist a center of glucose or a polyhydric alcohol partially or completely esterified with simple phenolic acids such as gallic acid (gallotannins) or hexahydroxydiphenic acid (ellagitannins) while condensed tannins are oligomers and polymers of flavonoids, specifically flavan-3-ols [4, 31, 34, 37, 38]. Ellagitannins (e.g., punicalagin [39]) (**Figure 3**) are esters of hexahydroxydiphenoic acid and monosaccharide (most commonly glucose) naturally occurred in some fruits (pomegranate, strawberry, blackberry, and raspberry), nuts (walnuts, almonds) and seeds. While ellagitannins are slowly hydrolyzed in

*Bioactive Compounds - Biosynthesis, Characterization and Applications*

like bitterness or astringency [4, 5, 20, 21].

a nutritional value provide health-promoting, and disease curing or prevention properties) [2] as functional ingredients to provide a health benefit beyond basic nutrition. Polyphenols are naturally occurring compounds in plants endowed with antioxidant and anti-inflammatory, immune, antitumor and prebiotic properties [3]; widely present in a wide variety of fruit, vegetables, seeds, herbs and beverages in particular in beer, red wine, fruit juice, coffee, tea, cocoa, chocolate and dry legumes and cereal [2, 4–8] and are therefore an integral part of the human diet [9]. From a chemical standpoint, this large family of secondary plant metabolites constitutes a large heterogeneous class of compounds characterized by hydroxylated phenyl moieties [2, 10–12] with more than 8000 identified compounds so far [2, 13–16]. Numerous food matrixes naturally enriched with dietary polyphenols are the most potent sources of plant-derived bioactive compounds eliciting many beneficial health effects in man. Despite their interesting biologic properties, their presence and abundance in nature, chemical instability of polyphenols during processing, handling and storage [17], the low oral bioavailability [3, 8] and rapid fastpass metabolism of polyphenols might greatly restrict their biologic effects and applications in the functional foods and nutraceuticals [18]. Further, these extracts or their isolated individual compounds have the potential to interact with other compounds in the environment in particular proteins, resulting in formation of sensory characteristics and organoleptic properties in foods and beverages including High Molecular Weight (HMW) brown color [19], flavor and taste attributes

In conclusion, the main drawback to using polyphenols as functional ingredients to develop functional food products and dietary supplements, nutraceuticals is their poor bioavailability and the variable bio-accessibility in the human body and variety of molecular interactions between polyphenols and other food components; however, in order to preserve the structural integrity, polyphenols need to be shielded by a finishing formulation that is, able to protect and to deliver them to the physiologic targets without losing any bioactivity [22]. Encapsulation system applied to polyphenols through the development of micro and nano-sized particle systems, as a reliable tool to overcome the problems related with the direct use of dietary polyphenols in their free form in food matrixes will ensure protection of these bioactive compounds and additionally, functional properties to the final product [23, 24]. The administration of encapsulated polyphenols instead of their free form can overcome the drawbacks of their instability; relieve unpleasant tastes or flavors in food matrixes, and as well improve their bioavailability in gastrointestinal tract (GIT). Numerous encapsulation processes have been developed to encapsulate polyphenols-based functional ingredients each with their own merits and demerits including Ionic gelation, layer-by-layer deposition, extrusion, coprecipitation, coacervation and phase separation, spray/freeze drying, emulsification/emulsion polymerization, inclusion complexation, liposome entrapment, fluidized bed coating, supercritical fluid, etc. [22, 25]. However, polyphenols are oxidized easily due to light, heat and oxidant; therefore, chemical instability of these compounds is the major constraint to encapsulation through the processes stated above since they mostly require heating and/ or pressure, and the use of strong and toxic organic solvents or expensive equipment [26]. In this regard, electro-hydrodynamic processing referring to the dynamics of electrically charged fluids has emerged as an Innovative and environmentally friendly alternative technology for encapsulation that needs neither temperature nor expensive equipment; therefore, heat-sensitive compounds such as dietary polyphenols may be successfully processed and also, the use of organic solvents can be avoided by adjusting some processing conditions (i.e., use of molten polymer). In this chapter the drawbacks related to the incorporation of dietary polyphenols as possible functional ingredients in food formulations and novel strategy to

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**Figure 2.**

*Structures of phenolic acids.*

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**Figure 1.** *Structures of flavonoids.*

*Electro-Spinning and Electro-Spraying as Innovative Approaches in Developing of a Suitable… DOI: http://dx.doi.org/10.5772/intechopen.98626*

*Bioactive Compounds - Biosynthesis, Characterization and Applications*

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**Figure 1.**

*Structures of flavonoids.*

the digestive tract releasing the ellagic acid molecule, the main determinant of the physicochemical properties and biologic activity is their chemical structure [39]. Based on the hydroxylation pattern of A- and B-rings, non-hydrolyzable taanins or PAs can be divided into procyanidins (e.g. procyanidin trimer C1), propelargonidins and prodelphinidins [4, 37].

Tyrosol, hydroxytyrosol and oleuropein (**Figure 4**) are the prominent types in phenylethanoid class, found mainly in olive leaf and oil [30, 36]. Besides, Rueda et al. reported that the minor values of both tyrosol and hydroxytyrosol present in other edible virgin vegetable oils (argan, wheat germ and sesame) [40].

Stilbenes are a family of hydrocarbons that share with similar chemical structure to flavonoids consisting of two phenyl groups linked by a methylene group (or "methylidene") that occur naturally in either a cis or a trans configuration [32, 33]. Resveratrol, pterostilbene, and piceatannol are primary representatives [4, 41] while resveratrol (3,5,40-trihydroxy-trans-stilbene) (**Figure 5**) presented in the both cis and trans

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**Figure 4.**

*Structure of phenylethanoid.*

iciresinol and matairesinol [32].

*Electro-Spinning and Electro-Spraying as Innovative Approaches in Developing of a Suitable…*

isomeric forms as well as its derivatives including glucosylated, prenylated, methylated, and hydroxylated modifications are the most widely known stilbenes that do are important from a health perspective. Polydatin, also known as piceid (resveratrol-3-Oβ-mono-D-glucoside, POLY) is a glucoside of resveratrol in which the glucoside group bonded in position C-3 substitutes a hydroxyl group. This substitution brings about conformational changes of the molecule resulting in changes in the biologic properties. There exist numerous reports suggesting trans-resveratrol to be the more stable form in nature and the most bioactive form of this molecule though upon exposure to UV light, trans-resveratrol (isomeric) can be readily converted to cis-resveratrol (isomeric) and also been unstable when exposed to high pH [42]. Stilbenes are reported to

Secoisolariciresinol and matairesinol (**Figure 6**) characterized by the union of two phenylpropanoid (C6C3) units with β-β or C8-C8 linkages are the major types of lignans [4, 28]; being present in the free form or glycosidically linked to different fiber-associated polyphenols [30]. Flaxseed [4], rye bran and flour, various berry fruits [43], legumes, vegetables, black and green tea [43] are sources of secoisolar-

be present in grapes, berries, peanuts and red wine [4, 31, 32, 42].

*DOI: http://dx.doi.org/10.5772/intechopen.98626*

*Electro-Spinning and Electro-Spraying as Innovative Approaches in Developing of a Suitable… DOI: http://dx.doi.org/10.5772/intechopen.98626*

**Figure 4.** *Structure of phenylethanoid.*

*Bioactive Compounds - Biosynthesis, Characterization and Applications*

the digestive tract releasing the ellagic acid molecule, the main determinant of the physicochemical properties and biologic activity is their chemical structure [39]. Based on the hydroxylation pattern of A- and B-rings, non-hydrolyzable taanins or PAs can be divided into procyanidins (e.g. procyanidin trimer C1), propelargoni-

Tyrosol, hydroxytyrosol and oleuropein (**Figure 4**) are the prominent types in phenylethanoid class, found mainly in olive leaf and oil [30, 36]. Besides, Rueda et al. reported that the minor values of both tyrosol and hydroxytyrosol present in

Stilbenes are a family of hydrocarbons that share with similar chemical structure to flavonoids consisting of two phenyl groups linked by a methylene group (or "methylidene") that occur naturally in either a cis or a trans configuration [32, 33]. Resveratrol, pterostilbene, and piceatannol are primary representatives [4, 41] while resveratrol (3,5,40-trihydroxy-trans-stilbene) (**Figure 5**) presented in the both cis and trans

other edible virgin vegetable oils (argan, wheat germ and sesame) [40].

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**Figure 3.**

*Structures of tannins.*

dins and prodelphinidins [4, 37].

isomeric forms as well as its derivatives including glucosylated, prenylated, methylated, and hydroxylated modifications are the most widely known stilbenes that do are important from a health perspective. Polydatin, also known as piceid (resveratrol-3-Oβ-mono-D-glucoside, POLY) is a glucoside of resveratrol in which the glucoside group bonded in position C-3 substitutes a hydroxyl group. This substitution brings about conformational changes of the molecule resulting in changes in the biologic properties. There exist numerous reports suggesting trans-resveratrol to be the more stable form in nature and the most bioactive form of this molecule though upon exposure to UV light, trans-resveratrol (isomeric) can be readily converted to cis-resveratrol (isomeric) and also been unstable when exposed to high pH [42]. Stilbenes are reported to be present in grapes, berries, peanuts and red wine [4, 31, 32, 42].

Secoisolariciresinol and matairesinol (**Figure 6**) characterized by the union of two phenylpropanoid (C6C3) units with β-β or C8-C8 linkages are the major types of lignans [4, 28]; being present in the free form or glycosidically linked to different fiber-associated polyphenols [30]. Flaxseed [4], rye bran and flour, various berry fruits [43], legumes, vegetables, black and green tea [43] are sources of secoisolariciresinol and matairesinol [32].

These compounds are potent antioxidant compounds able to counteract oxidative stress and chronic inflammation that could be separated or recovered from food waste and agricultural by-products [35, 44]; thus, this group of natural products could be used as additives and functional ingredients in the novel

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ingredients.

**Figure 6.**

*Structures of lignans.*

*Electro-Spinning and Electro-Spraying as Innovative Approaches in Developing of a Suitable…*

functional foods and beverages [45]. There are numerous *in-vitro* and *in-vivo* studies that have proved, poly-phenol intake is associated with a wide spectrum of potential biologic activities related to health-promoting properties including; anti-inflammatory, antioxidant, pro-DNA repair, anti-helmintic, anti-microbial, anti-viral, insecticidal, anti-cancer, anti-aging, and anti-radiation effects [36]; it is known as a preventive for the certain cancers, cardiovascular diseases, type 2 diabetes, osteoporosis, pancreatitis, gastrointestinal problems, lung damage, and neurodegenerative diseases [11, 46–51]. Due to these healthy characteristics, there is increasing interest in the development of new product with enhanced potential health-promoting action while the effectiveness of polyphenols depends on preserving the stability, bioactivity, and bioavailability of the active

Once ingested, polyphenols are metabolized by the human body as xenobiotic compounds which may undergo several biologic processes limiting their potential uptake by humans [10, 52, 53]. However, putative bioactivity and bio-efficacy [18, 54, 55] of dietary polyphenols are therefore strictly associated with related to the concepts of bio-accessibility and bioavailability. In this regard, to exploit

*DOI: http://dx.doi.org/10.5772/intechopen.98626*

*Electro-Spinning and Electro-Spraying as Innovative Approaches in Developing of a Suitable… DOI: http://dx.doi.org/10.5772/intechopen.98626*

*Bioactive Compounds - Biosynthesis, Characterization and Applications*

These compounds are potent antioxidant compounds able to counteract oxidative stress and chronic inflammation that could be separated or recovered from food waste and agricultural by-products [35, 44]; thus, this group of natural products could be used as additives and functional ingredients in the novel

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**Figure 5.**

*Structures of stilbenes.*

functional foods and beverages [45]. There are numerous *in-vitro* and *in-vivo* studies that have proved, poly-phenol intake is associated with a wide spectrum of potential biologic activities related to health-promoting properties including; anti-inflammatory, antioxidant, pro-DNA repair, anti-helmintic, anti-microbial, anti-viral, insecticidal, anti-cancer, anti-aging, and anti-radiation effects [36]; it is known as a preventive for the certain cancers, cardiovascular diseases, type 2 diabetes, osteoporosis, pancreatitis, gastrointestinal problems, lung damage, and neurodegenerative diseases [11, 46–51]. Due to these healthy characteristics, there is increasing interest in the development of new product with enhanced potential health-promoting action while the effectiveness of polyphenols depends on preserving the stability, bioactivity, and bioavailability of the active ingredients.

Once ingested, polyphenols are metabolized by the human body as xenobiotic compounds which may undergo several biologic processes limiting their potential uptake by humans [10, 52, 53]. However, putative bioactivity and bio-efficacy [18, 54, 55] of dietary polyphenols are therefore strictly associated with related to the concepts of bio-accessibility and bioavailability. In this regard, to exploit

the real biologic potential effect it is crucial to know the quantity of polyphenols properly released from food matrix during gastrointestinal digestion, which is the potential absorption of polyphenols to be available for subsequent metabolic pathways. This parameter is known as bio-accessibility, which can be defined as: "the fraction of a bioactive compound within the food matrix where it is contained, that has the potential to be bio-available and reach systemic circulation; this means that it has been released from the food matrix by the action of digestive enzymes [46, 52, 56, 57]. Potentially, bioavailability refers to the fraction of the bioaccessible ingested nutrient, either parent compound or active metabolite that reaches the systemic circulation and becomes available at the site of the action where it can exert biologic effects [46, 52, 58, 59]; in the case of polyphenols, this is the amount of polyphenols which can be absorbed and exert effects on specific tissues. As per this principle, bioavailability is a process that depends on the intrinsic and extrinsic factors of the host; this means that, the process depends on the food matrix ingested and the gastrointestinal conditions within the individual. Investigations have revealed which the bioavailability of polyphenols contains seven main digestive processes: (1) the release of polyphenols from food matrix (bio-accessible polyphenols); (2) changes in polyphenols during gastric and small intestine digestion conditions; (3) the cellular uptake of aglycones and conjugated forms of polyphenols; (4) microbial metabolism conjugated non-bio-accessible fraction polyphenols by the colonic micro-biota; (5) phase I (oxidation, reduction and hydrolysis) and particularly phase II (conjugation) bio-transformations in the enterocytes and then the hepatocytes, followed by generating methyl, glucuronide and sulfate derivatives; (6) transit to systemic circulation and tissue distribution; (7) urinary excretion or excretion back into the gut via bile and pancreatic juices [52, 57, 60]. Numerous studies have pointed out that the bioavailability of polyphenols is rather low and the magnitude of the relative urinary excretion of the intake fluctuates from 0.3% for anthocyanins to 43% for isoflavones that demonstrates the great variability in the bioavailability from one poly-phenol to another and the most abundant dietary poly-phenol was not necessarily the one leading to the highest levels of active metabolites in plasma [34, 51, 61]. Consequently, to explore and to determine the mechanisms of action of dietary polyphenols and their role in disease prevention, it is crucial to understand the factors that constrain bio-accessibility and bioavailability of polyphenols, some related to the food (e.g., chemical structure of the compound, food matrix, food processing and dose) while others depend on the individual (e.g., gastric emptying, intestinal transit time, composition of the micro-biota) [58, 62, 63]. However, the discussion of factors influencing the bio-accessibility and bioavailability of polyphenols will focus on food related factors such as the polyphenols' chemical structure, the nature of the food matrix and food processing, since these are the first hurdles that polyphenols face prior to absorption.

The interested reader may consult some of the accounts of the concentration and bio-accessibility of poly-phenol compounds with potential antioxidant activity as affected by simulated *in vitro* digestion; for a more detailed description, see the references [64–68].

#### **2.1 Factors leading to degradation of polyphenols and low bioavailability**

Dietary polyphenols to exert their health-promoting effect need to endure the food processing conditions; second, could be released from the food matrix and become bio-accessible in the gastrointestinal tract, and then undergo metabolism and reach the target tissue of interest. As a result, chemical structure of polyphenols, nature of food matrix as well as interaction with other food constituents in

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particular proteins, lipids and carbohydrates and food processing play a significant role upon coming to bio-accessibility and bioavailability of polyphenols, since they represent the first step in the challenging journey of well-known dietary polyphe-

Dietary polyphenols has been a most exotic topic in modern food chemistry not only as structural diversity and major plant secondary metabolites, but also as compounds that express a wide range of applications in various aspects of commercial as well as general public interests [27]. The importance of their molecular structure lies in the fact that the molecular size, the parent structure, degree of polymerization or glycosylation, solubility, hydrophobicity, isomer configuration and conjugation with other phenolics [5, 34, 60, 69, 70] have a strong impact on their bio-accessibility and bioavailability. Most of the polyphenols, especially those containing adjacent dihydroxyl groups (e.g. catechins and procyanidins) are especially prone to polymerization and loss through oxidation [71]. Relatively, simple phenolic derivatives such as phenolic acids (e.g., gallic acid, caffeic acid, vanillin, and coumaric acid) and flavonoids including isoflavones are readily absorbed through the gut tract that are followed by catechins, flavanones, and quercetin glucosides [34]. On the contrary, proanthocyanindins which are compounds of high molecular weight are very poorly absorbed as well as galloylated tea catechins and the anthocyanins [34, 60]. Among the various poly-phenol compounds, reported bioavailability is so highly variable that the highest bioavailability has been reported for isoflavones, followed by flavanols, flavanones and flavonol glycosides, while the proanthocyanidins, flavanol gallates and anthocyanidins are the most poorly

Food products fortified with dietary poly-phenol rich extracts may lead to changes in the nutritional, chemical and rheological properties of the fortified food. Apart from potential biologic activities related to health-promoting properties, when included in a food product depending on the type of extract, the poly-phenol compounds may impart an astringent and/or bitter taste, or introduce a degree of brown coloring [5, 21, 53, 73, 74]. Concerning taste, PAs resulting from oxidative reactions are mostly responsible for some unpleasant organoleptic properties such as astringency and bitterness [51, 70, 71]. "*Astringency is a tactile sensation defined as dryness, tightening and puckering sensations perceived in the oral cavity during the ingestion of astringent molecules, mainly tannins, alums and some metal ions*" [74]. Concerning color, it is worth to note that anthocyanins are one of the most important natural pigments though they represent a problem owing to

Polyphenols possess the ability to interact, both with food matrix constituents in particular carbohydrates, lipids and proteins, as well as with biologic compounds, namely proteins. All these interactions can affect the accessibility and availability both of polyphenols and other compounds as well as organoleptic properties of fortified food products and consumer acceptance. Polyphenols interact mostly to components of food matrix through non-covalent hydrophobic interactions but in the cases of interactions between polyphenols and proteins or/and carbohydrates, hydrogen bonds also contribute significantly. Nonetheless, some covalent bonds may also occur under certain food processing conditions [74]. Polyphenols form complexes with proteins that can be occurred by non-covalent interaction

*DOI: http://dx.doi.org/10.5772/intechopen.98626*

*2.1.1 Chemical composition and structure of polyphenols*

nols reaching the target tissues.

absorbed [34, 49, 51, 61, 72].

their high instability [74].

*2.1.2 Food matrix*

particular proteins, lipids and carbohydrates and food processing play a significant role upon coming to bio-accessibility and bioavailability of polyphenols, since they represent the first step in the challenging journey of well-known dietary polyphenols reaching the target tissues.
