A review of polyphenol and whey protein-based conjugates

Abstract

Proteins act as a primary food component obtained from different food sources. In contrast, polyphenols are metabolites and are abundantly present in plants, so their combination plays a crucial role in defining the functional properties of a food product. In the current review, the protein-polyphenol interactions have been briefly reviewed, along with the changes that occur because of their interaction. The mechanisms and the factors affecting the functionalities of the protein-polyphenol conjugates, e.g., the solubility, antioxidant, and gelling properties, have also been briefly reviewed. In addition, the interaction of polyphenols with whey proteins was been reviewed with various applications within the food industry, e.g., emulsifiers, foaming agents, and antioxidants. To end the review, future challenges were also highlighted.

INTRODUCTION

With more than 8000 different compounds, phenolic compounds are secondary metabolites with the same structure, i.e., an aromatic ring bonded to a hydroxyl group, and they are classified according to their number of carbon atoms (Kroll et al. 2003). Some examples of phenolic compounds are as follows: phenolic acids, flavonoids, lignans, and stilbenes in plants, which can react with protein molecules and undergo chemical change during food processing and even after consumption, as shown in Figs. 1a and 1b (Parada and Aguilera 2007; Crozier et al. 2009). The important factors determining polyphenol-protein interactions include the structural flexibility, molecular weight of the polyphenol, the side chain type, and the hydroxyl group number, as polyphenols with a higher molecular weight and abundant hydroxyl groups have greater protein affinity (Frazier et al. 2010; Xiao et al. 2011; Czubinki and Dwiecki 2017; Buitimea-Cantú et al. 2018). Protein-polyphenol interaction is classified into covalent interactions (irreversible) and noncovalent interactions (reversible), which are further reported as five groups, including electrostatic interactions, hydrogen bonds, pi (π) bonds, hydrophobic interactions, and van der Waals (Prigent et al. 2003; Frazier et al. 2010; Rawel and Rohn 2010; McRae and Kennedy 2011).

Fig. 1a. Major phenolic acid structures

Fig. 1b. Major flavonoid compounds

Hydrolysis causes modification to the functional properties of proteins. However, moderate hydrolysis of whey proteins increases their heat stability as a result of the reduced secondary structure. This development does not always translate directly to more complex systems such as emulsions made using hydrolyzed whey protein, where heat stability has been shown to be adversely affected by hydrolysis of whey protein. Conjugation of proteins with polyphenol reaction has been shown to be effective in altering protein functionality (Liu et al. 2012; Costa et al. 2021). Widespread research supporting the beneficial effects of protein modification through conjugation is available in the scientific literature; improved functional properties of proteins including solubility, emulsification, encapsulation, emulsion stability, and thermal stability as a result of conjugation are well documented (Akhtar and Dickinson 2003; Buamard and Benjakul 2017, 2018).

A protein can interact through hydrophobic interactions with polyphenols. Hydrogen bonds and hydrophobic interaction are the primary noncovalent interactions regulating protein-polyphenolic interactions and involved amino acids. Examples include valine, leucine, isoleucine, alanine, phenylalanine, methionine, tryptophan, glycine, cysteine, and tyrosine. Phenolic compounds form a hydrogen bond with the protein carboxyl group, as they are hydrogen donors, so a hydrogen bond is ultimately formed between the oxygen/nitrogen molecule of amino acids and a phenolic hydroxyl group (Prigent et al.2003; Rawel and Rohn 2010; Xiao et al.2011; Mulaudizi et al. 2012; Jongberg et al.2015; Tang et al 2021; Xiong and Guo 2021). The mechanism of the protein-polyphenol reaction is illustrated in Fig. 2. Phenolic compounds can produce a quinone radical via covalent bond formation, and in the presence of oxygen and an alkaline environment, a quinone radical is generated via enzymatic/non-enzymatic reactions (Jongberg et al.2015; Czajkowska–González et al. 2021; Zhao et al. 2021). In the second step, a quinone forms a dimer via a condensation reaction, known as tannins (which are brown-colored, with a high molecular weight), by reacting with the polypeptide amino acid chain via covalent bonding, and are re-oxidized and react with another polypeptide chain in the third step (Felton et al. 1989; Arts et al.2001; Buchner et al. 2006). Examples of covalent and noncovalent protein-polyphenol interactions are explained in Table 1 (Fig. 3 and Fig. 4).

Fig. 2. Phenolic acid compound reactions with polypeptide amino acid side chains

Fig. 3. Protein-polyphenol noncovalent conjugation and cross-linking of proteins via hydrogen bonding (a); hydrophobic-hydrophobic interaction (b); and ionic interaction (c)

Fig. 4. Protein-polyphenol covalent conjugation and cross-linking of protein via alkaline (a); and enzymatic (b) reactions

FACTORS AFFECTING THE INTERACTIONS BETWEEN PROTEINS AND PHENOLIC COMPOUNDS

Many factors affect protein-polyphenol reactions, including environmental factors, e.g., pH, temperature, salt concentration, and chemical presence. In addition, the protein type and phenolic compound structures are two important factors (Kroll et al. 2003; Ozdal et al. 2013; Czubinski and Dwiecki 2016) and are strongly influenced by the amino acid sequence, isoelectric point, and hydrophobicity (Frazier et al. 2006; Ali 2016). The higher molecular weight of protein has a higher binding affinity for phenolics, and protein size also plays a vital role in the binding affinity for proanthocyanidin (Siebert 1999; Dubeau et al. 2010). Phenolic compounds are different in terms of their hydroxylation degree, molecular weight, glycosylation, methylation, and hydrogenation. Temperature, an important factor that influences phenolic binding abilities for proteins, e.g., 5-O-caffeoylquinic acid, has a decreased affinity for bovine serum albumin (BSA) and sunflower seed at a higher temperature, primarily because of hydrogen bonding (Prigent et al. 2003; Guo and Xiong 2021; Guo et al. 2021). Another factor is pH, since additional protein-polyphenol precipitation was seen at the protein isoelectric point because of their lower solubility, showing that the optimum pH is near the isoelectric point, which varies for different proteins (Naczk et al. 1996, 2006; Groth et al. 2021). The isoelectric point of a protein is defined as the pH at which the net charge of a protein molecule is zero. Proteins are positively charged at a pH below their isoelectric point and negatively charged at a pH above their isoelectric point. The protein isoelectric point varies greatly from extremely acidic to highly alkaline values ranging from about 4.0 to 12.0. Moreover, isoelectric point values have long been used to distinguish between proteins in methods for protein isolation, separation, purification, crystallization, etc. (Tokamkov et al. 2021). Other influencing factors include the salt type, as a high salt concentration causes oligomeric protein dissociation, which causes a reduction in binding ability (Kanakis et al. 2011).

Various protein functional properties, e.g., emulsification, solubility, antioxidative ability, foaming ability, color, flavor, elasticity, and binding properties, could affect the quality and the sensory food property where the protein function could be affected by the phenolic compound (Abdelfatah 2013; Korpela et al. 2022). The protein-phenolic covalent interactions (Table 1, Fig. 4) could increase the gel network formation, including better mechanical strength and increased thermal stability, and modified proteins could be used as emulsifiers in foods to reduce the emulsion stability and increase the oil droplet size (Aewsiri et al. 2009). Based on the conjugates under typical conditions, it is concluded that foods properties will be affected by wide range of pH. Therefore, it might be useful for physiological saline solution.

Effects on Nutritional Properties

The nutritional value of proteins depends on various factors, e.g., the amino acid composition, protein source, essential amino acids ratio, processing environment, and hydrolysis sensitivity during digestion, but it has been reported that protein digestibility and nutritional value are decreased by phenolic interactions (Rubanza et al. 2005; Abdelfatah 2013). Milk protein interactions with caffeic acid while heating caused a reduction in the availability of thiol groups and lysine, which is related to the presence of quinones via caffeic acid oxidation and the formation of an amino acid complex (Kroll et al. 2003). Soy protein interactions with gallic acid/caffeic acid/chlorogenic acid/quercetin cause a reduction in lysine, tryptophan, and cysteine contents. The condensed tannins, which are present in sorghum, are responsible for reduced digestibility of the sorghum protein (Emmambux and Taylor 2003).

Protein-Polyphenol Conjugates

Promising alternative methods for the modified biomolecule synthesis of a novel compound with the desired physicochemical properties are conjugation, polymerization, or grafting; such approaches are used for yielding improved properties, e.g., sensorial and nutritional, with specific applications (Czubinski and Dwiecki 2016). Protein is present in eggs, meat, cereals, milk, legumes, and oilseed, with diversified amino acid sequences and compositions, making them different in terms of protein function, structure, and conformation (Ozdal et al. 2013). Protein is a major component, with different functions as well as allowing a different compound to be more effective in its role as an anti-oxidant and is widely applicable in the biomedical and pharmaceutical industries (Phillips and Williams 2011; Liu et al. 2015).

Table 2. Protein-Polyphenol Conjugation Changes and Methods in their Function

Phenolic compounds are natural antioxidants with an aromatic ring attached to hydroxyl groups, which prevents or delays oxidative losses. Some of the attained properties via protein-polyphenol conjugation are antimicrobial, antioxidant, and bacterial enzyme inhibition as well as decreasing the oxidative damage level in living cells, DNA, protein, carbohydrates, and lipids (Maqsood et al.2012; Liu et al. 2017). The protein-polyphenol interaction improves the quality of food, and a non-polar polyphenol-protein conjugate improves the surface hydrophobicity and protein emulsification. Protein-polyphenol conjugates are covalently formed via enzymatic (polyphenol oxidase, laccase, tyrosinase, etc.) or non-enzymatic (alkaline reaction or free-radical grafting) methods (Gu et al. 2017; Liu et al. 2017) (as shown in Table 2).

FACTORS AFFECTING THE FORMATION OF PROTEIN POLYPHENOL CONJUGATES

The two types of factors influencing protein-polyphenol conjugates include extrinsic factors (temperature and pH) and intrinsic factors (polyphenol/protein type and structure), which determine the covalent/noncovalent interactions (Ozdal et al. 2013; Czubinski and Dwiecki 2017). The two major effects that affect the protein-polyphenol interaction are temperature and pH. Temperature affects the protein-polyphenol interaction via hydrogen bonding or hydrophobic-hydrophobic interactions, as heat changes the protein conformation, exposing hydrophobic sites, which influences the hydrophobic compounds to bind (Kulmyrzaevet al. 2005). The hydrophobic effect between curcumin and casein has been observed, and the interaction of caffeic acid with tyrosine, lysine, and tryptophan residues was observed with ionic/hydrogen bonding at a temperature between 10 to 45 °C; as the temperature was increased to 40 to 90 °C, the binding tendency of bovine serum albumin(BSA) to polyphenols decreased (Bonomi et al. 1988; Suryaprakash et al. 2000; Rawel et al. 2005). The amount of hydrogen binding of neochlorogenic acid with sunflower seed protein rapidly decreased as the temperature increased from 30 to 55 °C, as heating at a particular temperature causes the exposure of binding sites via denaturation and conformational changes (Bourvellec and Renard 2012; Ozdal et al. 2013). Covalent interactions between proteins and polyphenols can be induced by heat, as polyphenol oxidation occurs, which results in quinone formation. In addition, at an alkaline pH, polyphenols oxidize to quinones, which covalently react with proteins, showing that the pH influences the protein and polyphenol structure and conformation (Rawel et al. 2005; Ozdal et al. 2014).

APPLICATIONS OF PROTEIN-POLYPHENOL CONJUGATES

Protein-based Films

Protein-based films are of great interest in terms of developing food packing materials, as they have renewable, biodegradable, and eco-friendly properties; however, they have lesser water vapor barrier properties, as they are a hydrophilic type of matrix (Prodpran et al. 2012; Nagarajan et al. 2015). Many hydrophobic substances, e.g., oil and fats, are added to the film-forming solution, and their incorporation overcomes oxidation, producing discoloration and off-odor to overcome this problem (Prodpran et al. 2012). Myofibrillar and legume proteins are soluble in an alkaline environment, and polyphenol is added, so their oxidation occurs, and a protein-polyphenol conjugate is formed (Kaewprachu et al. 2017). Plant extracts can be incorporated in protein films as an antioxidant (Adilah et al. 2018). The addition of a catechin-Bradon extract conjugate not only enhances the antioxidant properties but also the antimicrobial activity of fish myofibrillar film. In addition, soy protein isolate film and fish gelatin are enhanced when conjugated with mango kernel, as they show better antioxidant activity and tensile strength (Kaewprachu et al. 2017; Adilah et al. 2018). The conjugation of EGCG and fish skin gelatin was found to enhance its antioxidant properties and tensile strength and the water vapor barriers and gelatin film packing of chicken skin oil with EGCG decreased lipid oxidation in storage compared to polyethylene packing, so these packings are advised for oil and fat storage (Nilsuwan et al. 2019).

Emulsions

Protein-polyphenol conjugates, having enhanced emulsifying and antioxidative abilities, are used to improve food emulsion stability, e.g., a catechin-ovalbumin conjugate enhances the emulsion stability fish oil, which was produced by free-radical grafting, and the modified emulsions had better storage stability, lower lipid oxidation, and smaller droplet size (Feng et al. 2018). The modified protein surface hydrophobicity improved the emulsifying activity and the conjugated droplets repulsion improved the emulsion stability, as a WPI-EGCG conjugate prevented fish oil deterioration and prevented fish oil lipolysis (Liu et al. 2016a,b; Fanet al. 2018a,b). The oxidized tannic acid-gelatin conjugate stabilized menhaden oil-in-water emulsion and showed less phase separation and lipid oxidation compared to unmodified gelatin and a fish oil emulsion had better oxidative stability with the presence of a B-lactoglobulin-green tea polyphenol conjugate, having the same droplet size (Aewsiri et al. 2009; Von Staszewski et al. 2011). The oil-water emulsion was physically stabilized by a rice hull phenolic extract-rice bran protein hydrolysate conjugate, which made a rapeseed oil emulsion less flocculated and coalescence with a smaller oil droplet size (Cheetangdee and Benjakul 2017; Li et al. 2019). Additionally, many covalent polyphenol-protein conjugates, e.g., a-lactalbumin-catechin, lactoferrin-chlorogenic acid, β-lactoglobulin-catechin, catechin-egg albumin protein, and lactoferrin-EGCG, are used as antioxidants in an oil-in-water emulsion (Yin et al. 2014; Yi et al. 2015). Protein-polyphenol conjugates with enhanced interfacial properties can be absorbed on the oil surface and make the oil droplets stable from electrostatic repulsion and steric hindrance, as shown by milk proteins (Staszewski et al. 2012). Therefore, protein-polyphenol conjugates could be used as antioxidant emulsifiers in food products.

Protein Gels

Protein gel is formed by a three-dimensional protein chain network connected via covalent/noncovalent interaction and can be produced by different methods, e.g., environmental changes, mineral addition, pH adjustments, and enzyme cross-linking (Liu et al. 2017; Quan and Benjakul 2019). Oxidized polyphenols are primarily used in protein cross-linkers, which enhance gel formation, e.g., β-lactoglobulin-green tea polyphenol conjugate increased B-lactoglobulin gelatin by lowering the gelling time and temperature (Balange and Benjakul 2009a,b,c; Staszewski et al. 2011, 2012; Velickovic et al. 2017). The change in the gelling properties of yogurt could be because of the addition of cocoa polyphenol, which increases the syneresis and decreases the elasticity, and gelatin could be covalently modified with tannic acid, yielding an improved rigid structure (Yildirim-Elikoglu and Erdem 2017). Additionally, the gelatin hydrogel matrix could be improved by tannic acid/caffeic acid/Fructus chebulae extract by producing a compact structure. The addition of oxidized polyphenols could increase the strength of bigeye snapper surimi gel and a similar increase could be seen with the addition of coconut husk extract to sardine surimi (Balange and Bejakul 2009a,b,c). Tea polyphenol modification to egg albumen proteins enhances gurnard surimi gels, and studies showed that protein-polyphenol conjugates have a binding ability with both hydrophilic and/or hydrophobic compounds (Chanphai et al. 2018; Chanpai et al. 2019; Zhao and Sun 2018). Moreover, protein-polyphenol conjugated emulsifiers for delivering encapsulated bioactive compounds stabilizes the β-carotene oil-in-water emulsion by improving their stability in GIT conditions.

Whey Protein-Polyphenol Conjugates and Complexes

Whey proteins (WP), a globular protein series, are found in milk, e.g., α-lactalbumin, BSA, and β-lactoglobulin, which are used as a functional ingredient in the food industry, primarily as a foaming and emulsifying encapsulating agent or as a gel structure in different products (O’Connell and Fox 1999; Krolczyk and Janiszewska-Turak 2016). Whey proteins generate peptides, which have potentially beneficial properties, e.g., antioxidant, anti-hypertension, and cholesterol lowering. This gives them health benefits, but their consumption is limited, as they are functionally deteriorated because of numerous physical influences, e.g., temperature, pH, and ionic strength (Buggy et al. 2018; Minj and Anand 2020; Baba et al. 2021; Koningsveld et al. 2002; Tokmakov et al. 2021). These processes change the structure of WPs via biological activity alteration, so their health properties are changed, as there are numerous physicochemical modifications that need to be investigated to overcome these flaws and increase the functions of WPs (Madhan et al. 2005; Cao et al. 2018; Rasouli et al. 2019). The techno-functional properties of WPs are improved by their linking to food-grade products and are bonded to polysaccharides and polyphenols via covalent linkages or noncovalent linkages (Cao et al. 2018; Setiowati et al. 2020) and thereby improve the techno-functional qualities of the protein with the biological qualities (Doost et al. 2019; Khalifa et al. 2019; Pessato et al. 2019; Wang et al. 2020a,b; Zhong et al. 2021). Recently, there have been advancements in modified protein manufacturing that resulted in enhanced biological and techno-functional properties, with rapid advances in food science technology applications (Chen et al. 2021). This review presents and evaluates studies on the characterization, fabrication, and biological and techno-functional properties of WP-polyphenol complexes and conjugates, particularly their possible applications in food industries. The aims and reviews of this article are summarized in Fig. 1, which is also helpful for researchers in utilizing whey protein-polyphenol ingredients in food products and identifies the requirements for further research.

Whey Protein-Polyphenol Interactions

Whey proteins and polyphenols are linked via noncovalent (physical) or covalent (chemical) interactions and depend upon the nature and linkage type of the whey protein and polyphenols for determining the biological and functional properties of the complexes/ conjugates produced. The noncovalent bonding is reversible and weak, which includes hydrophobic attraction, hydrogen bonding, van der Waals forces, and electrostatic links, and contains hydrophobic residues, e.g., valine, isoleucine, leucine, and tryptophan, which form hydrophobic links with aromatic non-polar rings in the polyphenols (Yildirim-Elikoglu and Erdem, 2017; Charltonet al. 2002; Damodaran et al. 2007; Tang et al. 2016). Additionally, hydrogen bonds can be formed between the polar groups of WPs and the polyphenol hydroxyl groups. When the polyphenols are charged, electrostatic interactions could be present on oppositely charged protein groups (Zhang et al. 2010).

Covalent bond conjugates are formed between WPs and one or more polyphenols, which are irreversible and strong and involve the nucleophilic groups of the WPs, e.g., -SH or -NH₂groups. Some common chemical reactions involved are alkaline and free radical-induction methods, but various other methods are also used. In each method, the reaction conditions should be monitored appropriately to obtain the desired structure, function, and composition of the conjugates; the term pure refers to commercially procured polyphenols with a purity level greater than 98%.

Table 3. Whey Protein-polyphenol Covalent Conjugation: Detection, Functional, and Production Properties

Table 4. Whey Protein-polyphenol Noncovalent Conjugation; Detection, Function, and Production Properties

FOOD APPLICATION OF WHEY PROTEIN-POLYPHENOL (WP-P) CONJUGATES AND COMPLEXES

An important techno-functional property of proteins is water solubility. Determining their use in food products and the protein-polyphenol physical interaction alters the protein solubility, so their function is also changed. For example, the conjugation of whey protein with chlorogenic acid increases the water solubility. This is probably because of the polyphenol binding to the protein surface, which increases the hydrophilicity and decreases the hydrophobic interaction of the protein molecules (Tsai and She 2006; Arimboor et al. 2011; Jiang et al. 2018). A visible decrease in the surface hydrophobicity of WP was observed after the formation of an EGCG and gallic acid complex, while the water solubility of β-lactoglobulin increased with the formation of resveratrol and anthraquinones complexes, primarily because of the surface hydrophobicity reduction after binding (Wang et al. 2014; Cao and Xiong 2017). The WP-P complexes also affect the protein interfacial properties, which influences their stability to form emulsions and foams, as there the isolate foaming capacity of WPs increased when a complex was formed with chlorogenic acid and EGCG (Jianget al. 2018). Whey proteins have numerous charged groups, hydrogen receptors, and non-polar groups on their surface, which makes them available for hydrophobic interactions, electrostatic interactions, and hydrogen bonding (Bartolomé et al. 2000; Buitimea et al. 2016; Khalifa et al.2018). Whey protein fibril complexes with carvacrol improves the film-forming ability, emulsifying ability, and their antimicrobial activity; WP complex formation with xanthone enhances the protein emulsifying property compared to WPs alone (Rahayu et al. 2020; Wang et al. 2020a,b). The emulsion stability was improved because of the reduction in hydrophobic attraction and increased electrostatic and steric repulsion between the protein-coated oil drops. Jiang et al. (2020) and Li et al. (2020) studied the increasing foam stability and capacity after complexation with proanthocynidins in a dose-dependent way and these improvements were because of the increasing interfacial layer elasticity around the air bubbles or oil drops. The air bubbles inhibit them from coalescing or collapsing, and the increased emulsification is because of additional protein solubility after making the complex, as well as facilitating rapid protein transfer to the interfacial layers (Jiang et al. 2018). However, a protein-polyphenol complex must be carefully produced to obtain the desired interfacial properties (Zhan et al. 2020).

IMPACT OF WP-P ON HEALTH PROMOTING PROPERTIES

The whey protein-polyphenol complex has numerous effects on bioactive qualities; e.g., the complex can reduce the antioxidant ability of the polyphenol because of the masking effect (Adrar et al. 2019). Additionally, a WP complex with EGCG enhances the antioxidant activity of the polyphenol during the long-term storage and GIT conditions. Furthermore, it was explained by Chen et al. (2019a,b) that this complex preserved up to 27% of the antioxidant ability for 7 d of storage. The radical scavenging ability of EGCG-WPI complexes could be increased via sonication after storage, while the pre-heating of the milk protein polyphenol mixture reduces its antioxidant ability (Relkin and Shukat 2012; Clion et al. 2019). This could be because of the thermal denaturation of the WPs, which increases polyphenol binding to the protein exposed hydrophobic patches; however, additional study is still required to understand the required techniques for the production of WP complexes (Papadopoulou et al. 2004; Bayraktar et al. 2019). The radical scavenging ability of polyphenols is further reduced with α-lactalbumin compared to lactoferrin and β-lactoglobulin, which could be because of the polyphenol binding tendency for WPs, while the antioxidant activity of some anthraquinones–β-lactoglobulin complexes was reduced because of the complex formation (Stojadinovic et al. 2013; Xu et al. 2019a,b,c). Some WP-P complexes showed improved antioxidant activity compared to alone, e.g., resveratrol, phenolic acids, and curcumin, and the antioxidant property and heat stability of resveratrol was increased in a β-lactoglobulin complex. This could be because of the proteins’ ability to prevent the resveratrol from converting from the trans to cis form (Cheng et al. 2018; Guo and Jauregi 2018; Li et al. 2018; Wu et al. 2018a, b). The stability of grape skin anthocyanin extract was increased regarding color retention with different destabilizing agents, i.e., by β-lactoglobulin and β-lactoglobulin-quercetin complexes, as it was protected by a polysaccharide, and is a method to release the protected quercetin from acidic stomach degradation. In addition, it has been indicated in multiple studies that the β-lactoglobulin polyphenol complex enhances the polyphenol availability (Heet al.2016; Mirpoor et al. 2017; Shafaei et al. 2017; Chanphai et al. 2018). Protein-polyphenol complexes decrease the allergenicity of WPs, e.g., delphinidin-3-O-glucoside, theaflavins, and chlorogenic acid reduce β-lactoglobulins binding via IgE epitomes. The allergenicity of BSA and β-lactoglobulin was reduced by complexation with EGCG at different pHs and WP oral sensitization of WP was decreased when complexed with caffeic acid and EGCG (Pessato et al. 2018, 2019). As a result, many WPs are used as delivery systems to improve the function of polyphenols, and these systems are then used as functional food fortification for health benefits (Al-Hanish et al. 2016; Chanphai and Tajmir-Riahi 2019).

IMPACT OF WP-P ON TECHNO-FUNCTIONAL PROPERTIES

The covalent bonds of polyphenol-WPs modify their techno-functional properties; e.g., WPs conjugation causes the partial unfolding of WP molecules and exposes the surface hydrophobic sites, which causes enhanced emulsifying, foaming, and solubility properties of the proteins (Temdee and Benjakul 2015; Xu et al. 2019a,b,c). Whey protein complexes with lotus seed proanthocyanidins enhance the emulsifying/oxidative/thermal stability of the WP, and the conjugation of WPs with mulberry polyphenols enhances the solubility and textural properties and decreases their ability to foam glycated end products (Khaifa et al. 2019; Chen et al. 2021). Different polyphenols, e.g., gallic acid, chlorogenic acid, and EGCG, conjugate with lactoferrin via free radical scavenging, which enhances the emulsification and thermal stability as well as produces emulsions, and provides a resistance to salt, freezing, thawing, UV exposure, and thermal applications (Liu et al. 2015, 2017; Lang et al. 2019). Moreover, EGCG and chlorogenic acid prevent lactoferrin aggregation by producing steric/electrostatic repulsions in protein molecules and also change the protein isoelectric points to control pH-induced aggregation (Liu et al. 2015). β-Lactoglobulin-catechin conjugates improve the physicochemical stability of β-carotene, which results in storage carotenoid retention. In addition, α-lactalbumin-catechin conjugates also are stabilized chemically via the radical scavenging from surface polyphenols (Yi et al. 2014, 2016). β-Lactoglobulin-chlorogenic acid conjugates improve the stability and inhibit EGCG release, while BSA-caffeic acid conjugates have better antioxidant activity with enhanced chemical stability and resveratrol bioavailability (Liu et al. 2017; Fan et al. 2018a,b; Prasanna and Jing 2018). Whey proteins have improved interfacial stability with polyphenol conjugation, and when covalently linked covalently with EGCG, many WPs had enhanced interfacial properties compared to their noncovalent complexes (Wei et al. 2015). The improving tendency of WP-EGCG conjugates in terms of β-carotene emulsion stability is in the following order: β-lactoglobulin is greater or equal to α-lactalbumin, which is greater or equal to lactoferrin, as their functional properties depend on the polyphenol type (Ali 2019). In a study, a WP-rosmarinic acid conjugate, made via enzymatic methods, had better antioxidant and antimicrobial activity than the conjugate made via an alkaline method, so it should be necessary to further study the protein, polyphenols, and enzymes used to form different conjugates. Whey protein-polyphenol conjugates have health benefits with enhanced biological activity, as these conjugates have increased antioxidant properties because of the surface hydroxyl groups after adding polyphenol (Fan et al. 2017). Whey protein-chlorogenic acid conjugates have increased antioxidant quality and digestibility but decreased allergenicity, and it was also found that β-lactoglobulin-caffeic acid conjugates were DPPH radical scavengers, with more caffeic acid molecules attached to proteins (El-Maksoud et al. 2018; Xu et al. 2019a,b,c). Conjugates produced via the free radical method, e.g., β-lactoglobulin-chlorogenic acid/lactoferrin, have enhanced antioxidant properties; as such, EGCG-β-lactoglobulin conjugate is beneficial for LDL oxidation, inhibiting atherosclerosis, primarily because of the metal chelation and radical scavenging activity (Liu et al. 2015; Fan et al. 2017; Tao et al. 2019; Liang et al. 2007). Catechin-α-lactalbumin conjugate has an improved scavenging ability compared to its protein or polyphenol alone, which shows their synergistic effect, while a WP-onion extract/quercetin conjugate showed anticancer abilities in human lungs and WP-rosmarinic acid/ chlorogenic acid has improved antioxidant/antiviral activities compared to native proteins.

FUTURE DIRECTIONS

The biological and functional activities of protein-polyphenol complexes or conjugates depend on their nature and cross-linking method type, so more rational complexes or conjugates can be designed in the future. As such, a greater understanding is required in terms of the function structure relation of WP-P conjugates and complexes for specific applications, and modern techniques; e.g., high-pressure processing and sonication, must be utilized for system performance. For example, sonication increased the thermal stability and solubility of a cyanidin-3-galactoside-soy protein conjugate, whereas the performance of an α-lactalbumin pelargonidin-3-glucoside conjugate was improved via the high-pressure method (Xu et al. 2018; Zou et al. 2019). Until now, there have been limited studies on the GIT biological activity and WP-P conjugate/complex health benefits, as their interaction may change the generated peptide, so in terms of altering the protein bioactivity and allergenicity, additional focus is required in this area.

CONCLUSIONS

1. Protein-phenolic interaction can be covalent or noncovalent, but most of the published studies have focused on the noncovalent interactions, mostly because of the lack of methods for covalent bond analysis. Some of the primary factors affecting protein-polyphenol reactions are the protein type and structure and various environmental factors, e.g., pH, temperature, salt concentration, and presence of other reagents. As an exact process, the interactions are still unknown, and studies have been performed on the changes in the structural and functional protein properties.

2. Phenolic fortification could improve the health benefits of food products, but their interaction with food components (especially proteins) could have some undesirable effects on protein digestibility and antioxidative activity. Therefore, additional studies and research are required regarding the protein-phenolic interactions under different environmental conditions for the development of phenolic functional foods with the desired nutritional benefits.

3. Proteins and polyphenols have specific functions, e.g., proteins being able to produce gel or stabilize emulsion and polyphenols having bioactivity and antioxidant activity, which influences food quality. Protein-polyphenol interaction can occur via the enzymatic or non-enzymatic method which is affected by various environmental conditions such as pH, temperature, and structure of the protein/polyphenols.

4. Protein-polyphenol conjugates have improved emulsifying and antioxidative properties, which increases food efficacy, and must be further studied for developing products with enhanced functional, nutritional, and sensorial properties.

5. Whey protein-polyphenol produces conjugates or complexes via covalent/noncovalent bonding, which produces multiple food ingredients, e.g., foaming agents, antioxidants, emulsifiers, and structure formers. Their performance depends on the production method and WP-P type and concentration. A detailed understanding of protein-polyphenol interactions is essential to producing novel ingredients in a food system application, as their internal food system behavior is still not known.

6. The effect on bioactivity and functional properties of the ingredients are barely understood during the preparation, storage consumption, and digestion.

7. As there are a variety of polyphenol structures and functions, a protein-polyphenol ingredient must be produced with wider functions and rational designing. However, it is also important that these methods are viable economically and meet the food requirements.

ACKNOWLEDGEMENTS

The authors are thankful to the Universiti Malaysia Sarawak (Malaysia), South Ural State University (Russian Federation) and Zhangir Khan Agrarian Technical University (Republic of Kazakhstan) for their help and support in completing this work.

“Phenolic-protein interactions: Effects on food properties and health benefits,” Journal of Medicinal Food 21(2), 188-198. DOI: 10.1089/JMF.2017.0057[/RAW_REF_TEXT]

“Complexation of trans- and cis-resveratrol with bovine serum albumin, β-lactoglobulin or α-lactalbumin,” Food Hydrocolloids 81, 242-252. DOI: 10.1016/J.FOODHYD.2018.02.037[/RAW_REF_TEXT]

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