Recent advances on the stability of dietary polyphenols

This review highlights on recent advances in the stability of polyphenols in relation to their structure-stability relationship, new unstable products, and technologies to stabilize polyphenols. Dietary polyphenols are one of the most abundant groups of phytochemicals in food sources. Over 60,000 of structurally diverse natural polyphenols such as flavonoids, flavonoids, isoflavonoids, phenolic acids, stilbenoids, anthocyanins, and flavan-3-ols were reported in plants (Figure 1). Recently, more and more polyphenols were identified via metabolomics analysis based on high-resolution mass spectrometry and NMR spectroscopy. The epidemiological investigation and clinical studies have confirmed that polyphenols benefit human health by suppressing oxidative stress and free radical scavenging, which play a key role in preventing and managing inflammation, diabetes, obesity, cardiovascular disease, and cancer. Moreover, dietary supplements with polyphenols or polyphenol-rich extracts have been marketed to reduce the impact of insufficient vegetables and fruits intake. However, many polyphenols are unstable and highly prone to oxidation and/or degradation during processing and storage (Chandra et al., 2021). The stability of polyphenols depends on their chemical structure, as well as environments such as pH and temperature. Polyphenols are affected to a variable extent by different thermal and non-thermal processing technologies. A wide range of technologies has been applied to improve the stability of polyphenols during processing and storage. The number of publication on "polyphenol and stability" (Indexed by WOS) significantly improved since 2011 and the breakout increasing happened in the last 3 years (2019–2021) (Figure 2). This review highlights on recent advances in the stability of polyphenols in relation to their structure-stability relationship, new unstable products, and technologies to stabilize polyphenols. Several terms including concentration change, degradation time, reaction kinetics, and antioxidant potential have been applied to characterize the stability of polyphenols under certain designed experimental conditions. The concentration change of polyphenols in certain conditions did not reflect the nature of degradation. The degradation time, namely early degradation time (CT10) and half degradation time (CT50) is a reliable index to compare the stability between different polyphenols. The reaction kinetics is helpful to predict and control the degradation of polyphenols during processing (Cao et al., 2020, 2021). Moreover, the determination of antioxidant potential of polyphenols is another approach to exhibit the stability of polyphenols (Asem et al., 2020). However, the oxidation is not a main reason responsible for the unstable process. High-resolution MS is a pronouncedly convenient and advanced method to analyze the polyphenol and its unstable products in complex matrices. The UPLC-Q-TOF-MSn and UPLC-LTQ-Orbitrap-MSn are widely applied to screen and structure predict the degraded/oxidized products of polyphenols (Cao et al., 2020; Lin et al., 2022; M. L. Wang et al., 2022; H. L. Zhang et al., 2022). Moreover, NMR spectroscopy is important tool for qualitative and quantitative analysis of polyphenols, especially in structural elucidation and stereochemistry determination. Many factors in food systems contribute to the chemical changes of polyphenols, leading to the instability of the polyphenols. The stability of polyphenols in food matrixes is decided by various biochemical and chemical reactions, which are significantly affected by as pH value, photo/light, temperature, oxygen availability, metal ions, enzymes, proteins, nitrite salt, sulfur dioxide, other antioxidants, and interactions with other food constituents. pH value is a key factor influencing polyphenols' stability (Figure 3). A more acidic environment stabilizes polyphenols. In alkaline solution, the degradation, dimerization, and oxidation of polyphenols always tend to happen (M. L. Wang et al., 2022). For example, malvain 3-O-glucoside exhibits different colors under different pH conditions (Cao et al., 2021). The content of total anthocyanins significantly reduces during heating under neutral and alkaline pH (Oancea, 2021). The temperature is another important factor affecting the stability of polyphenols. Lower temperature is helpful to protect polyphenols. The polyphenol oxidase, polyphenol peroxidase, polyphenol glycosidase, and polyphenol esterase in fruits and vegetables will be released and catalyzed by the oxidation and degradation reactions of polyphenols when plant cells are destroyed (Montoya et al., 2021). Some polyphenols are decomposed in saliva to form phenolic acids (Rogozinska & Biesaga, 2020). The stability of polyphenols is dramatically different due to their structural variations. The stability of polyphenols can be changed by chemical modifications, such as hydroxylation, glycosylation, acylation, and pigmentation. It looks like the hydroxylation of polyphenols always reduces their stability, while other modifications improve the stability of polyphenols (Cao et al., 2021). The hydroxyl groups in polyphenols significantly influenced the stability in the following order resorcinol-type > catechol-type > pyrogallol-type, with the pyrogallol-type being the least stable. Co-pigmentation also occurs by hydrogen bonding between the phenolic groups of anthocyanins and flavonoids. In contrast, any glycosylation of polyphenols can enhance their stability. Polyphenols with trans form such as trans-resveratrol showed much more thermal stability than its cis form (Kosović et al., 2020). 3-O-caffeoylquinic acid is more stable than 4-O-caffeoylquinic acid (D. L. Wang et al., 2021). The acylated anthocyanins are more stable to temperature change than non-acylated anthocyanins (Oancea, 2021). Polyphenols are highly reactive molecules and undergo a series of enzymatic and chemical reactions with other components in plant cells, resulting in the system more complex (Wei et al., 2022). Enzymatic browning reactions of polyphenols in fruits form decarboxylated dihydro-1,4-benzothiazine derivatives as major intermediates to finally produce pigment (Mertens et al., 2021). During thermal processing, polyphenols in food will be rapidly converted into various derivatives mediated by heat. However, there are few studies on the changes and mechanisms of polyphenols in complex food systems during thermal processing, and there are few reports on thermal degradation products, oxidation products, and enzymatic hydrolysis products of polyphenols in complex food systems. Moreover, the antioxidants from other sources don't improve the stability of polyphenols in food matrix. The unpredictable influence of improving or inhibitory antioxidant activity of different polyphenols in food matrix is always reported. Ascorbic acid can enhance flavonols' stability but weaken the stability of anthocyanins and phenolic acids (Hanuka Katz et al., 2020). The stability of purified polyphenols is higher than that in the strawberry extract. The cinnamon and clove extract hardly changed the concentration of polyphenols in chokeberry juice (Sidor et al., 2020). Processing cranberries into sweetened dried cranberries significantly reduced anthocyanins and proanthocyanidins in cranberries (Kovacev et al., 2020). Interactions between polyphenols and polysaccharides have significant consequences on the bioavailability and extractability of the polyphenols. With the aid of mass spectrometry and NMR analysis, it can also identify the structure of unstable products of polyphenols in different experimental conditions. The main chemical reactions are dimerization, oxidation, hydroxylation, and nucleophilic attack cleavage. the unstable products of quercetin in boiling water are identified as 3,5-dihydroxyphenylglyoxylic acid, 1,3,5-trihydroxybenzene, 3,4,5-trihydroxybenzoic acid, 2,4,6-trihydroxybenzoic acid, 2,3-dihydro-2,3′,4′,5,7-pentahydroxy-3-oxoflavone, quercetin dimers, and quinones (Figure 4). Flavonols with a catechol or pyrogallol substitution pattern on ring B readily formed stable dimers and oxidized products in phosphate-buffered saline (pH = 7.4) at 4°C within 5 s (Figure 4) (Cao et al., 2020). Epimerization of tea catechins always happened in high temperature and pH value (Xu et al., 2019). Tea catechins can be auto-oxidized and degraded to gallocatechin and gallic acid in boiling water (Wu et al., 2019). Chlorogenic acid tends to be isomerized to neochlorogenic acid and cryptochlorogenic acid, and further be oxidized and degraded during extraction and food processing (Ianni et al., 2022). 3- and 4-O-caffeoylquinic acid can be converted to their isomers during degradation. The thermal degradation of non-acylated anthocyanins in fruits and vegetables will yield phloroglucinaldehyde via C3–C4 cleavage and phenolic acids via C2–C3 cleavage. The thermal oxidative degradation of anthocyanins can form 3,5,7-trihydroxycoumarin and 2,4,6-trihydroxyphenylacetic acid (Figure 5; Fenger et al., 2020). The gallic acid and phloroglucinaldehyde from anthocyanin degradation are further oxidized into pyrogallol and phloroglucinol (Figure 5; Y. Zhang et al., 2020). The stilbenoids in methanol solution are isomerized from a trans to cis form under UV irradiation by intramolecular cyclization to phenanthrene structures (Latva-Mäenpää et al., 2021). However, solid trans-stilbenoids are not sensitive to UV/fluorescent light, elevated temperature or humidity, or atmospheric oxidants at ambient conditions. Recently, novel technologies have been developing to improve the stability of polyphenols in food processing. Encapsulation, microcapsule, lyophilization, conjugation with biomacromolecules, and cold plasma are typical innovative sustainable technologies that provide significant advantages on processing polyphenols (Cao et al., 2021; Choudhury et al., 2021; Jagtiani, 2022). The interactions between polyphenol and β-cyclodextrin/protein/polysaccharide via microencapsulation and encapsulation can improve the stability, solubility, safety, bioavailability, biocompatibility, and bioactivity of polyphenols (Figure 6). The microencapsulation of polyphenols with β-cyclodextrin significantly improves the processing stability and bioaccessibility of mulberry polyphenols (Li et al., 2020), olive pomace polyphenols (Radić et al., 2020), citrus pomace polyphenols (Caballero et al., 2021). Application of polyphenol- protein/polysaccharide interaction to fabrication, nanoparticles, emulsion, and encapsulation has been applied to improve the thermal stability and antioxidant activity of EGCG, resveratrol, quercetin, chlorogenic acid, and isoflavone. Nanopolyphenols can provide more efficient delivery to improve bioavailability and therapeutic efficacy, which are possibly decided by the stability, bioavailability, and biocompatibility (Rambaran & Nordström, 2021). The stability of polyphenols in food matrixes are significantly affected by many exogenous factors and interactions with other constituents. During thermal processing, polyphenols in food will be rapidly converted into various derivatives. However, there are few studies on the changes and mechanisms of polyphenols in complex food systems during thermal processing, and there are few reports on thermal degradation products, oxidation products, and enzymatic hydrolysis products of polyphenols in complex food systems. The main reactions of polyphenols that happened in the thermal process are dimerization, oxidation, hydroxylation, and nucleophilic attack cleavage. During food processing, the reaction kinetics of different polyphenols in foods are different, and the interaction between polyphenols makes the food system more and more complicated. How to analyze the change law has always been a difficult problem. Polyphenols exist in the microstructure of plants as the forms of free polyphenols, physical polyphenols (embedded in cells or matrix), bound polyphenols (interacting with biomacromolecules), and insoluble polyphenols (Ren et al., 2020). Free polyphenols are easily extracted from food, so most studies focus on the chemical and biological properties of free polyphenols in food (Domínguez-Fernández et al., 2021). Compared with free polyphenols, the stability of bound polyphenols is greatly improved, and biomacromolecules protect small polyphenols molecules from reacting, and their protective ability is related to the affinity of polyphenols-biomacromolecule interactions. Although the bound polyphenols in fruit and vegetables account for 20%–60% of the total polyphenols content, however, few reports have clarified the changes and mechanisms of bound polyphenols during processing. This study was supported by Ramón y Cajal grant (RYC2020-030365-I).