Open access peer-reviewed chapter
Abstract
The current lifestyle and the greater awareness of the health benefits of wine are causing an increase in demand for wines with higher levels of bioactive compounds, principally red wine. Scientific evidence supports the benefits of wine, mainly related to their antioxidant and anti-inflammatory activities. This chapter, in its first section, reviews previous studies aiming to elucidate the action mechanisms through which the bioactive compounds act on the human organism in the prevention of diseases. According to the existing literature, studies dealing with specific procedures to enhance the bioactive profile of wines are scarce. Therefore, in the second section, we pay attention to some aspects related with applicable technological strategies during the winemaking process and its incidence in the extraction and stability of bioactive compounds. Furthermore, we discuss some applicable strategies in (i) the vineyard during the vine cultivation and (ii) the raw material level in pre-fermentative stage within winery, as well as, biotechnological strategies during the fermentation and aging. All these are directed to improve the content of bioactive compounds in the wine and, thus, transmit its benefits to the consumer’s health.
Keywords
- wine
- bioactive compounds
- bioactive compounds extraction
- disease prevention
1. Introduction
It is known that the content of bioactive compounds is greater in red wines, so that more health benefits can be expected by its consumption. This is the reason most studies are conducted on these wines.
Among the most studied compounds are the anthocyanins, which can be found in the skin and represent between 50 and 60% of the phenolic fraction in the red grapes (dry weight basis) [1]. For its part, the flavanols are mainly found in grape seeds with predominance of catechin over its isomer epicatechin [2], while the tannins are mostly grouped in procyanidins (catechin and epicatechin derivatives) and prodelphinidins (derived from gallocatechin and epigallocatechin) [3]. Other important groups are the stilbenes, mainly resveratrol, to which much of the protective effects of wine are attributed. Also, flavonols such as quercetin, myricetin, and kaempferol, predominant in
2. Health benefits of wine
2.1 Antioxidant activity
This activity is perhaps the most important concerning the prevention of diseases, due to the presence of phenolic compounds. Among the most important action mechanisms, the prevention of oxidative damage caused by free radicals stands out. This mechanism relies on the capture of unpaired electrons and generation of less reactive species, as well as well as the chelation of metal-ions such as Fe or Cu, to avoid the production of new free radicals [4, 5]. Other mechanisms include the interruption of self-oxidation chain reactions, deactivation of singlet oxygen, suppression of nitrosative stress, synergy with other antioxidants, activation of antioxidant enzymes, and inhibition of oxidant enzymes [6], among others.
The antioxidant efficacy would be determined by the chemical nature. For instance, the anthocyanin B-ring substitution rate is crucial due to its potential to neutralize free radicals [7], mostly in the malvidin, since it contains two methoxyl groups (-OCH3) and one hydroxyl (-OH) group in the B-ring.
Similar behavior has been observed in gallotannins (epicatechin gallate and epigallocatechin gallate) arising from high concentration of OH groups with higher antioxidant activity than the non-gallates (catechin and epicatechin) [8]. Moreover, the antioxidant activity might improve with the synergistic tannin-tannin interaction [8] or between tannins and other compounds such as quercetin and resveratrol, reducing the lipid peroxidation caused by physical activity, for instance, in athletes [9].
The resveratrol is one of the compounds with the most antioxidant activity as it shows anti-aging activity due to its stimulant action on sirtuins [10]. Also, it is able to suppress free radical production, regulate the antioxidant enzymes activity, and induce endogenous antioxidant defenses such as Nrf2 [nuclear factor (erythroid-derived 2)-like 2] pathway [11], which regulates the expression of inflammatory markers, protecting against diseases such as Parkinson’s [12].
The quercetin also contributes to reduce oxidative stress acting on the anion O2- and over the enzymes that produce it [13].
Also, the benefits of alcohol-free red wine have been observed, which include activity increase of SOD, catalase, and glutathione reductase enzymes [14] and the production of nitric oxide (NO) [15]. The latter is closely related to a lower cardiovascular risk [16].
2.2 Anti-inflammatory activity
Inflammation is a natural bodily response against the presence of injuries or harmful agents. Among these agents, free radicals can activate the production of pro-inflammatory mediators such as tumor necrosis factor alpha (TNF-α) [17], which in turn can lead to increased oxidative stress in a cycle that contributes to the progression of many diseases.
Anti-inflammatory compounds, such as resveratrol, have been proven to be effective against cyclooxygenase (COX) enzyme, which is involved in the production of prostaglandins that stimulate the growth of tumor cells [18]; in addition, resveratrol enhances the insulin sensitivity in diabetic patients by the activation of sirtuins, which are responsible for inhibiting inflammatory processes and the secretion of TNFα factor [19, 20]. Also, resveratrol acts on microglia, involved in the defense of an injury or disease of central nervous system (CNS) [21]. Thus, the inhibition of microglial activation may help prevent several disorders. Besides, resveratrol also presents protective activity against cardiovascular diseases (CVD), by inhibiting TNFα and interleukin 6 (IL-6) [22].
Specific cases related to some pathologies are discussed in detail below.
2.3 Protection against cardiovascular diseases
There is vast evidence linking the moderate consumption of wine to lower CVD predominance, with the reports by Renaud and de Logeril [23] and St. Leger et al. [24] being pioneers in the study of the known French paradox. These studies explained the lower incidence of CVD in France despite the high consumption of saturated fats. Later studies have shown the benefits for cardiovascular risk biomarkers (Figure 1), which are mainly attributed to phenolic compounds.
Figure 1.
Effects of wine components for cardiovascular risk factors. Adapted from Ref. [
Also, the presence of ethanol has been associated with low-density lipoprotein (LDL) and triglycerides level reduction and with the increase of high-density lipoprotein (HDL) at doses of 15–30 grams of ethanol per day [26]. Later studies suggest that moderate ethanol ingestion can increase HDL levels, apolipoprotein A1 (ApoA1) and adiponectin, in addition to lowering fibrinogen levels [27]. Nonetheless, such results suggest the need for further studies due to negative effects of excessive ingestion of ethanol.
Other compounds coming from grapes, such as melatonin and phytosterols (β-sitosterol, stigmasterol, and campesterol), have also shown protective effects against CVD either individually or in synergy with phenols [28]. Melatonin has shown effects against clinic indicators such as blood pressure, NO metabolism, and endothelial functions [29, 30] in addition to the effects on free radicals [31].
Moreover, β-sitosterol, stigmasterol, and campesterol have shown hypocholesterolemic effects by reducing the plasmatic levels of LDL (up to 10%), LDL/HDL ratio (up to 11.5%), and intestinal absorption of cholesterol (30–40%) [32, 33, 34].
2.4 Neuroprotective effects
2.4.1 Prevention of memory loss
Wine consumption could reduce the memory loss caused by cerebral circulatory insufficiency by increasing the acetylcholine levels, proteins responsible for the organization of brain cells [36], and the prevention of platelet aggregation by ethanol [37]. Other mechanisms include the resveratrol action on the telomerase enzyme, involved in preventing cell senescence and delayed cognitive impairment [38], or the action of the quercetin against cell aging by means of the activation of proteasome complex [39].
2.4.2 Action against cerebrovascular infarctions
In the Copenhagen City Heart Study, it was observed that participants who consumed wine moderately had 50% less risk of dying from cerebral infarction [40] due to the enhancement of the cerebral blood flow, the effect mainly attributed to resveratrol.
In addition, resveratrol interacts with estrogen receptors α and β, reducing cholesterol levels and the formation of atherosclerotic plaque and therefore the risk of stroke due to circulatory failure, for example, in postmenopausal women [41]. Resveratrol has also been shown neuroprotective activity against inflammatory mediators, such as interleukin 1β (IL-1β) and TNF-α, as well as keeping the levels of proteins occludin and claudin-5, of vital importance for the permeability and tissue integrity [42], and to attenuate the cellular apoptosis in ischemia-reperfusion injuries [43], which diminish cell death and the development of diseases such as Alzheimer’s.
2.4.3 Antidepressant effect
This effect has been studied in rodents by administration of resveratrol, which can regulate the monoaminergic system, increasing the levels of serotonin, noradrenaline, and dopamine [44]. Also, resveratrol, quercetin, ferulic acid, ellagic acid, and proanthocyanidins can modulate the hypothalamic-pituitary-adrenal (HPA) axis activity as well as the serotonergic neurotransmission [45, 46], which are important mechanisms against anxiety and depression.
2.5 Anticarcinogenic activity
Cancer development comprises the following stages: initiation, promotion, progression, invasion, and metastasis (Figure 2). Initiation corresponds to DNA damage by free radicals, inflammatory mediators, cigarette smoke, radiation, etc. [47, 48, 49], which may induce genetic mutation and reproduction of mutated cells giving rise to carcinogenesis.
Figure 2.
Potential protective mechanisms of the phenolic compounds at different cancer stages. Adapted from Ref. [
Greater protective effect has been observed with phenolic compounds, for example, apoptotic activity of ellagic acid [50] and delphinidin [51] in colon cancer cells. Delphinidin has also shown activity in leukemia, liver [52], and prostate cancer cells [53]. Resveratrol can also induce cell apoptosis [54].
For its part, proanthocyanidins can alter the migration and invasion processes in human pancreatic cancer [55]. Delphinidin and cyanidin has proven their antimetastatic activity in human colon cancer cells [56], while resveratrol has the same effect on lung cancer cells [57]. More specific mechanisms are shown in Figure 2.
2.6 Antimicrobial and antiviral activities
Red wine presents activity against
White wine also presents activity against
Besides, wine’s activity is also effective against some viruses, which include human immunodeficiency virus (HIV) [62], hepatitis virus and adenovirus (respiratory infections), cytomegalovirus (chickenpox and infectious mononucleosis), and norovirus and rotavirus (gastroenteritis) [60].
Nonetheless, it is worth mentioning that the antimicrobial and antiviral activities showed by the wine and/or their components cannot be compared to the one attributed to antibiotics. Therefore, wine should not be used for such purposes.
3. Enhancement of bioactive compounds content
3.1 Vineyard: synthesis of bioactive compounds
The wine composition is closely related with the grape composition that mainly depends on its variety. Some compounds, such as resveratrol can reach concentrations of up to 6 mg L−1 in wines made of Pinot noir grapes [63], quercetin, concentrations of up to 13 mg L−1 in wines made of Shiraz grapes [64], or β-sitosterol, up to 106 mg/100 g of dry skin in Groppello grapes [65].
Other factors which may also induce a better synthesis of bioactive compounds at the vineyard stage are the cultivation conditions and viticulture practices (Figure 3). Some examples include the increase in anthocyanin and tannin levels by exposing grape bunches to sunlight and UV radiation [66], which resembles the effect observed in quercetin [67] and resveratrol [68]. In addition, agrochemical elicitation may induce the synthesis of resveratrol [69], melatonin [70], β-sitosterol, and other sterols [65].
Figure 3.
Technological strategies to improve the content of bioactive compounds in red wines.
However, conditions, such as high temperatures, can slow down the synthesis of phenolic compound, mainly anthocyanins, promoting the synthesis and accumulation of sugars in berries [71] and affecting the levels of extractable bioactive compounds during winemaking process.
3.2 Pre-fermentation treatments
Although most of the procedures are intended to enhance the physicochemical stability and sensory profile, these can be advantageous to improve the bioactive profile of wine, considering that 50% of these compounds are extracted during the winemaking process [64].
The contact time between skins and grape-must/wine can affect the content of compounds such as resveratrol, whose maximum extraction can be realized after 10 days of contact [72]. Also, the use of pre-fermentation enzymes and cold maceration can assist in the extraction of anthocyanins and tannins [73].
Furthermore, the emerging technologies could also be useful. Traditionally, these technologies have been studied to control microbial load of food. However, they can also be useful to improve the extraction of phenolic compounds and other molecules with positive effects on the properties of the wine. Other benefits include aroma preservation and phenolic compound protection against oxidation, since the temperature of the treated product does not change [74] and reduce SO2 doses, an additive that can cause problems on the consumer’s health [75].
These technologies can also help improve the extraction in grapes with low phenolic content, as an alternative to conventional treatments such as the use of pectolytic enzymes or the “blended” with varieties of grapes with higher phenolic content [76]. It also allows to produce wines with greater varietal character, which is preferred in the markets.
3.2.1 High hydrostatic pressure
The high hydrostatic pressure (HHP) technique can improve the extraction and protect the phenolic compounds against oxidation, given that at pressures of 600–700 MPa partial inactivation of the polyphenol oxidase enzyme is achieved [77], which enables the enhancement of the antioxidant properties of wine and, consequently, reduces the SO2 doses [75]. HHP also allows for the maintenance of the integrity of the berry [74], facilitating the manipulation of the grape, without losses of raw material or risks of microbial contamination.
Pressures of 200 MPa have allowed the enhanced extraction of anthocyanin in red grapes, improving color intensity (26% higher) and total polyphenol index (TPI, 43% higher), with respect to the control [78]. Besides, HHP increases the selective extraction of acylated anthocyanins (up to 68% of
Higher pressures (600 MPa) were applied by Corrales et al. [79], increasing the acylated anthocyanin extraction by nine times with respect to the control at 70°C. In addition, pulsed electric field (PEF, at 3 kV cm−1) technique was applied, improving the antioxidant capacity by up to three times with HHP and four times with PEF. The latter may be associated with the inactivation of oxidant enzymes.
On the other hand, the HHP favors the formation of pyranoanthocyanins, mainly derived from vitisin A at 600 MPa and 70°C [80]. Nonetheless, the anthocyanin content, like the cyanidin, can be reduced as it occurs with pulsed light (PL) and e-beam irradiation [81, 82].
3.2.2 Pulsed electric fields
The pulsed electric fields (PEF) are efficient in the extraction of phenolic compounds due to its action over the skin cell walls, reaching rates of up to 50% or higher [83], in addition to reducing the maceration time by up to 50% at a dose of 5–10 kV cm−1 [84].
Like HHP, the selective extraction of acylated anthocyanins can be increased by more than six times with respect to the control at 3 kV cm−1 [79]. Also, a higher degree of polymerization of the skin tannins can be achieved due to the greater permeability and diffusion through the fractured cell walls [85], which reduce the sensation of astringency and bitterness in the produced wines.
Also, the content of flavanols, flavonols, and hydroxycinnamic acids and derivatives can be improved after 12 months of aging in wines obtained from grapes treated with PEF, as obtained by Puértolas et al. [86] when treating Cabernet Sauvignon grapes with doses of 50 a 122 Hz, 5 kV cm−1 y, and 3.67 kJ kg−1.
At the level of grape-musts treated with PEF, adverse effects have not been observed at doses of up to 29 kV cm−1 [87].
3.2.3 Ultrasound
The ultrasound (US) treatment of red grape-musts is an effective alternative to keep the level of anthocyanins up as high as 97% [88]. This fact clearly shows that the US preserves the chemical stability of these pigments. Combinations of US with heat and ethanol can also be exploited to increase the extraction of total phenols and anthocyanins and to increase the antioxidant capacity [79, 89].
3.2.4 Pulsed light
Pulsed light (PL) is a low-cost technological alternative with higher possibilities of being scaled to an industrial level than HHP, PEF, or e-beam irradiation [81]. Its efficacy varies as a function of the applied light’s features. Thus, better performance is achieved with PL than with UV-C, since the former, in addition to its intensity, includes the infrared component [90].
The UV-C light (254 nm, 8.4 kJ m−2, 15 min, 27°C) continuously applied produces micro-cracks in the skin of red grapes [90], inducing a high anthocyanin migration, although it is performed with lesser intensity than with HHP [74] or e-beam irradiation [82] and without affecting the external appearance of the treated berries, which facilitates their subsequent handling.
However, in wines obtained from red grapes treated with PL (12% UV-C, 10% UV-B, and 8% UV-A), a slight reduction of anthocyanins at doses of 10 pulses at 600 J has been noted. This may be associated with the oxidative degradation of these compounds by radiation [82]. Interestingly, vinylphenolic pyranoanthocyanins and vitisins have exhibited higher stability [81].
3.2.5 e-Beam irradiation
Electron beam (e-beam) irradiation can enhance the extraction of anthocyanins by up to 70% at 10 kGy [82], without affecting the external appearance of treated berries. Lower doses (0.5–3.0 kGy) have also shown improvements during extraction of anthocyanins from grape marc [91].
One disadvantage of this technology is the lowering of anthocyanin contents in the produced wines, as consequence of the induced oxidation by radiation [82]. Nonetheless, the content of vinylphenolic pyranoanthocyanins and vitisins is not affected due to the robustness of double bond in heteroaromatic ring under the induced oxidation by e-beam irradiation [82].
3.2.6 Ozone
Grapes exposed to ozone have shown greater contents of flavanols and resveratrol [92, 93]. However, the continuous exposure of berries to this gas (30 μL L−1, 24 h) may produce skin hardening, causing slower extractions without affecting the final content of anthocyanins and flavanols [94].
On the other hand, the efficacy of phenolic extraction has been related with the grape variety. Wines fabricated with grapes containing high level of flavanols (as Nebbiolo) improved their color stability during winemaking procedure, especially with short expositions to ozone (<72 h, 30 μL L−1) [95]. Accordingly, the anthocyanin extraction can be as high as 19% in Petit Verdot grapes treated with ozone, in addition to reduce the fermentation time [96].
3.3 Fermentation level strategies
3.3.1 Selected yeasts
The melatonin content can be increased by using
Another issue to be aware during the winemaking process is the use of yeast with lower expression of anthocyanin-β-glucosidase activity, which is responsible for hydrolysis of anthocyanins [100].
3.3.2 Pyranoanthocyanins synthesis
The most important are vinylphenolic pyranoanthocyanins and vitisins. They present high chemical stability due to the presence of a heteroaromatic fourth ring in their structure, formed by the integration of vinylphenols, pyruvate, or acetaldehyde in the structure of the anthocyanin precursor [101], which provides resistance against oxidation and discoloration in the presence of SO2 and/or increase of wine pH [102]. Moreover, pyranoanthocyanins possess microbiological stability, for instance, against
Fermentations with yeasts with hydroxycinnamate decarboxylase (HCDC+) activity have been studied as a strategy to improve the synthesis of vinylphenolic pyranoanthocyanins, from the condensation of anthocyanins with vinylphenols [101]. The vinylphenols are molecules released from hydroxycinnamic acids in grapes by the HCDC+ activity, which later on can serve as substrate to the synthesis of 4-ethylphenol by
Other interesting pyranoanthocyanin groups are the vitisins A and B, which arise from the condensation of pyruvic acid and acetaldehyde, respectively, together with the malvidin during or after the fermentation process [102].
Also, it is possible to increase vitisin A levels with
On the other hand, it is possible to enlarge the production of acetaldehyde by
3.4 Post-fermentation strategies
3.4.1 Traditional aging of red wine
The aging has direct effects on wine composition, since chemical and/or enzymatic oxidation processes, degradation of phenols on the presence of SO2, and condensation and polymerization reactions [108], among others, take place at this stage, contributing to modify the content of bioactive compounds.
In general, anthocyanin, resveratrol, and flavonol levels tend to diminish with aging process [1, 108, 109]. So that, more benefits to health are attributed to young red wines. Regarding the resveratrol, hydrolysis of the glycosidic form and cis/trans isomerization take place [108], affecting its availability and activity.
At the same time, the content of pyranoanthocyanins increases through anthocyanin condensation with other molecules [101, 102]. Besides, the anthocyanic polymerization or anthocyanin-tannin condensation can be potentially increased.
Likewise, it can augment the content of monomeric flavanols from the hydrolysis of oligomeric and polymeric forms [1]. In fact, monomeric tannins possess high antioxidant capacity to act against free radicals and chelate metals [4, 5, 8], inhibit oxidative stress in cardiac hypertrophy cases, and inhibit cardiomyocyte apoptosis [110] as well as provide antimicrobial activity against oral pathogens [58].
3.4.2 Aging on lees (AOL)
In the last years, this aging technique has gained relevance in the production of red wine [109]. It consists of the release of polysaccharides from cell walls of selected yeasts lees toward the wine during its stay in barrel [111]. These released polysaccharides can enhance, among other attributes, the protection of phenolic compounds against oxidation, due to the lees that have higher oxygen affinity [112].
Nonetheless, it has been noted that anthocyanin contents can be reduced during AOL [111], especially within the first months of aging. This is a consequence of the adsorbent capacity of lees, particularly, cinnamic anthocyanins [109]. Although the loss of anthocyanins can be reduced with lees of species like
4. Additional considerations and future perspectives
The protective effect ascribed to bioactive compounds from wine is not only related to only one compound but also to a combined effect of several of these compounds and to their interactions with other compounds present in food. Also, the moderate ingestion of wine is certainly an important factor.
Most studies have been conducted at preclinical levels (
Despite the existing evidence, there is no consensus regarding its acceptance as an alternative, which aids in the prevention of diseases. Hence, more studies at the clinical level, considering a larger number of volunteers of different ethnicities, lifestyles, and health conditions, are certainly required, with the special consideration that these bioactive compounds cannot be used to replace the medicaments, since they do not possess curative properties, rather they are components of a healthy diet that can help to prevent diseases.
Within the potential strategies, some viticulture practices might contribute to improve the synthesis of bioactive compounds during the vine cultivation. Later into the winery, a proper extraction from the grapes, as well as procedures to minimize the loss of such compounds during the fermentation and aging stages, can improve the bioactive profile of produced wines.
Another important issue is the presence of products such as alcohol-free wines in the markets, which have also shown effectiveness due to the high content of bioactive compounds but with the advantage of avoiding the problems associated with excessive ethanol ingestion.
4.1 Emerging technologies
These kinds of technologies have demonstrated their efficacy to improve the extraction of bioactive compounds in pre-fermentation stages although, until now, some disadvantages have been reported during their application. For instance, the HHP, PL, and e-beam irradiation can diminish the content of anthocyanins like cyanidin in treated grapes [78, 81, 82].
In addition, the high extraction of vitisin derivatives at 70°C by using of HHP, as previously reported by Corrales et al. [80], converts the temperature into a critical parameter that limits its applicability in the winery. This fact indicates the need for more studies to optimize the extraction process.
Likewise, during PL applications [81], it is important to ensure a uniform exposition of the berry surface. The authors suggest the use of roller conveyor belts to change the position of the irradiated berry in order to improve the extraction.
Finally, the scaling of these technologies at the industrial level is still a pending issue since most studies have been carried out in small volumes and in static systems at laboratory level. In order to implement such technologies in wineries, more studies concerning large volumes and continuous flow systems, like the one performed by González-Arenzana et al. [113] with PEF, are needed.
4.2 Pyranoanthocyanins and their effects on health
It has been observed that the antioxidant potential of wine may decrease in aged wines as a result of the reduction of anthocyanins, resveratrol, and flavonols and the simultaneous synthesis of condensation products.
In general, the vitisins have shown lower potential to neutralize free radicals like O2− with respect to their anthocyanin precursors [7], while the pyruvic adduct of the delphinidin has shown greater ability to neutralize OH− and O2− when compared with other pyranoanthocyanins.
The pyranoanthocyanin synthesis by incorporation of pyruvic acid in positions 4 and 5 of A-ring in the structure of the anthocyanin precursor can decrease the potential to suppress free radicals, which might be related to the loss of -OH from carbon 5, that together with -OH from carbon 7, favors the antioxidant activity of anthocyanins [114]. These condensations can be achieved at the fermentation level, although these mostly happen during the aging of wine. Thus, in accordance with the traditional winemaking process, these would be necessary as a strategy to provide physicochemical and microbiological stability to the wine.
As in anthocyanin precursor state, pyranoanthocyanins have shown antioxidant and anti-inflammatory activities. For example, against pro-oxidant (H2O2) and pro-inflammatory (TNF-α) molecules, in addition to neutralizing the secretion of interleukin 8 (IL-8) in cell cultivation of adenocarcinoma from the human colon [17]. Vitisin A has been shown a protective effect against the secretion of monocyte chemoattractant protein-1 (MCP-1) induced by TNF-α factor in human endothelial cell cultures [115], in addition to show great stability in simulated (
5. Conclusions
There is vast evidence regarding the health benefits of wine, especially red wine, that results from higher contents of bioactive compounds, which aid in the prevention of diseases and provide good health benefits when consumed in moderation. Studies carried out at the pre-clinical and clinical stages have been reviewed, mostly at the pre-clinical level. Therefore, the gathered studies contribute to the better understanding of the action mechanisms by which the bioactive compounds may act in the human organism (clinical level) taking advantage of the antioxidant, anti-inflammatory, antitumor, antithrombotic, and antimicrobial activity, among others, to prevent several diseases.
According to the reviewed literature, studies addressing specific procedures to improve the bioactive profile of wine are still scarce. Hence, we described potential technological strategies that may contribute to the increase in, or at least maintenance of, the levels of different bioactive compounds present in wine during the winemaking process. Starting from the production at the vineyard, cultivation strategies can be applied in order to stimulate the greater synthesis of certain compounds. Once into the winery, the pre-fermentative treatments can increase the extraction of bioactive compounds by treating the grapes with HHP, PEF, LP, US, e-beam irradiation, and ozonization. At the fermentative level, yeasts with low adsorption and/or consumption of bioactive compounds, low anthocyanin-β-glucosidase activity, and high production of pyranoanthocyanins and/or precursor molecules of these, among other strategies, can be utilized. Although, in most cases, the content of bioactive compounds can decrease during the aging period, novel strategies like AOL can help to maintain the levels of these compounds in wines. Also, recurrent chemical processes during aging, despite modifying the structures of the grape compounds, have the advantage of allowing the synthesis of pyranoanthocyanins, polymerization of anthocyanins and flavanols, and anthocyanin-tannin condensations, among others, while maintaining the bioactive profile of the wine to a certain degree. All the above are potential strategies to be considered as technological alternatives that are applicable during the winemaking process, which enhance the content of bioactive compounds in the wine, therefore transferring their benefits to the health of the consumer.
Acknowledgments
This work was funded by the Universidad Privada del Norte (UPN), Project UPN-20191001: Valorización de principios bioactivos y desarrollo de nuevas aplicaciones de excedentes y residuos agroindustriales.
References
- 1.
Lingua MS, Fabani MP, Wunderlin DA, Baroni MV. From grape to wine: Changes in phenolic composition and its influence on antioxidant activity. Food Chemistry. 2016; 208 :228-238. DOI: 10.1016/j.foodchem.2016.04.009 - 2.
Spranger I, Sun B, Mateus AM, Freitas V, Ricardo-da-Silva JM. Chemical characterization and antioxidant activities of oligomeric and polymeric procyanidin fractions from grape seeds. Food Chemistry. 2008; 108 (2):519-532. DOI: 10.1016/j.foodchem.2007.11.004 - 3.
Pascual-Teresa S, Rivas-Gonzalo JC, Santos-Buelga C. Prodelphinidins and related flavanols in wine. International Journal of Food Science and Technology. 2000; 35 (1):33-40. DOI: 10.1046/j.1365-2621.2000.00338.x - 4.
Ferlazzo N, Visalli G, Cirmi S, Lombardo GE, Laganà P, Di Pietro A, et al. Natural iron chelators: Protective role in A549 cells of flavonoids-rich extracts of Citrus juices in Fe3+-induced oxidative stress. Environmental Toxicology and Pharmacology. 2016; 43 :248-256. DOI: 10.1016/j.etap.2016.03.005 - 5.
Gupta A, Birhman K, Raheja I, Sharma SK, Kar HK. Quercetin: A wonder bioflavonoid with therapeutic potential in disease management. Asian Pacific Journal of Tropical Disease. 2016; 6 (3):248-252. DOI: 10.1016/S2222-1808(15)61024-6 - 6.
Carocho M, Ferreira ICFR. A review on antioxidants, prooxidants and related controversy: Natural and synthetic compounds, screening and analysis methodologies and future perspectives. Food and Chemical Toxicology. 2013; 51 :15-25. DOI: 10.1016/j.fct.2012.09.021 - 7.
García-Alonso M, Rimbach G, Sasai M, Nakahara M, Matsugo S, Uchida Y, et al. Electron spin resonance spectroscopy studies on the free radical scavenging activity of wine anthocyanins and pyranoanthocyanins. Molecular Nutrition & Food Research. 2005; 49 (12):1112-1119. DOI: 10.1002/mnfr.200500100 - 8.
Furlan AL, Jobin ML, Buchoux S, Grélard A, Dufourc EJ, Géan J. Membrane lipids protected from oxidation by red wine tannins: A proton NMR study. Biochimie. 2014; 107 :82-90. DOI: 10.1016/j.biochi.2014.07.008 - 9.
McAnulty LS, Miller LE, Hosick PA, Utter AC, Quindry JC, McAnulty SR. Effect of resveratrol and quercetin supplementation on redox status and inflammation after exercise. Applied Physiology, Nutrition, and Metabolism. 2013; 38 (7):760-765. DOI: 10.1139/apnm-2012-0455 - 10.
Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, et al. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science. 2004; 305 :390-392. DOI: 10.1126/science.1099196 - 11.
Rubiolo JA, Mithieux G, Vega FV. Resveratrol protects primary rat hepatocytes against oxidative stress damage: Activation of the Nrf2 transcription factor and augmented activities of antioxidant enzymes. European Journal of Pharmacology. 2008; 591 (1-3):66-72. DOI: 10.1016/j.ejphar.2008.06.067 - 12.
Rojo AI, Innamorato NG, Martin-Moreno AM, De Ceballos ML, Yamamoto M, Cuadrado A. Nrf2 regulates microglial dynamics and neuroinflammation in experimental Parkinson’s disease. Glia. 2010; 58 (5):588-598. DOI: 10.1002/glia.20947 - 13.
Perez-Vizcaino F, Duarte J, Jimenez R, Santos-Buelga C, Osuna A. Antihypertensive effects of the flavonoid quercetin. Pharmacological Reports. 2009; 61 (1):67-75. DOI: 10.1016/S1734-1140(09)70008-8 - 14.
Noguer MA, Cerezo AB, Navarro ED, Garcia-Parrilla M. Intake of alcohol-free red wine modulates antioxidant enzyme activities in a human intervention study. Pharmacological Research. 2012; 65 (6):609-614. DOI: 10.1016/j.phrs.2012.03.003 - 15.
Chiva-Blanch G, Urpi-Sarda M, Ros E, Arranz S, Valderas-Martínez P, Casas R, et al. Dealcoholized red wine decreases systolic and diastolic blood pressure and increases plasma nitric oxide. Short communication. Circulation Research. 2012; 111 :1065-1068. DOI: 10.1161/CIRCRESAHA.112.275636 - 16.
Chong E, Chang SL, Hsiao YW, Singhal R, Liu SH, Leha T, et al. Resveratrol, a red wine antioxidant, reduces atrial fibrillation susceptibility in the failing heart by PI3K/AKT/eNOS signaling pathway activation. Heart Rhythm. 2015; 12 (5):1046-1056. DOI: 10.1016/j.hrthm.2015.01.044 - 17.
Peng Y, Zhang H, Liu R, Mine Y, McCallum J, Kirby C, et al. Antioxidant and anti-inflammatory activities of pyranoanthocyanins and other polyphenols from staghorn sumac ( Rhus hirta L.) in Caco-2 cell models. Journal of Functional Foods. 2016;20 :139-147. DOI: 10.1016/j.jff.2015.10.026 - 18.
Jang M, Cai L, Udeani G, Slowing K, Thomas C, Beecher C, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science. 1997; 275 (5297):218-220. DOI: 10.1126/science.275.5297.218 - 19.
Gertz M, Nguyen GT, Fischer F, Suenkel B, Schlicker C, Franzel B, et al. A molecular mechanism for direct sirtuin activation by resveratrol. PLoS One. 2012; 7 (11):e49761. DOI: 10.1371/journal.pone.0049761 - 20.
Yoshizaki T, Schenk S, Imamura T, Babendure JL, Sonoda N, Bae EJ, et al. SIRT1 inhibits inflammatory pathways in macrophages and modulates insulin sensitivity. American Journal of Physiology Endocrinology and Metabolism. 2010; 298 (3):E419-E428. DOI: 10.1152/ajpendo.00417.2009 - 21.
Zhang F, Liu J, Shi JS. Anti-inflammatory activities of resveratrol in the brain: Role of resveratrol in microglial activation. European Journal of Pharmacology. 2010; 636 (1-3):1-7. DOI: 10.1016/j.ejphar.2010.03.043 - 22.
Timmers S, Konings E, Bilet L, Houtkooper RH, van deWeijer T, Goossens GH, et al. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metabolism. 2011; 14 (5):612-622. DOI: 10.1016/j.cmet.2011.10.002 - 23.
Renaud S, de Logeril M. Wine, alcohol, platelets and the French paradox for coronary heart disease. Lancet. 1992; 339 :1523-1526. DOI: 10.1016/0140-6736(92)91277-F - 24.
St. Leger AS, Cochrane AL, Moore F. Factors associated with cardiac mortality in developed countries with particular reference to the consumption of wine. Lancet. 1979; 1 :1017-1020. DOI: 10.1016/S0140-6736(79)92765-X - 25.
Iriti M, Varoni EM. Moderate red wine consumption in cardiovascular disease: Ethanol versus polyphenols. In: Preedy V, Watson RR, editors. The Mediterranean Diet. An Evidence-Based Approach. 1st ed. London: Academic Press; 2015. pp. 143-151. DOI: 10.1016/B978-0-12-407849-9.00014-2 - 26.
Baer DJ, Judd JT, Clevidence BA, Muesing RA, Campbell WS, Brown ED, et al. Moderate alcohol consumption lowers risk factors for cardiovascular disease in postmenopausal women fed acontrolled diet. The American Journal of Clinical Nutrition. 2002; 75 (3):593-599. DOI: 10.1093/ajcn/75.3.593 - 27.
Brien SE, Ronksley PE, Turner BJ, Mukamal KJ, Ghali WA. Effect of alcohol consumption on biological markers associated with risk of coronary heart disease: Systematic review and meta-analysis of interventional studies. British Medical Journal. 2011; 342 :d636. DOI: 10.1136/bmj.d636 - 28.
Iriti M, Varoni EM. The good health of Bacchus: Melatonin in grapes, the unveiled myth. LWT- Food Science and Technology. 2016; 65 :758-761. DOI: 10.1016/j.lwt.2015.09.010 - 29.
Cicero A, Borghi C. Evidence of clinically relevant efficacy for dietary supplements and nutraceuticals. Current Hypertension Reports. 2013; 15 (3):260-267. DOI: 10.1007/s11906-013-0333-8 - 30.
Grossman E, Laudon M, Zisapel N. Effect of melatonin on nocturnal blood pressure: Meta-analysis of randomized controlled trials. Vascular Health and Risk Management. 2011; 7 :577-584. DOI: 10.2147/VHRM.S24603 - 31.
Favero G, Rodella L, Reiter R, Rezzani R. Melatonin and its atheroprotective effects: A review. Molecular and Cellular Endocrinology. 2013; 382 (2):926-937. DOI: 10.1016/j.mce.2013.11.016 - 32.
Escurriol V, Cofán M, Serra M, Bulló M, Basora J, Salas-Salvadó J, et al. Serum sterol responses to increasing plant sterol intake from natural foods in the Mediterranean diet. European Journal of Nutrition. 2009; 48 (6):373-382. DOI: 10.1007/s00394-009-0024-z - 33.
Marangoni F, Poli A. Phytosterols and cardiovascular health. Pharmacological Research. 2010; 61 (3):193-199. DOI: 10.1016/j.phrs.2010.01.001 - 34.
Trautwein EA, Demonty I. Phytosterols: Natural compounds with established and emerging health benefits. Oilseeds and Fats, Crops and Lipids. 2007; 14 (5):259-266. DOI: 10.1051/ocl.2007.0145 - 35.
Dai J, Mumper RJ. Plant phenolics: Extraction, analysis and their antioxidant and anticancer properties. Molecules. 2010; 15 (10):7313-7352. DOI: 10.3390/molecules15107313 - 36.
Ruitenberg A, van Swieten J, Witteman J, Mehta K, van Duijn C, Hofman A, et al. Alcohol consumption and risk of dementia: The Rotterdam study. Lancet. 2002; 359 (9303):281-286. DOI: 10.1016/S0140-6736(02)07493-7 - 37.
Renaud S, Beswick A, Fehily A, Sharp D, Elwood P. Alcohol and platelet aggregation: The Caerphilly prospective heart disease study. The American Journal of Clinical Nutrition. 1992; 55 (5):1012-1017. DOI: 10.1093/ajcn/55.5.1012 - 38.
Wang XB, Zhu L, Huang J, Yin YG, Kong XQ , Rong QF, et al. Resveratrol-induced augmentation of telomerase activity delays senescence of endothelial progenitor cells. Chinese Medical Journal. 2011; 124 (24):4310-4315. DOI: 10.3760/cma.j.issn.0366-6999.2011.24.033 - 39.
Chondrogianni N, Kapeta S, Chinou I, Vassilatou K, Papassideri I, Gonos ES. Anti-ageing and rejuvenating effects of quercetin. Experimental Gerontology. 2010; 45 (10):763-771. DOI: 10.1016/j.exger.2010.07.001 - 40.
Szmitko PE, Verma S. Cardiology patient pages. Red wine and your heart. Circulation. 2005; 111 (2):e10-e11. DOI: 10.1161/01.CIR.0000151608.29217.62 - 41.
Lisabeth L, Bushnell C. Stroke risk in women: The role of menopause and hormone therapy. Lancet Neurology. 2012; 11 (1):82-91. DOI: 10.1016/S1474-4422(11)70269-1 - 42.
Jeong SI, Shin JA, Cho S, Kim HW, Lee JY, Kang JL, et al. Resveratrol attenuates peripheral and brain inflammation and reduces ischemic brain injury in aged female mice. Neurobiology of Aging. 2016; 44 :74-84. DOI: 10.1016/j.neurobiolaging.2016.04.007 - 43.
Li Z, Pang L, Fang F, Zhang G, Zhang J, Xie M, et al. Resveratrol attenuates brain damage in a rat model of focal cerebral ischemia via up-regulation of hippocampal Bcl-2. Brain Research. 2012; 1450 :116-124. DOI: 10.1016/j.brainres.2012.02.019 - 44.
Huang W, Chen Z, Wang Q , Lin M, Wu S, Yan Q , et al. Piperine potentiates the antidepressant-like effect of trans-resveratrol: Involvement of monoaminergic system. Metabolic Brain Disease. 2013; 28 (4):585-595. DOI: 10.1007/s11011-013-9426-y - 45.
Ogle WO, Speisman RB, Ormerod BK. Potential of treating agerelated depression and cognitive decline with nutraceutical approaches: A mini-review. Gerontology. 2013; 59 (1):23-31. DOI: 10.1159/000342208 - 46.
Pathak L, Agrawal Y, Dhir A. Natural polyphenols in the management of major depression. Expert Opinion on Investigational Drugs. 2013; 22 (7):863-880. DOI: 10.1517/13543784.2013.794783 - 47.
Costa D, Galvão AM, Di Paolo RE, Freitas AA, Lima JC, Quina FH, et al. Photochemistry of the hemiketal form of anthocyanins and its potential role in plant protection from UV-B radiation. Tetrahedron. 2015; 71 (20):3157-3162. DOI: 10.1016/j.tet.2014.06.092 - 48.
Decean H, Fischer-Fodor E, Tatomir C, Perde-Schrepler M, Somfelean L, Burz C, et al. Vitis vinifera seeds extract for the modulation of cytosolic factors BAX-α and NF-kB involved in UVB-induced oxidative stress and apoptosis of human skin cells. Clujul Medical. 2016;89 (1):72-81. DOI: 10.15386/cjmed-508 - 49.
Sudheer AR, Muthukumaran S, Devipriya N, Menon VP. Ellagic acid, a natural polyphenol protects rat peripheral blood lymphocytes against nicotine-induced cellular and DNA damage in vitro: With the comparison of N-acetylcysteine. Toxicology. 2007; 230 (1):11-21. DOI: 10.1016/j.tox.2006.10.010 - 50.
Larrosa M, Tomás-Barberán FA, Espín JC. The dietary hydrolysable tannin punicalagin releases ellagic acid that induces apoptosis in human colon adenocarcinoma Caco-2 cells by using the mitochondrial pathway. The Journal of Nutritional Biochemistry. 2006; 17 (9):611-625. DOI: 10.1016/j.jnutbio.2005.09.004 - 51.
Yun JM, Afaq F, Khan N, Mukhtar H. Delphinidin, an anthocyanidin in pigmented fruits and vegetables, induces apoptosis and cell cycle arrest in human colon cancer HCT116 cells. Molecular Carcinogenesis. 2010; 48 (3):260-270. DOI: 10.1002/mc.20477 - 52.
Feng R, Wang SY, Shi YH, Fan J, Yin XM. Delphinidin induces necrosis in hepatocellular carcinoma cells in the presence of 3-methyladenine, an autophagy inhibitor. Journal of Agricultural and Food Chemistry. 2010; 58 (7):3957-3964. DOI: 10.1021/jf9025458 - 53.
Hafeez BB, Siddiqui IA, Asim M, Malik A, Afaq F, Adhami VM, et al. A dietary anthocyanidin delphinidin induces apoptosis of human prostate cancer PC3 cells in vitro andin vivo : Involvement of nuclear factor-kappaB signaling. Cancer Research. 2008;68 (20):8564-8572. DOI: 10.1158/0008-5472.CAN-08-2232 - 54.
Mukherjee S, Dudley JI, Das DK. Dose-dependency of resveratrol in providing health benefits. Dose-Response. 2010; 8 (4):478-500. DOI: 10.2203/dose-response.09-015.Mukherjee - 55.
Prasad R, Katiyar SK. Grape seed proanthocyanidins inhibit migration potential of pancreatic cancer cells by promoting mesenchymal-to-epithelial transition and targeting NF-κB. Cancer Letters. 2013; 334 (1):118-126. DOI: 10.1016/j.canlet.2012.08.003 - 56.
Cvorovic J, Tramer F, Granzotto M, Candussio L, Decorti G, Passamonti S. Oxidative stress-based cytotoxicity of delphinidin and cyanidin in colon cancer cells. Archives of Biochemistry and Biophysics. 2010; 501 (1):151-157. DOI: 10.1016/j.abb.2010.05.019 - 57.
Busquets S, Ametller E, Fuster G, Olivan M, Raab V, Argilés JM, et al. Resveratrol, a natural diphenol, reduces metastatic growth in an experimental cancer model. Cancer Letters. 2007; 245 (1-2):144-148. DOI: 10.1016/j.canlet.2005.12.035 - 58.
Muñoz-González I, Thurnheer T, Bartolomé B, Moreno-Arribas MV. Red wine and oenological extracts display antimicrobial effects in an oral bacteria biofilm model. Journal of Agricultural and Food Chemistry. 2014; 62 (20):4731-4737. DOI: 10.1021/jf501768p - 59.
Queipo-Ortuño MI, Boto-Ordóñez M, Murri M, Gomez-Zumaquero JM, Clemente-Postigo M, Estruch R, et al. Influence of red wine polyphenols and ethanol on the gut microbiota ecology and biochemical biomarkers. The American Journal of Clinical Nutrition. 2012; 95 (6):1323-1334. DOI: 10.3945/ajcn.111.027847 - 60.
Friedman M. Antibacterial, antiviral, and antifungal properties of wines and winery byproducts in relation to their flavonoid content. Journal of Agricultural and Food Chemistry. 2014; 62 (26):6025-6042. DOI: 10.1021/jf501266s - 61.
Just JR, Daeschel MA. Antimicrobial effects of wine on Escherichia coli O157:H7 andSalmonella typhimurium in a stomach model system. Journal of Food Science. 2003;68 (1):285-290. DOI: 10.1111/j.1365-2621.2003.tb14154.x - 62.
Clouser CL, Chauhan J, Bess MA, Oploo JL, Zhou D, Dimick-Gray S, et al. Anti-HIV-1 activity of resveratrol derivatives and synergistic inhibition of HIV-1 by the combination of resveratrol and decitabine. Bioorganic & Medicinal Chemistry Letters. 2012; 22 (21):6642-6646. DOI: 10.1016/j.bmcl.2012.08.108 - 63.
Goldberg DM, Ng E, Karumanchiri A, Diamandis EP, Soleas GJ. Resveratrol glucosides are important components of commercial wines. American Journal of Enology and Viticulture. 1996; 47 :415-420 - 64.
Stockley C, Hoj P. Better wine for better health: Fact or fiction? Australian Journal of Grape and Wine Research. 2005; 11 (2):127-138. DOI: 10.1111/j.1755-0238.2005.tb00284.x - 65.
Ruggiero A, Vitalini S, Burlini N, Bernasconi S, Iriti M. Phytosterols in grapes and wine, and effects of agrochemicals on their levels. Food Chemistry. 2013; 141 (4):3473-3479. DOI: 10.1016/j.foodchem.2013.05.153 - 66.
Song J, Smart R, Wang H, Dambergs B, Sparrow A, Qian MC. Effect of grape bunch sunlight exposure and UV radiation on phenolics and volatile composition of Vitis vinifera L. cv. Pinot noir wine. Food Chemistry. 2015;173 :424-431. DOI: 10.1016/j.foodchem.2014.09.150 - 67.
Pastore C, Zenoni S, Fasoli M, Pezzotti M, Tornielli G, Filippetti I. Selective defoliation affects plant growth, fruit transcriptional ripening program and flavonoid metabolism in grapevine. BMC Plant Biology. 2013; 13 :30. DOI: 10.1186/1471-2229-13-30 - 68.
Berli F, D’angelo J, Cavagnaro B, Bottini R, Wuilloud R, Silva MF. Phenolic composition in grape ( Vitis vinifera L. cv. Malbec) ripened with different solar UV-B radiation levels by capillary zone electrophoresis. Journal of Agricultural and Food Chemistry. 2008;56 (9):2892-2898. DOI: 10.1021/jf073421+ - 69.
Bavaresco L, Mattivi F, De Rosso M, Flamini R. Effects of elicitors, viticultural factors, and enological practices on resveratrol and stilbenes in grapevine and wine. Mini Reviews in Medicinal Chemistry. 2012; 12 (13):1366-1381. DOI: 10.2174/13895575112091366 - 70.
Vitalini S, Gardana C, Zanzotto A, Fico G, Faoro F, Simonetti P, et al. From vineyard to glass: Agrochemicals enhance the melatonin content, total polyphenols and antiradical activity of red wines. Journal of Pineal Research. 2011; 51 (3):278-285. DOI: 10.1111/j.1600-079X.2011.00887.x - 71.
Vejarano R, Morata A, Loira I, González MC, Suárez-Lepe JA. Theoretical considerations about usage of metabolic inhibitors as possible alternative to reduce alcohol content of wines from hot areas. European Food Research and Technology. 2013; 237 (3):281-290. DOI: 10.1007/s00217-013-1992-z - 72.
Kostadinović S, Wilkens A, Stefova M, Ivanova V, Vojnoski B, Mirhosseini H, et al. Stilbene levels and antioxidant activity of Vranec and Merlot wines from Macedonia: Effect of variety and enological practices. Food Chemistry. 2012; 135 (4):3003-3009. DOI: 10.1016/j.foodchem.2012.06.118 - 73.
Federico Casassa L, Bolcato EA, Sari SE, Fanzone ML, Jofre VP. Combined effect of prefermentative cold soak and SO2 additions in Barbera D’Asti and Malbec wines: Anthocyanin composition, chromatic and sensory properties. LWT- Food Science and Technology. 2016; 66 :134-142. DOI: 10.1016/j.lwt.2015.10.026 - 74.
Morata A, Loira I, Vejarano R, González C, Callejo MJ, Suárez-Lepe JA. Emerging preservation technologies in grapes for winemaking. Trends in Food Science and Technology. 2017; 67 :36-43. DOI: 10.1016/j.tifs.2017.06.014 - 75.
Santos MC, Nunes C, Cappelle J, Gonçalves FJ, Rodrigues A, Saraiva JA, et al. Effect of high pressure treatments on the physicochemical properties of a sulphur dioxide-free red wine. Food Chemistry. 2013; 141 :2558-2566. DOI: 10.1016/j.foodchem.2013.05.022 - 76.
Donsi F, Ferrari G, Pataro G. Applications of pulsed electric field treatments for the enhancement of mass transfer from vegetable tissue. Food Engineering Reviews. 2010; 2 :109-130. DOI: 10.1007/s12393-010-9015-3 - 77.
Castellari M, Matricardi L, Arfelli G, Rovere P, Amati A. Effects of high-pressure processing on polyphenoloxidase enzyme activity of grape musts. Food Chemistry. 1997; 60 :647-649. DOI: 10.1016/S0308-8146(97)00050-2 - 78.
Morata A, Loira I, Vejarano R, Bañuelos MA, Sanz P, Otero L, et al. Grape processing by high hydrostatic pressure: Effect on microbial populations, phenol extraction and wine quality. Food and Bioprocess Technology. 2015; 8 (2):277-286. DOI: 10.1007/s11947-014-1405-8 - 79.
Corrales M, Toepfl S, Butz P, Knorr D, Tauscher B. Extraction of anthocyanins from grape by-products assisted by ultrasonics, high hydrostatic pressure or pulsed electric fields: A comparison. Innovative Food Science & Emerging Technologies. 2008; 9 :85-91. DOI: 10.1016/j.ifset.2007.06.002 - 80.
Corrales M, Butz P, Tauscher B. Anthocyanin condensation reactions under high hydrostatic pressure. Food Chemistry. 2008; 110 :627-635. DOI: 10.1016/j.foodchem.2008.02.055 - 81.
Escott C, Vaquero C, del Fresno JM, Bañuelos MA, Loira I, Han SY, et al. Pulsed light effect in red grape quality and fermentation. Food and Bioprocess Technology. 2017; 10 (8):1540-1547. DOI: 10.1007/s11947-017-1921-4 - 82.
Morata A, Bañuelos MA, Tesfaye W, Loira I, Palomero F, Benito S, et al. Electron beam irradiation of wine grapes: Effect on microbial populations, phenol extraction and wine quality. Food and Bioprocess Technology. 2015; 8 :1845-1853. DOI: 10.1007/s11947-015-1540-x - 83.
Yang N, Huang K, Lyu C, Wang J. Pulsed electric field technology in the manufacturing processes of wine, beer, and rice wine: A review. Food Control. 2016; 61 :28-38. DOI: 10.1016/j.foodcont.2015.09.022 - 84.
López N, Puértolas E, Condón S, Álvarez I, Raso J. Effects of pulsed electric fields on the extraction of phenolic compounds during the fermentation of must of Tempranillo grapes. Innovative Food Science & Emerging Technologies. 2008; 9 :477-482. DOI: 10.1016/j.ifset.2007.11.001 - 85.
Delsart C, Cholet C, Ghidossi R, Grimi N, Gontier E, Gény L, et al. Effects of pulsed electric fields on Cabernet Sauvignon grape berries and on the characteristics of wines. Food and Bioprocess Technology. 2014; 7 :424-436. DOI: 10.1007/s11947-012-1039-7 - 86.
Puértolas E, Saldana G, Condon S, Alvarez I, Raso J. Evolution of polyphenolic compounds in red wine from Cabernet Sauvignon grapes processed by pulsed electric fields during aging in bottle. Food Chemistry. 2010; 119 :1063-1070. DOI: 10.1016/j.foodchem.2009.08.018 - 87.
Puértolas E, López N, Condón S, Raso J, Álvarez I. Pulsed electric fields inactivation of wine spoilage yeast and bacteria. International Journal of Food Microbiology. 2009; 130 :49-55. DOI: 10.1016/j.ijfoodmicro.2008.12.035 - 88.
Tiwari BK, Patras A, Brunton N, Cullen PJ, O'Donnell CP. Effect of ultrasound processing on anthocyanins and color of red grape juice. Ultrasonics Sonochemistry. 2010; 17 :598-604. DOI: 10.1016/j.ultsonch.2009.10.009 - 89.
Ghafoor K, Choi YH, Jeon JY, Jo IH. Optimization of ultrasound assisted extraction of phenolic compounds, antioxidants, and anthocyanins from grape ( Vitis vinifera ) seeds. Journal of Agricultural and Food Chemistry. 2009;57 :4988-4994. DOI: 10.1021/jf9001439 - 90.
Fava J, Hodara K, Nieto A, Guerrero S, Alzamora SM, Castro MA. Structure (micro, ultra, nano), color and mechanical properties of Vitis labrusca L. (grape berry) fruits treated by hydrogen peroxide, UV-C irradiation and ultrasound. Food Research International. 2011;44 :2938-2948. DOI: 10.1016/j.foodres.2011.06.053 - 91.
Augustine S, Kudachikar VB, Vanajakshi V, Ravi R. Effect of combined preservation techniques on the stability and microbial quality and retention of anthocyanins in grape pomace stored at low temperature. Journal of Food Science and Technology. 2013; 50 :332-338. DOI: 10.1007/s13197-011-0325-0 - 92.
Artés-Hernández F, Aguayo E, Artés F, Tomás-Barberán FA. Enriched ozone atmosphere enhances bioactive phenolics in seedless table grapes after prolonged shelf life. Journal of the Science of Food and Agriculture. 2007; 87 (5):824-831. DOI: 10.1002/jsfa.2780 - 93.
Sarig P, Zahavi T, Zutkhi Y, Yannai S, Lisker N, Ben-Arie R. Ozone for control of post-harvest decay of table grapes caused by Rhizopus stolonifer . Physiological and Molecular Plant Pathology. 1996;48 (6):403-415. DOI: 10.1006/pmpp.1996.0032 - 94.
Laureano J, Giacosa S, Río Segade S, Torchio F, Cravero F, Gerbi V, et al. Effects of continuous exposure to ozone gas and electrolyzed water on the skin hardness of table and wine grape varieties. Journal of Texture Studies. 2016; 47 (1):40-48. DOI: 10.1111/jtxs.12158 - 95.
Paissoni MA, Río Segade S, Giacosa S, Torchio F, Cravero F, Englezos V, et al. Impact of post-harvest ozone treatments on the skin phenolic extractability of red winegrapes cv Barbera and Nebbiolo ( Vitis vinifera L.). Food Research International. 2017;98 :68-78. DOI: 10.1016/j.foodres.2016.11.013 - 96.
Bellincontro A, Catelli C, Cotarella R, Mencarelli F. Postharvest ozone fumigation of Petit Verdot grapes to prevent the use of sulfites and to increase anthocyanin in wine. Australian Journal of Grape and Wine Research. 2017; 23 :200-206. DOI: 10.1111/ajgw.12257 - 97.
Fernández-Cruz E, Álvarez-Fernández MA, Valero E, Troncoso AM, García-Parrilla MC. Melatonin and derived l-tryptophan metabolites produced during alcoholic fermentation by different wine yeast strains. Food Chemistry. 2017; 217 :431-437. DOI: 10.1016/j.foodchem.2016.08.020 - 98.
Morata A, Loira I, Suárez-Lepe JA. Influence of yeasts in wine colour. In: Morata A, Loira I, editors. Grape and Wine Biotechnology. London: IntechOpen; 2016. pp. 285-305. DOI: 10.5772/65055 - 99.
Barcia MT, Pertuzatti PB, Rodrigues D, Gómez-Alonso S, Hermosín-Gutiérrez I, Godoy HT. Occurrence of low molecular weight phenolics in Vitis vinifera red grape cultivars and their winemaking by-products from São Paulo (Brazil). Food Research International. 2014;62 :500-513. DOI: 10.1016/j.foodres.2014.03.051 - 100.
Wightman JD, Wrolstad RE. D-glucosidase activity in juice-processing enzymes based on anthocyanin analysis. Journal of Food Science. 1996; 61 :544-552. DOI: 10.1111/j.1365-2621.1996.tb13153.x - 101.
Morata A, Vejarano R, Ridolfi G, Benito S, Palomero F, Uthurry C, et al. Reduction of 4-ethylphenol production in red wines using HCDC+ yeasts and cinnamyl esterases. Enzyme and Microbial Technology. 2013; 52 (2):99-104. DOI: 10.1016/j.enzmictec.2012.11.001 - 102.
Bakker J, Timberlake CF. Isolation, identification, and characterization of new color-stable anthocyanins occurring in some red wines. Journal of Agricultural and Food Chemistry. 1997; 45 :35-43. DOI: 10.1021/jf960252c - 103.
Benito S, Palomero F, Morata A, Uthurry C, Suárez-Lepe JA. Minimization of ethylphenol precursors in red wines via the formation of pyranoanthocyanins by selected yeasts. International Journal of Food Microbiology. 2009; 132 :145-152. DOI: 10.1016/j.ijfoodmicro.2009.04.015 - 104.
Morata A, Benito S, Loira I, Palomero F, González MC, Suárez-Lepe JA. Formation of pyranoanthocyanins by Schizosaccharomyces pombe during the fermentation of red must. International Journal of Food Microbiology. 2012;159 :47-53. DOI: 10.1016/j.ijfoodmicro.2012.08.007 - 105.
Benito S, Morata A, Palomero F, González MC, Suárez-Lepe JA. Formation of vinylphenolic pyranoanthocyanins by Saccharomyces cerevisiae andPichia guillermondii in red wines produced following different fermentation strategies. Food Chemistry. 2011;124 :15-23. DOI: 10.1016/j.foodchem.2010.05.096 - 106.
Vejarano R. Saccharomycodes ludwigii , control and potential uses in winemaking processes. Fermentation. 2018;4 (3):71. DOI: 10.3390/fermentation4030071 - 107.
Vejarano R, Gil-Calderón A, Morata A. Effect of metabolic inhibitors on the alcoholic fermentation: Tolerant yeasts. In: Proceedings of the LACCEI International Multi-Conference for Engineering, Education and Technology; 2018; p. 171. DOI: 10.18687/LACCEI2018.1.1.171 - 108.
Monagas M, Bartolomé B, Gómez-Cordovés C. Evolution of polyphenols in red wines from Vitis vinifera L. during aging in the bottle. European Food Research and Technology. 2005;220 :331-340. DOI: 10.1007/s00217-004-1109-9 - 109.
Loira I, Vejarano R, Morata A, Ricardo-da-Silva JM, Laureano O, González MC, et al. Effect of Saccharomyces strains on the quality of red wines aged on lees. Food Chemistry. 2013;139 :1044-1051. DOI: 10.1016/j.foodchem.2013.01.020 - 110.
Sheng R, Gu ZL, Xie ML, Zhou WX, Guo CY. EGCG inhibits cardiomyocyte apoptosis in pressure overload-induced cardiac hypertrophy and protects cardiomyocytes from oxidative stress in rats. Acta Pharmacologica Sinica. 2007; 28 (2):191-201. DOI: 10.1111/j.1745-7254.2007.00495.x - 111.
Palomero F, Morata A, Benito S, Calderón F, Suárez-Lepe JA. New genera of yeasts for over-lees aging of red wine. Food Chemistry. 2009; 112 :432-441. DOI: 10.1016/j.foodchem.2008.05.098 - 112.
Salmon JM. Interactions between yeast, oxygen and polyphenols during alcoholic fermentations: Practical implications. LWT- Food Science and Technology. 2006; 39 :959-965. DOI: 10.1016/j.lwt.2005.11.005 - 113.
González-Arenzana L, Portua J, López R, López N, Santamaría P, Garde-Cerdán T, et al. Inactivation of wine-associated microbiota by continuous pulsed electric field treatments. Innovative Food Science & Emerging Technologies. 2015; 29 :187-192. DOI: 10.1016/j.ifset.2015.03.009 - 114.
Rice-Evans CA, Miller NJ. Total antioxidant status in plasma and body fluids. Methods in Enzymology. 1994; 234 :279-293. DOI: 10.1016/0076-6879(94)34095-1 - 115.
García-Alonso M, Rimbach G, Rivas-Gonzalo JC, de Pascual-Teresa S. Antioxidant and cellular activities of anthocyanins and their corresponding vitisins A–studies in platelets, monocytes, and human endothelial cells. Journal of Agricultural and Food Chemistry. 2004; 52 :3378-3384. DOI: 10.1021/jf035360v - 116.
McDougall GJ, Fyffe S, Dobson P, Stewart D. Anthocyanins from red wine–their stability under simulated gastrointestinal digestion. Phytochemistry. 2005; 66 :2540-2548. DOI: 10.1016/j.phytochem.2005.09.003