**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 (erythroidderived 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

**189**

**Figure 1.**

*Improvement of the Bioactive Profile in Wines and Its Incidence on Human Health…*

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

Specific cases related to some pathologies are discussed in detail below.

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.

Also, the presence of ethanol has been associated with low-density lipoprotein

Nonetheless, such results suggest the need for further studies due to negative effects

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

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%) [32–34].

endothelial functions [29, 30] in addition to the effects on free radicals [31].

*Effects of wine components for cardiovascular risk factors. Adapted from Ref. [25].*

(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].

(CVD), by inhibiting TNFα and interleukin 6 (IL-6) [22].

**2.3 Protection against cardiovascular diseases**

of excessive ingestion of ethanol.

*DOI: http://dx.doi.org/10.5772/intechopen.85861*

*Improvement of the Bioactive Profile in Wines and Its Incidence on Human Health… DOI: http://dx.doi.org/10.5772/intechopen.85861*

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**

*Advances in Grape and Wine Biotechnology*

**2. Health benefits of wine**

**2.1 Antioxidant activity**

among others.

vascular risk [16].

**2.2 Anti-inflammatory activity**

progression of many diseases.

protective effects of wine are attributed. Also, flavonols such as quercetin, myricetin, and kaempferol, predominant in *Vitis vinifera*, are also worth mentioning.

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],

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

the lipid peroxidation caused by physical activity, for instance, in athletes [9].

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 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 (erythroidderived 2)-like 2] pathway [11], which regulates the expression of inflammatory

The quercetin also contributes to reduce oxidative stress acting on the anion

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 cardio-

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

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

groups (-OCH3) and one hydroxyl (-OH) group in the B-ring.

markers, protecting against diseases such as Parkinson's [12].

O2- and over the enzymes that produce it [13].

**188**

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.

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%) [32–34].

**Figure 1.**

*Effects of wine components for cardiovascular risk factors. Adapted from Ref. [25].*

#### **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. [47–49], which may induce genetic mutation and reproduction of mutated cells giving rise to carcinogenesis.

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**.

**191**

**Figure 2.**

trations of up to 6 mg L<sup>−</sup><sup>1</sup>

*Improvement of the Bioactive Profile in Wines and Its Incidence on Human Health…*

*DOI: http://dx.doi.org/10.5772/intechopen.85861*

**2.6 Antimicrobial and antiviral activities**

and *Botrytis cinerea* [60], among other microorganisms.

white wine is not subjected to malolactic fermentation.

and norovirus and rotavirus (gastroenteritis) [60].

**3. Enhancement of bioactive compounds content**

**3.1 Vineyard: synthesis of bioactive compounds**

Red wine presents activity against *Streptococcus mutans*, *Streptococcus oralis*, *Fusobacterium nucleatum*, and *Actinomyces oris* implicated in the formation of dental cavities and periodontitis [58], in addition to *Clostridium* [59], *Candida albicans*,

*Potential protective mechanisms of the phenolic compounds at different cancer stages. Adapted from Ref. [35].*

White wine also presents activity against *Salmonella* [61]. However, the authors argued that the effect may be associated with the presence of malic acid, since the

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),

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.

The wine composition is closely related with the grape composition that mainly

in wines made of Pinot noir grapes [63], quercetin,

depends on its variety. Some compounds, such as resveratrol can reach concen-

*Improvement of the Bioactive Profile in Wines and Its Incidence on Human Health… DOI: http://dx.doi.org/10.5772/intechopen.85861*

**Figure 2.**

*Advances in Grape and Wine Biotechnology*

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

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

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

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

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. [47–49], which may induce genetic mutation and reproduction of mutated cells

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

on lung cancer cells [57]. More specific mechanisms are shown in **Figure 2**.

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

are important mechanisms against anxiety and depression.

cancer cells [53]. Resveratrol can also induce cell apoptosis [54].

**2.4 Neuroprotective effects**

*2.4.1 Prevention of memory loss*

proteasome complex [39].

resveratrol.

Alzheimer's.

*2.4.3 Antidepressant effect*

**2.5 Anticarcinogenic activity**

giving rise to carcinogenesis.

*2.4.2 Action against cerebrovascular infarctions*

**190**

*Potential protective mechanisms of the phenolic compounds at different cancer stages. Adapted from Ref. [35].*

#### **2.6 Antimicrobial and antiviral activities**

Red wine presents activity against *Streptococcus mutans*, *Streptococcus oralis*, *Fusobacterium nucleatum*, and *Actinomyces oris* implicated in the formation of dental cavities and periodontitis [58], in addition to *Clostridium* [59], *Candida albicans*, and *Botrytis cinerea* [60], among other microorganisms.

White wine also presents activity against *Salmonella* [61]. However, the authors argued that the effect may be associated with the presence of malic acid, since the white wine is not subjected to malolactic fermentation.

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<sup>−</sup><sup>1</sup> in wines made of Pinot noir grapes [63], quercetin,

concentrations of up to 13 mg L<sup>−</sup><sup>1</sup> 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].

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].

**193**

*Improvement of the Bioactive Profile in Wines and Its Incidence on Human Health…*

additive that can cause problems on the consumer's health [75].

losses of raw material or risks of microbial contamination.

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

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

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

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 *p*-coumarylated anthocyanins), since the HHP reduces the polarity of the grape-must due to the decrease of the water dielectric constant and the pH (molecular deprotonation at

Higher pressures (600 MPa) were applied by Corrales et al. [79], increasing the acylated anthocyanin extraction by nine times with respect to the control

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

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)

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

Like HHP, the selective extraction of acylated anthocyanins can be increased

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

Also, the content of flavanols, flavonols, and hydroxycinnamic acids and derivatives can be improved after 12 months of aging in wines obtained from grapes

) technique was

[79]. Also, a higher

high pressures). Thus, the solubility of these anthocyanins is improved.

at 70°C. In addition, pulsed electric field (PEF, at 3 kV cm<sup>−</sup><sup>1</sup>

by more than six times with respect to the control at 3 kV cm<sup>−</sup><sup>1</sup>

sensation of astringency and bitterness in the produced wines.

*DOI: http://dx.doi.org/10.5772/intechopen.85861*

preferred in the markets.

oxidant enzymes.

and e-beam irradiation [81, 82].

[84].

*3.2.2 Pulsed electric fields*

5–10 kV cm<sup>−</sup><sup>1</sup>

*3.2.1 High hydrostatic pressure*

#### **Figure 3.**

*Technological strategies to improve the content of bioactive compounds in red wines.*

#### *Improvement of the Bioactive Profile in Wines and Its Incidence on Human Health… DOI: http://dx.doi.org/10.5772/intechopen.85861*

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*

*Advances in Grape and Wine Biotechnology*

concentrations of up to 13 mg L<sup>−</sup><sup>1</sup>

compounds during winemaking process.

**3.2 Pre-fermentation treatments**

winemaking process [64].

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

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

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

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 mac-

eration can assist in the extraction of anthocyanins and tannins [73].

*Technological strategies to improve the content of bioactive compounds in red wines.*

synthesis of resveratrol [69], melatonin [70], β-sitosterol, and other sterols [65].

in wines made of Shiraz grapes [64], or

**192**

**Figure 3.**

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 *p*-coumarylated anthocyanins), since the HHP reduces the polarity of the grape-must due to the decrease of the water dielectric constant and the pH (molecular deprotonation at high pressures). Thus, the solubility of these anthocyanins is improved.

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<sup>−</sup><sup>1</sup> ) 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<sup>−</sup><sup>1</sup> [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<sup>−</sup><sup>1</sup> [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<sup>−</sup><sup>1</sup> y, and 3.67 kJ kg<sup>−</sup><sup>1</sup> .

At the level of grape-musts treated with PEF, adverse effects have not been observed at doses of up to 29 kV cm<sup>−</sup><sup>1</sup> [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<sup>−</sup><sup>2</sup> , 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<sup>−</sup><sup>1</sup> , 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<sup>−</sup><sup>1</sup> ) [95]. Accordingly, the

**195**

*Improvement of the Bioactive Profile in Wines and Its Incidence on Human Health…*

anthocyanin extraction can be as high as 19% in Petit Verdot grapes treated with

The melatonin content can be increased by using *Saccharomyces* and *non-Saccharomyces* strains with high production of this compound [97], as an additional source to the melatonin coming from grapes [28]. However, some compounds like the phytosterols may be reduced during the winemaking process, since some *Saccharomyces* strains might be able to use them as nutrients [65]. Besides, contents of anthocyanins [98] and resveratrol [99] can diminish, as a result of being

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

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 *Dekkera/Brettanomyces*, since this yeast is not able to hydrolyze these pigments [103]. 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 *Dekkera/Brettanomyces* [103]. By reducing the content of hydroxycinnamic acids, it is possible to prevent the synthesis of 4-ethylphenol and,

in turn, the content of vinylphenolic pyranoanthocyanins can be increased.

with the malvidin during or after the fermentation process [102].

alcohol dehydrogenase, which might enhance the synthesis of vitisin B.

and other molecules with positive impact on the wine.

**3.4 Post-fermentation strategies**

*3.4.1 Traditional aging of red wine*

Other interesting pyranoanthocyanin groups are the vitisins A and B, which arise from the condensation of pyruvic acid and acetaldehyde, respectively, together

Also, it is possible to increase vitisin A levels with *Schizosaccharomyces pombe* [104], of vinylphenolic pyranoanthocyanins in mixed fermentations of *S. cerevisiae* with *Pichia guilliermondii* [105] or by using species with high production of acetaldehyde, such as *Saccharomycodes ludwigii* [106], to improve the synthesis of vitisin B

On the other hand, it is possible to enlarge the production of acetaldehyde by *S. cerevisiae* in the presence of metabolic inhibitors [71, 107], due to their effect on the

The aging has direct effects on wine composition, since chemical and/or enzymatic oxidation processes, degradation of phenols on the presence of SO2, and

adsorbed by the yeast cell walls during the fermentation process.

*DOI: http://dx.doi.org/10.5772/intechopen.85861*

**3.3 Fermentation level strategies**

hydrolysis of anthocyanins [100].

*3.3.2 Pyranoanthocyanins synthesis*

*3.3.1 Selected yeasts*

ozone, in addition to reduce the fermentation time [96].

anthocyanin extraction can be as high as 19% in Petit Verdot grapes treated with ozone, in addition to reduce the fermentation time [96].
