**3.2. Corn and metabolism**

0.767 μmol of TE/g of sample were reported [34], whereas the total extracts of Italian genotype corn have reported antioxidant activity of 29 μmol of TE/g of sample [43]. These data suggest that carotenoids only contribute approximately 5% of the total antioxidant activity, while the phenolic fraction has the highest antioxidant activity. It should be noted that the antioxidant activity of carotenoids depends on their concentration, their distribution in the kernel, and the type of carotenoid, as studies have found activity values of 71 μmol of TE/g of sample in extracts of aleurone and 66.2 μmol of TE/g of sample in the endosperm. Other studies measured the antioxidant activity of the carotenoids contained in corn tortillas with the β-carotene/linoleate bleaching method, showing that the nixtamalization process can improve the antioxidant activity of carotenoids. In tortillas made of Mexican genotype corn of red or blue varieties, a decrease in whitening of approximately 27% has been reported, while in unprocessed kernels, the value reported was 15%. A value of 25% has been reported

When comparing the antioxidant activity of phenolic compounds of pigmented corn and the polyphenols of blue berries, it was shown that corn has a greater antioxidant capacity and greater reaction kinetics [14]. When evaluating the antioxidant capacity in phenolic compounds of the blue, red, white, yellow, and high carotenoid corn varieties by the peroxyl radical scavenging capacity assay (PSC), an activity of 41–49 μmol of vitamin C equivalent/100 g of sample was reported [15]. This fact has proven that the higher the phenolic content, the greater the antioxidant activity, not only in kernels, but this quality is also maintained in byproducts elaborated by the nixtamalization process, such as the tortilla. However, unlike carotenoids, corn phenolic compounds are affected by production processes such as nixtamalization, which causes a decrease in their nutraceutical properties. For example, in Mexican phenotype corn kernels of the blue variety, a concentration of 343 mg of gallic acid equivalent/100 g of sample has been reported, while in products such as tortillas made with this same kernel, 201 mg of gallic acid equivalent/100 g of sample has been found. Antioxidant capacity can be expressed as the inhibition of ABTS cation formation; this way, it was determined that the antioxidant activity of the kernel is approximately 63%, while for the tortilla, it was 44%. The antioxidant activity of corn is not only limited to inhibiting the formation of ROS, it can also regulate cellular enzymatic elements for the defense against oxidative stress. It has been shown that corn components can increase the activity of the QR enzyme [44]. Only some of the phenolic compounds contained in corn have biological activity; for example, phenolic acids have only been able to recognize the nutraceutical capacity of compounds such

Researchers from the University of Florida quantified and characterized the content of phenolic compounds in commercial genotype corn kernels of white varieties and of two blue varieties, one of Mexican genotype and the other North American, and reported a higher content of phenols in white corn, mainly ferulic acid, protocatechuic acid, and p-coumaric acid, while in blue corn, there were no traces of these acids. However, they found high concentrations of anthocyanins in the Mexican genotype, followed by the North American genotype. In addition, the antioxidant capacity of the three varieties was evaluated, demonstrating that the Mexican genotype has a greater capacity to inhibit the formation of ROS [46]. In this sense and due to their structural composition, the compounds contained in corn with a greater

for white corn tortillas and 12% for raw kernels [38].

36 Corn - Production and Human Health in Changing Climate

as ferulic acid, protocatechuic acid, and p-coumaric acid [45].

Obesity is currently a multifactorial etiology, chronic course disease, which involves genetic, environmental, and lifestyle aspects. Obesity is defined as the abnormal or excessive accumulation of fat harmful to health. One of the parameters that must be evaluated in order to determine if a person has obesity is the body mass index (BMI). Thus, a person with a BMI equal to or greater than 30 is considered obese. In recent years, obesity has been acknowledged as a global public health problem: an estimated 1900 million adults are overweight, and 600 million are obese [47]. Research carried out in rodents has shown that anthocyanins contained in purple corn can improve insulin resistance induced by a high-fat diet. For example, the cyanidin 3-glucoside present in purple corn may suppress the transcription of mRNA for the synthesis of enzymes involved in the production of fatty acids and triglycerides and reduce the sterol, a regulatory element that binds to the mRNA level of the protein-1 in white adipose tissue. The downregulation of protein-1 may contribute to the accumulation of triglycerides in white adipose tissue. These data, reported in 2003 by researchers from the University of Doshisha in Japan, have established the biochemical and nutritional bases for the use of cyanidin and anthocyanins in purple corn, as a functional food factor able to provide benefits for the prevention of obesity and diabetes [48]. Components of bioactive foods, such as resistant corn starch with a high content of amylose type 2 and sodium butyrate, reduce obesity in rodents [24].

Recently, an integral version has been used in a study carried out on humans, demonstrating greater postprandial satiety [49]. In addition, in vitro studies have shown a potential anti-obesity effect of purple corn stigmata in multiple stages of the adipocyte life cycle. The potential effects of high concentrations of purple corn stigmata extracts may inhibit adipocyte proliferation and adipogenesis, as well as induce lipolysis and apoptosis [50]. Another bioactive compound present in corn is maysin; the use of maysin in some studies has shown that it is a potent beneficial functional ingredient for health and a therapeutic agent in the prevention or treatment of obesity [51]. Menopause is a stage in which the production of estrogen is reduced, promoting the increase of body fat, and is a risk factor that contributes to obesity in older women. On the other hand, it is known that the modification of the gastrointestinal microbiota can reduce obesity by controlling energy expenditure. Therefore, adding prebiotics to the diet can contribute to the modification of the intestinal microbial flora, thus reducing obesity. Accordingly, the high-amylose type 2 resistant starch of corn can be used as a prebiotic, as has been proven in studies performed in ovariectomized rats. These studies showed that the bacterial levels increased with the addition of resistant starch of high corn amylose to the diet of the animals. In addition, the weight gain caused by the lack of estrogen was attenuated [52]. The consumption of fermentable corn fiber is recommended for postmenopausal women.

factor after consumption of purple corn, tested in diabetic mice [55]. It has also been reported that purple corn extract can have antidiabetic effects through the protection of the β cells of the pancreas, favoring the secretion of insulin and the activation of the AMPK pathway in diabetic mice. The extract also causes increased phosphorylation by AmpC-activated kinase protein (AmpK), decreases the activity of phosphoenolpyruvate carboxykinase (PEPCK), decreases the transcriptional activity of genes for glucose 6-phosphatase in the liver, and

The Maize Contribution in the Human Health http://dx.doi.org/10.5772/intechopen.78700 39

Another complication of diabetes is the formation of cataracts in the eye, caused by an optical dysfunction in the lens. Researchers from the KhonKaen University in Thailand conducted a study with rat enucleated lenses, which were incubated in artificial water humor containing 55 mM glucose with various concentrations of *Zea mays* L. (purple waxy corn), and found that the extract is capable of protecting against diabetic cataract in a dosedependent way, probably due to the reduction of oxidative stress, while with high doses of corn extract, an effect is exerted through the inhibition of aldose reductase, which limits the speed in the polyol pathway (sorbitol). However, it is necessary to conduct studies with in vivo models that support these findings [57]. Raw extracts of flavonoids contained in corn stigmata have been used in models of diabetic mice reporting a decrease in body weight, glycemia, and antidiabetic capacity, in addition to the reduction in the levels of total cholesterol, of triglycerides, of low-density lipoproteins and an increase in the levels of high-density lipoproteins, suggesting an anti-hyperlipidemic effect [58]. Therefore, corn is proposed as a nutraceutical food, with a potential therapeutic effect to improve the alterations associated with diabetes. The diversity of corn byproducts, such as tortillas, pozol (thick, cocoa- and corn-based drink of Mesoamerican origin that is consumed in southern Mexico), chicha (unfermented drink made with purple corn, flavored with pineapple peels, consumed in Peru), etc., contains a large amount of antioxidant hydrophilic phenolic compounds that are beneficial for the control and maintenance of intermediate metabolism, so they can be considered an alternative for the prevention or treatment of diseases associated

Cancer is among the leading causes of death in the world, resulting from the interaction between genetic factors and external physical factors, such as ultraviolet and ionizing radiation, chemical carcinogens such as asbestos and tobacco smoke, and biological carcinogens (some viral, bacterial, or parasitic infections). The consumption of pigmented corn, like purple, red, and blue varieties, has been shown to have anti-mutagenic properties due to anthocyanin content. Since 2001, research has been carried out to demonstrate the antineoplastic effects of corn anthocyanins, finding that it prevents carcinogenesis due to exposure to 2-amino-1-methyl-6-phenylimidazo pyridine (a free radical belonging to the nitrosamines group) [59]. Purple corn, in addition, has been shown to have chemopreventive properties in in vitro models of prostate cancer and in transgenic rats [60]. Also, maysin, one of the most abundant flavones in stigmata, can inhibit the growth of PC-3 cancer cells by stimulating apoptotic cell death dependent on the mitochondria [61]. These results suggest that maysin is a strong nutraceutical that can be used for the treatment of prostate cancer in humans who are

increases the expression of the glucose transporter 4 (GLUT4) in skeletal muscle [56].

with metabolic alterations.

**3.3. Corn and cancer**

Diabetes is one of the most severe chronic metabolic diseases with great impact on the health of the population; the complications that this pathology entails are serious, fatal, and disabling, in such a way that it significantly affects the socioeconomic level of a country. According to the International Diabetes Federation, worldwide, 425 million people have been reported with diabetes during the year 2017, and the failure to intervene in time is expected to increase this figure to 693 million by 2045, while in Latin America, the number of people with diabetes could reach between 25 and 40 million by the year 2030 [53]. It has been demonstrated that a diet with purple corn rich in anthocyanins can be useful in the prevention of obesity and diabetes in mice, since the alterations induced by a high-fat diet (hyperglycemia, hyperinsulinemia, and hyperleptinemia) were normalized in the group that consumed purple corn in addition to its conventional diet [48]. It was also observed that the diet added with purple corn can suppress the transcription of genes involved in the synthesis of fatty acids and triglycerides. Other studies have shown that the consumption of resistant starch contained in corn improves insulin sensitivity in humans [52], and several studies in animals have documented a reduction of glucose concentration and a change of blood lipid profile due to the consumption of resistant starch [54]. It has also been observed that anthocyanin consumption (1 g/day) in non-hypertensive diabetic patients is effective in reducing triglyceride levels, increasing HDL cholesterol and optimizing glucose control; ferulic acid seems to be responsible for these antidiabetic properties.

Diabetic nephropathy is one of the main complications in diabetes and is mainly caused by chronic renal failure, which is growing in prevalence. This disease is characterized by a microvascular injury that causes glomerular hyperfiltration, renal damage, and an increase in urinary albumin excretion, finally inducing a glomerular dysfunction with renal failure. The consumption of feruloylated oligosaccharides, derived from the esterification of ferulic acid or oligosaccharides, impacts common physiological functions and has been shown to be effective in the regulation of serum insulin levels, and, although not as effective as ferulic acid, this esterified compound can slow down weight loss in diabetic rats [45]. In addition, purple corn extract rich in anthocyanins has been used as a therapeutic agent focused on the regulation of the abnormal angiogenesis that occurs in diabetic nephropathy, which can lead to renal failure. This is mediated by the decrease in receptor 2 activity for vascular endothelial growth factor after consumption of purple corn, tested in diabetic mice [55]. It has also been reported that purple corn extract can have antidiabetic effects through the protection of the β cells of the pancreas, favoring the secretion of insulin and the activation of the AMPK pathway in diabetic mice. The extract also causes increased phosphorylation by AmpC-activated kinase protein (AmpK), decreases the activity of phosphoenolpyruvate carboxykinase (PEPCK), decreases the transcriptional activity of genes for glucose 6-phosphatase in the liver, and increases the expression of the glucose transporter 4 (GLUT4) in skeletal muscle [56].

Another complication of diabetes is the formation of cataracts in the eye, caused by an optical dysfunction in the lens. Researchers from the KhonKaen University in Thailand conducted a study with rat enucleated lenses, which were incubated in artificial water humor containing 55 mM glucose with various concentrations of *Zea mays* L. (purple waxy corn), and found that the extract is capable of protecting against diabetic cataract in a dosedependent way, probably due to the reduction of oxidative stress, while with high doses of corn extract, an effect is exerted through the inhibition of aldose reductase, which limits the speed in the polyol pathway (sorbitol). However, it is necessary to conduct studies with in vivo models that support these findings [57]. Raw extracts of flavonoids contained in corn stigmata have been used in models of diabetic mice reporting a decrease in body weight, glycemia, and antidiabetic capacity, in addition to the reduction in the levels of total cholesterol, of triglycerides, of low-density lipoproteins and an increase in the levels of high-density lipoproteins, suggesting an anti-hyperlipidemic effect [58]. Therefore, corn is proposed as a nutraceutical food, with a potential therapeutic effect to improve the alterations associated with diabetes. The diversity of corn byproducts, such as tortillas, pozol (thick, cocoa- and corn-based drink of Mesoamerican origin that is consumed in southern Mexico), chicha (unfermented drink made with purple corn, flavored with pineapple peels, consumed in Peru), etc., contains a large amount of antioxidant hydrophilic phenolic compounds that are beneficial for the control and maintenance of intermediate metabolism, so they can be considered an alternative for the prevention or treatment of diseases associated with metabolic alterations.

#### **3.3. Corn and cancer**

proliferation and adipogenesis, as well as induce lipolysis and apoptosis [50]. Another bioactive compound present in corn is maysin; the use of maysin in some studies has shown that it is a potent beneficial functional ingredient for health and a therapeutic agent in the prevention or treatment of obesity [51]. Menopause is a stage in which the production of estrogen is reduced, promoting the increase of body fat, and is a risk factor that contributes to obesity in older women. On the other hand, it is known that the modification of the gastrointestinal microbiota can reduce obesity by controlling energy expenditure. Therefore, adding prebiotics to the diet can contribute to the modification of the intestinal microbial flora, thus reducing obesity. Accordingly, the high-amylose type 2 resistant starch of corn can be used as a prebiotic, as has been proven in studies performed in ovariectomized rats. These studies showed that the bacterial levels increased with the addition of resistant starch of high corn amylose to the diet of the animals. In addition, the weight gain caused by the lack of estrogen was attenuated [52]. The consumption of fermentable corn fiber is recommended for postmenopausal women.

38 Corn - Production and Human Health in Changing Climate

Diabetes is one of the most severe chronic metabolic diseases with great impact on the health of the population; the complications that this pathology entails are serious, fatal, and disabling, in such a way that it significantly affects the socioeconomic level of a country. According to the International Diabetes Federation, worldwide, 425 million people have been reported with diabetes during the year 2017, and the failure to intervene in time is expected to increase this figure to 693 million by 2045, while in Latin America, the number of people with diabetes could reach between 25 and 40 million by the year 2030 [53]. It has been demonstrated that a diet with purple corn rich in anthocyanins can be useful in the prevention of obesity and diabetes in mice, since the alterations induced by a high-fat diet (hyperglycemia, hyperinsulinemia, and hyperleptinemia) were normalized in the group that consumed purple corn in addition to its conventional diet [48]. It was also observed that the diet added with purple corn can suppress the transcription of genes involved in the synthesis of fatty acids and triglycerides. Other studies have shown that the consumption of resistant starch contained in corn improves insulin sensitivity in humans [52], and several studies in animals have documented a reduction of glucose concentration and a change of blood lipid profile due to the consumption of resistant starch [54]. It has also been observed that anthocyanin consumption (1 g/day) in non-hypertensive diabetic patients is effective in reducing triglyceride levels, increasing HDL cholesterol and optimizing glucose control; ferulic acid

Diabetic nephropathy is one of the main complications in diabetes and is mainly caused by chronic renal failure, which is growing in prevalence. This disease is characterized by a microvascular injury that causes glomerular hyperfiltration, renal damage, and an increase in urinary albumin excretion, finally inducing a glomerular dysfunction with renal failure. The consumption of feruloylated oligosaccharides, derived from the esterification of ferulic acid or oligosaccharides, impacts common physiological functions and has been shown to be effective in the regulation of serum insulin levels, and, although not as effective as ferulic acid, this esterified compound can slow down weight loss in diabetic rats [45]. In addition, purple corn extract rich in anthocyanins has been used as a therapeutic agent focused on the regulation of the abnormal angiogenesis that occurs in diabetic nephropathy, which can lead to renal failure. This is mediated by the decrease in receptor 2 activity for vascular endothelial growth

seems to be responsible for these antidiabetic properties.

Cancer is among the leading causes of death in the world, resulting from the interaction between genetic factors and external physical factors, such as ultraviolet and ionizing radiation, chemical carcinogens such as asbestos and tobacco smoke, and biological carcinogens (some viral, bacterial, or parasitic infections). The consumption of pigmented corn, like purple, red, and blue varieties, has been shown to have anti-mutagenic properties due to anthocyanin content. Since 2001, research has been carried out to demonstrate the antineoplastic effects of corn anthocyanins, finding that it prevents carcinogenesis due to exposure to 2-amino-1-methyl-6-phenylimidazo pyridine (a free radical belonging to the nitrosamines group) [59]. Purple corn, in addition, has been shown to have chemopreventive properties in in vitro models of prostate cancer and in transgenic rats [60]. Also, maysin, one of the most abundant flavones in stigmata, can inhibit the growth of PC-3 cancer cells by stimulating apoptotic cell death dependent on the mitochondria [61]. These results suggest that maysin is a strong nutraceutical that can be used for the treatment of prostate cancer in humans who are resistant to chemotherapy, and more recently the non-amylaceous peptide polysaccharide of corn was isolated and characterized, and after a series of tests, it showed anticancer properties by blocking metastasis mediated by galectin-3 [62].

stands out, being an important source of anthocyanins, which is the natural pigment distributed widely in the plant that confers its characteristic color, also containing other polyphenols (non-anthocyanin flavonoids and phenolic acids) distributed through the plant, for example, in the ear and seeds, cyanidin-3-glucoside, pelargonidin-3-glucoside, peonidin-3-glucoside, and its malonated counterparts can be found. Many biological activities have been attributed to these anthocyanins, so it is considered that corn and its byproducts that contain them have

The Maize Contribution in the Human Health http://dx.doi.org/10.5772/intechopen.78700 41

Alzheimer's disease (AD) is a highly prevalent neurodegenerative disease, affecting approximately 10% of the population over 65 years of age, and it has been estimated that by the year 2050, only in the United States of North America, this disease will affect about 14 million people, with an expected incidence close to one million people per year [68], and it has been estimated that the global prevalence of AD will increase to 1 per 85 people in 2050 [69]. AD is the most common cause of dementia, conceived as a syndrome—a group of symptoms—that have been attributed to numerous causes, although the most characteristics are deficits in memory, language, and problem-solving capacity, together with other cognitive disorders that affect the performance of those who suffer from it and their ability to carry out daily activities [70]. The pathophysiology of AD is characterized by the formation of extracellular deposits of beta-amyloid peptide and the hyperphosphorylation of skeletons of intracellular tau proteins. Extensive research has been carried out with the aim of identifying the etiology of AD, although the specific mechanisms that cause neurodegenerative damage have not been well established yet. However, this disease is attributed to multiple factors, including the hypothesis of damage caused by oxidative stress on DNA, RNA, lipid peroxidation, and protein oxidation, responsible for the cognitive deterioration characteristic of the disease [71]. Studies carried out in patients diagnosed with AD have shown a decrease in antioxidant concentration in plasma, as well as an increase in the concentration of metabolites associated with the oxidation of lipids and proteins (distinctive markers of oxidative stress). It should be noted that this oxidative damage in the brain is implied in the toxicity induced by the β-amyloid fibrillar peptide (Aβ) [72].

Therefore, in recent years, the efforts of a large number of researchers in the world have focused on the search for natural alternatives that contribute to the prevention of neurodegenerative diseases such as Alzheimer's. Among the bioactive components with important biological activity, it has been reported that polyphenols (natural compounds present in fruits and vegetables) have the capacity to act as neuroprotective elements, although the ways in which they can perform this activity are still being studied. A series of studies are being carried out aimed at extracting molecules such as polyphenols for their potential use for preventive and/or therapeutic purposes, from different sources of fruits and vegetables, among which pigmented corn of the yellow, purple, brown, green, and blue varieties stand out [35]. Polyphenols exert biological action in the prevention of AD, due to their intrinsic capacity as reducing agents, and indirectly promote protection by activating endogenous defense systems, and by modulating cell-signaling processes related to the activation of the nuclear factor kappa B (NF-κB), of the protein-1 (AP-1)DNA binding activator, of the synthesis of glutathione, of the phosphatidylinositide-3 (PI3)-protein kinase B (Akt)pathway, of mitogen activated by protein kinase

an intrinsic capacity to prevent cognitive deterioration and memory decline [66, 67].

*3.4.1. Corn and Alzheimer's*

In 2015, Mexican researchers conducted a study with extracts of phenolic acids and blue corn anthocyanins, measuring their anticancer properties in breast, liver, colon, and prostate cancer cell lines; results indicated an antiproliferative effect in all cell lines, in which malonyl glucoside cyanidin was the anthocyanin with the greatest reduction in cell viability [28]. It has also been shown that the bioactive peptides of corn exert antitumor activity through key mechanisms such as (a) the induction of apoptosis mediated through specific proteases or caspases; strategies to overcome tumor resistance to apoptotic pathways include the activation of pro-apoptotic receptors, the restoration of p53 activity, the modulation of caspases, and the inhibition of the proteasome; (b) blocking the intermediate generation of tumors by regulating cellular mechanisms associated with cell proliferation and survival, or biosynthetic pathways that control cell growth; and (c) regulation of immune system functions, increasing the expression of antigens associated with the tumor (antigenicity) in cancer cells, activating the tumor cells for them to release warning signals that stimulate the immune response (immunogenicity), or increasing the predisposition of the tumor cells to be recognized and neutralized by the immune system (susceptibility) by means of autophagy and apoptosis [63]. The possible therapeutic use of corn peptide is still limited, since the bioavailability of these molecules depends on their capacity to remain active and intact elements during the digestive process, and the probability of reaching the general circulation to exert their physiological effects. Even so, some evidence supports the use of corn peptides as nutraceutical molecules with therapeutic capacity against a wide range of diseases related to oxidative damage, including cancer. The peptides contained in corn represent an important alternative due to their anticancer potential, but it is necessary to carry out more studies in patients, thus ensuring their therapeutic efficacy.

#### **3.4. Corn and the nervous system**

In addition to the nutritional benefits that corn consumption can bring, recent efforts have been made to evaluate its possible health benefits, especially on the nervous system. It is well recognized that a poor diet can contribute to the etiology of chronic diseases such as heart disease, cancer, and others. In view of this, aging should be considered as the main risk factor for chronic and/or chronic-degenerative diseases, among which are disabling disorders associated with cognitive and memory impairment, and dementia, all of them having a lasting impact on family life, as well as high costs for public health institutions [64]. In this sense, the consumption of bioactive nutrients contained in a diet rich in vitamins and polyphenols, and low in saturated fat content, can be a viable alternative for the preservation and/or delay of damage to the brain, since these elements can modify and preserve the state of health of the nervous system through the modulation of biochemical and biological processes [65].

A proper diet includes fruits, vegetables, grains, cereals, and other plants that can have beneficial effects on health, preventing the development of various diseases, thanks to the presence of bioactive components such as flavonols, flavones, catechins, flavonones, anthocyanidins, procyanidin B, among others [65]. Therefore, recently, special importance has been granted to the consumption of foods rich in these substances, among which purple corn (*Z. mays* L.) stands out, being an important source of anthocyanins, which is the natural pigment distributed widely in the plant that confers its characteristic color, also containing other polyphenols (non-anthocyanin flavonoids and phenolic acids) distributed through the plant, for example, in the ear and seeds, cyanidin-3-glucoside, pelargonidin-3-glucoside, peonidin-3-glucoside, and its malonated counterparts can be found. Many biological activities have been attributed to these anthocyanins, so it is considered that corn and its byproducts that contain them have an intrinsic capacity to prevent cognitive deterioration and memory decline [66, 67].

#### *3.4.1. Corn and Alzheimer's*

resistant to chemotherapy, and more recently the non-amylaceous peptide polysaccharide of corn was isolated and characterized, and after a series of tests, it showed anticancer properties

In 2015, Mexican researchers conducted a study with extracts of phenolic acids and blue corn anthocyanins, measuring their anticancer properties in breast, liver, colon, and prostate cancer cell lines; results indicated an antiproliferative effect in all cell lines, in which malonyl glucoside cyanidin was the anthocyanin with the greatest reduction in cell viability [28]. It has also been shown that the bioactive peptides of corn exert antitumor activity through key mechanisms such as (a) the induction of apoptosis mediated through specific proteases or caspases; strategies to overcome tumor resistance to apoptotic pathways include the activation of pro-apoptotic receptors, the restoration of p53 activity, the modulation of caspases, and the inhibition of the proteasome; (b) blocking the intermediate generation of tumors by regulating cellular mechanisms associated with cell proliferation and survival, or biosynthetic pathways that control cell growth; and (c) regulation of immune system functions, increasing the expression of antigens associated with the tumor (antigenicity) in cancer cells, activating the tumor cells for them to release warning signals that stimulate the immune response (immunogenicity), or increasing the predisposition of the tumor cells to be recognized and neutralized by the immune system (susceptibility) by means of autophagy and apoptosis [63]. The possible therapeutic use of corn peptide is still limited, since the bioavailability of these molecules depends on their capacity to remain active and intact elements during the digestive process, and the probability of reaching the general circulation to exert their physiological effects. Even so, some evidence supports the use of corn peptides as nutraceutical molecules with therapeutic capacity against a wide range of diseases related to oxidative damage, including cancer. The peptides contained in corn represent an important alternative due to their anticancer potential, but it is necessary to carry out more studies in patients, thus ensuring their therapeutic efficacy.

In addition to the nutritional benefits that corn consumption can bring, recent efforts have been made to evaluate its possible health benefits, especially on the nervous system. It is well recognized that a poor diet can contribute to the etiology of chronic diseases such as heart disease, cancer, and others. In view of this, aging should be considered as the main risk factor for chronic and/or chronic-degenerative diseases, among which are disabling disorders associated with cognitive and memory impairment, and dementia, all of them having a lasting impact on family life, as well as high costs for public health institutions [64]. In this sense, the consumption of bioactive nutrients contained in a diet rich in vitamins and polyphenols, and low in saturated fat content, can be a viable alternative for the preservation and/or delay of damage to the brain, since these elements can modify and preserve the state of health of the

nervous system through the modulation of biochemical and biological processes [65].

A proper diet includes fruits, vegetables, grains, cereals, and other plants that can have beneficial effects on health, preventing the development of various diseases, thanks to the presence of bioactive components such as flavonols, flavones, catechins, flavonones, anthocyanidins, procyanidin B, among others [65]. Therefore, recently, special importance has been granted to the consumption of foods rich in these substances, among which purple corn (*Z. mays* L.)

by blocking metastasis mediated by galectin-3 [62].

40 Corn - Production and Human Health in Changing Climate

**3.4. Corn and the nervous system**

Alzheimer's disease (AD) is a highly prevalent neurodegenerative disease, affecting approximately 10% of the population over 65 years of age, and it has been estimated that by the year 2050, only in the United States of North America, this disease will affect about 14 million people, with an expected incidence close to one million people per year [68], and it has been estimated that the global prevalence of AD will increase to 1 per 85 people in 2050 [69]. AD is the most common cause of dementia, conceived as a syndrome—a group of symptoms—that have been attributed to numerous causes, although the most characteristics are deficits in memory, language, and problem-solving capacity, together with other cognitive disorders that affect the performance of those who suffer from it and their ability to carry out daily activities [70].

The pathophysiology of AD is characterized by the formation of extracellular deposits of beta-amyloid peptide and the hyperphosphorylation of skeletons of intracellular tau proteins. Extensive research has been carried out with the aim of identifying the etiology of AD, although the specific mechanisms that cause neurodegenerative damage have not been well established yet. However, this disease is attributed to multiple factors, including the hypothesis of damage caused by oxidative stress on DNA, RNA, lipid peroxidation, and protein oxidation, responsible for the cognitive deterioration characteristic of the disease [71]. Studies carried out in patients diagnosed with AD have shown a decrease in antioxidant concentration in plasma, as well as an increase in the concentration of metabolites associated with the oxidation of lipids and proteins (distinctive markers of oxidative stress). It should be noted that this oxidative damage in the brain is implied in the toxicity induced by the β-amyloid fibrillar peptide (Aβ) [72].

Therefore, in recent years, the efforts of a large number of researchers in the world have focused on the search for natural alternatives that contribute to the prevention of neurodegenerative diseases such as Alzheimer's. Among the bioactive components with important biological activity, it has been reported that polyphenols (natural compounds present in fruits and vegetables) have the capacity to act as neuroprotective elements, although the ways in which they can perform this activity are still being studied. A series of studies are being carried out aimed at extracting molecules such as polyphenols for their potential use for preventive and/or therapeutic purposes, from different sources of fruits and vegetables, among which pigmented corn of the yellow, purple, brown, green, and blue varieties stand out [35]. Polyphenols exert biological action in the prevention of AD, due to their intrinsic capacity as reducing agents, and indirectly promote protection by activating endogenous defense systems, and by modulating cell-signaling processes related to the activation of the nuclear factor kappa B (NF-κB), of the protein-1 (AP-1)DNA binding activator, of the synthesis of glutathione, of the phosphatidylinositide-3 (PI3)-protein kinase B (Akt)pathway, of mitogen activated by protein kinase (MAPK)(regulation of extracellular signaling protein kinase (ERK), of c-Jun N-terminal kinase (JNK) and P38), and also related to the translocation of erythroid nuclear factor 2 (Nrf2) [73].

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Corn polyphenols, particularly flavonoids, can also modulate the neuronal signaling cascade activated by aging, acting on the ERK/CREB pathway involved in synaptic plasticity and longterm potentiation, improving learning and memory capacity in humans and animals [73]. They have also shown modulatory effects on the signaling pathway of kinases such as calcium calmodulin kinase II (CaMKII) and ERK, which control the activation of CREB (cAMP response element-binding) and increase the expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) at brain level [64]. As a matter of fact, it has been experimentally proven that polyphenols exert a protective effect on the hippocampus, preserving and promoting learning strategies and visuospatial memory in middle-aged rodents through the restoration of the mRNA levels of CaMKII, and the increase in the expression of hippocampal NGF [67]. Due to the above, the consumption of foods rich in molecules with biological potential, such as those present in corn, represents a nutritional alternative that can also help prevent the cognitive deterioration and dementia associated with age. However, it is still necessary to carry out studies that help prove their biological effectiveness in in vivo systems, and especially in the human population vulnerable to the development of neurodegenerative diseases.
