**3. Flavonoid and capsaicinoid contents in fruits of chili pepper landraces**

#### **3.1. Flavonoids in** *Capsicum*

In Mexico, there is a great diversity of phenotypic variants of chilis that are distinguished by color, flavor, spice, aroma, size and shape and are fundamental to and completely accepted in Mexican gastronomy. The species *C. annuum* originated in Mexico and is one of the most cultivated species in the world, with high genetic diversity [39, 43]. The organoleptic properties of each type of chilis are characterized by their chemical composition as a function of flavonoid content, capsaicinoids, phenolic acids, vitamins, minerals and various volatile compounds [40, 58–61]. Flavonoids and capsaicinoids are molecules that, in addition to influencing the sensory characteristics of the fruit, contribute to the prevention of chronic degenerative diseases [62, 63].

Flavonoids are secondary metabolites of low molecular weight that share a common skeleton with diphenylpropanes (C6-C3-C6) and comprise two phenyl rings (A and B) joined through a C ring of pyran (heterocyclic). Flavonoids are classified according to oxidation state and degree of unsaturation of the central heterocyclic ring. The primary families are flavones, isoflavones, flavanones, flavanols, antho-cyanidins and chalcones [64]. The structural diversity of flavonoids depends on the substitution of aromatic rings A and B by hydroxyl and methoxy groups and by extensive conjugations, including glucosides. In foods, flavonoids exist primarily as 3-O-glycoside and polymers [64, 65]. Flavonoids possess multiple properties for eliminating reactive oxygen species. Their activity as an antioxidant depends on the redox properties of their hydroxyphenolic groups and the structural relation between various components of the chemical structure [7]. Some of the characteristics that favor their antioxidant capacity are the ortho-hydroxylation of ring B, the number of free hydroxyl groups, a C2-C3 double bond at ring C and the presence of a 3-hydroxyl group [66].

In fruits and vegetables, it is estimated that more than 7000 flavonoids have been identified [64]. In chili fruit, the primary quantified flavonoids are quercetin, luteolin, kaempferol, catechin, epicatechin, rutin, luteolin, apigenin and myricetin [61, 67–76]. Variations in flavonoid concentrations are primarily the result of the diversity of genotypes, landraces, varieties and the ripening phase of the fruit; also implied are variations related to analytical laboratory parameters such as sample preparation, extraction method and quantification methods (**Table 4**).

In chili fruits, different flavonoids have been identified depending on morphotype, landrace, varietal group or variety. In sweet peppers (*C. annuum* L. cv. Vergasa), 23 flavonoids have been identified and quantified in the pericarp by high-performance liquid chromatographydiode array detection-electrospray ionization mass spectrometry (HPLC). These include O-glycosides of quercetin, luteolin and chrysoeriol and a large number of C-glycosyl flavones. The most abundant compounds were quercetin-3-O-rhamnoside and luteolin 7-O-(2-apiosyl-6-malonyl), which represented 41% of the total flavonoids [77]. Materska and Perucka [79] identified quercetin 3-O-α-L-rhamnopyranoside-7-*O*-*β*-D-glucopyranoside, luteolin 6-*C-β*-D-glucopyranoside-8-C-α-L-arabinopyranoside, apigenin 6-*C*-β-D-glucopyranoside-8-*C*-α-L-arabinopyranoside, lutoeolin 7-O-[2-(β-D-apiofuranosyl)-β-D-glucopyranoside], quercetin 3-*O*-α-L-rhamnopyranoside and luteolin 7-O-[2-(β-D-apiofuranosyl)-4-(β-D-glucopyranosyl)- 6-malonyl]-β-D-glucopyranoside. These flavonoids are present in four varieties of *C. annuum*. In the "Italian sweet" (green), "Lamuyo" (yellow) and "California wonder" (red) varieties, 23 flavonoids and their glycoside derivatives were identified by high-performance liquid chromatography coupled with diode array and electrospray time-of-flight mass spectrometry detectors (HPLC), highlighting the group of flavonols known as glycosylated quercetin derivatives (rutin pentoside, quercetin 3,7-di-O-α-Lrhamnopyranoside and quercetin 3-O-α-L-rhamnoside) [79]. Various flavonoids continue to be identified in all species of *Capsicum*, and depending on advances, it is inferred that the task continues and the work is incipient in Mexican landraces.

**3. Flavonoid and capsaicinoid contents in fruits of chili pepper landraces**

**Table 3.** Typical dishes of the Mexican cuisine where main ingredients are the diversity of landraces or improved

**Typical dishes of the Mexican cuisine1 Landrace used or improved variety**

**(a)** Blanck mole: Ancho, Chilhuacle **(b)** Red mole: Ancho and Guajillo

spiced chilis can be used.

Jalapeño, Serrano, Ancho, Pasilla

Chili Piquín milled with sal

Árbol

Chiles rellenos (stuffed chili peppers) Poblano, Ancho, De Agua, Güeros, Jalapeños

Chili in encurtidos (pickled peppers) Usually Jalapeño and Serrano but all chili peppers can

be used.

**(c)** Green mole: Jalapeño, Rayado and Serrando

**(b)** Dry: Ancho, Pasilla, De árbol, Cascabel

**(a)** Immature: Jalapeño, Serrano, De Agua

**(b)** Muture: Habanero, Manzano, Bell, Anaheim o California

**(a)** Freh: Commonly Jalapeño o Serrano buta ll high

Jalapeño, Serrano, Ancho, Guajillo, Pasilla, Cascabel, De

Known molee: negro, coloradito, chichilo, rojo, verde, pipián, amarrillo, poblano (turkey in deep-brown sauce), "estofado", "manchamantel", de caderas, de hongos, de

416 Flavonoids - From Biosynthesis to Human Health

Salsas (sauces) prepared with fresh and dry chilis: Borracha ("drunk"), verde, roja, de ancho, de guajillo

Chilaquiles: verdes (green), rojos (red), de mole (made

Tamales de verdes (greenish) o rojos (red), de mole, de

Elotes (cob) o frutas (tropical fruits) with powdery dry

Immature peppers or green to mature but fresh to slice and combine with onion and lemon, regionally known as

Sources: Urdaneta and Kanter [56] and Katz [57].

Chileatole Serrano

Traditional guacamole Serrano, Jalapeño

Tortas ahogadas and Pambazos Pasilla, Guajillo

Chile en chipotle (smoked peppers) Jalapeño and Rayado

Roasted chili to slice o eat directly ("morder") o en rajas: Regularly Serrano and Jalapeño

Chiles en nogada (dish name) Ancho, Poblano, Miahuateco

Flautas ahogadas (dish name) Jalapeño, Serrano Mixiote verdes de pollo (dish name) Jalapeño, Serrano

frijol, relleno negro, almendrado

rajas de chile (with slices of chili)

with mole)

chili pepper

1

"gatos" or "pico de gallo"

varieties of chili pepper.

In Mexico, there is a great diversity of phenotypic variants of chilis that are distinguished by color, flavor, spice, aroma, size and shape and are fundamental to and completely accepted in Mexican gastronomy. The species *C. annuum* originated in Mexico and is one of the most cultivated species in the world, with high genetic diversity [39, 43]. The organoleptic properties of each type of chilis are characterized by their chemical composition as a function of flavonoid

**3.1. Flavonoids in** *Capsicum*


1 Quercetin, catechin or quercetin + luteolin equivalents (μg/g or g/g), ND = Not determined.

Sources: Vera-Guzmán et al. [61], Howard et al. [67], Miean and Mohamed [69], Kim et al. [71], Blanco-Ríos et al. [72], Zhuang et al. [73], Lee et al. [74], Rochín-Wong et al. [75], Álvarez-Parrilla et al. [76].

**Table 4.** Flavonoid contents in fruits of *Capsicum annuum* and *C. frustences*.

The structure of each flavonoid influences antioxidant capacity, which varies between species and genotypes of chili. Materska [80] isolated three glycosylated flavonoids (luteolin 6-C-glucoside, luteolin 6,8-di-C-glucoside and apigenin 6-C-glucoside-8-C-arabinoside) from the chili fruit (*C. annuum* var. Capel Hot) and determined their antioxidant activity using in vitro methods to generate radicals in hydrophilic (superoxide radical) and lipophilic (2,2-diphenyl-1-picrylhydrazyl—DPPH—and peroxide radicals) media. This study demonstrates that luteolin 6-C-glucoside and luteolin 6,8-di-C-glucoside have a greater ability to eliminate superoxide radicals generated in enzymatic and non-enzymatic systems and thus engender high antioxidant activity [80]. The high and effective antioxidant capacity confers functional and nutraceutical properties to the fruit for health.

Metabolism, biochemical synthesis and concentration of flavonoids in chili fruits depend on species, genotype, landrace or commercial varieties [61, 67–69, 81] interacting with agroecological characteristics and crop management [82]. Evidence indicates that the concentration of flavonoids is related to the degree of maturity of the fruit. Bhandari et al. [83] observed that fruits had a higher flavonoid content in the initial-to-intermediate phases (breaker stage) than in the phase immediately after maturity (green mature phase) and red ripe phase. Similarly, Howard et al. [67] observed that total flavonoid content was reduced in the immature-tomature phase of the fruit (**Table 4**). This fact is consistent with other studies; green fruits (immature) reach four to five times the flavonoid content of mature fruits [67, 72, 77, 84]. In C. *chinense* Jacq. (Habanero), flavonoid content also decreases with ripening [85]. However, the behavior of Morrón peppers is different because the peppers ripen in different colors; for example, quercetin and luteolin flavonoid content was higher in red fruits than in green [68]. Differences in the composition of flavonoids and other compounds define the organoleptic characteristics of each chili fruit and are directly related to usage and consumption preferences [86].

Chili fruits are considered a natural source of antioxidants for their bioactive compounds [61, 77, 87]. Phenolic compounds increase the antioxidant activity of chili fruits and are related to the structure of their molecules. In the case of Caribe and Bell varieties (*C. annuum*), the major antioxidant activity was the result of the content of the flavonoids catechin, epicatechin and rutin, among other compounds [81]. In addition, high activity has been reported when quercetin 3-Oα-L-rhamnopyranoside was identified; such activity was comparable with quercetin activity [78]. Quercetin is a highly antioxidative aglycone and is generated by enzymatic hydrolysis of the glycoside bond of rutin (quercetin 3-O-rhamnoglucoside) [66]. In evaluating the fruits of the landraces De Árbol, Chipotle, Guajillo and Morita (*C. annuum*), it was determined that there was greater bioaccessibility of polyphenols in the small intestine in a range of 72–77%. Therefore, these landraces are considered important sources of polyphenols and bioaccessible bioactive compounds in the intestine [88].

#### **3.2. Capsaicinoids in chili pepper landraces**

The structure of each flavonoid influences antioxidant capacity, which varies between species and genotypes of chili. Materska [80] isolated three glycosylated flavonoids (luteolin 6-C-glucoside, luteolin 6,8-di-C-glucoside and apigenin 6-C-glucoside-8-C-arabinoside) from the chili fruit (*C. annuum* var. Capel Hot) and determined their antioxidant activity using in vitro methods to generate radicals in hydrophilic (superoxide radical) and lipophilic (2,2-diphenyl-1-picrylhydrazyl—DPPH—and peroxide radicals) media. This study demonstrates that luteolin 6-C-glucoside and luteolin 6,8-di-C-glucoside have a greater ability to eliminate superoxide radicals generated in enzymatic and non-enzymatic systems and thus engender high antioxidant activity [80]. The high and effective antioxidant capacity confers

Sources: Vera-Guzmán et al. [61], Howard et al. [67], Miean and Mohamed [69], Kim et al. [71], Blanco-Ríos et al. [72],

*C. annuum* **landrace and variety groups** *C. frutescens* **Jalapeño Serrano Ancho Güero Morron Cayenne Piquin Tabasco**

276.0

448.0

244.0

71–73]

6.0–22.9 ND 2.2

3.7–24.7 ND 0.9

5.9.0–7.2 ND ND

544.6

425.0

[67] [61, 75] [67, 73]

45.8

36.5

functional and nutraceutical properties to the fruit for health.

**Flavonoids1 Maturation stage**

418 Flavonoids - From Biosynthesis to Human Health

Total Flavonoids

1

Quercetin Immature 4.3.–151.2 9.30–159.8 276.0 42.4–210.2 4.76–

Mature ND 8.1 ND 23.9–64.4 3.29–

Kaempferol Immature 5.9 2.1 ND ND ND 2.0–4.7 ND ND

Catechin Immature 0.1 1.0 ND ND 1.85–5.13 ND ND ND

Epicatechin Immature 0.1 1.2 ND ND 3.70–7.35 ND ND ND Rutin Immature 0.2 2.0 ND ND 0.38–1.90 ND ND ND Luteolin Immature 0.20–37.5 0.57–41.40 3.6 15.7–51.5 0.35–9.32 2.0–19.1 ND 43.6

Myricetin Immature ND ND ND ND 658.0 2.1.0–2.1 ND ND

Apigenin Immature ND ND ND ND 272.0 ND ND ND

Immature 10.2–332.0 11.4–441.0 309.6 58.1–309.0 5.4–31.7 10.0–48.8 97.40–

Mature 4.6 9.5 ND 29.9–81.3 3.6–892.0 42.1–44.3 50.1–

Mature ND ND ND ND 171.0–

References [74, 76] [74, 76] [74] [67, 74] [67, 69,

Zhuang et al. [73], Lee et al. [74], Rochín-Wong et al. [75], Álvarez-Parrilla et al. [76].

**Table 4.** Flavonoid contents in fruits of *Capsicum annuum* and *C. frustences*.

Quercetin, catechin or quercetin + luteolin equivalents (μg/g or g/g), ND = Not determined.

Mature 1.4 ND ND ND ND 6.3–6.4 ND ND

Mature ND ND ND ND 5.28–6.41 ND ND 8.1

Mature 3.2 1.4 ND 5.96–16.8 0.36–11.0 7.1–17.3 ND 0.84–35.6

Capsaicinoids are compounds that confer pungency or spice to chili fruits and are synthesized by the condensation of vanillylamine with a branched short chain fatty acid. Their chemical structure comprises a phenolic nucleus joined by an amide bond to a fatty acid. The phenolic portion is vanillylamine and is synthesized from phenylalanine in the phenylpropanoid pathway. The fatty acid is generated from branched chain amino acids, valine or leucine [89]. Currently, more than 20 capsaicinoids are known [90], and differences in structures occur because of the nature of the side chain, which can vary between 8 and 10 carbons, and the number of double bonds. Capsaicinoids are classified into three groups of compounds: capsaicins possessing a methyl branched acyl residue with a carbon-carbon double bond, dihydrocapsaicins analogous to the previous class but being saturated compounds and N vanillyl-n-acylamides comprising saturated, unbranched alkyl chains [91]. Capsaicin [(E)-N(4 hydroxy-3-methoxybencil)-8-methyl-6-nonenamide)] and its analogue 6,7-dihydrocapsaicin represents more than 90% of total capsaicinoids in chili fruits (**Table 2**), primarily accumulating in the placenta of the fruit [58]. Schweiggert et al. [91] identified and characterized 15 capsaicinoids in the red fruits of *C. frutescens*, primarily capsaicin, dihydrocapsaicin and nordihydrocapsaicin, with nornorcapsaicin, norcapsaicin, homocapsaicin I and II, nornordihydrocapsaicin, homodihydrocapsaicin isomers I and II, N-Vanillyl-octanamide, N-vanillylnonanamide and N-anillyl-decanamide as minor compounds (**Figure 1**).

Capsaicinoids are synthesized in the placenta of the fruit and are genetically determined (*Pun1* allele of pungency) by the presence of the *Pun1* or *pun1* gene with EST- or AT3-type cofactors that induce a quantitative effect of the gene and variations in the pungency of the fruit. In consequence, not all chili peppers are spicy, and various consumers consider chili varieties that carry the *pun1* recessive gene to be sweet fruits [11]. In practical terms, it is difficult to determine the exact content of capsaicinoids in chili fruits, and the estimates or patterns that are obtained vary enormously depending on genotypes, ecological-environmental conditions, crop systems, the maturity of the fruit and harvest season, among other aspects [61, 87, 92–95]. **Table 5** presents the estimates of the capsaicinoid content in fruits of different landraces and varietal groups. Various studies have demonstrated that capsaicinoid content is greater in mature fruits than in immature one [58, 73, 78]. Some of the landraces with notable concentrations of capsaicinoids are Piquín, De Árbol and Serrano, and those with lower concentrations are the Morrón group (California, Bell, Anaheim), Pasilla, Ancho and Guajillo, among others [59, 95, 96].

Ecological-environmental conditions are factors that influence the accumulation of capsaicinoids in fruits; among the primary climatic elements are temperature and precipitation or irrigation interacting with crop management. For example, González-Zamora et al. [95] observed that temperatures of 40–48°C reduce the concentrations of capsaicinoids from 32.5 to 61.5% and

**Figure 1.** Structures of major capsaicinoids identified in *Capsicum* species.


Flavonoid and Capsaicinoid Contents and Consumption of Mexican Chili Pepper (*Capsicum annuum* L.) Landraces http://dx.doi.org/10.5772/68076 421

15 capsaicinoids in the red fruits of *C. frutescens*, primarily capsaicin, dihydrocapsaicin and nordihydrocapsaicin, with nornorcapsaicin, norcapsaicin, homocapsaicin I and II, nornordihydrocapsaicin, homodihydrocapsaicin isomers I and II, N-Vanillyl-octanamide, N-vanillyl-

Capsaicinoids are synthesized in the placenta of the fruit and are genetically determined (*Pun1* allele of pungency) by the presence of the *Pun1* or *pun1* gene with EST- or AT3-type cofactors that induce a quantitative effect of the gene and variations in the pungency of the fruit. In consequence, not all chili peppers are spicy, and various consumers consider chili varieties that carry the *pun1* recessive gene to be sweet fruits [11]. In practical terms, it is difficult to determine the exact content of capsaicinoids in chili fruits, and the estimates or patterns that are obtained vary enormously depending on genotypes, ecological-environmental conditions, crop systems, the maturity of the fruit and harvest season, among other aspects [61, 87, 92–95]. **Table 5** presents the estimates of the capsaicinoid content in fruits of different landraces and varietal groups. Various studies have demonstrated that capsaicinoid content is greater in mature fruits than in immature one [58, 73, 78]. Some of the landraces with notable concentrations of capsaicinoids are Piquín, De Árbol and Serrano, and those with lower concentrations are the Morrón group (California, Bell, Anaheim), Pasilla, Ancho and Guajillo,

Ecological-environmental conditions are factors that influence the accumulation of capsaicinoids in fruits; among the primary climatic elements are temperature and precipitation or irrigation interacting with crop management. For example, González-Zamora et al. [95] observed that temperatures of 40–48°C reduce the concentrations of capsaicinoids from 32.5 to 61.5% and

Capsaicin (CAP) Dihydrocapsaicin (DIH)

Homocapsaicin I Nordihydrocapsaicin

Homodihydrocapsaicin I Homodihydrocapsaicin II

**Figure 1.** Structures of major capsaicinoids identified in *Capsicum* species.

nonanamide and N-anillyl-decanamide as minor compounds (**Figure 1**).

among others [59, 95, 96].

420 Flavonoids - From Biosynthesis to Human Health


**Table 5.** Capsaicinoid contents in fruits of chili landrace and varietal groups. 32.5% in Jalapeño and De Árbol chilis, respectively. By contrast, in Guajillos and Serranos, the identical temperature generated up to a three-fold increase; a similar effect was identified in Puya and Ancho but only 21 and 8.6% more, respectively. In a trial in three regions of Peru, the change in temperature from 19.4 to 26.8°C generated a decrease in capsaicinoid content [92].

#### **3.3. The effect of traditional processing on flavonoid and capsaicinoid contents**

Chili fruits are consumed fresh, dried or processed. The chili's condition or processing experience changes their chemical composition because of the effects of temperature changes, pH, solar radiation, smoking or other treatment. For example, the composition of Chiltepín chili fruits changes because of the effect of the pickling process (cooked in 1:1 water and vinegar). In this case, total flavonoids, capsaicin and antioxidant activity are reduced to less than 25%. However, no significant changes are shown as a result of sun drying (temperatures between 34 and 40°C for 32 h) [75]. Similarly, Álvarez-Parrilla et al. [76] identified reductions in capsaicinoids in Serrano and Jalapeño chilis from the pickling process. During the preparation of salsas with Chiltepín, losses in capsaicinoids were detected from changes in pH and the milling process; with pH 2.7, the reduction of capsaicin and dihydrocapsaicin was 90% [98].

Regarding processing for consumption, in Mexico, the preparation of mole paste (a traditional dish) prepared with Pasilla (landrace) chili generates a decrease in the content of flavonoids, phenols and antioxidant activity as a result of cooking and changes in pH, which induce degradation of these compounds [99]. Ornelas-Paz et al. [97] indicated that cooking in water at only 96°C or on the grill at 210°C generates moderate losses of 1.1 and 28.1% of the initial content in Poblano, Bell, Chilaca, Caribe, Jalapeño and Serrano landraces of *C. annuum*, Habanero (*C. chinense*) and Manzano (*C. pubescens*). In the particular case of the Jalapeño landrace, the decrease was 10.6– 52.2%. The roasting process increased capsaicin content from 6.1 to 924.9%, dihydrocapsaicin from 2.6 to 57% and nordihydrocapsaicin from 6.6 to 206.8%, depending on genotype. Notably, the compounds are highly volatile, and the increase from heat treatment is attributed to dehydration of the fruit, cell breakdown and inactivation of enzymes that degrade capsaicinoids, such as peroxidases [100]. In this sense, Turkmen et al. [101] observed that cooking by boiling, vapor and microwaves produces increases from 2 to 26% of phenolic compounds and up to 30% in antioxidant activity in spicy chilis. In *C. frutescens* cv. Sina and *C. annuum* cv. Coduion, Shaimaa et al. [102] identified increases in phenolic compounds, flavonoids and antioxidant activity by boiling.

In Mexico, a smoked-drying or oven-drying method (65% of humidity and 75°C) is used with Jalapeño landraces, producing what is known as "chipotle chilis" (special preparation). This process increases the content of flavonoids and antioxidant capacity up to 10 times as a result of the combined liberation of phenolic compounds and flavonoids, including flavonoids generated by wood combustion. By contrast, there is a reduction in capsaicinoid content because of increase in temperature [103].

#### **3.4. Flavonoids and capsaicinoids in health**

**Landrace or** 

**Capsaicin (CAP)1**

**Dihydrocapsaicin (DIH)**

**Nordihydro-capsaicin**

**Homo-CAP and** 

**References**

**Homo-DIH**

**varietal groups**

**Immature**

> Güero

Costeño De agua

Sucurre Pico paloma

Ya´x ik Chawa Xcat ik

Bobo Dulce Miahuateco

Copi Tecomatlán

Morrón Cayenne Tabasco2

**Table 5.**

Capsaicinoid contents in fruits of chili landrace and varietal groups.

ND

746.8 1Content in μg/g of fresh or dry weight, 2*Capsicum frutescens*, ND = Not determined.

ND

496.1 Sources: Cazáres-Sánchez et al. [40], Cisneros-Pineda et al. [58], Morán-Bañuelos et al. [59], Vera-Guzmán et al. [61], Kim et al. [71], Zhuang et al. [73], Rochín-Wong et al.

[75], Álvarez-Parrilla et al. [76], Bae et al. [84], Othman et al. [93], González-Zamora et al. [95], Orellana-Escobedo et al. [96], Ornelas-Paz et al. [77].

ND

ND

ND

[73]

20.8–149.5

53.7–211.7

72.0

40.1–114.6

ND

ND

ND

[84]

1.8–143.1

1.2–134.5

55.6–99.0

57.5–113.4

ND

ND

ND

[73, 84]

ND

54.6

ND

35.7

ND

ND

ND

[59]

ND

267.4

ND

167.7

ND

ND

ND

[59]

ND

63.6

ND

45.5

ND

ND

ND

[59]

ND

42.4

ND

58.9

ND

ND

ND

[40]

ND

204.7

ND

372.2

ND

ND

ND

[40]

ND

748.4–3189

ND

831.3

ND

ND

ND

[40, 58]

12815

1415–11822

2175

1317–5555

ND

ND

ND

[40, 58]

ND

1777.6

ND

1811

ND

ND

ND

[40]

ND

2456.4

ND

1928

ND

ND

ND

[40]

26945

2930–18995

3652.0

4355–5043

ND

ND

ND

[40, 58]

ND

4.9

ND

1.6

ND

ND

ND

[61]

ND

14.6

ND

4.0

ND

ND

ND

[61]

422 Flavonoids - From Biosynthesis to Human Health

44.5

ND

6.8

ND

ND

ND

ND

[61]

**Mature**

**Immature**

**Mature**

**Immature**

**Mat.**

**Immature**

Chili fruits, in addition to conferring sensory characteristics on foods, also provide nutritional advantages from their chemical composition of vitamins, minerals, carotenoids, flavonoids and capsaicinoids, among others [40, 58, 59, 61]. Controversy remains regarding the beneficial and unfavorable health effects of chili consumption. Recently, Chopan and Littenberg [18] determined that there is no direct relation between high consumption of red chilis and mortality in various populations of North America and Europe. In these cases, adult consumers of red chilis showed a 13% lower risk of death than non-consumers. Lv et al. [104] also observed no direct relation between consumption of fresh or dried chilis and causes of mortality from cancer, diabetes, respiratory or cardiac diseases. Other reports argued that the bioactive or phytochemical compounds of *Capsicum* have anti-inflammatory, antidiabetic, antimicrobial, anticholesterolemic, anticoagulant and antioxidant properties [63].

Cancer is one of the primary causes of morbidity and mortality worldwide. Oxidative stress is implied in the etiology of this disease and results from imbalances in the production of reactive oxygen species (ROS) and the antioxidant defense system of cells. ROS deregulate redox homeostasis and promote formation of tumors by aberrant induction of signaling pathways that cause cancerous tumors [105]. ROS modulate different pathways of cell signaling, which are mediated by the transcription factors NF-κB and STAT3, hypoxia-inducible factor, growth factors, kinases and other proteins and enzymes involved in the development of cancer [106]. In this carcinogenic process, it is argued that capsaicinoids (capsaicin and hydrocapsaicin) help eliminate reactive oxygen species and consequently demonstrate anticarcinogenic, antimutagenic and preventative properties [107, 108]. These properties help prevent the proliferation of cells, migration and induction of apoptosis [109]. In in vivo and in vitro trials, capsaicin inhibited the growth and proliferation of prostate cancer [110]. In addition, capsaicin stimulates the cascade of MAP protein kinase signaling, extracellular signal-regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK), which have antiproliferative effects [111]. Capsaicin also induces apoptosis of both androgen receptors AR-positive (LNCaP) and -negative (PC-3, Du-145) prostate cancer cell lines by increasing p53, p21 and Bax [112]. Other studies determined that capsaicin can regulate the increase in IL-6 by secretion of TNF-α and the signaling responsible for activation of Akt, ERK and PKC-α [110].

Capsaicin can prevent the growth of colorectal cancer cells by suppression of pathways dependent on β-catenin/TCF by proteosomal degradation of β-catenin and breakdown of β-catenin/TCF-4 interactions [113]. In addition, capsaicin induces apoptosis in gastric cancer cells and can serve as an antitumor agent in gastric cancer [114]. In other studies, capsaicin generates ROS through mitochondria and the depletion of intracellular antioxidants and generates mitochondrial damage and apoptosis in pancreatic cancer cells [115].

Dihydrocapsaicin showed strong antibacterial activity against *Helicobacter pylori*, the bacteria associated with gastric cancer [116]. In biological trials in vivo, oral administration of quercetin generated decreases in infection from *H. pylori* in gastric mucosa and reduced the inflammatory response and lipid peroxidation [62].

Flavonoids are molecules that not only act as conventional antioxidant hydrogen donors but also exert a modulatory action on the signaling of protein and lipid kinases of cells [117]. The apigenin flavonoid is an inhibitor of protein kinases and has an antiproliferative effect on breast cancer cells [118]. The aglycone of quercetin has a protective effect on DNA, which is induced by mitomycin C and antiproliferative activities in human lymphocytes [119]. This molecule also contributes to the protective effect of nerve cells against neurotoxicity induced by oxidative stress, including in Alzheimer's [120].

Chili consumption can promote weight loss by the effect of capsaicin [121]. Capsaicin stimulates lipolysis, causing a reduction in intercellular lipids from the increase in the hydrolysis of triacylglycerol in adipocytes. This effect is mediated by the regulation of genes associated with the catabolic pathway of lipids, HSL and CPT-Ia and genes involved in thermogenesis such as UCP2 [16]. Capsaicin promotes the removal of visceral fat and prevents obesity induced by diets high in fats. Capsaicin activates transient receptor potential cation channel sub-family V member 1 (TRPV1) channels, increases levels of Ca2+ ions mediated by connexin 43 (Cx43) and promotes lipolysis in adipocytes and fat reduction [122]. Capsaicinoids demonstrate hypocholesterolemic activity from stimulation of the conversion of cholesterol to bile acids by expression of the cholesterol 7-hydrolase gene and increased secretion of bile acids in feces [123].
