Bell Peppers (Capsicum annum L.) Losses and Wastes: Source for Food and Pharmaceutical Applications

4.1. Phenols and Flavonoids

Phenols and flavonoids are one of the most abundant phytochemicals in fruits and vegetables. They have shown antioxidant effects and exhibited potential health benefits for the human body [33]. In this context, bell pepper fruits are an excellent source of phenolic acids and flavonoids [34], as listed in Table 2.

In general, the concentration of polyphenol compounds in bell peppers varies with variety and color, ranging from 5.59 to 52.65 mg of gallic acid equivalent per gram of edible portion [22,23,24]. The main phenolic compounds found in green bell peppers include myricetin (658 µg/g), pyrogallol (572 µg/g), chlorogenic acid (290 µg/g), catechol (279 µg/g), protocatechuic acid (116 µg/g), caffeic acid (108 µg/g), ellagic acid (106 µg/g), and gallic acid (89 µg/g) [23,27,35]. In red bell pepper, pyrogallol (757 µg/g), P-OH benzoic acid (395 µg/g), myricetin (244 µg/g), chlorogenic acid (221 µg/g), ellagic acid (172 µg/g), gallic acid (115 µg/g), and benzoic acid (111 µg/g) [23,26,27,35] were found; while in yellow bell pepper, pyrogallol (2175 µg/g), catechol (225 µg/g), ellagic acid, benzoic acid (173 µg/g), myricetin (151 µg/g), ellagic acid (144 µg/g), chlorogenic acid (136 µg/g), and P-OH benzoic acid (123 µg/g) [23,27] were found. Furthermore, it has been reported that orange bell pepper contains gallic acid (900 µg/g), chlorogenic acid (117 µg/g), myricetin (100 µg/g), resveratrol (89 µg/g), caffeic (38 µg/g), ferulic (13.45 µg/g) and p-coumaric acids (13.45 µg/g) [29,30,35]. Additionally, the presence of gallic acid has been reported in purple (1200 µg/g) and dark violet (1150 µg/g) bell peppers [35]. These compounds exert potent antioxidant activity against reactive oxygen species and reactive nitrogen species [36].

Similar to phenolic acids, the flavonoid content depends on the variety and color of bell peppers, ranging from 2.1 to 41 mg of quercetin equivalent per gram of edible portion [23,24,34]. The main flavonoids reported in green bell pepper were hesperidin (1065 µg/g), quercetin (394 µg/g), catechin (295 µg/g), naringin (275 µg/g), luteolin 7-glucose (181 µg/g), Apig. 6-rhamnose 8-glucose (170 µg/g), and Apig. 6-arbinose 8-galactose (151 µg/g) [29,30,31,34,35]; while in red bell pepper, hesperidin (1513 µg/g), catechin (793 µg/g), luteolin 7-glucose (413 µg/g), Apig. 6-rhamnose 8-glucose (314 µg/g), rutin (290 µg/g), quercetin (241 µg/g), and Apig. 6-arbinose 8-galactose (156 µg/g) [22,23,24,27] were reported. On the other hand, in the yellow bell pepper, catechin (745 µg/g), hesperidin (213 µg/g), naringin (190 µg/g), quercetin (102 µg/g), luteolin (95 µg/g), luteolin 7-glucose (92 µg/g), and Apig. 6-arbinose 8-glucose (77 µg/g) [29,30,31,34,35] were reported. Moreover, the presence of quercetin (92 µg/g) and luteolin (56 µg/g) has been reported in orange bell pepper fruit [30]. Additionally, other colored bell peppers, such as purple and dark violet, have been reported to contain catechin (3.67 and 15.54 µg/g, respectively) and quercetin (38.04 and 117.58 µg/g) [35]. These compounds have shown antioxidant, anti-inflammatory, and antidiabetic effects [37,38].

Evidence indicates that bell pepper fruits are rich in phenolic compounds and flavonoids that may improve the human health status [22,23]; moreover, there is an association between uptake diets rich in phytochemicals and the risk reduction of chronic non-communicable diseases such as diabetes, osteoporosis, and cancer [16]. In most cases, the biological effects of polyphenols and flavonoids have been attributable to their antioxidant capacity, which can mitigate oxidative stress [27]. Thus, the regular consumption of bell peppers can improve human health and prevent degenerative diseases [38,39].

4.2. Carotenoids

Carotenoids are natural and lipophilic pigments found in colored fruits and vegetables [16]. They are isoprenoid compounds and are responsible for the exotic color in red, yellow, and orange bell peppers [40]. In general, carotenoids have antioxidant activity and exhibit essential functions in human nutrition and health [41]. Table 3 shows the carotenoid content of bell pepper.

In general, the concentration of carotenoids in bell pepper depends on their color [26] and ripening state [44], where the highest concentration was reported in red bell pepper (7137–8800 µg/g), followed by orange (5292 µg/g), yellow (2236.3–2834 µg/g), and green (1219–1513.5 µg/g) peppers [23,26,27,42]. The main carotenoids reported in green peppers include neoxanthin (190 µg/g), chlorophyll (150 µg/g), lutein (76 µg/g), zeaxanthin (35 µg/g), and capsanthin (16 µg/g) [22,24,43,44], while, in red bell peppers, the most reported carotenoids were 5,6,-epoxide capsanthin (513 µg/g), lycopene (322 µg/g), capsanthin (178 µg/g), cucurbitaxanthin (81 µg/g), and Zeaxanthin (70 µg/g) [22,27,43,44,46,47]. In yellow bell peppers, the most common were lutein (115 µg/g), chlorophyll (61 µg/g), zeaxanthin (48 µg/g), capsanthin (45 µg/g), and α-carotene (21 µg/g) [22,24,34,44,45]. Moreover, the main carotenoids reported in orange bell peppers were zeaxanthin (191 µg/g), β-carotene (56 µg/g), lutein (45 µg/g), capsanthin (45 µg/g), and β-cryptoxanthin (19 µg/g) [22,27,34,44,45]. Carotenoids are excellent antioxidant compounds with several human health benefits; their consumption may prevent coronary heart diseases and some types of cancer (gastrointestinal, lung, prostate, and breast), and can reduce the risk of age-related macular degeneration, as well as having a beneficial effect on cognitive function [46]. However, specific carotenoids may provide specific health benefits; for example, α- carotene, β-carotene, and β- cryptoxanthin are provitamin A compounds [48]. Moreover, β-carotene has positive effects on cognitive functions, while lutein and zeaxanthin provide eye protection [48]. Furthermore, lycopene exhibited potent antioxidant activity and may reduce cholesterol in animals [48]. According to these data, the regular consumption of bell pepper fruits may improve human health.

4.3. Other Phytochemicals Identified in Bell Peppers Fruits, Seeds, and Leaves

Other bioactive compounds such as colneleic acid, capsoside A, gingerglycolipid A, and blumenol C glucoside have been qualitatively identified in red and yellow bell pepper fruits [36]. Stuliff et al. [31] reported 57 glycerolipids and glycerophospholipids, two sphingomyelin compounds and ceramides in green, yellow, and red bell peppers. These compounds could exert interesting biological activities. Additionally, some glycosides, saponins, and alkaloids have been identified in yellow, red, and green bell peppers [23]. Furthermore, Adami et al. [49] reported that green sweet pepper contains pectic polysaccharides composed of uronic acids (67%), with minor amounts of rhamnose (1.6%), arabinose (6.4%), xylose (0.3%), galactose (6.7%), and glucose (4.4%) and reported that these compounds exhibited antineoplastic effects against mammary tumor cells.

Blanco-Rios et al. [27] stated that green, red, orange, and yellow bell peppers contained α-tocopherol (0.98, 3.65, 1.92, and 1.23 mg/g, respectively) and mentioned that this compound is important to human health due to its strong antioxidant activity. Furthermore, González-Zamora et al. [50] reported that bell peppers contain homodihydrocapsaicin (0.41 mg/g).

On the other hand, Silva et al. [51] reported that seeds of bell peppers contain sterols, and triterpens such as botulin (161 mg/kg), campesterol (54.1 mg/kg), stigmasterol (9.3 mg/kg), and β-sistosterol (67.4 mg/kg), as well as fatty acids such as myristic (236 mg/kg), pentadecylic (157 mg/kg), palmitoleic (764 mg/kg), palmitic (15,041 mg/kg), margaric (22,463 mg/kg), stearic (11,693 mg/kg), and arachidic (689 mg/kg). These compounds exert antioxidant activity and acethylcholinesterase-inhibitory effects.

Additionally, Dias-Games et al. [52] isolated a Hevein-like peptide from the leaves of bell pepper crops. These compounds showed antibacterial and antifungal activities and exhibited great potential for biotechnological use [53].

5.1. Antioxidant Activity

Bell peppers are characterized by their exotic colors and nutritional value, but also provide significant amounts of phytochemicals such as phenolic, flavonoid, and carotenoids with a strong antioxidant capacity [54]. Table 4 lists various reports on the antioxidant effects of bell pepper fruit extracts (pulp, juice, and seeds), where the most studied models include DPPH, ABTS, and FRAP.

The antioxidant activity of any fruit or vegetable is determined by different bioactive compounds, showing different action mechanisms to inhibit radicals. Therefore, more than one method should be used to clarify the mode of action of each extract or compound from bell peppers. In this context, the antioxidant properties of bell peppers are an important parameter for establishing their health functionality.

Chávez-Mendoza et al. [54] reported that the antioxidant activity of ethanolic extract from grafted bell peppers depends on the cultivar, color, concentration, and type of bioactive compound. They demonstrated that red bell peppers exhibited higher antioxidant capacity (79.65%), followed by green (78%), orange (70%), and yellow (64.90%) peppers, using the DPPH test, which was associated with the phenolic and β-carotene content of each cultivar; this behavior, in antioxidant activity, was promoted by grafting [46]. Conversely, Guil-Guerrero et al. [45] reported that ethanolic extract from yellow bell pepper showed the highest antioxidant activity (80% by DPPH assay) compared to the orange (75%), red (50%), and green (40%). According to Navarro et al. [47], the content of antioxidant compounds depends on the harvest conditions and the ripening stage. On the other hand, ethanolic extracts from bell peppers exhibited similar inhibition values to oxidize the DPPH radical compared to commercial antioxidants (50 to 80%) [45]. This information supports the use of plant materials for a myriad of disease conditions.

Similarly, Abdalla et al. [23] reported that red, yellow, and green bell pepper extracts (IC₅₀ from 1114 to 1832 µg/mL) exhibited higher antioxidant activity than commercial antioxidant BHT (IC₅₀ of 145.23 µg/mL) using DPPH assay in a fruit-color-dependent manner; where the highest antioxidant activity was obtained by yellow bell pepper extract (IC₅₀ of 3267 µg/mL). Additionally, the same extracts showed a higher reducing power activity (IC₅₀ from 451 to 3813 µg/mL by FRAP assay) in comparison with ascorbic acid (IC₅₀ of 196 µg/mL), where the highest activity was observed in red bell pepper extracts (IC₅₀ of 3813 µg/mL). These results were associated with the bioactive compounds, particularly with the flavonoid content in bell peppers, which can reduce oxidative stress.

Park et al. [55] investigated the antioxidant activity of methanolic extracts from four different-colored bell peppers by different methods (ABTS, DPPH, and SOD-like activity). They informed that extracts from orange bell peppers showed the highest antioxidant activity by ABTS test (880 µmol TE/g) compared to the red (800 µmol TE/g), yellow (790 µmol TE/g), and green (630 µmol TE/g) bell peppers; in contrast, the green bell pepper exhibited the highest antioxidant activity by DPPH assay (1153 µg/mL) compared to red (882 µg/mL), yellow (811 µg/mL), and orange (694 µg/mL) bell peppers. Furthermore, the green bell pepper showed the highest SOD-like activity (IC₅₀ = 1472 µg/mL) compared to the yellow (IC₅₀ = 1676 µg/mL), red (IC₅₀ = 1826 µg/mL), and orange (IC₅₀ = 1893 µg/mL) bell peppers. The authors argued that differences in results in colored bell peppers are attributable to the mode of action of each bioactive compound present in the extract and their ability to reduce or inhibit oxidative stress, which is dependent on the color of the fruit. Additionally, the extracts from the four bell peppers exhibited a protective effect against H₂O₂- and HNE-induced DNA damage at low concentrations (1 µg/mL), preventing cellular damage at physiological levels. These compounds could form a reversible complex that may act as a desmutagenic molecule or interceptor, inhibiting genotoxicity [55].

Qiao et al. [59] informed that the antioxidant activity of green, red, and yellow bell pepper extracts could be classified as FRAP > DPPH > ABTS. Nonetheless, the highest antioxidant activity was observed in yellow bell pepper in DPPH and ABTS methods, while, for FRAP, this was observed in the green bell pepper extract. Moreover, these extracts showed anti-inflammatory properties.

Thupairo et al. [22] investigated the effect of solvent extraction (hexane, ethyl acetate, and aqueous-ethanol) on the antioxidant properties (DPPH, FRAP, and ORAC tests) of colored bell peppers (green, red, orange, and yellow). They showed that the antioxidant activity of all fruits was dependent on solvent extraction, where the highest activity was obtained using aqueous-ethanol extraction (2- to 8-, and 300 to 80-fold higher than ethyl acetate and hexane extraction, respectively). According to the authors, the polarity of ethanol promotes the extraction of phenolic compounds, which exhibited potent antioxidant activity. On the other hand, the highest antioxidant activity was obtained in green bell pepper by all three investigated methods (25.15, 30.15, and 61.96 µmol TE/g, respectively), followed by the red (23.79, 28.12, and 54.81 µmol TE/g, respectively), orange (22.20, 25.20, and 51.12 µmol TE/g, respectively), and yellow (18.63, 19.87, and 51.65 µmol TE/g, respectively) peppers. This behavior was attributed to the higher ascorbic acid and phenolic content of green and red bell peppers, especially by p-coumaric and ferulic acids. Moreover, these extracts exhibited cholinesterase inhibitory effects. Additionally, Zhuang et al. [26] reported that red bell pepper showed antioxidant activity (by DPPH and FRAP assays) that may prevent lipid peroxidation. Similar trends were reported by Prabakaran et al. [63], who informed that ethanolic red bell pepper extract showed higher antioxidant activity than chloroform and ethyl acetate extracts in both DPPH and FRAP tests; however, their effects were dose-dependent. Furthermore, Bae et al. [65] reported that a higher DPPH scavenging activity was detected in the hexane extracts from bell pepper fruits, whereas the reducing power (FRAP) was detected in ethyl acetate and acetone extracts.

Blanco-Rios et al. [27] showed that phenolic and oily fractions of colored (red, green, orange, and yellow) bell peppers exhibited antioxidant activities using ABTS and DPPH tests. They demonstrated that the highest antioxidant properties were detected in phenolic fractions compared to oily fractions (associated with carotenoids and tocopherol content) in both studied methods. Ilić et al. [61] reported that lipophilic fraction from orange bell pepper (Sympathy cv.) exhibited higher antioxidant activity using the ABTS test (5.20 µmol TE/g) than red (4.05 µmol TE/g, Selika cv.), and yellow (3.33 µmol TE/g, Dynamo cv.) bell peppers. These results evidenced the potential of bell peppers to improve human health.

Norafida and Aminah [56] reported that blanching treatments (microwave > hot water > steam) influenced the antioxidant properties of frozen green bell peppers. Similar trends were reported in cooked bell peppers by microwave and stir-frying without using water [64]. Moreover, it has been reported that sun-drying significantly increases the antioxidant properties (ABTS and DPPH tests) (55.64 µmol TE/g and 76%) compared to a fresh product (17.33 µmol TE/g and 48%) using the ABTS and DPPH tests [62]. According to Shotorbani et al. [58], during thermal treatments, the generation of different compounds with different degrees of antioxidant activity can occur, promoting higher antioxidant properties. The antioxidant activity of fresh bell pepper (regardless of cultivar) significantly increased during ripening; therefore, consumption in the fresh state is recommended at the mature stage [35].

Furthermore, an increase in the antioxidant activity (reduction in DPPH radicals from 54 to 70%) of red bell peppers cv. “California Wonder”, by applying a nanostructured coating of chitosan functionalized with Byrsonima crassiflora extracts, has been reported by González-Saucedo et al. [42]. This behavior could be attributable to the elicitor properties of chitosan, as demonstrated by Garcia-Mier et al. [66]. They showed that the antioxidant activity of bell pepper fruits increased with the elicitor agents (jasmonic acid, hydrogen peroxide, and chitosan) during postharvest. In addition, the bell pepper juice from green, yellow, orange, and red fruits exhibited antioxidant activity using the DPPH and ABTS methods, which could make it a viable option for bell pepper consumption [60].

Additionally, it has been reported that seed extract from bell pepper exhibited higher antioxidant activity than pulp. For example, Sousa-Sora et al. [57] studied the antioxidant activity of bell pepper fruits and seeds using DPPH, ABTS, and FRAP methods. They informed that seed extracts exhibited the highest antioxidant capacity (11.32, 89.25, and 9.94 µmol TE/g, respectively) than the pulp extracts (2.28, 17.17, and 3.99 µmol TE/g, respectively), which were associated with the total phenolic content of seeds (409 mg GAE/g) and pulp (119 mg GAE/g). Similarly, Silva et al. [51] informed that bell pepper seed extracts exhibited antioxidant activity in a dose-dependent response (IC₂₅ of 0.413 µg/mL by DPPH assay), whereas, at higher concentrations, a pro-oxidant effect was noticed. Moreover, the seed extract showed an effect against nitric oxide radicals (IC₂₅ of 0.105 µg/mL).

According to the evidence, colored bell peppers (pulp, juice, and seeds) are a good source of antioxidant compounds important for dietary consideration because they can prevent the formation of free radicals that can be harmful to human cells. Nonetheless, they have a key role in protecting against diverse non-communicable diseases.

5.2. Antimicrobial Activity

Natural extracts from leaves, seeds, and fruits are commonly used as antimicrobial agents. Table 5 shows the antimicrobial properties of bell pepper extracts.

Dorantes et al. [67] investigated the antimicrobial properties of bell pepper extracts against some foodborne pathogenic bacteria and showed that extracts exhibited effectiveness regarding the inhibition of Listeria monocytogenes (inhibition zone of 12 mm), Bacillus cereus (inhibition zone of 11 mm), Staphylococcus aureus (inhibition zone of 7 mm), and Salmonella tiphimurium (inhibition zone of 5 mm), which was associated with the presence of m-coumaric and cinnamic acids in the extract. Similarly, it has been reported that methanolic extracts from red and yellow bell peppers showed antimicrobial activity against some pathogenic bacteria. Hu et al. [68] showed that a minimal inhibitory concentration of red and yellow bell pepper extracts to inhibit the microbial growth was seen in a strain-dependent response. In particular, the extracts from red bell pepper were more active against B. cereus (0.20 mg/mL), Escherichia coli (0.50 mg/mL), S. aureus (0.30 mg/mL), and Pseudomonas aeruginosa (0.60 mg/mL) than the yellow extracts (0.40, 0.50, 0.40, and 0.60 mg/mL, respectively). According to the authors, these differences may be attributed to the phytochemical profile nature of each extract. Nonetheless, both extracts from bell peppers induced cell-wall damage, as demonstrated by transmission electron microscopy studies.

Mokhtar et al. [73] reported that extract from a bell pepper rich in polyphenols showed antimicrobial effects against S. aureus, L. monocytogenes, S. typhimurium, E. coli, B. subtilis, and P. mirabilis in a strain- and dose-dependent response. The authors argue that the polyphenols can alter the cell wall of pathogens, leading to cell death; moreover, they showed that the growth of Lactobacillus acidophilus and L. plantarum were stimulated by the presence of polyphenols, and mentioned that these compounds may exert a prebiotic-like effect via modulation of the gut microbiota. Additionally, Careaga et al. [71] reported that extracts from bell peppers are effective in preventing the growth of S. typhimurium and P. aeruginosa and mentioned that the extract showed a bacteriostatic (0.3 mL/100 g of meat) or bactericidal (3 mL/100 g of meat) effect in a dose-dependent response. Similarly, Aljaloud et al. [72] showed that crude extract from bell peppers showed antimicrobial activity against E. coli O157H:7 in a dose-dependent manner. These extracts could be used as an antimicrobial agent to preserve beef meat [71,72].

On the other hand, Días-Games et al. [53] investigated the in vitro antimicrobial activity of bioactive compounds extracted from bell pepper leaves. They showed that the extract exhibited antimicrobial effects against Clavibacter michiganensis spp. michiganensis, Ralstonia solanacearum, Pseudomonas syringae pv. tomato, Xanthomonas axonopodis pv. phaseoli, Erwinia carotovora spp. carotovora in a strain- and concentration-dependent response and mentioned that peptide compounds could be used as a biotechnological alternative for biological control of phytopathogens. Similarly, Dias-Games et al. [52] showed that the Hevein-like peptide extracted from bell pepper leaves showed antimicrobial properties against Clavibacter michiganensis spp. michiganensis (Gram-positive) and Ralstonia solanacearum (Gram-negative). These results were associated with the cationic character of the molecule due to their chitin-binding domain, which may induce changes in the bacterial cell wall, inducing cell death.

Additionally, it has been reported that ethanolic extracts from red bell peppers showed antifungal activity against F. andiyasi and Cochliobolus spp., associated with the phenolic content in the extract and their ability to alter the fungal cell wall, leading to cell death [69]. Moreover, the ethanolic extract of red bell peppers exhibited antifungal effects against Colletotrichum gloeosporioides in a dose-dependent manner, which could be used as an alternative to biocontrol of phytopathogens [70].

According to these data, the extracts from bell pepper fruits or leaves exhibited antibacterial and antifungal activities, which could potentially be used for food and pharmaceutical applications.

5.3. Immunomodulatory Activity

Table 6 lists reports on the various immunomodulatory effects exerted by bell pepper extracts (fruits and leaves), including immunosuppressive and immunostimulant effects.

Sancho et al. [74] reported that the nordihydrocapsiate (NHC), a compound extracted from sweet bell peppers, exhibited anti-inflammatory properties in a concentration dependent manner. They found that NCH inhibited the anti-CD3, anti-CD3 plus, and anti-CD28, promoting apoptosis (VR1-independent pathway) in primary T cells and inhibiting the NF- kBis by phosphorylation of MAPK p38. Similar trends were reported by Hazekawa et al. [75], who showed that the aqueous extract from bell pepper leaves strongly suppressed the stimulated T-cell activation and the iNOS and NF-κB expression levels in mouse spleen cells by Con-A in a dose-dependent manner, after 72 h of stimulation. Moreover, it has been reported that a pectic polysaccharide extracted from bell pepper fruit exhibited anti-inflammatory properties in a male BALB/c mice model [76]. According to Popov et al. [76], after 24 h of oral administration of pectic polysaccharides at concentrations of 40 to 100 mg/kg, the TNF-α release was decreased, with no impact on the number of monocytes and neutrophils.

Additionally, it has been reported that the administration of red and green bell pepper extracts stimulates the production of antibodies in murine spleen cells [77,78,79]. Goto et al. [79] reported that the red bell pepper extract enhanced the IgM production (by up to 350%) in a dose-dependent response (1.5 mg/mL) in mice spleen cells, due to an increase in DNA synthesis in B cells and CD138+ cells. Recently, Sarker et al. [77] showed that the red bell pepper extract promotes anti-keyhole limpet hemocyanin IgM and IgG antibodies production in a dose-dependent response (from 0.75 to 1.5 mg/mL). Furthermore, the red bell pepper extract promotes B cell differentiation to plasma cells, enhancing the production of antigen-specific antibodies. Additionally, Sarker et al. [78] reported that red bell pepper extracts promoted polyclonal IgM and IgG antibody production in murine spleen cells, which was associated with the phytochemical profile in the extract. According to the literature, the consumption of bell peppers improves the immune system, which was mainly attributed to the content of phenols, flavonoids, and carotenoids [68].

In general, the extracts from bell peppers (fruits and leaves) can modulate the immune response, exerting anti-inflammatory properties and promoting the production of antibodies. However, further studies are needed to understand the mechanism of action and potential applications.

5.4. Effect of Bell Pepper Extracts on Diverse Pathologies

Table 7 lists studies that reported the anti-hyperglycemic, cytotoxic, and neuroprotective effects of bell pepper extracts.

The antidiabetic properties of the bell pepper extract have been investigated in recent years. Park et al. [80] investigated the inhibitory effects of ethanolic extract from green bell pepper against α-glucosidase, and its insulin-like action, as an alternative to diabetes mellitus. They found that the extracts showed antidiabetic effects due to their ability to decrease intestinal glucose absorption. Moreover, bell pepper extracts exhibited insulin-like effects, which can induce 3T3-L1 cell differentiation. However, further studies are needed to understand the mechanism of action of each constituent in the extract that promotes antidiabetic properties. Conversely, Shukla et al. [84] showed that the methanolic extract from yellow bell pepper exhibited higher α-glucosidase-inhibitory effects than green or red bell pepper extracts, and prevents lipid peroxidation. These effects were attributed to the phytochemical composition of each extract and its antioxidant properties. The authors mentioned that bell pepper extracts might be helpful in diabetes mellitus management. Fuentes et al. [82] mentioned that red bell pepper extracts prevent the formation of protein islet amyloid polypeptide (IAPP) aggregates, indicating that the extracts exhibited potential antidiabetic properties and may slow disease progression.

Lahmood [83] showed that the mixture comprising a red bell pepper extract and virgin olive oil exhibited α-amylase- and α-glucosidase-inhibitory effects in a dose-dependent response (2 to 8 mL/kg body weight). Moreover, the mixture promotes a decrease in the serum glucose concentration and increases the insulin concentration in treated rats, which are key parameters in the management of diabetes mellitus type 2. Additionally, Nagasukeerthi et al. [81] reported that consuming 100 mL of bell pepper fruit juice twice a day reduces post-prandial blood glucose, systolic blood pressure, pulse pressure, and rate pressure compared to the control group. According to the authors, the antioxidant compounds of the extract may reduce the oxidate damage, increasing the sensitivity of pancreas β-cells to glucose.

According to these data, the extracts from bell pepper fruits exhibited antidiabetic effects, which were mainly associated with their phytochemicals and antioxidant properties and their ability to modulate the digestion of carbohydrates and improved insulin secretion and sensitivity.

Furthermore, the anticancer properties of bell pepper extracts have been studied in diverse cancer cell lines in recent years. E-Hamss et al. [85] investigated the antimutagenic properties of bell peppers Drosophila melanogaster larva (2-day-old). They reported that the bell pepper aqueous extract (10 v/w) significantly reduced the mutation induced by a promutagen agent (ethyl carbamate), associated with the ability of bioactive compounds in the extract (mainly carotenoids) and their ability to inhibit mutagens by modulating microsomal cytochrome. Moreover, the extracts did not show genotoxic effects against D. melanogaster.

Adami et al. [49] investigated the antineoplastic activity of green bell pepper pectic polysaccharides (GBPPP) against mammary tumor cells (in vivo and in vitro). They found that GBPPP reduces Ehrlich tumor development (from 28 to 54%) in a dose-dependent manner (50 to 150 mg/kg) compared to the control group, due to GBPPP’s ability to reduce the gene expression of Ehrlich tumors. Furthermore, the GBPPP showed inhibitory effects on tumor cell proliferation and viability against MCF-7, MDA-MB-231, and MDA-MB-436 cancer cell lines in a cell-line-dependent response. According to the authors, these effects were associated with increased intramural IL-6, which effectively stimulated angiogenesis.

Additionally, Hu et al. [68] investigated the effect of yellow and red bell pepper extracts against cancerous cells. They found that the extracts exhibited selective cytotoxic effects against the A549 cancer cell line at 125 µg/mL, whereas the extracts did not show any cytotoxic effect against NIH3T3 cells. Moreover, the red bell pepper extract is more active against the A549 cell line compared to the green extract. The anticancer effects were associated with the bioactive compounds (mainly carotenoids) that can induce apoptosis in cancer cell lines via the inactivation of NADH-oxidase. Jeong et al. [86] mentioned that the type and concentration of polyphenols strongly influenced the anticancer properties of bell pepper extracts. They found that the polyphenol mixture extracts effectively affected the viability of cancer cells (human gastric adenocarcinoma cells, A549 human lung carcinoma cells, and HeLa human cervical carcinoma cells) in a dose- and cell-type-dependent response (0.2 to 2 mg/L). These results were attributed to the strong antioxidant activity of the polyphenol mixture extract, which is composed of quercetin, luteolin, and their derivates; nonetheless, it has been reported that these compounds effectively inhibit the viability and proliferation of diverse human cancer cell lines.

According to the evidence, extracts or isolated compounds from bell peppers have the potential to treat different types of cancer. However, further studies are required for targeted antiproliferative activities.

On the other hand, it has been reported that bell pepper extracts exhibited beneficial effects in Alzheimer’s disease [87]. Ogunruku et al. [87] showed that the aqueous extracts from bell pepper can inhibit β-secretase in a dose-dependent manner, associated with the polyphenol compounds, and their antioxidant properties may cross the blood–brain barrier. Moreover, the extracts promote a decrease in peptide aggregation due to its ability to disaggregate fibrils, which could be a viable strategy in the prevention and management of Alzheimer’s disease. According to the literature, the dietary supplementation of phytochemicals exerts beneficial effects in the central nervous system due to its anti-aggregative and neuroprotective properties [88].

In general, phytochemicals present in bell pepper can also exert antihyperglycemic, cytotoxic, and neuroprotective effects. Further studies are still needed to validate these bioactivities.

5.5. Applications of Bioactive Compounds from Bell Peppers in Food Industry

In addition to the biological activities, natural compounds from bell pepper fruits have been used for diverse food industrial applications, as listed in Table 8.

Careaga et al. [71] reported that extracts from bell peppers are effective in extending the shelf life of raw beef meat (7 days stored at 7 °C) and prevent the growth of Salmonella typhimurium and Pseudomona aeruginosa, due to the bactericidal (3 mL/100 g of meat) effect of the extract. Likewise, the extracts from red bell peppers (5% v/v) effectively extend the shelf life or ground beef, associated with the ability of the natural extract to reduce microbial growth, particularly for E. coli O157H:7 [72].

On the other hand, bioactive compounds extracted from red bell peppers have been used as natural colorants of yogurt and isotonic drinks [20,89,90]. Mendes-Gomes et al. [89] added encapsulated bioactive compounds extracted from bell peppers to improve the color, sensory attributes, and nutritional value of yogurt. Furthermore, Šeregelj et al. [20] showed that the fortification of yogurt with natural colorants (from bell pepper wastes) improved its sensory attributes and positively affected the viability of lactic acid bacteria in yogurt during storage. Additionally, Lobo et al. [90] demonstrated that extracts from yellow bell peppers could be used as a natural pigment in isotonic drinks. In general, adding bioactive compounds from bell pepper wastes to foods as a functional ingredient is a technological and viable alternative to the valorization of food wastes [91].

According to the evidence, the phytochemicals present in bell pepper fruits could be used as antimicrobial agents for food preservation or as additives/bioactive ingredients to elaborate functional foods that may improve human health status.