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  • Review
  • Open Access

24 July 2024

36 Pages

Alliums as Potential Antioxidants and Anticancer Agents

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1
National Agrobiodiversity Centre, National Institute of Agricultural Science, Rural Development Administration, Jeonju 54874, Republic of Korea
2
Council for Scientific and Industrial Research, Plant Genetic Resources Institute, Bunso P.O. Box 7, Ghana
3
Department of Data Science, Jeju National University, Jeju 63243, Republic of Korea
4
Department of Applied Plant Science, Chonnam National University, Gwangju 61186, Republic of Korea

Abstract

The genus Allium plants, including onions, garlic, leeks, chives, and shallots, have long been recognized for their potential health benefits, particularly in oxidative and cancer prevention. Among them, onions and garlic have been extensively studied, unveiling promising biological activities that are indicative of their potential as potent antioxidant and anticancer agents. Research has revealed a rich repository of bioactive compounds in Allium species, highlighting their antioxidative properties and diverse mechanisms that target cancer cells. Compounds such as allicin, flavonoids, and organosulfur compounds (OSCs) exhibit notable antioxidant and anticancer properties, affecting apoptosis induction, cell cycle arrest, and the inhibition of tumor proliferation. Moreover, their antioxidant and anti-inflammatory attributes enhance their potential in cancer therapy. Studies exploring other Allium species beyond onions and garlic have revealed similar biological activities, suggesting a broad spectrum of natural products that could serve as promising candidates for developing novel anticancer treatments. Understanding the multifaceted potential of Allium plants will pave the way for innovative strategies in oxidative and cancer treatment and prevention, offering new avenues for pharmaceutical research and dietary interventions. Therefore, in this review, we compile an extensive analysis of the diversity of various Allium species, emphasizing their remarkable potential as effective agents.

1. Introduction

Allium L. is the largest genus of the Amaryllidaceae family, with petaloid monocotyledons constituting an estimated 1063 species, distributed worldwide from northern temperate regions to alpine regions [1]. The Amaryllidaceae family is a notable source of bioactive phytochemicals known for their potential in developing drugs with diverse pharmacological activities. These compounds exhibit significant antioxidant, antimicrobial, and immunomodulatory effects, making them valuable in medicinal research and pharmaceutical applications. Natural products from Amaryllidaceae are traditionally utilized to treat noncommunicable and infectious human diseases [2]. This family is often referenced in phytochemical and pharmacological literature, either in the context of plants or their alkaloids [3]. The bioactive compounds from the Amaryllidaceae family exhibit a wide range of bioactivities, including antioxidant, anti-inflammatory, antimicrobial, antifungal, antiviral, antiplasmodial, anticarcinogenic, antispasmodic, antiplatelet, antiasthmatic, antithrombotic, antitumor, antihyperlipidemic, antihyperglycemic, antiarthritic, antimutagenic, and immunomodulatory properties. The Allium genus is characterized by its superior ovary; it is an inflorescence scapose umbellate that bears flowers on the top scape in a bracted umbel and membranous bracts, with species that have characteristic features differing in leaves, inflorescences, bulb/rhizome, taste, and odor. Nearly 30 species have been frequently used for human consumption purposes, even though fewer than half are subjected to farming, with the most important being onions, garlic, leeks, chives, and shallots [4]. Their diverse biological properties combat bacteria and fungi, proving beneficial in treating various gastrointestinal diseases. Cultivated primarily for dietary and medicinal purposes, the most widely utilized Allium species include Allium cepa, A. hirtifolium, A. sativum, A. schoenoprasum, and A. tuberosum [5,6]. Traditionally employed in medicinal practices, Allium plants are valued for their therapeutic benefits [7]. These plants boast a rich array of active phytoconstituents comprising amino acids and phenolic compounds, including flavonoids such as anthocyanins, fatty acids, 63 organosulfur molecules, saponins, organic acids, steroids, and vitamins. These obversions showcase the diversity of Allium species and provide a deeper understanding of the broad spectrum of antioxidant and anticancer attributes present within various Allium plants, highlighting their significance in potential therapeutic interventions as active agents.

2. Origin

The genus Allium’s center of evolution primarily stretches along the Irano-Turanian phytogeographical zone, with additional centers in the Mediterranean basin and Northwestern America. Allium species are widespread in the Northern Hemisphere [8,9]. Most Allium species are commonly found in the dry subtropics–boreal zone, and some grow wild in the sub-Arctic belt [9,10]. The origin of the onion (A. cepa) is believed to be in Persia and Baluchistan (Iran and Pakistan). There is also a possibility that onions are indigenous to the Palestine–India region. Onions have been cultivated for more than a thousand years and are not known to grow wild. Their distribution is widespread, including China, Europe, Japan, North and South Africa, and the Americas. Allium has been used for thousands of years as a flavor enhancer in foods and in traditional medicines [9].

3. Methodology

Extensive research was conducted using Google Scholar and PubMed, with relevant keywords including “Allium species”, “Allium sativum”, “Garlic”, “Allium cepa”, “Onion”, “Allium ampeloprasum”, “Allium tuberosum”, “Allium fistulosum”, “Allium schoenoprasum”, “Antioxidants”, and “Anticancer”. Peer-reviewed scientific articles were retrieved from Web of Science, Scopus, MEDLINE, ScienceDirect, SpringerLink, Wiley Online Library, Semantic Scholar, and Europe PMC. The articles were assessed for authenticity, reliability, and relevance, resulting in the selection of 134 articles for inclusion in this review. Accepted plant names and recognized synonyms for each species were referenced from Plants of the World Online (POWO) [1], International Union for Conservation of Nature (IUCN) categorization was determined using the IUCN Red List [11], and data related to gene banks and crop information was retrieved from Genesys-Plant Genetic Resources (https://www.genesys-pgr.org/ accessed on 3 January 2024).

4. IUCN Redlist Allium Species

The Allium genus is included in the IUCN Red List, with 151 species categorized as critically endangered (6 species), endangered (16 species), vulnerable (7 species), near threatened (11 species), least concern (53 species), and data-deficient (58 species) (Figure 1 and Table 1). The genus Allium is under threat in the environment due to the development of residential and commercial urban housing areas (20%); tourism and recreation areas (15%); intrusions and disturbances from human recreational activities (16%), roads, railroad transportation, and service corridors (14%); natural ecosystem modifications (12%); overexploitation of biological resources for intentional species target usages (11%); agriculture and aquaculture by small-holder farming (9%); nomadic grazing (9%); livestock farming and ranching by small-holder grazing and ranching (9%); and unknown scale recorded (8%). These threats have caused significant stress to the species and highlight the importance of their conservation [11].
Figure 1. IUCN Red List category of Allium species, depicting the percentage of species classified as critically endangered (CR), endangered (EN), vulnerable (VU), near threatened (NT), least concern (LC), and data-deficient (DD).
Table 1. IUCN red-listed Allium species with high vulnerability.

5. Allium in Genebanks

Allium genetic resources have been assessed through genebanks (such as Genesys, EUROCISO, and FAO-WIEWS) for more than two decades, simplifying the exchange of large data collections globally [12]. The identification of gaps that need to be filled exclusively due to ongoing genetic loss is possible by evaluating the overall genetic resources held worldwide. Threats to genetic resources, including traditional cultivation loss, environmental destruction, and climate change, have led to an increase in extinction risks. Conserving genetic resources for agriculture, particularly for breeders, is of great importance. A highly diverse gene pool of crops is a vital asset (Figure 2 and Figure 3).
Figure 2. The major genebanks worldwide with Allium accessions.
Figure 3. Countries with total crop (a), Allium (b) accessions, accession-holding institute (c), species name provided to accession during the submission (d), and germplasm storage type (e) from the data accessed through Genesys on 30 December 2023.

6. Allium as a Potent Resource

Plants are widely recognized as sources of medicines, and phytochemicals are essential for discovering anticancer agents. Allium contains strong antioxidants, sulfur, and abundant phenolic compounds, garnering significant attention in the food industry [13]. It has been used for several years in treating diabetes, arthritis, colds, cough, headache, hemorrhage, asthma, atherosclerosis, and inflammatory diseases [14]. In addition, it possesses antibacterial [15], antifungal, antiviral, antiprotozoal, antiproliferative, antimotility [16], and cytotoxic properties that are conventionally used for cancer treatment [17]. As the world’s second most relevant and cultivated horticulture vegetable crop, Allium is distributed in over 175 countries and covers approximately six million hectares of land worldwide. Approximately two-thirds (66%) of global Allium production emanates from Asia, with China and India being the top producers [18]. It serves as a valuable resource for researchers investigating anticancer properties. Wild Allium species have been used as vegetables, spices, condiments, medicine, and ornamentals, playing a significant role in hill agriculture in the Indian Himalayan region [19]. The majority of clinically approved drugs contain medicinal plants, which are common sources of phytoactive compounds with therapeutic potential and are traditionally used for treating various forms of tumors. Plant-based drugs include vincristine, camptothecin, vinblastine, topotecan, taxol, irinotecan, and podophyllotoxin. Bioactive compounds have the potential to enhance their anticancer properties [20]. Kuete et al. [21] explored 280 Korean medicinal plants from 73 families and 198 genera, finding a significant correlation between the response of cancer cell lines and the use of therapeutic plants and natural constituents for tumor treatment. Drug development can be improved by selecting and enhancing their absorption, distribution, metabolism, and excretion properties while also reducing their toxicity and side effects [22]. The practice of traditional medicine is still common in therapeutics worldwide [23].

7. Phytochemistry of Allium

Allium species are renowned for their abundance of secondary metabolites with notable biological activities [24]. Economically significant Allium crops, such as garlic and onion, play a vital role in daily diets, serving as both vegetables and medicinal ingredients. The genus Allium is a rich source of compounds with diverse bioactivities, both in vivo and in vitro, containing a wide variety of metabolites. Both wild and cultivated species possess numerous key metabolites and other sulfur-rich substances, such as allicin [25]. Compounds derived from Allium species offer a wide range of health benefits, including antiviral, antibacterial, antifungal, antidiabetic, anticancer, antiplatelet, antispasmodic, antiseptic, anthelmintic, antithrombotic, antiasthmatic, carminative, antioxidant, anti-inflammatory, antihypertensive, hypoglycemic, hypotensive, lithontriptic, and hypocholesterolemic properties [26].
Alkaloids have been identified from this genus, including three pyridine-N-oxide alkaloids with disulfide functional groups isolated from A. stipitatum: 2-(methyldithio) pyridine-N-oxide, 2-(methylthiomethyl)dithio] pyridine-N-oxide, and 2,2′-dithio-bis-pyridine-N-oxide. Additionally, the thiosulfinate natural product allicin, commonly found in the genus Allium, was synthesized from 2-(methyldithio) pyridine-N-oxide using a straightforward method by Kitson and Loomes and isolated as yellow and orange oils [25].
Flavonoids and their derivatives have been isolated from numerous Allium species, including A. cepa, A. sativum, and A. schoenoprasum. These flavonoids exhibit antioxidant, antitumor, anti-inflammatory, and antimutagenic activities [27]. Various types of flavonoids, such as flavone, flavonol, and flavanone, have been identified across different Allium species.
Allium species contain high amounts of carbohydrates, with significant carbohydrate levels also found in A. cepa and A. porrum. A. cepa contains fructo-oligosaccharides, while A. porrum contains active polysaccharides like glucuronic acid, galactose, and rhamnose. These polysaccharides, separated by water extraction, have high polyuronic and protein content but low sugar levels. A. sativum primarily contains reducing sugars such as glucose, fructose, sucrose, and maltose, which are known to stimulate the human immune system [28].
Sulfur compounds such as di-allyl sulfide, sulfinate, allyl propyl sulfide, and S-methyl-L-cysteine sulfoxide have been isolated from Allium species. Allicin (diallyl thiosulfinate), a defense molecule found in A. sativum, exhibits a broad range of biological activities, including cancer, diabetes, and cardiovascular disease prevention [27]. Cysteine sulfoxides (alliin) have been isolated in several Allium species, including A. sativum. Twenty-seven volatile sulfur-rich compounds, including sulfides; disulfides; trisulfides; and tetrasulfides with ethyl, butyl, and pentyl groups, have been extracted from A. tuberosum [27,29]. Thioethyl and thiopentyl compounds have also been reported in A. schoenoprasum. These sulfur-containing compounds exhibit potent antioxidant and antitumor activities.

8. Antioxidant Properties of Various Allium Species

Antioxidants play a crucial role in protecting our bodies from oxidative stress caused by free radicals and reactive oxygen species (ROS). This oxidative stress occurs due to an imbalance between the formation of ROS and their detoxification, leading to cellular damage. Chronic oxidative stress can result in several diseases, including cancer, coronary heart disease, and osteoporosis [30]. Free radicals, such as superoxide anion (O2•), perhydroxyl radicals (HO2•), hydroxyl radicals (•OH), and nitric oxide, along with other species like hydrogen peroxide (H2O2), singlet oxygen (1O2), hypochlorous acid (HOCl), and peroxynitrite (ONOO-), can attack biomolecules, especially the polyunsaturated fatty acids in cell membranes [31]. The formation of ROS begins with the uptake of oxygen (O2), which activates NADPH oxidase, producing superoxide anion radicals. These radicals are then converted to hydrogen peroxide (H2O2) by superoxide dismutase (SOD) [32]. Antioxidants interrupt the chain reactions of free radicals by donating electrons to stabilize them without becoming free radicals themselves [33].
Antioxidants are classified into two types based on their activity: enzymatic and non-enzymatic. Enzymatic antioxidants include enzymes such as glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD), which catalyze the neutralization of free radicals and ROS [34]. Non-enzymatic antioxidants, found in natural materials such as fruits and onions, include flavonoids, alkaloids, carotenoids, and phenolic groups [31,34]. The antioxidant activity of these compounds can be assessed using various methods, including the DPPH free radical-scavenging assay, oxygen radical absorbance capacity (ORAC) assay, Trolox equivalent antioxidant capacity (TEAC) assay, ferric-reducing antioxidant power (FRAP) assay, cupric reducing antioxidant capacity (CUPRAC) assay, and the reducing power assay. Allium species play a significant role in human health as they contain various health-promoting bioactive compounds, such as flavonoids (polyphenols), sulfur compounds, vitamins, and minerals with antioxidant activity [35]. In this comprehensive review, we have extensively explored the antioxidant potential exhibited by diverse Allium species shown in Table 2.

8.1. Allium ampeloprasum L.

A. ampeloprasum (var. kurrat) originates from West Asia and S. Europe and can be cultivated in various regions. It is a good source of fiber, zinc, polyunsaturated fatty acids, and linoleic acid, as well as lipophilic and hydrophilic bioactive compounds with antioxidant activity [36]. Analysis of its extracts, including butanol, methanol, and ethyl acetate fractions, has revealed the existence of the total flavonoid content (TFC), total phenol content (TPC), caffeic acid, coumaric acid, chlorogenic acid, gallic acid, kaempferol, quercetin, tannin, and vanillic acid, all known for their high antioxidant activities [37]. Italian landraces onion’s volatile compounds and sulfur-containing compounds exhibit high antioxidant activity, with high pungency (9–14 μmol/g FW) due to alliinase activity and high levels of citric and malic acids in all parts. Fructose is the most abundant soluble sugar, followed by sucrose and glucose, with the growth temperature affecting the quality parameters [38]. Organosulfur compounds in garlic, elephant garlic, and onion have been evaluated, revealing significant γ-glutamyl peptides and high alliin in elephant garlic but not in onion. Antioxidant abilities measured using ABTS, DPPH, and ORAC radical-scavenging activity showed that garlic had higher activity compared to elephant garlic and onion. This indicates a connection between organosulfur compounds and antioxidants in Allium species [39].

8.2. Allium cepa L.

A. cepa compared with A. fistulosum spring cultivars plant parts were studied with the catalase, glutathione-peroxidase, superoxide-dismutase, and peroxidase activities with autumn A. fistulosum. A. fistulosum exhibits higher SOD, C-ase, GP-ase activities, while A. cepa L. has high P-ase and SOD activity in leaves. A. fistulosum spring has a high resistance to oxidative stress [40]. A. fistulosum (green-leaf and white-sheath var.) antioxidant activity was high in red plants, and that of the yellow variety was equal to green onion and lower in white Welsh onion when studied using FRAP and TEAC. Similarly, TFC was high in red and lower in yellow, green, and white Welsh onion. A. cepa contains quercetin (a major flavonoid), while A. fistulosum has kaempferol. Green Welsh onion is an effective antioxidant, similar to yellow onion, and it is a source of kaempferol. The thermal treatment of green Welsh onion results in an increase in antioxidant activity but a decrease in flavonoid content compared to yellow and red varieties of A. cepa [41].
A. cepa varieties (green, red, violet, and white) have been studied for their TPCs (gallic, ferulic, quercetin, protocatechuic acid, and kaempferol), which range widely from 4.6 to 74.1 mg g−1 GAE. In addition, antioxidant (13.6–84.1%) and free-radical-scavenging activities (0.1–15.2 mg ml−1 in IC50), as well as the concentration of efficient (4.3–660.8 mg mg−1 in EC50) and antiradical power (0.15–23.2), have been reported. Dried outer layers of red and violet varieties inhibit lipid peroxidation, non-site-specific hydroxyl radical-induced deoxyribose degradation, and nitro blue tetrazolium chloride (NBT) reduction, while the inner layers exhibit a high Fe+-chelating capacity. The outer layers of non-utilized red varieties are rich in quercetin with high bioactivity, significantly protecting DNA damage by free radicals [42]. Indian onion cultivars N-53, Pusa red, Sel-383, and Sel-402 (red cultivars) exhibit high TPC (>100 mg/100 g), while TFC is high in Pusa red, Sel-402, H-44, and N-53 (>40 mg/100 g). Pusa white flat, Pusa white round, and early grano (white cultivars) consistently show low TFC, TPC, and antioxidant activity. The total antioxidant activity, measured through FRAP and CUPRAC, is high in N-53, Pusa red, Sel-126, and Sel-383 cultivars. Sel-383 and Pusa red are cultivars with a high antioxidant content [43].
The A. cepa L. var. tropeana (red onion) seed shows high levels of calcium, crude protein, fiber, oil, and potassium, as well as a low sodium content and six cysteine derivatives. In addition, S-propyl mercapto-cysteine has been recently recorded. Both FRAP and DPPH assays indicate a significant increase in antioxidant capacity after boiling, though culinary preparation causes a notable loss of cysteine derivatives in water [44]. Garlic and red onion are commonly used in Malaysian cuisine. Their contents with medicinal and antioxidant properties have been compared. The results suggest that red onion has a higher total phenolic content (53.43 ± 1.72 mg GAE 100 g−1) and EC50 value compared to garlic (37.60 ± 2.31 mg GAE 100 g−1), indicating stronger free radical-scavenging activity in red onion. FIC assay data show that red onion has a higher Fe+-chelating effect (45.00 ± 1.73%) than garlic, while both exhibit slightly higher ion-chelating effects than BHA (43.14 ± 1.07%) but lower than EDTA (97.9 ± 0.07%). The analyses also indicate a negative correlation between DPPH radical-scavenging activity, FIC, and TPC. The evaluation of Allium species as natural antioxidant sources is crucial for future prospects [45]. Methanolic extracts of A. cepa L. (green, red, and white subspecies), A. kurrat L., A. porrum L., and A. sativum L. have revealed that A. cepa (sub sp. red) and A. porrum exhibit high phenolic contents and high in vitro antioxidant activity, as assessed through DPPH radical, phosphomolybdate, and reducing power assays [46].

8.3. Allium porrum L. and Allium roseum var. Odoratissimum (Desf.) Coss

A. porrum ethanolic extracts have a TPC of 93.34 mg/g and a TFC of 25.14 mg/g. They also contain apigenin, quercetin, rosmarinic acid, and rutin, which exhibit antioxidant and DPPH radical-scavenging properties and are associated with TPC and TFC. A. roseum var. odoratissimum methanolic extracts have been found to have high TFC and TPC in the flowers and leaves, as well as apigenin, kaempferol derivatives, and luteolin, which have high antioxidant activity. Extract analyses show that Enterococcus faecium is more liable, and the stalk extract inactivates Bacillus subtilis, Enterococcus faecium, E. coli, and Staphylococcus aureus, indicating antibacterial activity [47].

8.4. Allium sativum L.

A. sativum L. is well-known for its antioxidant activity due to the presence of unstable and irritating organo-sulfur contents. When garlic is extracted for an extended period, it produces an odorless aged garlic extract that contains stable and water-soluble organo-sulfur compounds that can scavenge free radicals and prevent oxidative damage. It is important to use caution when heating Alliums and treating them with acid during food preparation and processing to preserve their antioxidant activity [48]. The formation of allicin in bulbs has been analyzed in bakeri garlic, Chinese chive, Chinese leek, garlic, onion, shallot, and scallion to evaluate their antioxidant activity using a liposome model. In addition, pH treatments and salt concentration have been reported to have no effect on the antioxidant activity of these foods. However, the antioxidant activity of most foods is affected by heat (65/100 °C) and a low pH [48].
Garlic contains high levels of sulfur and polyphenol compounds with antioxidant activity (AA). The shelf lives of fresh garlic and commercial products have been analyzed in a study. The findings indicate that fried garlic exhibits high antioxidant activity, while the free radical-scavenging activity declines over time in commercial products due to a decrease in TPC [49]. The red onion peel (A. cepa L.) ethyl acetate (EA) fraction exhibits a high TFC (165.2 ± 3.2 mg QE g−1), TPC (384.7 ± 5.0 mg GAE g−1), ARP (75.3 ± 4.5), AOA (97.4 ± 7.6%), and RP (1.6 ± 0.3 ASE mL−1). It also contains ferulic, gallic, kaempferol, quercetin, and protocatechuic acids, which have a high antioxidant capacity against hydroxyl radicals, ferric chloride-induced lipid peroxidation, nitric oxide, protein fragmentation, and superoxide anion radicals. It also inhibits the Salmonella typhimurium strains (TA102) via tobacco-induced mutagenicity, and plasmid pUC18 DNA hydroxyl radical-induced nicking as antimutagenic activity could be used as a natural antioxidant [50].
The A. sativum polysaccharide, consisting of fructose, glucose, and galactose (monosaccharides), with a β-glycosidic bond, has a potent scavenging capacity for superoxide anions and hydroxyl radicals [51]. Onion cultivars have been evaluated for different physicochemical properties, including TBARS (malondialdehyde), TPC, and Trolox equivalent antioxidant capacity. The results indicate variations in carbohydrate contents that affect the essence and suitability of the onions. The outermost layers of the bulb show a high concentration of antioxidant compounds, with a slight decline in the innermost layers [52].
Garlic dry extract, which contains flavonoid aglycones and phenols, has been evaluated using the DPPH method. It reduces DPPH radical formation, demonstrating free radical-scavenging activity, neutralizes hydrogen peroxide, and inhibits lipid peroxidation (LP) in Fe2+/ascorbate and Fe2+/H2O2 induction systems [53]. The black, fresh, and steamed garlic extracts in hot water and ethanol show differences in flavonoid content, with higher levels in the ethanol extract compared to the hot water extract. Phenolic compounds are stable and have been studied to determine their antioxidant capacities. Hydroxyl radical and DPPH radical-scavenging activity was high in the ethanolic extract, with over 60% inhibition (conc. 5 mg mL−1). Black garlic shows high reducing power and antioxidant activity for linoleic acid, particularly after 4 days of storage [54].
Garlic and onion (green, yellow, red, and purple) have been examined for their chain-breaking activity, H2O2 scavenging, free radical-scavenging (RAS), reducing capacity, and TPCs. Garlic has a high RAS, while green onion shows a low RAS. Green onion shows a higher (0.48) chain-breaking activity than the garlic extract (0.029). The high ability of onion and garlic to scavenge hydrogen peroxide (60–90%) is well known. Garlic also possesses a high reducing capacity (196%), indicating its potency [55].
In vitro investigations of the antioxidant activity of hydroethanolic extracts (15%) from leaves and bulbs of various endemic Italian Alliums, including A. neapolitanum Cyr., A. roseum L., and A. subhirsutum L., using the DPPH test and FRAP tests indicate that the leaves have high antioxidant activity [56]. The evaluation of TPC and antioxidant properties of A. cepa L. (white, red, and yellow), A. sativum L., A. schoenoprasum L., and A. ursinum L. using the Folin–Ciocalteu reagent DPPH revealed an antioxidant activity that ranged from 12.29% to 76.57%. In addition, chives possess a high TPC and antioxidant activity, while white onions have the least [57].
A. atroviolaceum, A. dictyoprosum, A. nevsehirense, A. scrodoprosum subsp. rotundum, and A. sivasicum extracts have been assessed using β-carotene/linoleic acid and DPPH free radical-scavenging tests. A. atroviolaceum (IC50 of 79.0 ± 2.75 μg mL−1) shows the highest activity, while the inhibition of linoleic acid oxidation due to A. atroviolaceum and A. dictyoprosum are similar (71.2% ± 2.20% and 72.3% ± 1.20%). The synthetic antioxidant BHT exhibited 96% inhibition [58]. Overall, A. sativum is a promising antioxidant agent.

8.5. Allium subhirsutum L. and Allium paradoxum (M.Bieb.) G.Don

A. subhirsutum L. extracts contain p-coumaric acid as a major TPC, along with amino acids, amino alcohols, alkaloids, amides, fatty amides, glycerolipids, limonoids, octadecanoids, aminoglycoside antibiotics, sterol lipids, cationic sphingoids, isoprenoids, fatty acyls, octadecanoids, and lipids. In vitro assays using DPPH indicate antioxidant activity through antiradical activity and reducing power. These extracts inhibit the growth of Mat-LyLu and Walker 256/B cells, induce apoptosis, and exhibit strong chemo-preventive properties by reducing angiogenesis and osteolytic metastases [59]
The aerial part extract of A. paradoxum has higher TFC and TPC than the bulb extract. It also exhibits higher antioxidant activity and reducing power compared to the bulb, but it is not as effective as vitamin C. The DPPH radical-scavenging activity (890.9 ± 43.2 and 984.9 ± 33.5 µg/mL in IC50) and iron (Fe2+)-chelating ability (530 ± 24 and 959 ± 47 µg/mL in IC50) are higher in the aerial parts compared to the bulbs. Both extracts show hydrogen peroxide-scavenging activity. It exhibits antioxidant and antihemolytic activity [60].

8.6. Allium Species

A. atroviolaceum Bois., A. flavum L., A. scorodoprasum L., A. sphaerocephalum L., A. vienale L., and cultivars of A. cepa L., A. nutans L., A. fistulosum L., A. pskemense B. Fedtsch, A. sativum L., A. schenoprasum L., and A. vienale L. leaves have been quantified for chlorophylls (a, b), carotenoids, soluble proteins, TFCs, Vit-C, and hydroxyl radicals; malonyldialdehyde superoxide; and reduced glutathione. They have also been evaluated for antioxidative activities using catalase, glutathione peroxidase, peroxidase, and superoxide dismutase enzymes [61]. Štajner et al. also analyzed different plant parts of A. nutants L. [62], A. psekemense B. Fedtsch [63], A. schoenoprasum L. [64], A. giganteum [65], A. ursinum [66], and A. sphaerocephalon [67]. ESR analysis with phosphate buffer (pH 7) extract indicates that DMPO-OH spin adducts are reduced by 78.48% (A. nutants) and 54.3% (A. psekemense), while PBN-OH radical adducts are reduced by 64.51% (A. sphaerocephalon), 74.19% (A. giganteum), and 87.61% (A. ursinum).
Lee et al. [68] utilized wild edible plants as a resource for the creation of new crops and analyzed their antioxidant and anti-obesity properties. Korean wild vegetables A. tuberosum Rottl., A. senescens L., A. thunbergii G. Don., and A. sacculiferum Maxim. have been evaluated for their antioxidant activity using ABTS+ and DPPH-scavenging methods, as well as their anti-adipogenic effects on adipocytes. This study indicates that A. tuberosum and A. sacculiferum have a large amount of phenol, and they also contain caffeic acid, a compound that protects against adipocytes and has anti-adipogenic properties. A. thunbergii, A. tuberosum, and A. sacculiferum exhibit the highest levels of antioxidative and antiadipogenic effects, with potential benefits against obesity [68].
A. tenuissimum flowers exhibit superior antioxidant activity and inhibitory effects on nitrosation [69]. Volatile components have been identified through GC-MS analysis, with terpenoid compounds and sulfurous compounds, specifically dimethyl trisulfide, found in the highest concentrations. The antibacterial effectiveness against foodborne pathogens and the antioxidant impact have also been evaluated through the scavenging capacity of DPPH, ABTS+, and OH. Antimicrobial activity is present in the oil and aids in protection against Aspergillus flavus, Bacillus subtilis, E. coli, Saccharomyces cerevisiae, and Staphylococcus aureus, serving as an antibacterial and antioxidant agent [70].
Table 2. Antioxidant activities of different Allium species.

10. Antioxidant and Anticancer Effects of Allium

Allium species, including A. sativum, A. cepa, and A. porrum, are well-known for their rich phytochemical profiles, which exhibit potent antioxidant and anticancer properties. The primary bioactive compounds found in these species are organosulfur compounds (OSCs) such as allicin, diallyl-disulfide (DADS), diallyl trisulfide (DATS), and S-allylcysteine (SAC), as well as flavonoids and saponins.

10.1. Antioxidant Mechanism

Allium phytochemicals combat oxidative stress through multiple mechanisms, including the direct neutralization of free radicals and enhancement of the body’s antioxidant defenses. Allicin, the major component in garlic, undergoes rapid transformation into various OSCs, which are responsible for its biological activity [148]. These OSCs act as electron donors to reactive oxygen species (ROS), converting them into less reactive molecules and preventing cellular damage [27]. One significant antioxidant mechanism involves the modulation of the body’s endogenous antioxidant enzyme systems. Enzymes such as catalase, glutathione peroxidase, and superoxide dismutase are crucial for detoxifying ROS. Studies have shown that DADS and DATS can upregulate the expression of these enzymes, thereby enhancing the detoxification of ROS and reducing oxidative stress [149]. Additionally, flavonoids present in Allium species have been found to scavenge free radicals directly and chelate metal ions that catalyze free radical formation [150]. Moreover, Allium phytochemicals can modulate cellular signaling pathways associated with oxidative stress. For instance, SAC has been shown to activate the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, leading to the upregulation of various antioxidant genes. This pathway plays a critical role in maintaining cellular redox homeostasis and protecting cells from oxidative damage [151].

10.2. Anticancer Mechanism

The anticancer effects of Allium phytochemicals are multifaceted, involving the induction of apoptosis, inhibition of cell proliferation, suppression of angiogenesis, and modulation of immune responses [152].
Induction of Apoptosis: apoptosis is a critical mechanism through which the body eliminates cancer cells. OSCs present in A. sativum, such as DADS and DATS, have been found to induce apoptosis in cancer cells through the activation of both intrinsic and extrinsic apoptotic pathways [153]. These compounds increase the expression of pro-apoptotic proteins (Bax, Bak) and decrease the expression of anti-apoptotic proteins (Bcl-2, Bcl-xL), leading to mitochondrial dysfunction and the release of cytochrome c. This release activates caspases, which are essential for the execution of apoptosis [154]. In addition, DATS has been shown to induce endoplasmic reticulum (ER) stress in cancer cells, which triggers the unfolded protein response (UPR) and leads to apoptotic cell death. This mechanism highlights the ability of Allium phytochemicals to target multiple cellular pathways to induce apoptosis in cancer cells [155].
Inhibition of Cell Proliferation: Allium phytochemicals inhibit cancer cell proliferation by arresting the cell cycle at various checkpoints. For instance, SAC and DADS can cause cell cycle arrest at the G2/M phase by downregulating cyclin B1 and Cdc25C and upregulating p21 and p27, which are cyclin-dependent kinase inhibitors [156,157]. This arrest prevents the progression of the cell cycle, thereby inhibiting the proliferation of cancer cells. Moreover, allicin has been shown to inhibit the growth of colon cancer cells by downregulating the expression of genes involved in cell proliferation and survival, such as c-Myc and cyclin D1. This inhibition of proliferative signaling pathways underscores the potential of Allium phytochemicals in cancer therapy [150].
Suppression of Angiogenesis: Angiogenesis, the formation of new blood vessels, is essential for tumor growth and metastasis. Allium phytochemicals, particularly DATS, have been shown to suppress angiogenesis by downregulating vascular endothelial growth factor (VEGF) and its receptor (VEGFR) [158]. This inhibition hinders the angiogenic signaling pathways, thereby reducing the supply of nutrients and oxygen to the tumor and inhibiting its growth. In addition, garlic-derived OSCs have been found to inhibit the migration and invasion of endothelial cells, which are crucial steps in the angiogenesis process. By targeting multiple aspects of angiogenesis, Allium phytochemicals can effectively suppress tumor growth and metastasis [159].
Modulation of Immune Responses: the immune system plays a vital role in identifying and eliminating cancer cells. Allium phytochemicals enhance the immune system’s ability to fight cancer by modulating the activity of various immune cells. For instance, allicin and its derivatives have been shown to boost the activity of natural killer (NK) cells and macrophages, which are essential for identifying and destroying cancer cells [160]. Also, A. sativum extracts have been found to enhance the production of cytokines, such as interleukin-2 (IL-2) and interferon-gamma (IFN-γ), which are critical for the activation and proliferation of immune cells. This immunomodulatory effect of Allium phytochemicals highlights their potential as adjuvants in cancer immunotherapy [157,161].

11. Conclusions

Allium species are highly desirable and widely used in culinary arts, including several wild species used in traditional and folklore medicine in certain regions. The consumption of Allium species reduces the risk of gastrointestinal tract cancer. Organosulfur compounds found in these species inhibit carcinogen activation; enhance immune function; and have antioxidant, antibacterial, antifungal, antiviral, and anticancer properties.
By analyzing the structure–activity relationships, we can understand the mechanisms through which diverse bioactive compounds contribute to the antioxidant efficacy of Allium species. This knowledge can guide the development of more effective antioxidant agents based on Allium-derived compounds. The regular consumption of Allium vegetables, such as garlic and onions, can significantly decrease the risk of cancer in organs, including the brain, breast, esophagus, liver, lung, prostate, skin, and stomach.
Allium species, with their rich phytochemical content, offer a multifaceted approach to combating oxidative stress and cancer. The antioxidant effects are primarily due to the direct scavenging of free radicals, modulation of antioxidant enzymes, and activation of the Nrf2 pathway. The anticancer effects involve the induction of apoptosis, inhibition of cell proliferation, suppression of angiogenesis, and modulation of immune responses. These mechanisms highlight the potential of Allium phytochemicals as complementary therapies in the prevention and treatment of cancer.
The antioxidant and anticancer activities of Allium species indicate their potential against diseases driven by reactive oxygen species. Therefore, studies on Allium plants can lead to innovative strategies in oxidative and cancer treatment and prevention, offering new avenues for pharmaceutical exploration and dietary interventions, utilizing their remarkable potential as effective agents.

Author Contributions

Conceptualization, methodology, investigation, writing—original draft preparation, K.I., B.-K.H. and S.-H.K.; writing—review and editing, K.I., K.O. and Y.A.S.; supervision, S.-H.K. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

IUCN—International Union for Conservation of Nature; GENESYS—Global Information System on Plant Genetic Resources; EUROCISO—European Cooperative Programme for Plant Genetic Resources; FAO-WIEWS—Food and Agriculture Organization–World Information and Early Warning System; TPC—total phenolic content; TFC—total flavonoid content; DPPH—2,2-Diphenyl-1-picrylhydrazyl; ABTS—2,2′-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid); ORAC—oxygen radical absorbance capacity; FRAP—ferric-reducing antioxidant power; TEAC—Trolox Equivalent Antioxidant Capacity; FIC—ferrous ion-chelating; NBT—Nitro Blue Tetrazolium Chloride; EC50—Half-Maximal Effective Concentration; IC50—Half-Maximal Inhibitory Concentration; mg—milligram; g—gram; GAE—Gallic Acid Equivalent; QE—Quercetin Equivalent; ARP—Antiradical Power; AOA—antioxidant activity; RP—reducing power; RD—Rhabdomyosarcoma; ASE—Ascorbic Acid Equivalent; Vit-C—vitamin C; SOD—superoxide dismutase; GP-ase—glutathione peroxidase; C-ase—catalase; P-ase—peroxidase; ROS—reactive oxygen species; RBCs—Red Blood Cells; ATCC—American Type Culture Collection; CRL—Cell Research Laboratories; MAPK—Mitogen-Activated Protein Kinase; T-ALL—T-cell acute lymphoblastic leukemia; MTT—3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide; HUVEC—Human Umbilical Vein Endothelial Cells; PGE2—Prostaglandin E2; EGFR—Epidermal Growth Factor Receptor; B-Raf—B Rapidly Accelerated Fibrosarcoma; K-Ras—Kirsten Rat Sarcoma Viral Oncogene; PI3K—Phosphoinositide 3-Kinase; LAB—lactic acid bacteria; ESR—Electron Spin Resonance; DMPO—5,5-Dimethyl-1-pyrroline-N-oxide; PBN—N-tert-Butyl-α-phenylnitrone; NSCLC—Non-Small Cell Lung Cancer; TBARS—Thiobarbituric Acid Reactive Substances; HA—hyaluronic acid; HA-ELISA—Hyaluronic Acid-Enzyme-Linked Immunosorbent Assay; AQP3—Aquaporin-3; HAS2—Hyaluronan Synthase 2; KRT1—Keratin 1; FLG—Filaggrin; CHK2—Checkpoint Kinase 2; BAX—Bcl-2 Associated X Protein; Bcl-2—B-cell Lymphoma 2; MTs—Microtubules; AgNPs—silver nano particles; SK-MES-1—squamous cell carcinoma cell line; HeLa—Henrietta Lacks Cells; L929—Mouse Fibroblast Cells; SK-BR-3—breast cancer cell line; Hs 281—Human Cell Line Hs 281; MDA-MB-231—Breast Cancer Cell Line MDA-MB-231; H2O2—hydrogen peroxide; BHT—Butylated Hydroxytoluene; OSCs—organosulfur compounds; DADS—Diallyl Disulfide; DATS—Diallyl Trisulfide; SAC—S-Allylcysteine; Nrf2—Nuclear Factor Erythroid 2-related Factor 2; VEGF—Vascular Endothelial Growth Factor; VEGFR—Vascular Endothelial Growth Factor Receptor; ER—Endoplasmic Reticulum; UPR—Unfolded Protein Response; IL-2—Interleukin-2; IFN-γ—Interferon-Gamma; AREs—Antioxidant Response Elements; Bak—Bcl-2 Antagonist/Killer 1; Bcl-xL—B-cell Lymphoma-extra Large; MOMP—Mitochondrial Outer Membrane Permeabilization; c-Myc—Cellular Myelocytomatosis Oncogene; CDK—Cyclin-dependent Kinase; CUPRAC—Cupric Ion-Reducing Antioxidant Capacity; GAE—Gallic Acid Equivalents; PBN-OH—Phenyl N-tert-butylnitrone Hydroxyl Radical; ESR—Electron Spin Resonance; pUC18—Plasmid containing the lacZ Gene used in cloning; MMP—Matrix Metalloproteinase; BHT—Butylated Hydroxytoluene; PC3—Prostate Cancer Cell Line 3; A549—Human Lung Adenocarcinoma Cell Line; HT-29—Human Colorectal Adenocarcinoma Cell Line; HeLa—Henrietta Lacks Cell Line; MCF-7—Michigan Cancer Foundation-7 Breast Cancer Cell Line; GBM—Glioblastoma Multiforme; AP-1—Activator Protein 1; SDS—Sodium Dodecyl Sulfate; PBS—Phosphate-Buffered Saline; HepG2—Human Liver Cancer Cell Line.

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