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Home , Allium ampeloprasum, Allium chinense, Allium fistulosum, Allium flavum, Allium galanthum, Allium giganteum

Bioactive Compounds of 14 Rajeev Bhat

Contents 1 Introduction ...... 278 2 Botanical Distribution and Bioactive Compounds ...... 278 3 Bioactivity ...... 281 3.1 Antioxidant Activity ...... 281 3.2 Anticancer Activity ...... 283 3.3 Antimicrobial Activity ...... 284 3.4 Antihyperlipidemic/Anti-hypercholesterolemic Activity ...... 285 3.5 Other Bioactivities ...... 285 4 Toxicity...... 286 5 Conclusions ...... 287 References ...... 287

Abstract Evaluation of different species of Allium has resulted in identification of several bioactive constituents/phytochemicals. Some of the bioactive phytochemical constituents include organosulfur compounds, thiosulfinates, polysulfanes, polyphenols, tannins, flavonoids, alkaloids, saponins, fructans, fructo-oligosaccharides, essential oils, amino acids, , pigments, and much more. Traditionally, majority of the belonging to Allium sp. have been proved to be effective in treating flu, cold, cough, asthma, headache, stomachache, arthritis, and other common ailments. Besides, bioactive compounds identified in some of the commonly used Allium sp., they are scientifically proven to contribute towards a wide range of bioactivities such as antioxidant, antimicrobial, anti-inflammatory, antidiabetic, anticancer, anti-

R. Bhat (*) ERA-Chair for Food (By-) Products Valorisation Technologies (VALORTECH), Estonian University of Life Sciences, Tartu, Estonia e-mail: [email protected]; [email protected]

© Springer Nature Switzerland AG 2021 277 H. N. Murthy, K. Y. Paek (eds.), Bioactive Compounds in Underutilized and Legumes, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-57415-4_17 278 R. Bhat

hypercholesterolemic activities and much more. In the present chapter, attempts have been made to identify and report on some of the popular, widely consumed, and scientifically proven bioactivities of plants belonging to Allium species.

Keywords Allium species · Bioactivity · Bioactive compounds · · Phytochemicals · Toxicity

1 Introduction

Nutraceutically valued plant-based food offers wide prospective to provide health benefits with a natural approach. Effective utilization of traditionally recognized agri-food produce (e.g. herbs and spices) not only supports reduction in the costs incurred for health care but can also be a potential source of revenue for farming communities. Among a wide array of herbs traditionally used for culinary and therapeutic uses, plants belonging to Allium sp. command high value. Allium species comprises of plants which serve the purpose either as an ornamental, as a culinary ingredient, or as a traditional therapeutic agent, routinely used in traditional herbal drug preparations. Nevertheless, since time immemorial, edible plant parts of Allium sp. have been used in cooking as a flavoring agent/spice or are consumed raw (as salads) or extracted with solvents (mainly water) for medicinal purposes. Being natural, majority of the edible plants of Allium sp. are safe for consumption without any undue toxicity exhibited in humans. Plants belonging to Allium sp. are com- monly referred to as “ crops” or as “bulb vegetables.” In traditional medicines, herbal formulations prepared from majority of the Allium sp. have been used to treat or manage common flu, cold, cough, asthma, headache, stomachache, and arthritis. Besides being abundant in nutrition, this group of plants is also high in bioactive compounds and exhibits rich bioactivity (e.g. antioxidant, antimicrobial, anticancer, anti-cholesterolemic activity). Some of the common and popular plants belonging to Allium sp. include , , Welsh onion, Chinese onion, (wild garlic, white garlic, and rosy garlic), , wild leeks, , and others. In the present chapter, attempt has been made to identify and report on some of the popular, widely consumed, and scientifically proven bioactivities of plants belonging to Allium sp.

2 Botanical Distribution and Bioactive Compounds

The distribution of plants of Allium sp. is covered under family and sub-family /Alliaceae. Previously, this group of plants was placed under family Liliaceae. The plants belonging to this species extensively grow in a varied range of temperatures (temperate, tropical, and subtropical conditions). It is broadly considered that there might be nearly 800–900 species of plants belonging to Allium. However, onion (Allium cepa), Welsh onion (Allium fistulosum), Chinese onion 14 Bioactive Compounds of Allium Species 279

(), or the Egyptian walking onion (A. cepa var. viviparum/ proliferum), garlic (Allium sativum var. ophioscorodon and var. sativum), leeks (), chives (Allium schoenoprasum), and shallots (Allium hirtifolium) remain as the most widely consumed species. In Fig. 1, a pictorial representation of some of the popular plants of Allium sp. is shown. Besides, there are wildly growing species without much commercial values such as Allium altaicum, Allium roylei, , and Allium pskemense. Some of the other species are reported to have presence of high amounts of bioactive compounds exhibiting good bioactivity, and these include Allium ascalonicum, Allium autumnale, (var. porrum), Allium fistulosum, Allium hirtifolium (), Allium jesdianum, A. melanantherum, A. flavum, , , Allium schoenoprasum, and Allium thunbergii. Majority of the plants belonging to Allium sp. are perennial. Further, depending on the species, the edible portion remains either single or clustered bulbs, flowers, leaves, stem, and/or stalks. The size of the bulbs and leaves varies depending on the plant types. The plants generally have a taproot system and grow up to a height of 120–150 cm [1]. In some species, the height recorded is as low as 5–10 cm. Further, the flowers are produced on the upper part of leafless stalk and represent the form of an . In general, majority of the Allium sp. plants contain bioactive phytochem- icals such as sulfur (organosulfur compounds), alliin, alliinase, along with polyphenols, quercetin, tannins, flavonoids, gallic acid, ferulic acids, cinnamic acid, N-caffeoyltyramine, carotenoids, anthocyanins, polysulfanes, alkaloids, saponins, vitamins (B1, B2, C, and E), selenium, organoselenium, fructo-oligosaccharides, and chlorophyll [2–6].

Fig. 1 Pictorial representation of some popular plants of Allium sp. (a) onion; (b) green onion; (c) tree onion; (d) altai onion; (e) ; (f) wild 280 R. Bhat

Besides, soluble dietary fibers such as fructans and fructosyl are present in ample amounts too. Nevertheless, most of the edible bulbs have a unique and a character- istic intense sulfurous aroma (odor). Henceforth, relationship of sulfur compounds in Allium sp. imparting unique flavor quality has been well established [7–9]. On the other hand, there are black and black garlic bulbs that possess a distinctive odor and are less pungent compared to fresh ones. This is owed to decreased levels of organosulfur compounds and nitrogen oxides during processing stages [9–11]. Recently, hairy garlic () which is widely consumed as a spice in the Mediterranean regions was identified to contain rich amounts of flavonoids, sulfur compounds, and phenylpropanoid derivatives and is recommended to be a good alternative for garlic (A. sativum)[12]. Bulbs of wild onions (genus Allium sect. Codonoprasum) have a mild odor and distinctive flavor and contains dimethyl disulfide and methiin (S-methyl-L-cysteine sulfoxide) as the dominant volatiles [13, 14]. In shallots, volatile compounds involved in imparting flavor were identified to be sulfides, dimethyl trisulfide, furfural, 2,5-dimethylpyrazine, and thiophenes [15]. In black garlic, presence of amino acids like leucine, isoleucine, and phenylalanine is reported [10]. Same authors observed substantial increase of amino acids during production of black garlic. Additionally, significant increase in fructose during black garlic production is also stated [11]. Further, wild leeks (Allium ampeloprasum) are reported to contain copious amounts of flavor precursor compounds as methiin and propiin [13]. The precursors of distinctive flavor and health-promoting potential of Allium sp. vegetables are linked with S-alk(en)ylcysteine sulfoxides [16, 17]. It was observed that bioactive sulfur compounds are released after their enzymatic breakdown in combination with other polyphenolic compounds imparting various bioactivities [18, 19]. In fresh garlic, S-allyl-L-cysteine sulfoxide (or the alliin) alone forms majority of the cysteine sulfoxides. Chive flowers have been reported to contain sulfur compounds like 3,5-dihydroxy-6-methyl-2,3-dihydro-4H-pyran-4-one, pro- ved to prevent colon cancer in humans [20–22]. Of late, new Allium are being developed with distinctive and sweet aroma devoid of sulfur compounds and which holds a pleasant mouth feel for consumers [23]. Fatty acid composition of edible parts of onion, garlic, and leek is reported to have linoleic (~45–50%), palmitic (~20–23%), oleic (~4–13%), and linolenic (~3–7%) acids as the major fatty acids [24]. obtained from onion seeds () was identified to contain nearly 48 compounds [25]. Further seed oil of onion and chives is reported to contain ample amount of which ranged between 25–30% and 16%, respectively [26], with linoleic acid (~44%) being the major fatty acid detected. Fatty acid analysis of chive flowers was reported to contain palmitic acid (5–17%), linoleic acid (8–14%), stearic acid (3–31%), γ-sitosterol (3– 6%), campesterol (0.3–0.6%), and fucosterol (0.3–0.5%) [21]. Further, Nehdi et al. [27] investigated wild leeks seed oil (Allium ampeloprasum) and found them to have approximately 18% of oil with major components being linoleic acid (~72%), oleic acid (~14%), and palmitic acids (~7%). Moreover, γ- and δ-tocotrienols (~80% and 52% of oil, respectively) were detected to be the main tocols in the oil. Additionally, ramp bulbs () have been described to contain ample amounts of 14 Bioactive Compounds of Allium Species 281 sulfur compounds, mainly thiosulfinate allicin in ramp bulbs [28]. Leaves of wild leeks have been reported as a good source of C, while in stem portion, the major flavonol glycosides identified were quercetin and kaempferol sophoroside glucuronide conjugates [29, 30]. In Fig. 2, structure of some of the bioactive compounds isolated from Allium species is provided.

3 Bioactivity

In general, bioactivities exhibited by plants belonging to Allium sp. include antioxidant, anti-flu, antibacterial, antiviral, anti-asthmatic, antidiabetic, antitumor, antimutagenic, antiprotozoal, antiproliferative, anti-inflammatory, and chemo-pre- ventative activities [31–45]. In the preceding text, some of the vital biological activities exhibited by various plants belonging to Allium sp. are being highlighted.

3.1 Antioxidant Activity

Studies available have indicated rich antioxidant potential of plants belonging to Allium species. A range of polyphenolic compounds and phenolic acids have been isolated, which are established antioxidant compounds. Some of the main polyphe- nolic acids identified include gallic, ferulic, p-coumaric, protocatechuic, and sinapic acids [46]. Flavonoids identified in vegetables of Allium sp. were quercetin aglycone and quercetin di-glucosides [47, 48]. In onion and garlic, bioactive flavonoids, quercetin, cyanidin, and selenium have been correlated with the antioxidant activities exhibited [19, 49–52]. It is opined that onion by-products possess rich antioxidant properties, which can find potential applications as a functional food components [53]. Furthermore, Škerget et al. [54] have reported free radical scav- enging activity of skin wastes and edible pulp part of red onions. Varied skin-colored onions (red, white, and yellow from Pusa, ) have been identified for high antioxidant activities [52, 55]. Interesting reports are available wherein each of the layers in the onion bulb (red and yellow colored) had varied flavonoid contents, which contributed for the observed antioxidant activity [56]. Onion essential oil has also been shown to have antioxidant potential. Effectiveness of onion oil to minimize oxidative damage produced in rats (via nicotine) was comparable with [57]. Onion oil extracted with supercritical CO2 has been demonstrated to show antioxidant properties [58]. Accordingly, results of this study for ABTS+ and DPPH metal chelating assay indicated IC50 to be 0.67, 0.63, and 0.51 mg/ml, respectively. Rich antioxidant potential of leaves, stalk, and bulb of chives is described by Stajner et al. [59]. Moreover, Persian shallot (A. hirtifolium) is presented to exhibit free radicals scavenging/antioxidant activity, and this was owed to the presence of high polyphenolic contents [60]. Further, spring onion (A. ascalonicum L.) is also shown to exhibit rich antioxidant activities [61, 62]. On studying the antioxidant effects of garlic and aged garlic extracts, high polyphenolic content was recorded when compared to raw and heated garlic extracts [63]. With regard to chives, antioxidant 282

Fig. 2 Structure of some bioactive compounds isolated from Allium species: (a) alliin; (b) allicin; (c) cycloalliniin; (d) quercetin; (e) diallyl disulfide; (f) γ- glutamyl-S-allyl-L-cysteine; (g) E-ajoene; (h) methiin .Bhat R. 14 Bioactive Compounds of Allium Species 283 activity (aerial parts and bulb) has been correlated to the presence of kaempferol, quercetin, dl-α-tocopherol, sulfur, and polyphenolic compounds [64–66].

3.2 Anticancer Activity

The majority of studies undertaken on antitumor/anticancer activities in Allium sp. have focused mainly on onion and garlic. Regular consumption of onion and garlic is reported to minimize occurrence of esophageal, breast, colon, and prostate cancers. Organosulfur compounds and allicin have been linked with providing protective effects against many cancer cell lines [67–72]. Regular consumption of onion is related to significant reduction in the occurrence and risks associated with endome- trial, cervical, stomach, and colorectal cancers [42, 73–76]. The mechanism of action is related to the presence of flavonoids, quercetin, polyphenols, and organosulfur compounds that are capable of constraining tumor cells and inhibition of enzymes such as protein tyrosine kinases and fatty acid synthase along with alteration of phase II detoxifying enzymes [77–79]. Further, consumption of garlic on daily basis is reported to show reduction in gastric cancer [80], and this type of anticancer effect has been correlated to inhibition of nitrosamines [81]. Allicin’s role in interference with tumor angiogenesis and anti-apoptotic proteins is well established [82, 83]. Induction of apoptosis by activation of proapoptotic “Bax molecule” in ovarian cancer cell lines is documented for allicin [84]. Restriction of leukemia cell lines via bioactive compound ajoenea derivative of allicin is described [85, 86]. Nevertheless, crushing of garlic cloves prior to cooking is reported to retain their anticancer properties [87]. Cytotoxic potential against various cancer cell lines by saponins derived from A. porrum is documented [88, 89]. Chinese chive (A. tuberosum) has been confirmed to impart anti-inflammatory and anticancer effects [90]. In addition, chive flowers have been proved to exhibit anti-proliferative and antitumor activities in HaCaT cancer cells. Antitumor potential against Ehrlich carcinoma in mice by aqueous extracts of chive (Allium schoenoprasum) leaves is reported by Shirshova et al. [91]. Anticancer activity against human colon cancer cell lines by chives extract is also reported [92]. Further, Ismail et al. [93] have confirmed Persian shallot (A. hirtifolium) to exhibit effective anticancerous activity. Azadi et al. [94] recorded inhibition of HeLa and MCF7 cancer cells in solvent extracts (chloroform and water) of Persian shallot in mouse used as animal model. In another study, methanolic extract of A. jesdianum was reported to exhibit cytotoxic effect and inhibition of HeLa and K562 cell lines [95]. The mechanism is correlated to the presence of polyphenolic compounds and chive-derived glycolipids [96]. Chive flowers containing sulfur compound such as 3,5-dihydroxy-6-methyl-2,3-dihydro-4H-pyran-4-one has been proved to prevent colon cancer in human cell lines [20–22]. Dry and fresh spring onion (A. ascalonicum/shallot) has been reported to be a potential resourceful material effective against HepG2 cancer cell line [37]. Efficiency of shallot plants as a potential candidate for developing novel anticancer drugs is specified by Abdelrahman et al. [97]. Welsh onion (A. fistulosum)is 284 R. Bhat quantified to exert DNA protective effects against genotoxic materials and showed anticancer activities [98]. Aerial parts of methanolic extract of wild edible onion A. flavum exhibited anti-proliferative activities against human colorectal carcinoma, breast adenocarcinoma, and cervix epithelioid carcinoma [99–101]. These plants contain high amounts of aglycones, polyphenols, quercetin, and flavonoids capable of imparting high antioxidant and cytotoxic activities. Besides, methanolic extract of A. cornutum was proved to exhibit genotoxic effects and inhibit cancer cells [32]. Besides, methanolic extract of Egyptian Allium kurrat is shown to impart cytotoxic and antitumor effects against the HepG2 and Caco-2 cancer cell lines [102]. Further, Isbilen et al. [34] have reported anticancer potential of A. autumnale extracts against breast cell lines (MCF-7 and MDA-MB-231).

3.3 Antimicrobial Activity

Antimicrobial effects imparted by Allium species have been well documented [40, 103–105]. The presence of various bioactive compounds is recognized to contribute against human bacterial and viral pathogens. Thiosulfinates present in onion, garlic, ramp, and other Allium species are documented to impart antimicrobial activities [106–109]. Thiosulfinate analogues of allicin are also reported to impart rich anti- microbial activities against Gram-positive and Gram-negative bacteria, fungi, and virus [110]. Effective use of shallots as a potential antimicrobial agent to treat dermatomycosis, as an antifungal agent (to be used as a possible alternative for chemical-based antifungal agents), and as a potential anti-candida agent to treat chronic candidiasis is reported by many researchers [111–113]. Influenza A virus inhibitory activities of fructan obtained from Welsh onion (A. fistulosum) has been established in animal models [114]. Antiviral activities of shallots, garlic, onions, leeks, and green onions extract against adenovirus were investigated by Chen et al. [115]. Results of this study revealed shallots to exhibit highest antiviral activity for both ADV41 and ADV3, followed by garlic and onions. Freshly prepared garlic extract is reported to have high anti-candida activity compared to extracts prepared using dried . Water extract of A. tripedale, a wild onion species was highly effective against Candida sp. infection [116]. Methanolic and water extracts of Persian shallot (A. hirtifolium) is reported to exhibit antimicrobial properties [40, 103]. Further, chive essential oil is reported to possess antimicrobial activities. Sulfur compounds (diallyl disulfide, diallyl tri- sulfide, and diallyl tetrasulfide) in chive oil offers bactericidal activity [117]. Going ahead, inhibitory activity of chives essential oil against food-borne pathogenic bacteria such as Bacillus cereus, Campylobacter jejuni, Staphylococcus aureus, etc. is reported by Mnayer et al. [66]. Significant reduction in pathogenic E. coli bacteria with a corresponding increase in Lactobacillus and Streptococcus sp. was established in onion-fed broilers [118, 119]. Further, antimicrobial effects of A. schoenoprasum extracts (water and alcoholic) on bacterial pathogens have been described [120]. Phytochemicals in A. sativum extract were used for CuO nanopar- ticle synthesis, which showed antimicrobial activity, and this was considered 14 Bioactive Compounds of Allium Species 285 effective against bacteria as well as fungi [121]. Recently, by employing in silico method, 11 compounds from onion oil (Allium cepa) were evaluated for their binding efficiency with selected proteins of dengue virus. Results showed hexa- decanoic acid (and compound K) to be having high binding affinity for the selected proteins and is recommended to be used as an efficient target drug to treat dengue virus [122]. Recently, use of Allium sativum as a preventive measure against COVID-19 infection to enhance the immune system as well as to suppress pro- inflammatory cytokine production is also being reported [123].

3.4 Antihyperlipidemic/Anti-hypercholesterolemic Activity

Various plants of Allium sp. are well established for their active role played in reducing cholesterol levels under in vitro and in vivo conditions. Investigating on effect of garlic in chicken hepatocytes, Qureshi et al. [124] have reported inhibition of fatty acid biosynthesis in liver enzymes as well as cholesterol. Antihyperlipidemic effects of onion peels are reported in animal models [125]. Further, in STZ-induced diabetic rats, Baragob et al. [126] have reported antihyperlipidemic effects of ethanolic extracts of onion. Results of this study revealed significant reductions in the serum total choles- terol, triglycerides, and the LDL or the bad cholesterol within insulin-treated groups. Inhibition of cholesterol synthesis by constraining 3-hydroxy-3-methyl-glutaryl-coen- zyme-A reductase via organosulfur compounds is reported [127]. Cardioprotective role via reduction in blood pressure, vasodilator, smooth muscle relaxant, and hypo- tensive potential of allicin and ajoene, obtained from garlic, is confirmed [128]. Cholesterol-lowering effects are also attributed to steroidal saponins (e.g., in garlic), wherein inhibition of cholesterol absorption and metabolism is regulated [129]. Improved vasodilatation, reduction in bad cholesterol, and suppression of cholesterol biosynthesis are reported for many of the Allium sp. [130, 131]. Reports on black garlic have indicated reduction in blood lipid parameters [132]. Significant effects imparted by garlic in management of dyslipidemia, hypertension, and protection against cardiovascular risk factors are also well established [133–135].

3.5 Other Bioactivities

Anti-inflammatory activities of A. jesdianum (an onion species mainly grown in ) with unconfirmed mechanism are reported [136]. Anti-inflammatory properties 2-[(methylthio)methyldithio]pyridine N-oxide compound isolated from Persian shal- lot have been confirmed by Krejcova et al. [137]. Anti-inflammatory properties of extract obtained from chive leaves against turpentine oil-induced inflammation in rat model are documented by Parvu et al. [138]. Antihypertensive activity of chives bulb extract was confirmed via in vivo studies undertaken in Wistar rats [139]. Anti-obesity effects/ability to manage adipogenesis by onion peel extract possessing high quercetin contents is validated [140–142]. Aqueous extract of root was investigated for their effectiveness on adipogenesis in 3T3-L1 cells and 286 R. Bhat high- diet-induced obese mice models [143]. Results of this study revealed extracts to augment metabolic alteration by altering the gene expression levels are involved in adipogenesis, lipogenesis, and lipolysis. Antiplatelet activity of Allium sp. is reported (mainly for garlic) and is related with pyruvates produced by alliinase on crushing [144–146]. Human platelet anti- aggregation activity is reported in leeks, and the activity was attributed to isolated steroidal saponin and flavonoids [147]. In case of garlic cloves, to retain antiplatelet activity and minimize decline in thiosulfinate contents, it is advised to crush the cloves prior to use [144]. Combination of garlic and onion showed significant decrease in liver steatosis, serum liver enzymes, and lipid peroxidation. Antithrombotic potential is reported for ajoene obtained from onions [148]. Anthelmintic activity of chives and onion powder revealed decrease in worm counts in mice intestine [149]. Protective role of extract prepared from shallot is reported to be effective against CsA-induced nephrotoxicity in rat models [150]. Angiogenesis disease disorder preventive role of shallots is well documented [151]. Regarding leeks, immune-stimulating role of two isolated pectic polysaccharides (galacturonic and glucuronic acid) is documented [152]. Regular intake of leek (Allium ampeloprasum) was found to improve sexual impotency [153, 154]. Besides, administration of leeks over a month is showed to be useful in the management of diabetes mellitus too [155]. Effects of Allium mongolicum Regel on constipation were studied in mice model by Chen et al. [156]. Results of this study revealed oral administration of 50% ethanolic extract to significantly enhance the luminal side water content as well as regulate intestinal movement rhythm to normalize the stool. This effect was contributed to the presence of three major flavonoids present in A. mongolicum. Antiallergic activity of shallot (Allium ascalonicum) extract was investigated by Arpornchayanon et al. [157]. Improvement of posttreatment visual analog scores of overall symptoms after 4 weeks of treatment was observed among 63% of patients in shallot group and 38% patients in control group. Edible plants of Allium sp. as a potential source of nutrition and as a poultry feed additive have been reviewed recently [158], thus opening up a new phase of research avenue.

4 Toxicity

In majority of the instances, toxicity is linked with inappropriate consumption or with wrong identity of plants considered to belong to edible Allium species. For example, mistaken identity for wild garlic () had led to accidental poisoning (misidentity with Autumn crocus or the ). The patient who had consumed this had showed mild gastrointestinal symptoms followed by agranulocytosis, paraparesis, and delirium [159]. Death camas (Toxicoscordion venenosum), a plant looking like Allium sp., is considered as highly poisonous. However, these plants are devoid of the unique odor of garlic or onion [160]. Further there are ornamental onions ( or Allium procerum), which have pink- to purple-colored flowers with garlic onion odor, but are non-edible. These 14 Bioactive Compounds of Allium Species 287 plants grow naturally in hilly regions of Himalayas and can be mildly poisonous if not properly processed and cooked. Reports are available wherein some of the Allium species have led to toxicity in domesticated animals like cattle, horse, sheep, and dogs [161–165]. Onion and garlic poisoning via oxidizing sulfur-containing compounds is also being documented [166]. Onion stimulated hemolytic anaemia from allyl-propylisulfide and di-pro- pyl-disulfide is well-defined [165, 167]. Formation of Heinz body in erythrocytes leading to hemolytic anemia in dogs is reported on intake of boiled onions [168]. However, reports available on toxicity induced in humans still remain scarce.

5 Conclusions

Plants belonging to Allium species have tremendous potential to be used in food and pharmaceutical applications. Majority of the popular plants have been proved to have traditional values and have been used over centuries for many of the culinary and medicinal purposes. With a wide range of bioactivity exhibited by a range of phytochemicals isolated and identified, definitely there is ample scope for future innovations to be undertaken on the use of natural plant-based bioactive compounds from Allium sp. over those of chemically synthesized ones. Though only few selected plant species of Allium has been studied, it is worth to explore the potential of other wild and underutilized species too. In this regard, research focus needs to be initiated to collect, preserve, and assess the germplasm of superior genotypes to study bioactive compounds of interest. In majority of the instances, studies under- taken on bioactivity still remains scattered. Hence, research efforts need to be initiated to undertake in vitro and in vivo studies toward establishing the bioactive potential of various edible plants of Allium sp. On the other note, modern-day green processing methods (e.g. supercritical CO2 extraction, microwaves, ultra- sound, etc.) can be explored for better extraction of bioactive compounds. Besides, biotechnological tools such as metabolic engineering, omics data, tissue culture, and others can be explored for better understanding of the therapeutic potential of plants belonging to Allium sp. Nevertheless, going with the present-day trend, efforts need to be initiated to effectively and efficiently valorize the wastes and by-products (e.g. onion and garlic skin, stem, stalk, and other wastes) which are envisaged to encom- pass rich amounts of bioactive compounds of economic importance.

Acknowledgments The theme of this chapter is based on ongoing project VALORTECH, which has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 810630.

References

1. Peters R (2018) Seed production in onions and some other Allium species. In: Onions and allied crops, vol 1. CRC Press, Milton, pp 161–176 288 R. Bhat

2. Banerjee SK, Maulik SK (2002) Effect of garlic on cardiovascular disorders: a review. Nutr J 1:4 3. Borek C (2001) Antioxidant health effects of aged garlic extract. J Nutr 131:1010–1015 4. Ernst MK, Chatterton NJ, Harrison PA, Matitschka G (1998) Characterization of fructan oligomers from species of the genus Allium L. J Plant Physiol 153:53–60 5. Stajner D, Mili N, Canadanovi-Brunet J, Kapor A, Stajner M, Popovi BM (2006) Exploring Allium species as a source of potential medicinal agents. Phytother Res 20:581–584 6. Vaughan JG, Geissler CA (2009) The new Oxford book of food plants. Oxford Press, Oxford, p 188 7. Randle WM, Lancaster JE (2002) Sulphur compounds in in relation to flavor quality. In: Rabinowitch H-D, Currah L (eds) Allium crop science: recent advances. CABI Publishing, Wallingford, p 330. https://doi.org/10.1079/9780851995106.0329 8. Shouk R, Abdou A, Shetty K, Sarkar D, Eid AH (2014) Mechanisms underlying the antihypertensive effects of garlic bioactives. Nutr Res 34:106–115 9. Wang D, Liu P, Ma Y, Wang Y, Zhao X (2015) Discrimination of black onion flavor using the electronic nose. In: 6th International conference on manufacturing science and engineering, pp 414–417 10. Kimura S, Tung YC, Pan MH, Su NW, Lai YJ, Cheng KC (2017) Black garlic: a critical review of its production, bioactivity, and application. J Food Drug Anal 25:62–70 11. Martínez-Casas L, Lage-Yusty M, López-Hernández J (2017) Changes in the aromatic profile, , and bioactive compounds when purple garlic is transformed into black garlic. J Agric Food Chem 65:10804–10811 12. Sut S, Maggi F, Bruno S, Badalamenti N, Quassinti L, Bramucci M, Beghelli D, Lupidi G, Dall’Acqua S (2020) Hairy garlic (Allium subhirsutum) from Sicily (Italy): LC-DAD-MSn analysis of secondary metabolites and in vitro biological properties. Molecules 25(12):2837. https://doi.org/10.3390/molecules25122837 13. Fritsch RM, Keusgen M (2006) Occurrence and taxonomic significance of cysteine sulphoxides in the genus Allium L. (Alliaceae). Phytochemistry 67:1127–1135 14. Simin N, Mitić-Ćulafić D, Pavić A, Orcic D, Nemes I, Cetojevic-Simin D, Mimica-Dukić N (2019) An overview of the biological activities of less known wild onions (genus Allium sect. Codonoprasum). Biol Serbica 41(2):57–62 15. Chyau CC, Lin YC, Mau JL (1997) Storage stability of deep-fried shallot flavoring. J Agric Food Chem 45:3211–3215 16. Kubec R, Dadáková E (2009) Chromatographic methods for determination of substituted cysteine derivatives. J Chromatogr A 41:6957–6963 17. Rose P, Whiteman M, Moore PK, Zhu YZ (2005) Bioactive S-alk(en)yl cysteine sulfoxide metabolites in the genus Allium: the chemistry of potential therapeutic agents. Nat Prod Rep 22 (3):351–368 18. Shukla Y, Kalra N (2007) Cancer chemoprevention with garlic and its constituents. Cancer Lett 247:167–181 19. Upadhyay RK (2016) Nutraceutical, pharmaceutical and therapeutic uses of Allium cepa: a review. Int J Green Pharm 10(1):46–64 20. Ban JO, Hwang IG, Kim TM, Hwang BY, Lee US, Jeong HS, Yoon YW, Kim DJ, Hong JT (2007) Anti-proliferate and pro-apoptotic effects of 2,3-dihydro-3,5-di-hydroxy-6-methyl-4H- pyranone through inactivation of NF-KB in human colon cancer cells. Arch Pharm Res 30:1455–1463 21. Grzeszczuk M, Wesolowska A, Jadczak D, Jakubowska B (2011) Nutritional value of chive edible flowers. Acta Sci Pol Hortorum Cultus 10:85–94 22. Leino ME (1992) Effect of freezing, freeze-drying, and air-drying on odor of chive characterized by headspace gas chromatography and sensory analyses. J Agric Food Chem 40:1379–1384 23. Ríos-Ríos KL, Montilla A, Olano A, Villamiel M (2019) Physicochemical changes and sensorial properties during black garlic elaboration: a review. Trends Food Sci Technol 88:459–467 14 Bioactive Compounds of Allium Species 289

24. Tsiaganis MC, Laskari K, Melissari E (2006) Fatty acid composition of Allium species lipids. J Food Compos Anal 19:620–662 25. Najjaa H, Neffati M, Zouari S et al (2007) Essential oil composition and antibacterial activity of different extracts of Allium roseum L. a North African endemic species. C R Chim 10:820–826 26. Kowalski R, Rodkiewicz T (2009) Fatty acids in oil from Allium seeds. Chem Nat Compd 45(3):409–410 27. Nehdi IA, Sbihi HM, Tan CP, Al-Resayes SI, Rashid U, Al-Misned FA, El-Serehy HA (2020) Chemical composition, oxidative stability, and antioxidant activity of Allium ampeloprasum L. (Wild Leek) seed oil. J Oleo Sci 69(5):413–421 28. Calvey EM, White KD, Matusik JE, Sha D, Block E (1998) Allium chemistry: identification of organosulfur compounds in ramp (Allium tricoccum) homogenates. Phytochemistry 49:359–364 29. Dabeek WM, Kovinich N, Walsh C, Marra MV (2019) Characterization and quantification of major flavonol glycosides in ramps (Allium tricoccum). Molecules 24:3281. https://doi.org/ 10.3390/molecules24183281 30. Zennie T, Ogzewalla D (1977) Ascorbic acid and vitamin A content of edible wild plants of and Kentucky. Econ Bot 31:76–79 31. DeLeon ER, Gao Y, Huang E, Olson KR (2016) polysulfides: H2S-and O2-inde- pendent prooxidants in buffer and antioxidants in cells. Am J Physiol Regul Integr Comp Physiol 310:1212–1225 32. FredotovićŽ, Šprung M, Soldo B, Ljubenkov I, Budić-Leto I, Bilušić T, Čikeš-Čulić V, Puizina J (2017) Chemical composition and biological activity of Allium cepa L. and Allium  cornutum (Clementi ex Visiani 1842) methanolic extracts. Molecules 22(3):448. https://doi.org/10.3390/molecules22030448 33. Guan MJ, Zhao N, Xie KQ, Zeng T (2018) Hepatoprotective effects of garlic against ethanol- induced liver injury: a mini-review. Food Chem Toxicol 111:467–473 34. Isbilen O, Rizaner N, Volkan E (2018) Anti-proliferative and cytotoxic activities of Allium autumnale PH Davis (Amaryllidaceae) on human breast cancer cell lines MCF-7 and MDA- MB-231. BMC Complement Altern Med 18:30 35. Mollica A, Zengin G, Locatelli M, Picot-Allain CMN, Mahomoodally MF (2018) Multidirectional investigations on different parts of Allium scorodoprasum L. subsp. rotundum (L.) Stearn: phenolic components, in vitro biological, and in silico propensities. Food Res Int 108:641–649 36. Oommen S, Anto RJ, Srinivas G, Karunagaran D (2004) Allicin (from garlic) induces caspase- mediated apoptosis in cancer cells. Eur J Pharmacol 485:97–103 37. Pandurangan V, Amanulla SSD, Ramanathan K (2016) Anticancer efficacy of dry and fresh Allium ascalonicum (shallot) against HepG2 cell line. Nat J Physiol Pharm Pharmacol 6:196–199 38. Park HS, Choi EJ, Lee JH, Kim GH (2013) Evaluation of Allium vegetables for anti- adipogenic, anti-cancer, and anti-inflammatory activities in vitro. J Life Sci 5:127–132 39. Rahimi-Madiseh M, Heidarian E, Kheiri S, Rafieian-Kopaei M (2017) Effect of hydroalcoholic Allium ampeloprasum extract on oxidative stress, diabetes mellitus and dyslipidemia in alloxan-induced diabetic rats. Biomed Pharmacother 86:363–367 40. Satvati SAR, Shooriabi M, Amin M, Shiezadeh F (2017) Evaluation of the antimicrobial activity of Tribulus terrestris, Allium sativum, Salvia officinalis, and Allium hirtifolium Boiss against Enterococcus faecalis. Int J Enteric Pathog 5:63–67 41. Suleria HR, Butt MS, Anjum FM, Arshad M, Khalid N (2013) Aqueous garlic extract mitigate hypercholesterolemia and hyperglycemia; rabbit experimental modelling. Ann Nutr Metab (Conf Proc) 63:271 42. Suleria HR, Butt MS, Anjum FM, Saeed F, Khalid N (2015) Onion: nature protection against physiological threats. Crit Rev Food Sci Nutr 55(1):50–66 43. Sultan MT, Buttxs MS, Qayyum MMN, Suleria HAR (2014) Immunity: plants as effective mediators. Crit Rev Food Sci Nutr 54(10):1298–1308 290 R. Bhat

44. Upadhyay RK (2017) Garlic induced apoptosis, cell cycle check points and inhibition of cancer cell proliferation. J Cancer Res 5(2):35–54 45. Yao ZH, Qin ZF,Yao XS (2016) Phytochemistry and pharmacology of Allii Macrostemonis bulbus, a traditional Chinese medicine. Chin J Nat Med 14(7):481–498 46. Parvu M, Toiu A, Vlase L, Parvu EA (2010) Determination of some polyphenolic compounds from Allium species by HPLC-UV-MS. Nat Prod Res 24:1318–1324 47. Leighton T, Ginther C, Fluss L, Harter WK, Cansado J, Notario V (1992) Molecular characterization of quercetin and quercetin glycosides in Allium vegetables: their effects on malignant cell transformation. Proc ACS Symp Ser 507:220 48. Miean KH, Mohamed S (2001) Flavonoid (myricetin, quercetin, kaempferol, luteolin, and apigenin) content of edible tropical plants. J Agric Food Chem 49:3106–3112 49. Cai Y, Luo Q, Sun M, Corke H (2004) Antioxidant activity and phenolic compounds of 112 traditional Chinese medicinal plants associated with anticancer. Life Sci 74:2157–2184 50. Marlett JA (2000) Changes in content and composition of dietary fiber in yellow onions and red delicious apples during commercial storage. J AOAC Int 83:992–996 51. Shon MY, Choi SD, Kahng GG, Nam SH, Sung NJ (2004) Antimutagenic, antioxidant and free radical scavenging activity of ethyl acetate extracts from white, yellow and red onions. Food Chem Toxicol 42:659–666 52. Singh BN, Singh B, Singh R, Prakash D, Singh D, Sarma BK, Upadhyay G, Singh HB (2009) Polyphenolics from various extracts/fractions of (Allium cepa) peel with potent antioxidant and antimutagenic activities. Food Chem Toxicol 47:1161–1167 53. Roldán E, Sánchez-Moreno C, de Ancos B, Cano MP (2008) Characterisation of onion (Allium cepa L.) by-products as food ingredients with antioxidant and antibrowning properties. Food Chem 108:907–916 54. Škerget M, Majhenič L, Bezjak M, Knez Ž (2009) Antioxidant, radical scavenging and antimicrobial activities of red onion (Allium cepa L.) skin and edible part extracts. Chem Biochem Eng Q 23:435–444 55. Nile SH, Park SW (2013) Total phenolics, antioxidant and xanthine oxidase inhibitory activity of three coloured onions (Allium cepa L.). Front Life Sci 7:224–228 56. Cheng A, Chen X, Jin Q, Wang W, Shi J, Liu Y (2013) Comparison of phenolic content and antioxidant capacity of red and yellow onions. Czech J Food Sci 31:501–508 57. Helen A, Krishnakumar K, Vijayammal PL, Augusti KT (2000) Antioxidant effect of onion oil (Allium cepa Linn) on the damages induced by nicotine in rats as compared to alpha- tocopherol. Toxicol Lett 116:61–68 58. Ye CL, Dai DH, Hu WL (2013) Antimicrobial and antioxidant activities of the essential oil from onion (Allium cepa L.). Food Control 30:48–53 59. Stajner D, Canadanovi-Brunet J, Pavlovi A (2004) Allium schoenoprasum L., as a natural antioxidant. Phytother Res 18:522–524 60. Pirbalouti AG, Ahmadzadeh Y, Malekpoor F (2015) Variation in antioxidant, and antibacterial activities and total phenolic content of the bulbs of mooseer (Allium hirtifolium Boiss). Acta Agric Slovenica 105:15–22 61. Leelarungrayub N, Rattanapanone V, Chanarat N, Gebicki JM (2006) Quantitative evaluation of the antioxidant properties of garlic and shallot preparations. Nutrition 22:266–274 62. Trakranrungsie N, Chatchawanchonteera A, Khunkitti W (2008) Ethnoveterinary study for antidermatophytic activity of Piper betle, Alpinia galanga and Allium ascalonicum extracts in vitro. Res Vet Sci 84(1):80–84 63. Park JH, Park YK, Park E (2009) Antioxidative and antigenotoxic effects of garlic (Allium sativum L.) prepared by different processing methods. Plant Foods Hum Nutr 64:244–249 64. Nuutila AM, Puupponen-Pimiä R, Aarni M, Oksman-Caldentey K (2003) Comparison of antioxidant activities of onion and garlic extracts by inhibition of lipid peroxidation and radical scavenging activity. Food Chem 81:485–493 65. Souri E, Amin G, Farsam H, Andaji S (2004) The antioxidant activity of some commonly used vegetables in Iranian diet. Fitoterapia 75:585–588 14 Bioactive Compounds of Allium Species 291

66. Mnayer D, Fabiano-Tixier A-S, Petitcolas E, Hamieh T, Nehme N, Ferrant C, Fernandez X, Chemat F (2014) Chemical composition, antibacterial and antioxidant activities of six essen- tials oils from the Alliaceae family. Molecules 19:20034–20053. https://doi.org/10.3390/ molecules191220034 67. Chen C, Pung D, Leong V, Hebbar V, Shen G, Nair S, Li W, Kong ANT (2004) Induction of detoxifying enzymes by garlic organosulfur compounds through transcription factor Nrf2: effect of chemical structure and stress signals. Free Radic Biol Med 37:1578–1590 68. Galeone C, Pelucchi C, Levi F, Negri E, Franceschi S, Talamini R, Giacosa A, La Vecchia C (2006) Onion and garlic use and human cancer. Am J Clin Nutr 84:1027–1032 69. Grudzien M, Rapak A (2018) Effect of natural compounds on NK cell activation. J Immunol Res 11:4868417. https://doi.org/10.1155/2018/4868417 70. Pan Y, Zheng YM, Ho WS (2018) Effect of quercetin glucosides from Allium extracts on HepG2, PC-3 and HT-29 cancer cell lines. Oncol Lett 15:4657–4661 71. Putnik P, Gabrić D, Roohinejad S, Barba FJ, Granato D, Mallikarjunan K, Lorenzo JM, Kovačević DB (2018) An overview of organosulfur compounds from Allium spp.: from processing and preservation to evaluation of their bioavailability, antimicrobial, and anti- inflammatory properties. Food Chem 276:680–691 72. Rose P, Moore PK, Zhu YZ (2018) Garlic and gaseous mediators. Trends Pharmacol Sci 39:624–634 73. Amy E, Amy F, Barry I, Ulrike P, Richard B et al (2007) Fruit and vegetable intake and prevalence of colorectal adenoma in a cancer screening trial. Am J Clin Nutr 86:1754–1764 74. Lai WW, Hsu SC, Chueh FS, Chen YY, Yang JS, Lin JP, Lien JC, Tsai CH, Chung JG (2013) Quercetin inhibits migration and invasion of SAS human oral cancer cells through inhibition of NF-κB and matrix metalloproteinase-2/-9 signaling pathways. Anticancer Res 33:1941–1950 75. Roy M, Mukherjee A, Sarkar R, Mukherjee S, Biswas J (2015) In search of natural remediation for cervical cancer. Anticancer Agents Med Chem 15:57–65 76. Shivappa N, Hébert JR, Zucchetto A, Montella M, Serraino D, La Vecchia C, Rossi M (2016) Dietary inflammatory index and endometrial cancer risk in an Italian case–control study. Br J Nutr 115:138–146 77. Sengupta A, Ghosh S, Bhattacharjee S (2004) Allium vegetables in cancer prevention: an overview. Asian Pac J Cancer Prev 5(3):237–245 78. Wang HC, Pao J, Lin SY, Sheen LY (2012) Molecular mechanisms of garlic-derived allyl sulfides in the inhibition of skin cancer progression. Ann N Y Acad Sci 1271(1):44–52 79. Zeng Y, Li Y, Yang J, Pu X, Du J, Yang X, Yang T, Yang S (2017) Therapeutic role of functional components in alliums for preventive chronic disease in human being. Evid Based Complement Alternat Med 3:13. https://doi.org/10.1155/2017/9402849 80. Li Z, Ying X, Shan F, Ji J (2018) The association of garlic with Helicobacter pylori infection and gastric cancer risk: a systematic review and meta-analysis. Helicobacter 23:12532 81. Atanasova-Goranova V, Dimova P, Pevicharova G (1997) Effect of food products on endogenous generation of n-nitrosamines in rats. Br J Nutr 78:335–345 82. Bagul M, Kakumanu S, Wilson TA (2015) Crude garlic extract inhibits cell proliferation and induces cell cycle arrest and apoptosis of cancer cells in vitro. J Med Food 18:731–737 83. Londhe V (2011) Role of garlic (Allium sativum) in various diseases-an overview. J Pharm Res Opin 1:129–134 84. Xu L, Yu J, Zhai D, Zhang D, Shen W et al (2014) Role of JNK activation and mitochondrial Bax translocation in allicin-induced apoptosis in human ovarian cancer SKOV3 cells. Evid Based Complement Alternat Med Article ID 378684, 1–6. https://doi.org/10.1155/ 2014/378684 85. Saedi TA, Md Noor S, Ismail P, Othman F (2014) The effects of herbs and fruits on leukaemia. Evid Based Complement Alternat Med Article ID 494136, 1–8. https://doi.org/10.1155/2014/ 494136 86. Thomson M, Ali M (2003) Garlic [Allium sativum]: a review of its potential use as an anti-cancer agent. Curr Cancer Drug Target 3(1):67–81 292 R. Bhat

87. Song K, Milner JA (2001) The influence of heating on the anticancer properties of garlic. J Nutr 131:1054–1057 88. Fattorusso E, Lanzotti V, Taglialatela-Scafati O, Di Rosa M, Ianaro A (2000) Cytotoxic saponins from bulbs of Allium porrum L. J Agric Food Chem 48:3455–3462 89. Shaikh A, Shrivastava B, Apte K, Navale S (2016) Medicinal plants as potential source of anticancer agents: a review. J Pharmacogn Phytochem 5:291–295 90. Park KW, Kim SY, Jeong IY, Byun MW, Park KH, Yamada K, Seo KI (2007) Cytotoxic and antitumor activities of thiosulfinates from Allium tuberosum L. J Agric Food Chem 55:7957–7961 91. Shirshova TI, Beshlei IV, Deryagina VP (2013) Chemical composition of Allium schoenoprasum leaves and inhibitory effect of their extract on tumor growth in mice. Pharm Chem J 46:672–675 92. Timité G, Mitaine-Offer AC, Miyamoto T, Tanaka C, Mirjolet JF, Duchamp O, Lacaille- Dubois MA (2013) Structure and cytotoxicity of steroidal glycosides from Allium schoenoprasum. Phytochemistry 88:61–66 93. Ismail S, Jalilian FA, Talebpour AH, Zargar M, Shameli K, Sekawi Z, Jahanshiri F (2013) Chemical composition and antibacterial and cytotoxic activities of Allium hirtifolium Boiss. Biomed Res Int 25:1–9 94. Azadi HG, Ghaffari SM, Riazi GH, Ahmadian S, Vahedi F (2008) Antiproliferative activity of chloroformic extract of Persian shallot, Allium hirtifolium, on tumor cell lines. Cytotechnology 56:179–185 95. Dorosti N, Zarabi S, Ahmadi S, Rostami R, Pour MR (2017) Evaluation of anticancer activity of methanolic extract of Allium Jesdianum and Nectaroscordeum coelzi against HeLa and K562 cell lines. Yafteh 19:31–41 96. Kucekova Z, Mlcek J, Humpolicek P, Rop O, Valasek P, Saha P (2011) Phenolic compounds from Allium schoenoprasum, Tragopogon pratensis and Rumex acetosa and their anti- proliferative effects. Molecules 16:9207–9217 97. Abdelrahman M, Mahmoud HYAH, El-Sayed M, Tanaka S, Tran LS (2017) Isolation and characterization of Cepa2, a natural alliospiroside A, from shallot (Allium cepa L. Aggregatum group) with anticancer activity. Plant Physiol Biochem 116:167–173 98. Smith C, Lombard KA, Peffley EB, Liu W (2016) Genetic analysis of quercetin in onion (Allium cepa L.) ‘Lady Raider’. Tex J Agric Nat Resour 16:24–28 99. Simin N, Orcic D, Cetojevic-Simin D, Mimica-Dukic N, Anackov G, Beara I, Mitic-CulaficD, Bozin B (2013) Phenolic profile, antioxidant, anti-inflammatory and cytotoxic activities of small (Allium flavum L. subsp. flavum, Alliaceae). LWT Food Sci Technol 54:139–146 100. Rezgui A, Mitaine-Offer AC, Paululat T, Delemasure S, Dutartre P, Lacaille-Dubois MA (2014) Cytotoxic steroidal glycosides from Allium flavum. Fitoterapia 93:121–125 101. Mitić-Ćulafić D, Nikolic B, Simin N, Jasnic N, Cetojevic-Simin D, Krstic M, Knezevic- Vukcevic J (2016) Effect of Allium flavum L. and Allium melanantherum Panc. extracts on oxidative DNA damage and antioxidative enzymes superoxide dismutase and catalase. Plant Foods Hum Nutr 71:28–34 102. Abdel-Hady H, El-Sayed MM, Abde-Gawad MM, El-Wakil EA, Abdel-Hameed ESS, Abdel- Lateef EES (2018) LC-ESI-MS analysis, antitumor and antioxidant activities of methanolic extract of Egyptian Allium kurrat. J Appl Pharm Sci 8:85–92 103. Ashrafi F, Akhavan Sepahi A, Kazemzadeh A (2010) Effect of aqueous extract of shallot (Allium ascalonicum) on inhibition of growth of Pseudomonas aeruginosa. Iran J Pharm Res 3 (2):71–71 104. Sharifi-Rad J, Mnayer D, Tabanell G, Stojanović-Radić Z, Sharifi-Rad M, Yousaf Z, Vallone L, Setzer WN, Iriti M (2016) Plants of the genus Allium as antibacterial agents: from tradition to pharmacy. Cell Mol Biol 62:57–68 105. Snoussi M, Trabelsi N, Dehmeni A, Benzekri R, Bouslama L, Hajlaoui B, Al-sieni A, Papetti A (2016) Phytochemical analysis, antimicrobial and antioxidant activities of Allium roseum var. odoratissimum (Desf.) Coss extracts. Ind Crop Prod 89:533–542 14 Bioactive Compounds of Allium Species 293

106. Calvey EM, Matusik JE, White KD, DeOrazio R, Sha D, Block E (1997) Allium chemistry: supercritical fluid extraction and LCÀAPCIÀMS of thiosulfinates and related compounds from homogenates of garlic, onion, and ramp. Identification in garlic, ramp, and synthesis of 1- propanesulfinothioic acid S-allyl ester. J Agri Food Chem 45:4406–4413 107. Khar A, Banerjee K, Jadhav MR, Lawande KE (2011) Evaluation of garlic ecotypes for allicin and other allyl thiosulphinates. Food Chem 128:988–996 108. Mylona K, Garcia-Cela E, Sulyok M, Medina A, Magan N (2019) Influence of two garlic- derived compounds, propyl propane thiosulfonate (PTS) and propyl propane thiosulfinate (PTSO), on growth and mycotoxin production by Fusarium species in vitro and in stored cereals. Toxins 11:495. https://doi.org/10.3390/toxins11090495 109. Sterling SJ, Eagling RD (2001) Agronomic and allicin yield of Australian grown garlic. Acta Hortic 555:63–73 110. Leontiev R, Hohaus N, Jacob C, Gruhlke MCH, Slusarenko AJ (2018) A comparison of the antibacterial and antifungal activities of thiosulfinate analogues of allicin. Sci Rep 8:6763. https://doi.org/10.1038/s41598-018-25154-9 111. Amin M, Montazeri EA, Mashhadizadeh MA, Sheikh AF (2009) Characterization of shallot, an antimicrobial extract of Allium ascalonicum. Pak J Med Sci 25:948–952 112. Nasiri Kashani MJ, Mehraban F, Motevalian M, Yazdanparast SA, Fateh RA (2009) In vitro antifungal activity extract and its comparison with miconazole. Qom Univ Med Sci J 3:13–18 113. Falahati M, Fateh R, Sharifinia S (2011) Anti-candidal effect of shallot against chronic candidiasis. Iran J Pharmacol Ther 10:49–51 114. Lee JB, Miyake S, Umetsu R, Hayashi K, Chijimatsu T, Hayashi T (2012) Anti-influenza A virus effects of fructan from Welsh onion (Allium fistulosum L.). Food Chem 134:2164–2168 115. Chen C-H, Chou T-W, Cheng L-H, Ho C-W (2011) In vitro anti-adenoviral activity of five Allium plants. J Taiwan Inst Chem Eng 42(2):228–232 116. Shirani M, Samimi A, Kalantari H, Madani M, Zanganeh AK (2017) Chemical composition and antifungal effect of hydroalcoholic extract of Allium tripedale (Tvautv) against Candida species. Curr Med Mycol 3(1):6–12 117. Rattanachaikunsopon P, Phumkhachorn P (2008) Diallyl sulfide content and antimicrobial activity against food-borne pathogenic bacteria of chives (Allium schoenoprasum). Biosci Biotechnol Biochem 72:2987–2991 118. Goodarzi M, Nanekarani S, Landy N (2014) Effect of dietary supplementation with onion (Allium cepa L.) on performance, carcass traits and intestinal microflora composition in broiler chickens. Asian Pac J Trop Dis 4:297–301 119. Shargh MS, Dastar B, Zerehdaran S, Khomeiri M, Moradi A (2012) Effects of using plant extracts and a probiotic on performance, intestinal morphology, and microflora population in broilers. J Appl Poult Res 21:201–208 120. Ghasemian A, Mostafavi S, Kh S (2018) Antimicrobial effects of aqueous and alcoholic extracts of Allium schoenoprasum on some bacterial pathogens. Infect Epidemiol Microbiol 4:1–5 121. Velsankara K, Aswin Kumara RM, Preethia R, Muthulakshmib V, Sudhahara S (2020) Green synthesis of CuO nanoparticles via Allium sativum extract and its characterizations on anti- microbial, antioxidant, antilarvicidal activities. J Environ Chem Eng 8:104123. https://doi.org/ 10.1016/j.jece.2020.104123 122. Tataringa G, Spac A, Sathyamurthy B, Zbancioc A (2020) In silico studies on some dengue viral proteins with selected Allium cepa oil constituents from Romanian source. Farmacia 68 (1):48–55 123. Donma MM, Donma O (2020) The effects of Allium sativum on immunity within the scope of COVID-19 infection. Med Hypotheses 144:109934. https://doi.org/10.1016/j. mehy.2020.109934 124. Qureshi AA, Abuirmeileh N, Din ZZ, Elson CE, Burger WC (1983) Inhibition of cholesterol and fatty acid biosynthesis in liver enzymes and chicken hepatocytes by polar fractions of garlic. Lipids 18:343–348 125. Kim HY (2007) Effects of onion (Allium cepa) skin extract on pancreatic lipase and body weight-related parameters. Food Sci Biotechnol 16:434–438 294 R. Bhat

126. Baragob AE, Al-Wabel NA, Ahmed NA, Babiker MF, Abdalkarim AS, Elboshra MI (2015) Study to investigate the pancreatic regeneration and evaluation of the antidiabetic and anti- hyperlipidemic potential of aerial parts of Allium cepa. Biochem Biotechnol Res 3:19–29 127. Gebhardt R, Beck H (1996) Differential inhibitory effects of garlic-derived organosulfur com- pounds on cholesterol biosynthesis in primary rat hepatocyte cultures. Lipids 31:1269–1276 128. Martin N, Bardisa L, Pantoja C, Román R, Vargas M (1992) Experimental cardiovascular depressant effects of garlic (Allium sativum) dialysate. J Ethnopharmacol 37:145–149 129. Sobolewska D, Michalska K, Podolak I, Grabowska K (2016) Steroidal saponins from the genus Allium. Phytochem Rev 15:1–35 130. Rahman MS (2007) Allicin and other functional active components in garlic: health benefits and bioavailability. Int J Food Prop 10:245–268 131. Kumar R, Chhatwal S, Arora S, Sharma S, Singh J, Singh N, Bhandari V, Khurana A (2013) Antihyperglycemic, antihyperlipidemic, anti-inflammatory and adenosine deaminase-lower- ing effects of garlic in patients with type 2 diabetes mellitus with obesity. Diabetes Metab Syndr Obes 6:49–56 132. Jung ES, Park SH, Choi EK, Ryu BH, Park BH, Kim DS, Kim YG, Chae SW (2014) Reduction of blood lipid parameters by a 12-wk supplementation of aged black garlic: a randomized controlled trial. Nutrition 30:1034–1039 133. Kwak JS, Kim JY, Paek JE et al (2014) Garlic powder intake and cardiovascular risk factors: a meta-analysis of randomized controlled clinical trials. Nutr Res Pract 8(6):644–654 134. Ried K (2016) Garlic lowers blood pressure in hypertensive individuals, regulates serum cholesterol, and stimulates immunity: an updated meta-analysis and review. J Nutr 146 (2):389S–396S. https://doi.org/10.3945/jn.114.202192 135. Xiong XJ, Wang PQ, Li SJ, Li XK, Zhang YQ, Wang J (2015) Garlic for hypertension: a systematic review and meta-analysis of randomized controlled trials. Phytomedicine 22 (3):352–361. https://doi.org/10.1016/j.phymed.2014.12.013 136. Khaksarian M, Gholami E, Alipour M, Sabooteh T, Asadi-Samani M (2017) Investigation of the effects of the essence and extract of Allium jesdianum on the activity of COX-1 and COX-2 enzymes. Int J Adv Biotechnol Res 8:1095–1101 137. Krejcova P, Kucerova P, Stafford GI, Jager AK, Kubec R (2014) Antiinflammatory and neurological activity of and related sulfur-containing pyridine N-oxides from Persian shallot (Allium stipitatum). J Ethnopharmacol 154:176–182 138. Parvu AE, Parvu M, Vlase L, Miclea P, Mot AC, Silaghi-Dumitrescu R (2014) Anti-inflam- matory effects of Allium schoenoprasum L. leaves. J Physiol Pharmacol 65:309–315 139. Amalia L, Sukandar EY, Roesli RMA, Sigit JI (2008) The effect of ethanol extract of kucai (Allium schoenoprasum L.) bulbs on serum nitric oxide level in male Wistar rats. Int J Pharmacol 4:487–491 140. Bae CR, Park YK, Cha YS (2014) Quercetin-rich onion peel extract suppresses adipogenesis by down-regulating adipogenic transcription factors and gene expression in 3T3-L1 adipocytes. J Sci Food Agric 94:2655–2660 141. Moon J, Do HJ, Kim OY, Shin MJ (2013) Antiobesity effects of quercetin-rich onion peel extract on the differentiation of 3T3-L1 preadipocytes and the adipogenesis in high fat-fed rats. Food Chem Toxicol 58:347–354 142. Yoshinari O, Shiojima Y, Igarashi K (2012) Anti-obesity effects of onion extract in Zucker diabetic fatty rats. Nutrients 4:1518–1526 143. Kim HJ, Lee MJ, Jang JY, Lee SH (2019) Allium hookeri root extract inhibits adipogenesis by promoting lipolysis in high fat diet-induced obese mice. Nutrients 11(10):2262. Published 2019 Sep 20. https://doi.org/10.3390/nu11102262 144. Cavagnaro PF, Camargo A, Galmarini CR, Simon PW (2007) Effect of cooking on garlic (Allium sativum L.) antiplatelet activity and thiosulfinates content. J Agric Food Chem 55:1280–1288 145. Goldman I, Kopelberg M, Debaene JP, Schwartz BS (1996) Antiplatelet activity in onion (Allium cepa L.) is sulfur dependent. Thromb Haemost 76:450–452 14 Bioactive Compounds of Allium Species 295

146. González R, Carolina S, María S, Alejandra C, Claudio G (2009) Variability of solids, organosulfur compounds, pungency and health-enhancing traits in garlic (Allium sativum L.) cultivars belonging to different ecophysiological groups. J Agric Food Chem 57:10282–10288 147. Fattorusso E, Lanzotti V, Taglialatela-Scafati O, Cicala C (2001) The flavonoids of leek, Allium porrum. Phytochemistry 57:565–569 148. Apitz-Castro R, Badimon JJ, Badimon L (1992) Effect of ajoene, the major antiplatelet compound from garlic, on platelet thrombus formation. Thromb Res 68:145–155 149. Klimpel S, Abdel-Ghaffar F, Al-Rasheid KA, Aksu G, Fischer K, Strassen B, Mehlhorn H (2011) The effects of different plant extracts on nematodes. Parasitol Res 108:1047–1054 150. Wongmekiat O, Leelarugrayub N, Thamprasert K (2008) Beneficial effect of shallot (Allium ascalonicum L.) extract on cyclosporine nephrotoxicity in rats. Food Chem Toxicol 46(5): 1844–1850 151. Seyfi P, Mostafaie A, Mansouri K, Arshadi D, Mohammadi-Motlagh HR, Kiani A (2010) In vitro and in vivo anti-angiogenesis effect of shallot (Allium ascalonicum): a heat-stable and flavonoid- rich fraction of shallot extract potently inhibits angiogenesis. Toxicol In Vitro 24:1655–1661 152. Kratchanova M, Nikolova M, Pavlova E, Yanakieva I, Kussovski V (2010) Composition and properties of biologically active pectic polysaccharides from leek (Allium porrum). J Sci Food Agric 90:2046–2051 153. Kamtchouing PG, Mbongue-Fandio TS, Dimo HL, Jasta BN (2002) Evaluation of androgenic activity of Leek extract in male rats. Asian J Androl 4:299–301 154. Morakino AO, Adeniyi OS, Arikawem AP (2008) Effects of Allium ampeloprasum on reproductive functions of the male rat. Afr J Biomed Res 2:329–339 155. Roghani M, Aghaie M (2007) The effect of Allium ampeloprasum on nociceptive response intensity in diabetic rats. J Gorgan Uni Med Sci 9:96 156. Chen Y, Ding Z, Wu Y et al (2019) Effects of Allium mongolicum Regel and its flavonoids on constipation. Biomolecules 10(1):14. Published Dec 20. https://doi.org/10.3390/biom 10010014 157. Arpornchayanon W, Klinprung S, Chansakaow S et al (2019) Antiallergic activities of shallot (Allium ascalonicum L.) and its therapeutic effects in allergic rhinitis. Asian Pac J Allergy Immunol. https://doi.org/10.12932/AP-300319-0529 158. Kothari D, Lee WD, Niu KM, Kim SK (2019) The genus Allium as poultry feed additive: a review. Animals (Basel) 9(12):1032. https://doi.org/10.3390/ani9121032 159. Galland-Decker C, Charmoy A, Jolliet P, Spertini O, Hugli O, Pantet O (2016) Progressive organ failure after ingestion of wild garlic juice. J Emerg Med 50:55–60 160. Peterson RP (1982) A field guide to edible wild plants: Eastern and Central . Houghton Mifflin, Boston 161. Aslani MR, Mohri M, Movassaghi AR (2005) Heinz body anemia associated with onion (Allium cepa) toxicosis in a flock of sheep. Comp Clin Pathol 14:118–120 162. Hutchinson TW (1977) Onions as cause of Heinz body anemia and death in cattle. Can Vet J 18:358–360 163. Munday R, Munday JS, Munday CM (2003) Comparative effects of mono-, di-, tri-, and tetrasulfides derived from plants of the Allium family: redox cycling in vitro and hemolytic activity and phase 2 enzyme induction in vivo. Free Radic Biol Med 34:1200–1211 164. Smith CH, Ellison RS (1986) Concurrent onion poisoning and haematuria in a dog. N Z Vet J 34:77–78 165. Tang X, Xia Z, Yu J (2008) An experimental study of hemolysis induced by onion (Allium cepa) poisoning in dogs. J Vet Pharmacol Ther 31(2):143–149 166. Yamato O, Kasai E, Katsura T, Takahashia S, Shiota T, Tajima M et al (2005) Heinz body hemolytic anemia with eccentrocytosis from ingestion of Chinese chive (Allium tuberosum) and garlic (Allium sativum) in a dog. J Am Anim Hosp Assoc 41(1):68–73 167. Houston DM, Myers SL (1993) A review of Heinz-body anemia in the dog induced by toxins. Vet Hum Toxicol 35:158–161 168. Yamato O, Hayashi M, Yamasaki M, Maede Y (1998) Induction of onion-induced haemolytic anemia in dogs with sodium n-propylthiosulphate. Vet Rec 142(9):216–219