Allium ursinum as a Centuries-old Medicinal Plant. Short Review of Anti-inflammatory and Antimicrobial Properties of the Rare Garlic Species

Abstract

Wild garlic (Allium ursinum) is a wild plant growing in Middle and Eastern Europe that has been traditionally applied in local cuisine and herbal medicine practices. The leaves of the plant contain numerous bioactive compounds, i.e., flavonols, flavanols, phenolic acids, and thiopolysulfides. The aim of the study is to present the antioxidant, anti-inflammatory, and antimicrobial properties of this plant. The leaves of Allium ursinum possess strong antioxidant activity, which varies depending on extractant use and plant origin. The plant has limited capacity for ferric ion reduction in a FRAP test, as well. The previous studies showed that the high content of phenolic compounds was prevalently responsible for the high antiradical capacity. On the other hand, the thiopolysulfides present in the plant are responsible for its anti-inflammatory effect, observed as inhibition of TNF-α and interleukins, and as a bactericidal effect against skin pathogenic microflora. Wild garlic has a negative effect on cancer cell line viability, while it enhances the viability of non-cancerogenic tissue cells. All these effects clearly show that wild garlic is an interesting and potent raw material that should be more often applied in todayʼs functional foods, as well as a novel additive for dietary supplements, herbal remedies, or materials with topical anti-bacterial action.

 

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Keywords

Allium ursinum - Allioideae - thiopolysulfides - antioxidant activity - anti-inflammatory effect - antibacterial effect

Abbreviation

AA: ascorbic acid

ABTS: 2,2-azino-bis-(3-ethyl-benzthiazoline-6-sulfonic acid

CFU: colony-forming unit

CUPRAC: cupric-ion-reducing antioxidant ability

d. m.: dry mass

DPPH·: 1,1-Diphenyl-2-picrylhydrazyl

EC₅₀ : half of maximal effective concentration

f. m.: fresh matter

FRAP: ferric-reducing antioxidant potential

IC₅₀ : half of maximal inhibiting concentration

IFN-γ : interferon gamma

IL: interleukin

N3MeG: N₃-methylguanine

ROS: reactive oxygen species

SC₅₀ : half of maximal scavenging concentration

SEM: scanning electron microscopy

TE: Trolox equivalent

TEAC: Trolox-equivalent antioxidant capacity

TEM: transmission electron microscopy

TNF-α : tumor necrosis factor α
 

Introduction

Allium ursinum L. (Allioideae Herbert), also known as wild garlic or bear garlic, is a plant growing in the middle and eastern regions of Europe. It is regularly applied as an ingredient of local cuisine and herbal medicine [1], [2]. The plant grows in mountain and forestall areas with fertile soil and high moisture, especially ravine, alder gallery and oak-hornbeam forests [3], [4], [5]. However, it may also be cultivated in regular agrarian conditions in ultra-high-fertile soil of cernozem or in co-cultivation of horseradish (Armoracia rusticana G. Gaertn.) [6], [7].

The edible part is the lancet leaves of the plant, which are carriers of numerous antioxidant, antimicrobial, and anti-inflammatory agents. Wild garlic grows actively starting in February, and its vegetation lasts until June. The three-limbed stem of the plant may grow up to 40 cm, and two or three elliptical leaves surround it. At the top of the stem, white flowers flourish between April and May [7]. The leaves are usually collected in this period. Then, they are dried or macerated in alcohol to prepare local food products, such as rennet cheeses, fermented milk products, and tinctures [8], [9], [10].

This aims to discuss the current proceedings on bioactive compounds of Allium ursinum and the biological effects observed for them individually and the synergistic effect of the whole plant. To prepare this paper, we browsed papers published mostly since 2005 involving the following key words: “Allium ursinum”, “ransom”, “wild garlic”, “anti-inflammatory”, “anti-oxidant”, “allicin”, and “anti-microbial activity”. We browsed the Google Scholar, PubMed, and Scopus databases.

Searching methods

References were sought using Publish or Perish software. We browsed the PubMed, Cross Reference, and Google Scholar bases. Most of the literature search was based on papers published from 2015 to 2024 and included at least one of the following keywords: “Allium ursinum”, “ramson”, or “wild garlic”, as well as one of the following “antioxidant potential”, “anti-inflammatory”, “chemical composition”, “bactericidal effect”, and “anti-tumor effect”. Then, the list of papers was enriched with other papers published between 2005 and 2024 supporting the claims from the prior literature search.

 

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Chemical Composition of Allium ursinum

Phenolics

Wild garlic as a leafy vegetable has relevant amounts of phenolic compounds including phenolic acids and flavonols. Total phenolic content in methanolic extracts is up to 33.29 ± 0.29 mg gallic acid equivalents/g dry matter (d. m.) and is associated with antioxidant activity [11], [12]. Thereby, depending on the harvest period in March compared to in May, total phenolic content [38 – 47 mg of gallic acid equivalents/100 g of fresh matter (f. m.)] and antioxidant activity increase [13].

First of all, it should be noted that wild garlic is poor in phenolic acids when compared with other medicinal plants (free phenolic acids: 3.24 ± 0.29 mg/g d. m., bound phenolic acids: 1.10 ± 0.17 mg/g d. m.). Among the free phenolic acids, mainly ferulic acid and vanillic acid were observed ([Fig. 1]) and additionally, among the bound ones, p-coumaric acid [11], [14], [15], [16].

Fig. 1 The predominant phenolic compounds present in Allium ursinum. Wild garlic painting authored by Carl Axel Magnus Lindman.

Kaempferol glycosides are the main compounds in wild garlic leaves with up to 253 mg/100 g f. m. [11], [15], [16]. Based on mass spectrometric studies, a few main compounds could be tentatively identified. These are kaempferol-3-neohesperidoside-7-glucoside, kaempferol-3-neohesperidoside-7-coumaroyl-diglucoside, kaempferol-3-neohesperidoside, kaempferol-3-neohesperidoside-7-coumaroyl-glucoside, and the acetylated forms thereof [17], [18]. The amounts of kaempferol-3-neohesperidoside-7-glucoside and kaempferol-3-neohesperidoside-7-coumaroyl-diglucoside were observed at ca. 2 mg/g d. m. each. Among flavonols, NMR studies have identified the following compounds: kampferol-3-neohesperidoside-7-coumaroyl-glucoside, kaempferol-3-neohesperidoside-7-coumaroyl-glucoside dodeca acetate, kaempferol-3-neohesperidoside-7-feruloyl-glucoside, kaempferol-3-neohesperidoside-7-coumaroyl-glucoside dodeca acetate, kaempferol-3-neohesperidoside-7-coumaroyl-diglucoside, and kaempferol-3-neohesperidoside-7-coumaroyl-diglucoside pentadeca acetate [19].

In wild garlic flowers, similar compounds were detected, including kaempferol-3-glucoside, kaempferol-3-glucoside-7-glucoside, kaempferol-3-neohesperidoside, and kaempferol-3-neohesperidoside-7-glucoside [20].

 

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Thiopolysulfides

Like all Allium plants, wild garlic contains sulfur compounds that contribute to its characteristic aroma. These include alliin and its degradation product–allicin, from which further aroma components are formed: diallyl disulfide, diallyl trisulfide, 3-vinyl-(4H)-ditiin, and 2-vinyl-(3H)-1,3 ditiin [21]. Furthermore, degradation products of S-methyl cysteine sulfoxide, namely dimethly disulfide, dimethyl trisulfide, and dimethylthiosulfonate, also contribute to the aroma of wild garlic. It is shown that the sulfur compounds from wild garlic are effective against Candida spp, Aspergillus niger, Botrytis cinerea, or Pennecillium gladioli [22], [23]. Other pathogenic microorganisms can also be reduced by wild garlic extracts [11]. Furthermore, alliin is shown to increase during plant development from 25 to 45% of the cystein sulfoxid pattern [24].

Compared to other Allium species, the number of thiosulfinate esters measured by HPLC and NMR is low. The main four compounds are 2-propene-1-sulfinothioic acid S-2-propenyl ester (28%), 2-propene-1-sulfinothioic acid S-methyl ester (16%), methanesulfinothioic acid S-(E)-propenyl ester (34%), and methanesulfinothioic acid S-methyl ester (20%) [25].

Thereby, studies show the most quantitatively relevant volatile sulfur compounds are methyl-2-propenyl trisulfides (14%), di-2-propenyl disulfides (25%), and di-2-propenyl trisulfides (16.5%) [20], [26]. During plant development, methyl 2-propenyl disulfide decreases from ca. 35% to ca. 12%, while di-2-propenyl sulfide increases from ca. 2% to ca. 5%, and di-2-propenyl disulfide remains unchanged. Other volatile compounds remain essentially unchanged at lower concentrations [24].

 

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Antioxidant activity of Allium ursinum

Recent papers show that wild garlic possesses diverse antiradical capacity. However, the results differ noticeably between the studies, which results from differences in post-collection treatment, solvent type, and extraction time ([Table 1]). The best described is the antiradical capacity measured with the scavenging of a 2,2-diphenyl-1-picrylhydrazyl radical (DPPH^· test). Nonetheless, the activity of the plant against this compound is rather moderate. Scavenging of 50% of present radicals (SC₅₀) ranges from 154 to 1400 µg in aqueous leaf extracts, while in the methanolic and ethanolic extracts, it is roughly 111 µg and 1100 µg, respectively [11], [27], [28]. Meanwhile, for butyryl hydroxytoluene and butyryl hydroxyanisole SC₅₀ was 2.82 µg/mL and 2.44 µg/mL, respectively [28], and for Allium tuberosum var. Rottler ex Spreng, the half-scavenging dose equaled 97.46 µg/mL in the ethanolic extract and 141.68 in the aqueous one [29]. The antiradical capacity of the plant results mainly from the high content of phenolics but is not limited by the content of these secondary plant metabolites [7], [30]. The study of Nikkhani et al. [26] showed that the phenolic constituents may chelate zinc and manganese, which decreases its antiradical capacity. The chelating ability of Mn ions was the highest in the aqueous extract (nearly 99% yield), while for Zn, the best chelator was the ethanolic extract (93%). Meanwhile, in the food matrix, the chelating ability of Allium ursinum remains high (over 68%), but its antiradical ability against DPPH^· is very low (0.4 µmol TE/mL) [31].

Table 1 Antiradical activity of Allium ursinum leaves.

Extractant/Food matrix	ABTS+· test	DPPH· test	FRAP test	Reference
n/e – not examined; AA – ascorbic acid; EC50 – 50%-scavenging activity; TE – Trolox equivalent; d. m. – dry matter; f. w. – fresh weight
Water	n/e	10.1 mM TE/g d. m.	42.1 mM TE/g d. m.	Petkova et al. [35]
	n/e	EC50 – 471.0 µg/mL	n/e	Nikkhahi et al. [27]
	n/e	EC50 – 154.2 µg/mL	n/e	Krivoklapic et al. [72]
	n/e	EC50 – 1400.0 µg/mL	n/e	Pavlović et. [28]
70%-MeOH	n/e	8.3 – 16.4%	n/e	Jedrszczyk et al. [73]
80%-MeOH	n/e	35.7 – 48.0%	n/e	Kovarović et al. [30]
	79.7 µmol TE/g f. w.	2.0 µmol TE/g f. w.	8.6 µmol TE/g f. w.	Lachowicz et al. [13]
	91.7 µmol TE/g d. m.	n/e	11.7 µmol TE/g d. m.	Lachowicz et al. [18]
	n/e	EC50 – 1100.0 µg/mL	n/e	Pavlović et. [28]
	n/e	EC50 – 66.7 – 77.2 µg/mL	n/e	Pejatović et al. [37]
	72.3 µmol TE/g d. m.	2.5 µmol TE/g d. m.	n/e	Škrovánková et al. [34]
MeOH	n/e	raw material – 88.4%; dried material – 40.7 – 53.3%	n/e	Lukinac and Jukić [32]
	n/e	EC50 – 111.0 µg/mL	n/e	Krivoklapic et al. [72]
	n/e	EC50 – 630.0 µg/mL	n/e	Pavlović et. [28]
70%-EtOH	n/e	EC50 – 46.1 – 77.2 µg/mL	n/e	Pejatović et al. [37]
	n/e	EC50 – 1030.0 µg/mL	n/e	Pavlović et al. [28]
	n/e	EC50 – 532.0 µg/mL	n/e	Nikkhahi et al. [27]
80%-EtOH	1.7 – 2.2 µmol TE/mL	n/e	n/e	Voća et al. [12]
	n/e	45.3%	n/e	Lenková et al. [74]
96%EtOH	n/e	EC50 – 850.0 µg/mL	n/e	Pavlović et al. [28]
	n/e	EC50 – 4,936.6 µg/mL	14.5%	Jovanova et al. [41]
EtOH	n/e	EC50 – 643.0 µg/mL	n/e	Nikkhahi et al. [27]
80%-Acetone	n/e	22.0 – 27.9%	0.6 – 0.9 mg AA/g f. w.	Gordanić et al. [7]
Chloroform	n/e	EC50 – 391.8 µg/mL	n/e	Krivoklapic et al. [72]
Corn snacks	n/e	19.2 – 87.7%	n/e	Kasprzak-Drozd et al. [47]
Meat and potato-based infant formula	n/e	0.4 µmol TE/mL	n/e	Stanislavljević et al. [31]
Tincture	n/e	SC50 – 45.0 – 50.0 µg/mL	n/e	Pejatović et al. [37]

The high deviation in antiradical capacity between the referred studies may originate from different soil conditions during the plant cultivation. Gordanić et al. [7] compared Allium ursinum cultivated in different soils. Their study showed that Fluvisol and Chernozem positively affected the scavenging abilities against DPPH.

The drying method of the leaves may significantly change their antioxidant capacity. In the study of Lukinac and Jukić [32], it was noted was that an air temperature of 40 °C decreased DPPH^· scavenging activity by over a third, and a drying temperature of 60 °C showed the highest efficiency in phenolic acids and flavonols amount in the final drought [33].

Conversely to DPPH^·, the antiradical activities against ABTS^+· are noticeably higher–almost 30-fold for 80%-methanol extracts [34]. Nonetheless, the properties against ABTS^+· differed significantly between different growing locations, which showed that the overall antiradical potential relates from the cultivation yield and cultivation conditions [12]. What is more, the authors of the cited study [12] noted that flowering negatively affects the antiradical capacity even by half. This information seems to be important, as the plant leaves are usually collected after the flowering period. On the other hand, Lachowicz et al. [13] observed higher antioxidant capacity against both radicals for summer collections than for the spring ones. However, no statistical significance was found between them.

Wild garlic leaves are also good iron (III)-reducing agents, which may be observed in the ferric-reducing activity capacity (FRAP). The reducing ability oscillates between 8 and 12 µmol TE/g d. m. ([Table 1]). In contrast, Petkova et al. [35] observed significantly higher values for aqueous extract–over 42 mmol TE/g d. m. Except for the different extractants used, the last study involved high temperature of the extraction process and remaceration of the raw material, which could result in a higher yield of the process. The analogical tendency was observed in the super-critical extraction of wild garlic leaves by Tomšik et al. [36], who observed higher ABTS^+· activity along with rising process temperature. However, for DPPH^· ability, they noted an opposite relation. This conclusion may be supported by Pejatović et al. [37], who showed that long-time extraction in ambient temperature effects in the lowest doses of extract needed to halve DPPH^· activity (EC₅₀ values). On the other hand, da Silva Araujo et al. [38] showed that the temperature effect on the activity against DPPH^· is not as significant as the ethanol concentration in the extractant and the opposite tendency for the activity measured in FRAP test. This stands in line with proceedings on DPPH^· activity measured in ethanolic extracts, in which EC₅₀ values declined with the growing concentration of ethanol in the extractant ([Table 1]).

According to Gordanić et al. [7], iron-reducing ability also depends on soil fertility, with the highest activity noted for cultivars grown in chernozem and the lowest for arenosol-grown. The authors of the cited study noted that FRAP values range between 3.5 and 4.9 µmol ascorbic acid (AA) per gram of fresh leaves [7], which follows the previous observation, in which ascorbic acid in the FRAP assay generates a stronger positive response than other standards [39]. The values by are nearly 30- to 40-fold lower than for flowers of Allium cepa and 10- to 13-fold lower than flowers of Cucurbita maxima [40]. Nonetheless, the reductive effect of A. ursinum may be comparable with 250 µg AA and stronger than for A. schoenoprasum L., a plant commonly used in meal preparations [41].

CUPRAC (cupric-ion-reducing antioxidant ability) is a test applied instead of FRAP to illustrate the reducing potential of the tested analyte against the heavy metals. For wild garlic leaves, the Cu²⁺-reducing ability oscillates between 6.2 and 15.3 µmol AA/g [7].

The high capacity measured with this ABTS^+·-scavenging test (TEAC) relates to high chlorophyll and carotenoids content, especially neoxanthin, lutein, and α- and β-carothene [18]. The authors observed that carotenoids are responsible for ferric ion reduction in a FRAP test, as well. Comparable ability to scavenge ABTS^+· and Fe³⁺ was noted for xanthophylls, especially for violaxanthin, neoxanthin, and lutein, in another study [42]. However, Lachowicz et al. [18] observed a stronger relation between the xanthophylls and the ABTS^+· test than the FRAP test, but for violaxanthin, the statistical effect was poor for both. The similar strong effect noted for the FRAP and ABTS^+· results from the similar mechanism of single-electron transfer between the reagent and the active compound. Carotenoids, due to the presence of cyclic ligands and conjugated bonds, may delocalize electron deficiency [43]. Meanwhile, the DPPH^· scavenging ability of herbal plants originates mainly from total flavonoids, total phenolics, and the synergistic effect of all bioactive phytocompounds present (r² values 0.91, 0.90 and 0.96, respectively), but the effect of the carotenoids present is also very strong (r² = 0.87) [44]. Since a proton donation mechanism neutralizes DPPH^·, the wide range of phytocompounds with unsaturated cyclic or aromatic groups with hydrogen ligands may be effective agents [45]. For Allium species, DPPH^· scavenging also relates to the high content of total phenolic content (TPC) (r² = 0.90). However, a stronger correlation was noted between TPC and FRAP (r² = 0.96) [41]. The high scavenging effect of the first is based on the fact that similar compounds are responsible for the reaction occurring in both assays, especially flavanoles [46].

Alium urisnum added to food products may enhance their antioxidant activity ([Table 1]). Kasprzak-Drozd et al. [47] analyzed the effect of wild garlic leaves on extruded corn snacks and observed positive relation between the wild garlic addition and the time of the extrusion on the antiradical activity against DPPH^·. According to the authors, a 10-minute extrusion of snacks enriched in 4% addition of the leaves increased the DPPH· scavenging activity from nearly 59% to over 82%. Moreover, the snacks enriched with the leaves had higher activity after in vitro gastric and duodenal digestion by approximately 22 and 18% points, respectively. Similar results were delivered by Stanisavljević et al. [31] in their study of A. ursinum effect on the antioxidant effect of infant food composed of turkey meat and potatoes. They noted that the addition of the leaves could increase the antioxidant activity against DPPH^· by 84 to 137% and even raise it after the simulated digestion process by a third, compared with the values before the digestion. These observations seem to be key in the context of future applications of wild garlic to food products, as the first mentioned food product in this paragraph corresponds well with similar snack products available on the market and is usually categorized as convenient snacks for active persons and youth. Due to the similarity of the other food product discussed to the composition of the traditional dinner meal, the results of the Stanisavljević et al. [48] study may be applied in designing novel variants of traditional foods and meals in countries with meat- and starch-based based cuisines, e.g., Polish, German, and Czech dishes.

This leads to the conclusion that wild garlic may be added to numerous foods, dietary supplements, and other products to boost their antioxidant and other functional effects. Moreover, the literature on the subject shows that the antioxidant activity of phytocompounds highly relates with their anti-inflammatory, inhibitory, and antimicrobial properties [28], [31], [41], [49].

 

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Anti-inflammatory effects of Allium ursinum L.

Garlic and the organosulfur compounds present in the immune system have a positive effect on it ([Fig. 2]). This effect has been demonstrated in studies and is based on several main mechanisms: on immune response, on anti-inflammatory response, and on interleukins as a response to oxidative stress [50]. Allicin and derivatives present in garlic, at 10 µg/ml of garlic extract, inhibited the synthesis of multiple pro-inflammatory cytokines (TNF-α, IL-12, IL-1α, and IL-1β), as well as other inflammation-related cytokines (IL-2, IL-6, IL-8, and IFN-γ) in patients with specific inflammatory bowel disease [51], [52].

Fig. 2 Allicin and its anti-inflammatory and antimicrobial effect. Wild garlic painting authored by Carl Axel Magnus Lindman.

 

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Toxicity of Allium ursinum L.

Wild garlic constituents have been described as anti-tumor and anti-parasite agents ([Table 2]). In the study of Krstin et at. [53], a hydrophobic extract of Allium ursinum bulbs significantly inhibited the viability of T b. brucei and Leishmania tarentolae cells, while the toxicity against the HaCaT human skin line was respectively 20-fold and 4-fold poorer. Moreover, Xu et al. [54] also noted cytotoxic effect of Allium ursinum on a cancer cell line. In their study, an aqueous extract of wild garlic leaves significantly increased the apoptosis of the AGS cancer cell line and almost completely cleaved the presence of cyclin B in the cells. Cyclin B is a key marker of solid tumor progression. Its high levels are connected with an unrestricted cell cycle and cell malignant transformation [55]. However, the authors of the cited AGS-based study had found no information on the potential mechanism of the anti-tumor effect of the extract. They considered the observed effects with the presence of thiopolysulfides.

Table 2 Summary of Allium ursinum effects on different cell lines.

Allium ursinum extract/compound	Organism	Tissue	Cell line	Dose	Reference
Bulb extract in dichloromethane 3 : 10 (m/v)	T. b. brucei	N/A	N/A	IC50 1.45 µg/mL	Krstin et al., [53]
	Leishmania tarentolae	N/A	N/A	IC50 5.87 µg/mL
	Human	Skin	HaCaT	IC50 23.71 µg/mL
Leaf extract in methanol 1 : 20 (m/v)	Rat	Embryo	H9c2	50 µg/mL+ 1 µM doxo – 25% viability	Pop et al., [60]
Leaf extract in water 1 : 20 (m/v)	Rat	Embryo	H9c2	50 µg/mL+ 1 µM doxo – 70% viability
Leaf extract in methanol 1 : 25 (m/v) + 1% AcOH	Human	Xenograft tumor	AGS	IC50 16.2 µM	Xu et al., [54]
Diallyl trisulfide	Human	Lung cancer	H358	40 µM – 45% apoptosis	Xiao et al., [56]
			H460	40 µM – 45% apoptosis
		Bronchial epithelium	BEAS-2B	40 µM – 12% apoptosis
	Human	Colon cancer	DLD-1	IC50 13.3 µM	Hosono et al. [75]
			HCT-12	IC50 – 11.5 µM
Diallyl disulfide	Human	Neuroblastoma	SH-SY5Y	50 µM – 28% apoptosis

The hypothesis that the anti-tumor properties of Alii ursini folia depend on the presence of thiopolysulfides may be confirmed by numerous papers highlighting the potential of these compounds to induce apoptosis of cancer cell lines. In the work of Xiao et al. [56], a dose of 40 µM diallyl trisulfide halved the population of H358 and H460 (45% apoptosis). The toxicity against these lung cancer cell lines was almost fourfold higher than observed in the bronchide epilethium cell line of BEAS-2B exposed to the analogical dose of the compound. The higher apoptosis ratio of the cancer lines was related to significantly higher DNA damages observed in them [57]. The metabolism of cancer cells tends to generate ROS at higher levels than normal cells in different biological pathways. The rapid metabolism of the tumor cells produces a large number of ROS, i.e., superoxide (O²⁻), hydroxyl radical (^·OH), and hydrogen peroxide (H₂O₂). Moreover, carcinogenesis can also be associated with aberrations of genomic DNA methylation, such as hypermethylation and hypomethylation of the promoter or first exon of cancer-related genes [58]. The process of hypomethylation accelerates tumor development further by activating the transcription of protooncogenes and proteins involved in genomic instability and malignant cell metastasis. On the other hand, the main products of DNA methylation, i.e., N₃-methyladenine and N₃-methylguanine (N₃MeG), are able to trigger apoptosis by affecting the additional DNA strand breaks [59].

Meanwhile, extracts and bioactive ingredients of wild garlic may protect non-cancer cells against different toxic agents. In the study of Pop et al. [60], murine cardiomyoblasts of line H9c2 were exposed to doxorubicin in the presence of A. ursinum extract constituents. The authors observed that a methanolic extract of wild garlic had significant positive effect on cell viability but had no significant effect on the release of reactive oxygen species from the cells and from their mitochondria. Conversely, the aqueous extract decreased the ROS release from the cells and the mitochondria by 40 and 25%, respectively.

 

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Antibacterial activity of Allium ursinum

Wild garlic has a beneficial effect on skin conditions, skin inflammation, as well as accelerating the wound healing process. Moreover, Allium ursinum has been proven to have antimicrobial activity against certain bacteria, both Gram-positive and Gram-negative ([Fig. 2]). This interaction is mainly related to alliin and other thiosulfates, as well as to their products (diallyl thiosulfinate, methyl and diallyl sulfides, et al.) showing antimicrobial activity. Alliinases catalyze the conversion of odorless cysteine sulfoxides to volatile thiosulfates [61], [62].

Allicin alone at a dose of 4.2 mg/day compared to ascorbic acid and β-carotene contributed to complete eradication of Helicobacter pylori, also compared to other treatments for this infection in patients [63]. Moreover, analyses of the anti-inflammatory activity for compounds present in garlic were also conducted for the treatment of hernia in an in vivo model in rabbits [64]. It was shown that the inclusion of allicin (900 µg/ml) into a chlorhexidine digluconate solution (concentration 0.05%) in the polypropylene mesh resulted in antimicrobial activity against gastrointestinal bacteria Sa ATCC25923, and therefore, it can be successfully used in prophylactic to resist infection during such treatment. The essential component for such antimicrobial effects was allicin.

The antibacterial effect of allicin has been found against Staphylococcus epidermidis. In the case of joint prosthetics, biofilm infection can result in severe health consequences, as antibiotic resistance in biofilm is up to 1000 times higher. A study by Zhai et al. [65] showed that allicin (4 mg/l) strongly enhanced the antimicrobial properties of vancomycin (20 mcg/mL), compared to their separate use (vancomycin: 4.75 log₁₀ CFU/mL and allicin 3.56 log₁₀ CFU/mL), resulting in inhibition of S. epidermidis biofilm formation on the prosthetic surface of rabbits suffering from prosthetic joint infections to a level of 1.71 log₁₀ CFU/mL. In a study on 60 adult male Sprague–Dawley rats, garlic-derived compounds showed synergistic effects with ciprofloxacin (a bactericidal drug for urinary tract infections) in inhibiting the growth of Escherichia coli Z17 [66].

The broad spectrum of antimicrobial activity is largely dependent on sulfhydryl compounds such as cysteine. Ajoene, as an unsaturated disulfide, has inhibitory properties (reduction by cysteine abolishes antimicrobial activity), especially against Gram-positive bacteria and yeast [67].

Also, in relation to Candida albicans fungal infections, the value of allicin use in terms of animal survival was found. In a mouse model of systemic candidiasis, the efficacy of allicin was verified in comparison to the antifungal fluconazole (resistance to this agent is steadily increasing), and allicin (5 mg/kg per day) was shown to be less effective than fluconazole while increasing mean survival time by up to twofold [68]. Against Trichophyton rubrum, allicin from garlic has also been identified as an important biological tool for dermatophytosis, based on results obtained by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) [69].

On the other hand, with regard to skin problems, in mice with Leishmania major, the application of 50 µM of allicin cream promoted the reduction in inflammatory cells and the protection of the epidermis, significantly contributing to the healing of the animals [70].

Given that the antiradical activity exhibited by the raw materials is reflected in the anti-inflammatory activity, it is also worth noting the volatile oils found in A. ursinum.

In food production, garlic ingredients are also used in a preservative context due to their antimicrobial activity. Modified atmosphere packaging, which is gaining popularity, allows food preservation and reduction in heat treatments while increasing the safety of such food products. Researchers Cosmai et al. [71], by adding garlic extract (0.1%) to olive paste packaged with MAP1 (75% Ar, 23% CO₂, and 2% H₂), showed that this significantly increased the antimicrobial inhibition and shelf life of this product by an additional 14 days. The component responsible for this effect was identified to be allicin from garlic [71].

 

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Conclusions

The leaves and bulbs of wild garlic have been reported to possess numerous phenolic compounds and high levels of thiopolysulfides, a group of organic compounds characteristic of all Allium species. The methanol-soluble and aqueous fractions of the leaves have high antioxidant capacity. However, the antioxidant capacity varies strongly depending on the differences in extraction procedure and collection site of the plant. Nonetheless, the literature on the subject that was reviewed in this paper clearly shows that Allium ursinum (especially the leaves of the plant) has strong anti-inflammatory and antibacterial properties. The active compounds present in wild garlic may inhibit the growth of pathogenic bacteria and affect the cytokine release in cells subjected to the source of inflammation. Moreover, the thiopolysulfides present in the plant significantly arrest the grow of the cancer cell line and possess a selective cytoxic effect compared to the low effect on non-cancerogenic tissue cells.
Taking all this into account, wild garlic is a potent, half-wild plant, the bioactive effects of which could be applied in novel functional foods or as a source of anti-inflammatory and bactericidal effects in herbal ointments or other preparations.

 

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Contributorsʼ Statement

Conceptualization: O. Szczepaniak, T. Esatbeyoglu; Data curation: O. Szczepaniak; Investigation: O. Szczepaniak, S. Neugart, M. Przeor; Supervision: T. Esatbeyoglu; Validation: M. Przeor, T. Esatbeyoglu; Visualization: M. Przeor; Writing – original draft: O. Szczepaniak, S. Neugart, M. Przeor; Writing – review & editing: T. Esatbeyoglu

 

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Conflict of Interest

The authors declare that they have no conflict of interest.

• References

• 1 Błażewicz-Woźniak M. Vegetative reproduction and yield of bear garlic (Allium ursinum L.) in field cultivation. Acta Agrobot 2024; 77: 190228
• 2 Pawera L, Łuczaj Ł, Pieroni A, Polesny Z. Traditional plant knowledge in the White Carpathians: Ethnobotany of wild food plants and crop wild relatives in the Czech Republic. Hum Ecol 2017; 45: 655-671
• 3 Morschhauser T, Rudolf K, Botta-Dukát Z, Oborny B. Density-dependence in the establishment of juvenile Allium ursinum individuals in a monodominant stand of conspecific adults. Acta Oecologica 2009; 35: 621-629
• 4 Djurdjevic L, Dinic A, Pavlovic P, Mitrovic M, Karadzic B, Tesevic V. Allelopathic potential of Allium ursinum L. Biochem System Ecol 2004; 32: 533-544
• 5 Kovalenko O, Kalista M. Allium ursinum L.(Amaryllidaceae)–a new species for the flora of National Nature Park “Pyriatynskyi” (Poltava oblast, Ukraine). Plant Introduction 2022; 95/96: 53-56
• 6 Amagova Z, Matsadze V, Kavarnakaeva Z, Golubkina N, Antoshkina M, Sękara A, Tallarita A, Caruso G. Joint cultivation of Allium ursinum and Armoracia rusticana under foliar sodium selenate supply. Plants 2022; 11: 2778
• 7 Gordanić S, Radanović D, Vuković S, Kolašinac S, Kilibarda S, Marković T, Moravčević Đ, Kostić AŽ. Phytochemical characterization and antioxidant potential of Allium ursinum L. cultivated on different soil types- a preliminary study. Emir J Food Agric 2023; 34: 904-914
• 8 Gębczyński P, Bernaś E, Słupski J. Usage of Wild-Growing Plants as Foodstuff. In: Hernik J, Walczycka M, Sankowski E, Harris BJ. ed. Cultural Heritage–Possibilities for Land-Centered Societal Development. Cham: Springer Nature Switzerland; 2022: 269-283
• 9 Pluta-Kubica A, Najgebauer-Lejko D, Domagała J, Štefániková J, Golian J. The effect of cow breed and wild garlic leaves (Allium ursinum L.) on the sensory quality, volatile compounds, and physical properties of unripened soft rennet-curd cheese. Foods 2022; 11: 3948
• 10 Znamirowska A, Szajnar K, Rożek P, Kalicka D, Kuźniar P, Hanus P, Kotula K, Obirek M, Kluz M. Effect of addition of wild garlic (Allium ursinum) on the quality of kefirs from sheepʼs milk. Acta Sci Pol Technol Aliment 2018; 16: 209-215
• 11 Krivokapic M, Bradic J, Petkovic A, Popovic M. Phytochemical and pharmacological properties of Allium ursinum . Serb J Exp Clin Res 2021; 22: 357-362
• 12 Voća S, Žlabur JŠ, Uher SF, Peša M, Opačić N, Radman S. Neglected potential of wild garlic (Allium ursinum L.) – Specialized metabolites content and antioxidant capacity of wild populations in relation to location and plant phenophase. Horticulturae 2022; 8: 24
• 13 Lachowicz S, Kolniak-Ostek J, Oszmiański J, Wiśniewski R. Comparison of phenolic content and antioxidant capacity of bear garlic (Allium ursinum L.) in different maturity stages. J Food Process Preserv 2017; 41: e12921
• 14 Djurdjević L, Gajić G, Jarić S, Kostić O, Mitrović M, Pavlović P. Analysis of benzoic and cinnamic acid derivatives of some medicinal plants in Serbia. Arch Biol Sci 2013; 65: 603-610
• 15 Vlase L, Parvu M, Parvu EA, Toiu A. Chemical constituents of three Allium species from Romania. Molecules 2013; 18: 114-127
• 16 Parvu M, Toiu A, Vlase L, Parvu EA. Determination of some polyphenolic compounds from Allium species by HPLC-UV-MS. Nat Prod Res 2010; 24: 1318-1324
• 17 Wu H, Dushenkov S, Ho CT, Sang S. Novel acetylated flavonoid glycosides from the leaves of Allium ursinum . Food Chem 2009; 115: 592-595
• 18 Lachowicz S, Oszmiański J, Wiśniewski R. Determination of triterpenoids, carotenoids, chlorophylls, and antioxidant capacity in Allium ursinum L. at different times of harvesting and anatomical parts. Eur Food Res Technol 2018; 244: 1269-1280
• 19 Carotenuto A, De Feo V, Fattorusso E, Lanzotti V, Magno S, Cicala C. The flavonoids of Allium ursinum . Phytochemistry 1996; 41: 531-536
• 20 Ivanova A, Mikhova B, Najdenski H, Tsvetkova I, Kostova I. Chemical composition and antimicrobial activity of wild garlic Allium ursinum of Bulgarian origin. Nat Prod Commun 2009; 4: 1934578X0900400
• 21 Abe K, Hori Y, Myoda T. Characterization of key aroma compounds in aged garlic extract. Food Chem 2020; 312: 126081
• 22 Bagiu RV, Vlaicu B, Butnariu M. Chemical composition and in vitro antifungal activity screening of the Allium ursinum L. (Liliaceae). Int J Mol Sci 2012; 13: 1426-1436
• 23 Pârvu M, Vlase L, Roşca-Casian O, Pârvu O. Antifungal properties of Allium ursinum L. ethanol extract. J Med Plants Res 2011; 5: 2041-2046
• 24 Schmitt B, Schulz H, Storsberg J, Keusgen M. Chemical characterization of Allium ursinum L. depending on harvesting time. J Agric Food Chem 2005; 53: 7288-7294
• 25 Block E. The organosulfur chemistry of the genus Allium – Implications for the organic chemistry of sulfur. Angewandte Chemie Int Ed Eng 1992; 31: 1135-1178
• 26 Godevac D, Vujisić L, Mojović M, Ignjatović A, Spasojević I, Vajs V. Evaluation of antioxidant capacity of Allium ursinum L. volatile oil and its effect on membrane fluidity. Food Chem 2008; 107: 1692-1700
• 27 Nikkhahi M, Souri E, Sarkhail P, Baeeri M, Mohammadhosseini N. Evaluation of anti-tyrosinase activity of Allium ursinum extracts and their metal complexes. Acta Sci Pol Technol Aliment 2018; 17: 219-226
• 28 Pavlović DR, Veljković M, Stojanović NM, Gočmanac-Ignjatović M, Mihailov-Krstev T, Branković S, Sokolović D, Marčetić M, Raduović N, Radenković M. Influence of different wild-garlic (Allium ursinum) extracts on the gastrointestinal system: spasmolytic, antimicrobial and antioxidant properties. J Pharm Pharmacol 2017; 69: 1208-1218
• 29 Nhut PT, An TNT, Minh LV, Truc TT, Anh NHT. Phytochemical screening of Allium tuberosum Rottler. ex Spreng as food spice. IOP Conf Ser Mater Sci Eng 2020; 991: 012021
• 30 Kovarovič J, Bystrická J, Urminská D, Harangozo Ľ, Vollmannová A, Trebichalský P, Timoracká M, Carbonell-Barrachina AA. Evaluation and comparison of total polyphenols content and antioxidant activity of wild garlic (Allium ursinum l.) In selected morphological parts. J Microbiol Biotechnol Food Sci 2019; 9: 492-495
• 31 Stanisavljević N, Soković Bajić S, Jovanović Ž, Matić I, Tolinački M, Popović D, Popović N, Terzić-Vidojević A, Golić N, Beškoski V, Samardžić J. Antioxidant and antiproliferative activity of Allium ursinum and their associated microbiota during simulated in vitro digestion in the presence of food matrix. Front Microbiol 2020; 11: 601616
• 32 Lukinac J, Jukić M. Influence of drying temperature on the organoleptic properties, antioxidant activity and polyphenol content in dried leaves of Allium ursinum L. subsp. ucrainicum . Ukr Food J 2022; 11: 2-26
• 33 Przeor M, Flaczyk E, Beszterda M, Szymandera-Buszka KE, Piechocka J, Kmiecik D, Szczepaniak O, Kobus-Cisowska J, Jarzębski M, Tylewicz U. Air-drying temperature changes the content of the phenolic acids and flavonols in white mulberry (Morus alba L.) leaves. Ciência Rural 2019; 49: e20190489
• 34 Škrovánková S, Mlček J, Snopek L, Planetová T. Polyphenols and antioxidant capacity in different types of garlic. Potravinarstvo Slovak J Food Sci 2018; 12: 267-272
• 35 Petkova NT, Ivanov IG, Raeva M, Topuzova MG, Todorova MM, Denev PP. Fructans and antioxidants in leaves of culinary herbs from Asteraceae and Amaryllidaceae families. Food Res 2019; 3: 407-415
• 36 Tomšik A, Pavlić B, Vladić J, Ramcić M, Brindza J, Vidović S. Optimization of ultrasound-assisted extraction of bioactive compounds from wild garlic (Allium ursinum L.). Ultrason Sonochem 2016; 29: 502-511
• 37 Pejatović T, Samardžić D, Krivokapić S. Antioxidative properities of a traditional tincture and several leaf extracts of Allium ursinum L. (collected in Montenegro and Bosnia and Herzegovina). J Mat Environ Sci 2017; 8: 1929-1934
• 38 da Silva Araújo C, Vimercati WC, Macedo LL, Pimenta CJ. Effect of solvent, method, time and temperature of extraction on the recovery of phenolic compounds and antioxidants from spent coffee grounds. Int J Food Eng 2022; 18: 325-336
• 39 Olszowy-Tomczyk M. How to express the antioxidant properties of substances properly?. Chem Papers 2021; 75: 6157-6167
• 40 Halder S, Dutta S, Khaled KL. Evaluation of phytochemical content and in vitro antioxidant properties of methanol extract of Allium cepa, Carica papaya and Cucurbita maxima blossoms. Food Chem Adv 2022; 1: 100104
• 41 Jovanova B, Kulevanova S, Kadifkova Panovska T. Determination of the total phenolic content, antioxidant activity and cytotoxicity of selected aromatic herbs. Agr Conspectus Sci 2019; 84: 51-58
• 42 Müller L, Fröhlich K, Böhm V. Comparative antioxidant activities of carotenoids measured by ferric reducing antioxidant power (FRAP), ABTS bleaching assay (αTEAC), DPPH assay and peroxyl radical scavenging assay. Food Chem 2011; 129: 139-148
• 43 Pérez-Gálvez A, Viera I, Roca M. Carotenoids and chlorophylls as antioxidants. Antioxidants 2020; 9: 505
• 44 Luta G, Gherghina E, Balan D, Israel-Roming F. Bioactive compounds and antioxidant properties of some wild plants with potential culinary uses. Rev Chim 2020; 71: 179-184
• 45 Nie Z, Liu KJ, Zhong CJ, Wang LF, Yang Y, Tian Q, Liu Y. Enhanced radical scavenging activity by antioxidant-functionalized gold nanoparticles: A novel inspiration for development of new artificial antioxidants. Free Radic Biol Med 2007; 43: 1243-1254
• 46 Platzer M, Kiese S, Tybussek T, Herfellner T, Schneider F, Schweiggert-Weisz U, Eisner P. Radical scavenging mechanisms of phenolic compounds: A Quantitative Structure-Property Relationship (QSPR) study. Front Nutr 2022; 9: 882458
• 47 Kasprzak-Drozd K, Oniszczuk T, Kowalska I, Mołodoch J, Combrzyński M, Gancarz M, Dobrzański B, Kondracka A, Oniszczuk A. Effect of the production parameters and in vitro digestion on the content of polyphenolic compounds, phenolic acids, and antiradical properties of innovative snacks enriched with wild garlic (Allium ursinum L.) leaves. Int J Mol Sci 2022; 23: 14458
• 48 Stanisavljević N, Soković Bajić S, Jovanović Ž, Matić I, Tolinački M, Popović D, Popović N, Terzić-Vidojević A, Golić N, Beškoski V, Samardžić J. Antioxidant and antiproliferative activity of Allium ursinum and their associated microbiota during simulated in vitro digestion in the presence of food matrix. Front Microbiol 2020; 11: 601616
• 49 Rankovic M, Krivokapic M, Bradic J, Petkovic A, Zivkovic V, Sretenovic J, Jeremic N, Bolevich S, Kartashova M, Jeremic J, Bolevich S, Jakovlievic V, Tomcovic M. New insight into the cardioprotective effects of Allium ursinum L. extract against myocardial ischemia-reperfusion injury. Front Physiol 2021; 12: 690696
• 50 Imran M, Nadeem M, Saeed F, Imran A, Khan MR, Khan MA, Ahmed S, Rauf A. Immunomodulatory perspectives of potential biological spices with special reference to cancer and diabetes. Food Agric Immunol 2017; 28: 543-572
• 51 Hodge G, Hodge S, Han P. Allium sativum (garlic) suppresses leukocyte inflammatory cytokine production in vitro: Potential therapeutic use in the treatment of inflammatory bowel disease. Cytometry 2002; 48: 209-215
• 52 Keiss H-P, Dirsch VM, Hartung T, Haffner T, Trueman L, Auger J, Kahane R, Vollmar AM. Biochemical and molecular actions of nutrients garlic (Allium sativum L.) modulates cytokine expression in lipopolysaccharide-activated human blood thereby inhibiting NF-B activity 1. J Nutr 2003; 133: 2171-2175
• 53 Krstin S, Sobeh M, Braun MS, Wink M. Tulbaghia violacea and Allium ursinum extracts exhibit anti-parasitic and antimicrobial activities. Molecules 2018; 23: 313
• 54 Xu XY, Song GQ, Yu YQ, Ma HY, Ma L, Jin YN. Apoptosis and G2/M arrest induced by Allium ursinum (ramson) watery extract in an AGS gastric cancer cell line. Onco Targets Ther 2013; 6: 779-783
• 55 Ye C, Wang J, Wu P, Li X, Chai Y. Prognostic role of cyclin B1 in solid tumors: a meta-analysis. Oncotarget 2016; 26: 2224-2232
• 56 Xiao D, Zeng Y, Hahm ER, Kim YA, Ramalingam S, Singh SV. Diallyl trisulfide selectively causes bax- and bak-mediated apoptosis in human lung cancer cells. Environ Mol Mutagen 2009; 50: 201-212
• 57 Zhao Y, Ye X, Xiong Z, Ihsan A, Ares I, Martinez M, Lopez-Torres B, Martínez-Larrañaga MR, Anadón A, Wang X, Martínez MA. Cancer metabolism: The role of ROS in DNA damage and induction of apoptosis in cancer cells. Metabolites 2023; 13: 796
• 58 Łuczak MW, Jagodzinski PP. The role of DNA methylation in cancer development. Folia Histochem Cytobiol 2006; 44: 143-154
• 59 Roos WP, Kaina B. DNA damage-induced cell death: From specific DNA lesions to the DNA damage response and apoptosis. Cancer Lett 2013; 332: 237-248
• 60 Pop RM, Bocsan IC, Buzoianu AD, Chedea VS, Socaci SA, Pecoraro M, Popolo A. Evaluation of the antioxidant activity of Nigella sativa L. and Allium ursinum extracts in a cellular model of doxorubicin-induced cardiotoxicity. Molecules 2020; 25: 5259
• 61 Sobolewska D, Podolak I, Makowska-Wąs J. Allium ursinum: botanical, phytochemical and pharmacological overview. Phytochem Rev 2015; 14: 81-97
• 62 Štajner D, Popović BM, Čanadanović-Brunet J, Štajner M. Antioxidant and scavenger activities of Allium ursinum . Fitoterapia 2008; 79: 303-305
• 63 Koçkar C, Öztürk M, Bavbek N. Helicobacter pylori eradication with beta carotene, ascorbic acid and allicin. Acta Med 2001; 44: 97-100
• 64 Pérez-Köhler B, García-Moreno F, Brune T, Pascual G, Bellón JM. Preclinical bioassay of a polypropylene mesh for hernia repair pretreated with antibacterial solutions of chlorhexidine and allicin: An in vivo study. PLoS One 2015; 10: e0142768
• 65 Zhai H, Pan J, Pang E, Bai B. Lavage with allicin in combination with vancomycin inhibits biofilm formation by Staphylococcus epidermidis in a rabbit model of prosthetic joint infection. PLoS One 2014; 9: e102760
• 66 Sohn DW, Han CH, Jung YS, Kim SI, Kim SW, Cho YH. Anti-inflammatory and antimicrobial effects of garlic and synergistic effect between garlic and ciprofloxacin in a chronic bacterial prostatitis rat model. Int J Antimicrob Agents 2009; 34: 215-219
• 67 Kyung KH. Antimicrobial properties of Allium species. Curr Opin Biotechnol 2012; 23: 142-147
• 68 Khodavandi A, Alizadeh F, Harmal NS, Sidik SM, Othman F, Sekawi Z, Jahromi MAH, Ng KP, Chong PP. Comparison between efficacy of allicin and fluconazole against Candida albicans in vitro and in a systemic candidiasis mouse model. FEMS Microbiol Lett 2011; 315: 87-93
• 69 Aala F, Yusuf UK, Nulit R, Rezaie S. Inhibitory effect of allicin and garlic extracts on growth of cultured hyphae. Iran J Basic Med Sci 2014; 17: 150-154
• 70 Metwally DM, Al-Olayan EM, El-Khadragy MF, Alkathiri B. Anti-leishmanial activity (in vitro and in vivo) of allicin and allicin cream using Leishmania major (sub-strain Zymowme LON4) and Balb/c Mice. PLoS One 2016; 11: e0161296
• 71 Cosmai L, Campanella D, Summo C, Paradiso VM, Pasqualone A, De Angelis M, Caponio F. Combined effects of a natural Allium spp. extract and modified atmospheres packaging on shelf life extension of olive-based paste. Int J Food Sci Technol 2017; 52: 1164-1175
• 72 Tomovic M, Krivokapic M, Jakovljevic V, Sovrlic MM, Bradic JV, Petkovic AM, Radojevic ID, Brankovic SR, Comic LR, Andjic MM, Kocovic AG, Tomovic MT. Biological activities of different extracts from Allium ursinum leaves. Acta Pol Pharm Drug Res 2020; 77: 121-129
• 73 Jedrszczyk E, Kopec A, Szymanowski M, Skowera B. Proximate chemical composition and concentrations of selected bioactive compounds in the leaves, stems and bulbs of wild garlic (Allium ursinum L.). Fresenius Environ Bull 2019; 28: 4778-4785
• 74 Lenková M, Bystrická J, Tóth T, Hrstková M. Evaluation and comparison of the content of total polyphenols and antioxidant activity of selected species of the genus Allium . J Central Eur Agr 2016; 17: 1119-1133
• 75 Hosono T, Fukao T, Ogihara J, Ito Y, Shibha H, Seki T, Ariga T. Diallyl trisulfide suppresses the proliferation and induces apoptosis of human colon cancer cells through oxidative modification of β-tubulin. J Biol Chem 2005; 280: 41487-41493

Publication History

Received: 25 February 2025

Accepted: 29 May 2025

Article published online:
09 July 2025