1. Introduction
Fusarium head blight (FHB) and Gibberella ear rot, mainly caused by Fusarium graminearum Schwabe and Fusarium culmorum (W.G. Smith) Sacc., are two of the most devastating diseases of small grain cereals and corn [1]. These fungi substantially reduce grain yield and affect grain quality. Mycotoxin contamination of human food and animal feed has become a more important aspect than direct yield losses in affecting the economics of small grain production [2,3,4]. Many mycotoxins are produced in culture, but the most important are trichothecenes (which include deoxynivalenol [DON], also known as vomitoxin, nivalenol [NIV], HT-2 and T-2 toxins), zearalenone (ZEA), and fumonisins [5]. Consumption of grains containing trichothecenes may cause intestinal irritation in mammals, feed refusal in livestock, vomiting, skin dermatitis, and immunological problems [6]. Fusarium culmorum, F. graminearum, and F. pseudograminearum (O’Donnell and T. Aoki; group I) (=Gibberella coronicola) are the most devastating fungal pathogens on small grain cereals [7]. F. graminearum sensu lato is today the most frequently isolated causal agent of FHB worldwide [8,9]. The F. graminearum species complex (FGSC) includes 16 phylogenetic species: F. graminearum, F. asiaticum (O’Donnell et al.), F. austroamericanum (T. Aoki et al.), F. brasilicum (T. Aoki et al.), F. cortaderiae (O’Donnell et al.), F. meridionale (T. Aoki et al.), F. boothii (O’Donnell et al.), F. mesoamericanum (T. Aoki et al.), F. acaciae-mearnsii (O’Donnell et al.), F. pseudograminearum, F. gerlachii (T. Aoki et al.), F. vorosii (B. Tóth et al.), F. aethiopicum (O’Donnell et al.), F. nepalense (T. Aoki et al.), F. louisianense (Gale et al.), and F. ussurianum (T. Aoki et al.) [10].
Among the several means of fighting this disease includes the use of fungicides, cultural practices, resistant cultivars, and biological agents [11]. As true of most plant diseases, host resistance is recommended as the most effective and economical method of management [12,13]. Fully resistant cultivars are not available to date, but some cultivars have usable levels of partial resistance that limit yield loss and mycotoxins accumulation [14].
This article discusses the main secondary metabolites and antioxidants of wheat that can contribute to resistance in wheat species and cultivars. Although they are contained in relatively small amounts in cereals, they can work together to enhance antioxidant efficiency and resistance to Fusarium.
Current information is presented regarding the contents and effects of these metabolites and antioxidants in relation to wheat species’ and genotypes’ resistance to FGSC.
2. Infection Process
Plants are constantly subjected to biological pressures that could compromise their development. Plant and pathogen interests are opposed and antagonistic, thus generating an evolutionary dynamic between the two. This is stimulated by the confrontation between the plant’s resistance and the ability of the pathogen to generate infection of the plant. Significant progress has been made in recent years toward better understanding the processes involved in FHB infection, and especially in the case of F. graminearum [15,16,17]. F. graminearum’s infection process includes a biotrophic phase, occurring within six hours post inoculation (hpi). The pathogen then shifts to a necrotrophic phase between 24 and 72 hpi via production of trichothecenes and cell wall-degrading enzymes [18]. Fusarium spp. are able to penetrate and invade a host with the help of secreted cell wall-degrading enzymes, thus enabling the pathogen to infect, penetrate, and grow through the wheat tissue. Among cell wall-degrading enzymes are important pectinases, xylanases, cellulases, feruloyl esterases, proteases, endo-peptidases, and lipases [19]. The glycogen synthase kinase gene (FGK3) in F. graminearum is known to be an important virulence factor for this pathogen [20].
The cell wall-degrading enzymes produced by F. culmorum and F. graminearum facilitate rapid colonization of wheat spikes [21]. Lipases are important for phytotoxicity of F. graminearum [22]. F. verticillioides lactamases constitute another group of enzymes in wheat, rye, and corn get part in the resistance process of fungi to antimicrobial environment [23]. Important for these enzymes to be active and function is the presence of encoding genes, such as the lactamase encoding gene FVEG_08291 in F. verticillioides [23] that imparts resistance against lactams with benzoxazinoid rings produced by wheat, corn, and rye [24]. It is noteworthy that Fusarium spp. possess more than 40 lactamase encoding genes [23].
Infection with Fusarium species can result in the contamination of cereals with health-threatening mycotoxins. These are mainly type A and type B trichothecenes, such as T-2 and HT-2, or nivalenol (NIV) and deoxynivalenol (DON). Fusarium mycotoxins include also other toxic secondary metabolites, such as fusaproliferin, moniliformin, and enniatins [25]. Another minor Fusarium mycotoxin on wheat is beauvericin, which, in addition to its toxic activity in higher animals, possesses insecticidal, antifungal, and antibacterial activity [25]. Mycotoxins play an important role in the infection process. It has been found that toxin-producing ability correlates positively with the level of a pathogen’s aggressiveness [26]. DON kills the host cells by disrupting the cell membrane, thus causing cellular electrolyte leakage and an increase in cytoplasmic Ca2+ ions that leads to imbalance in cellular homeostasis [27,28]. Increased production of such mycotoxins as DON and the emerging mycotoxin culmorin (CUL) having synergistic toxic effects resulting in increased pathogen aggressiveness and enhanced host colonization [29]. Lu and Edwards [30] revealed small, secreted cysteine-rich proteins as a common source of F. graminearum–wheat interaction effectors involved in triggering resistance or susceptibility between wheat and Fusarium. In a recent study by Fabre et al. [31] examining the aggressiveness of three F. graminearum strains, the findings show that contrasts were based not upon the existence of strain-specific molecules, but rather upon the ability of a strain to accumulate sufficient effector protein abundance. Protein abundance variance was mostly driven by the strain genetics and part was also influenced by the host cultivar; however, strains by cultivar interactions were marginally detected, depicting that strain-specific protein accumulations did not depend on the host cultivar.
3. Plant Defense
3.1. Mechanisms of Resistance
Cultivar resistance is an important factor that may significantly affect infection of plants, and cultivated genotypes may have different mechanisms of resistance. Wheat’s resistance against FHB includes many resistance mechanisms [32]. In the case of Fusarium infection, this includes the following components: type I, resistance to initial infection; type II, resistance to spread of symptoms [33]. After types I and II resistance, there also exists a type III resistance to toxin accumulation [34,35]. Mesterházy [36,37] distinguished the following components (types) of head blight resistance: I. resistance to invasion; II. resistance to spreading; III. resistance to kernel infection; IV. Tolerance; V. resistance to toxin accumulation; VI. resistance to late blighting; and VII. resistance to head death above infection site. All these types of resistance are interdependent, but they are presumably based upon different mechanisms and inherited independently.
There are two types of plant protection against infection, active and passive.
3.1.1. Active Resistance
The interaction of F. graminearum with small grain cereals has been studied in various cellular, molecular, and biochemical areas. Plant defenses are based on both physical barriers, such as the cell wall and its modifications, as well as chemical defense mechanisms that are induced in response to external stimuli [38,39,40].
After recognizing the pathogen, the host plants’ basal defense responses lead to activation of several resistance mechanisms. These include production of reactive oxygen species (ROS), enzymatic and non-enzymatic antioxidants [41], cell wall reinforcement associated with phenylpropanoid metabolism [32], and callose deposition [42]. ROS accumulation and removal are controlled in plant–pathogen interactions by enzymatic and non-enzymatic antioxidants. Such enzymatic antioxidants as peroxidase (POX) and catalase (CAT) are involved in scavenging H2O2, whereas superoxide dismutase is a scavenger of O2− and changes this molecule to H2O2 in living cells [43]. The soluble phenols play a significant function in redox regulation in plants and can have an effect as antimicrobial compounds. In addition to ROS, there are several types of reactive nitrogen species (RNS), including nitric oxide (NO). In particular, this signaling molecule might be involved in defense reactions mediated by ROS, such as production of phytoalexins and polyamines, transcription activation, or cell wall reinforcement [43]. Recently, Khaledi et al. [44] found that NO production increased in ears and seedlings of wheat varieties after inoculation with F. graminearum, and a greater increase was characteristic of the more resistant variety compared to the susceptible one. Therefore, NO might be involved in wheat defense responses to the pathogenic Fusarium species and the relationship between ROS and RNS should be investigated in more detail.
ROS accumulation and programmed cell death as its consequence would be helpful defense strategies leading to reduced progress of the hemibiotrophic F. graminearum in the host tissues and increased resistance at the early time points after inoculation, when this pathogen is in its biotrophic phase [43]. Wheat plants’ secondary metabolites can play an important active role in their resistance against Fusarium spp. A wide range of secondary metabolites with both antioxidant and pro-oxidant properties (depending upon their concentrations), such as phenolic compounds, carotenoids, and linoleic acid-derived hydroperoxides, are synthesized and act as modulators of mycotoxin biosynthesis [26,45].
In addition to the induction of phenolics and phytoalexins, active plant defense also involves expression of pathogenesis-related (PR) proteins. When stimulated by various pathogens or conditions that mimic the effects of pathogen infection, the host is thought to inhibit growth, multiplication, and/or spread of the invading pathogen by synthesizing PR proteins [40,46]. PR proteins are presently grouped into 17 families based upon their protein sequence similarities, enzymatic activities, and biological functions [47,48].
Carotenoid and tocopherol effects on FHB and trichothecene accumulation are less investigated [49]. Boba et al. [50] were able in their study to decrease carotene content through the suppression of a lycopene β-cyclase gene. The suppression of this gene in transgenic flax then led to an increase in tocopherols, squalene, gibberellic acid, and menthol. An increase in Fusarium resistance was driven by these changes in the transgenics.
Table 1 reports determined contents of endogenous wheat phytochemicals and metabolites potentially involved in protection against oxidative stress caused by Fusarium spp. in wheat. Anthocyanins in wheat are based upon six aglycons–anthocyanidins, which differ only in their glycosylation patterns in attached sugar moieties and/or their esterification with phenolic acids [51]. This may be due to the antioxidant activity of anthocyanins, which is known to increase plant resistance [52].
3.1.2. Passive Resistance
Plant morphology can play an important role during infection and provide a passive way of resistance or susceptibility to FHB [72,73,74]. In general, Steiner et al. [72] and Jones et al. [73] confirm that earlier flowering varieties and taller plant height show greater resistance compared to later flowering and shorter varieties [75,76,77]. Positive correlations between spike compactness and FHB severity have recently been reported from a study by Giancaspro et al. [76]. Other traits associated with FHB include heading time, degree of anther extrusion, and presence or absence of awns. The extent of anther retention after flowering and FHB severity were shown to be positively correlated with the semi-dwarfing allele Rht-D1b [78].
4. Secondary Metabolites
Many naturally occurring secondary metabolites in plants are involved in resistance mechanisms against FHB. The majority of these are phenolic compounds with antioxidant properties. Significantly contained in wheat are phenolic acids (in free, conjugated, and bound forms) [79], flavonoids [80,81], alkylresorcinols [82], benzoxazinoids [83], phytohormones [84], and volatile organic compounds [85].
4.1. Phenolic Compounds/Antioxidants
Constituting a broad spectrum of genetic plant defense mechanisms against pathogens, the accumulation of phenolic compounds has been shown to inhibit in vitro growth and reproduction across a wide array of fungal genera and can help in reducing Fusarium trichothecene mycotoxin accumulation in cereal grains [86]. Phenolic compounds are secondary metabolites produced by the phenylpropanoid pathway and are synthesized by plants from the amino acid phenylalanine [87]. Plant biosynthesis produces various phenols that are commonly grouped as phenolic acids and flavonoids.
4.1.1. Phenolic Acids
Phenolic acids are predominant in cereal grain extracts and are derivatives of either cinnamic acid or benzoic acid (Figure 1). In wheat, they include (in descending quantity) ferulic, sinapic, 4-hydroxybenzoic, vanillic, and caffeic acids [67]. Their contents in common wheat are substantially greater as compared with durum wheat (Table 1). This corresponds to the facts that durum wheat (Triticum turgidum sp. durum) is notable for its extreme susceptibility to FHB and that sources of FHB resistance are rare in the gene pool of the tetraploid wheat [77]. Indeed, Stuper-Szablewska and Perkowski [67] found in durum wheat only ferulic, p-coumaric, and syringic acids, whereas common wheat contained in addition gallic, 4-hydroxybenzoic, vanillic, chlorogenic, caffeic, and sinapic acids. Phenolic acids can be ranked as follows in ascending order of toxicity toward F. graminearum: chlorogenic acid < p-hydroxybenzoic acid < caffeic acid < syringic acid < p-coumaric acid < ferulic acid [80]. Martin [68] found a weak but significant effect of ferulic acid (FA) on resistance against Fusarium according to FA levels in grains but suggests that FA levels in grains are generally low (Table 1). Across all genotypes, however, the FA content increased significantly from 97.1 mg kg−1 in flowering tissues to 120.4 mg kg−1 10 days after anthesis. The effectiveness of phenolic acids against Fusarium spp. could be related to their antioxidant activity, which Verma et al. [66] measured in six wheat cultivars. In their study, high antioxidant activity as determined by ABTS test using 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) was proven for trans-ferulic acid, syringic acid, sinapic acid, and caffeic acid, all of which were obtained by acid hydrolysis. Among the alkaline hydrolyzed phenolic acids, higher antioxidant activity was shown for ferulic acid, p-coumaric acid, sinapic acid, and vanillic acid, respectively. Generally, the total content of all phenolic acids may be an important factor in their protective effect against Fusarium spp.
Phenolic acids found in cereals exist in both soluble (free) and insoluble (cell wall-bound) forms [88]. For free phenolic acids, 80% ethanol [66,89], methanol/water (80:20, v/v) [88,90], or methanol-water (70:30, v/v) acidified with 0.1% formic acid is generally used [91]. In addition, different ratios methanol/water are used (7:3, 1:1, v/v) [56,92], but also 95% ethanol or dimethyl sulfoxide has been used [93]. Bound or conjugated phenolic acids should be released by alkaline (with 2 M NaOH) and acidic hydrolysis (with 6 M HCl) [56,66,88]. Martini et al. [60] used, for extraction of phenolic acids, ethanol/water (80:20, v/v) and ethyl acetate, alkaline hydrolysis after initial ethanol/water extraction with 2 m sodium hydroxide, and successive extraction with ethyl acetate.
The major part of phenolic compounds is in the germ and bran tissues of grains. Moreover, phenolic acids, and most predominantly ferulic and p-coumaric acids, have an important role in limiting polysaccharide degradation by exogenous enzymes, where they act as a cross-link between polysaccharides and between polysaccharides and lignin [89]. Phenolic compounds in plants are involved in the pathogen and plant interaction. In wheat (winter and spring cultivars), significantly greater amounts of free phenolic compounds were detected in the glumes, lemmas, and paleas of the spring cultivars prior to and at all sampling times after inoculation compared to the winter wheat cultivars [94]. The spring cultivars show resistance against initial infection by the fungus [94]. Inasmuch as p-coumaric acid increases significantly in the glumes, lemmas, and paleas of the spring cultivars, it appears that phenolic compounds play a role in cultivars’ resistance to F. culmorum. In cereals, cell wall-bound ferulic acid (FA), along with its dehydrodimers, as well as free chlorogenic acid and its hydrolyzed product caffeic acid, could be key components of resistance to toxigenic Fusarium species [95]. In a later study by Schöneberg et al. [93], FA had a significant influence on the growth of Fusarium species (F. poae, F. graminearum, and F. langsethiae) in comparison with the control treatment (p < 0.001). In their study, the black oat varieties Gailette and Zorro differed significantly and had as much as two times higher levels of FA compared with the yellow or white varieties Canyon and Husky. Inoculation with F. langsethiae caused reduction relative to the controls (by as much as 96–100% for FA and 97–100% for p-hydroxybenzoic acid). The reduction was complete after F. langsethiae inoculation in the case of vanillic acid across all examined varieties. Despite the overall reduction, the black oat varieties had significantly higher FA levels in comparison with white and yellow-hulled varieties. FA had a significant effect on the growth of all Fusarium species. In the case of F. graminearum, increasing FA concentration significantly decreased fungal growth relative to the control treatment, the reduction ranging from 3% (at 100 μg FA g−1, p > 0.05) to 64% (at 1000 FA μg g−1, p < 0.001) and to 88% (at 5000 μg FA g−1, p < 0.001) [93]. The same trend in reduction was observed for F. langsethiae. In contrast to FA, however, F. poae and F. graminearum exhibited an increase in growth when exposed to p-hydroxybenzoic acid and vanillic acid, whereas F. langsethiae showed mostly a decrease in growth. FA and p-hydroxybenzoic acid showed no significant effect on any mycotoxin, whereas quercetin had a minor but significant decreasing effect on neosolaniol and diacetoxyscirpenol. Giordano et al. [96] observed a significant negative correlation between DON contamination in corn (Zea mays L.) at harvest maturity and free phenolic acids and total antioxidant activity at the beginning of kernel development, whereas no significant correlation was observed with fumonisin contamination. Ferulic, p-coumaric, and caffeic acids were the main cell wall-bound phenolic acids during kernel development, whereas chlorogenic acid was the main free phenolic acid. In a study of fungal biotransformation of chlorogenic acid with F. graminearum, Gauthier et al. [95] demonstrated that F. graminearum possesses the ability to degrade chlorogenic acid into caffeic, hydroxychlorogenic, and protocatechuic acids, as well as caffeic acid into protocatechuic and hydroxycaffeic acids. Some of these metabolic products can contribute to the inhibitory efficiency of chlorogenic acid, thereby corroborating the contribution of chlorogenic acid to the chemical defense that cereals employ to counteract F. graminearum and its production of mycotoxins. Among the phenolic acids, derivatives of cinnamic acid, such as caffeic, ferulic, and p-coumaric acids, are most recognized as contributors to FHB resistance [91,95]. Cinnamic acid derivatives also have strong antioxidant properties, which constitute an important primary factor for the ability of phenolic acids to modulate mycotoxin production [95]. Similarly, in corn, the most efficient resistance factors were shown to be pericarp propanoids, mainly trans-ferulic acid, cis-ferulic acid, p-coumaric acid, and diferulates [97].
Another phenolic acid, salicylic acid, plays a significant role in plant immunity as a signaling molecule in eliciting resistance and increases its activity during the early phase of infection by F. graminearum [98,99]. In a recent study, Rocheleau et al. [99] reported that F. graminearum could utilize salicylic acid as a sole source of carbon to grow. Salicylate 1-monooxygenase and catechol 1,2-dioxygenase are two of the first key enzyme steps for salicylate degradation via catechol in the β-oxoadipate pathway. There also exists, however, a nonoxidative decarboxylation pathway of salicylic acid conversion to catechol via 2,3-dihydroxybenzoic acid [99].
Deoxynivalenol (DON) accumulation is enhanced by peroxide stress [92], and the inhibition of its production by phenolic acids is consistent with their ability to scavenge reactive oxygen radicals [91]. Nevertheless, there exist differences between strains of F. graminearum and F. culmorum carrying the DON chemotype, where enhancement of deoxynivalenol and acetyldeoxynivalenol production was recorded, and those strains carrying the nivalenol chemotype, wherein the same treatment yielded a 2.4- to 7-fold decrease in nivalenol and fusarenone accumulation [100,101]. There should be further investigation of interactions between different phenolic compounds that frequently co-occur in cereal grains [93].
4.1.2. Anthocyanins and Flavonoids
Flavones, flavonols, flavanones, flavan-3-ols, anthocyanidins, isoflavones, coumarins, stilbenes, and lignans are the main flavonoids and have various functions, including pigmentation and resistance to pathogens in plants [102,103]. The abundance and composition of these compounds in cereal grains contribute to either constitutive or induced synthesis and are highly variable depending upon the species, cultivar, and environmental conditions (Figure 2). Many phenolic compounds are bound to the cell wall, indicating that they are parts of the preformed general defense system against potential pathogens [104]. The specific biochemical pathways and mechanisms of their antifungal activity are not yet fully understood, however. Flavonoids comprise another group of compounds with antioxidant activity and have been identified from many plants. Some of them suppress trichothecene biosynthesis [49,52,93]. Anthocyanins have a protective role under conditions of extreme temperature, drought, and/or salinity, as they prevent lipid oxidation and protect the plasma membrane from damage [105]. Because infection of plants by various pathogens is accompanied by oxidative stress, the presence of anthocyanins in a plant may have a positive effect on the resistance to abiotic stress [106].
Anthocyanins in a plant are extracted with acidified methanol with HCl-methanol/hydrochlorid acid (85:15, v/v) [68,107], flavonoid aglycones [90] with 96% ethanol [9], for flavonoid glycosides methanol and acetonitrile are eluents, followed by alkaline hydrolysis (water/2 M NaOH, 1:4, v/v) [9,64] and acid hydrolysis (6 M HCl) and diethyl ether. Additionally, dimethyl sulfoxide (DMSO, 0.5–100 μM) can be used [102]. Several anthocyanins were identified by NMR spectroscopy and mass spectrometry after sequential extraction of blue bread wheat ‘UC66049’ with solvents of various polarities and multiple chromatographic fractionations [108].
Antifungal activity of grain-endogenous flavonoids has recently been reported in barley and wheat cultivars resistant to FHB [109]. The dihydroquercetin-accumulating barley mutant ant 18–159 inhibits hyphal penetration by F. graminearum and F. culmorum into the grain testa. This resistance has been attributed to the mutant’s excessive production of dihydroquercetin due to a specific mutation in the gene encoding for dihydroflavonol reductase [93,110]. Furthermore, wheat varieties with dark and purple-colored grains have been shown to contain large amounts of FA and vanillic acid [93,111]. It is nevertheless likely that the fungus metabolized an extensive amount of the endogenous phenolic compounds, thereby leading to the observed differences between control and inoculated treatments. This was reported also by Bilska et al. [9]. In their study, trichothecene accumulation by F. culmorum and F. graminearum was significantly reduced by quercetin, kaempferol, luteolin, apigenin, and naringenin, although this effect was dependent upon the fungal strain and flavonoid levels (Figure 3). Nevertheless, correlation between antiradical and antioxidant properties of flavonoids and their effect on Fusaria was established. Antioxidant properties of flavonoids such as quercetin can interfere with mycotoxin production, but FA is considered the most potent phenolic acid with antifungal activity against Fusarium species [80]. It is clear that the antioxidant properties of phenolic acids and flavonoids apply here. In fact, the most consistent overall inhibition of mycelial growth was observed with FA treatments. Nevertheless, impacts of naringenin, apigenin, kaempferol, and quercetin at concentrations 400 mg kg−1 and 800 mg kg−1 in inhibiting mycotoxin accumulation were also reported [9]. The flavanone naringenin with a single bond between C2 and C3 was more efficient than apigenin having a double bond between these two carbon atoms. In a study by Bollina and Kushalappa [112], naringenin at LD50 concentration 1.58 mM and quercetin at LD50 concentration 2.95 mM totally inhibited biosynthesis of DON and 3-acetyldeoxynivalenol in barley, as similarly did p-coumaric, sinapic, ferulic, and caffeic acids, respectively, at LD50 concentrations 1.15, 1.74, 1.76, and 2.50 mM. Levels of apigenin, kaempferol, luteolin, naringenin, quercetin, rutin, and vitexin were significantly increased in winter wheat after inoculation with Fusarium culmorum [64] (Table 1). Gunnaiah and Kushalappa [113] found that in resistant wheat cultivars, accumulation of such phenylpropanoids as syringyl-rich monolignols and their glucosides reduced pathogen colonization and increased wheat cell wall thickening. They considered phenylpropanoid pathway genes responsible for flavonoid biosynthesis to have enhanced host resistance mechanisms and reduced pathogen growth due to the antifungal and antioxidant properties of biosynthesized flavonoids and lignols [113] (Figure 3).
Lignans have been discovered in different parts of plants, including seeds [114]. These are vascular plant secondary metabolites, which are attributed for a wide range of physiological functions and beneficial properties [115]. Pathogen attack may accelerate the rate of lignin and lignans synthesis and deposition, which results in an inhibition of pathogen growth and its confinement [116].
4.1.3. Alkylresorcinols
Alkylresorcinols (AR), also known as resorcinolic lipids, are phenolic lipids composed of long aliphatic chains and resorcinol-type phenolic rings (Figure 4). Alkylresorcinols are relatively rare in nature, with the main known sources being wheat, rye, barley, and triticale (i.e., cereal grasses). Alkylresorcinols are present in large amounts in the bran layer (e.g., pericarp, testa, and aleurone layers) of wheat and rye (0.1–0.3% of dry weight) [117]. Alkylresorcinols can also be found in rice, though not in the edible parts of the rice plant [118]. They are present in the endosperm (the part of cereal grain used to make white flour) only in exceptionally low amounts, which means that alkylresorcinols can be used as biomarkers for people who eat foods containing wholegrain wheat and rye rather than cereal products based upon white flour [54,119]. Similarly, in a study by Ziegler et al. [53] bread wheat (761 ± 92 mg g−1 DM) and spelt (743 ± 57 mg g−1) belonging to the hexaploid species showed higher AR levels than did the tetraploid durum (654 ± 48 mg g−1, p < 0.05), while the levels found in the diploid einkorn (737 ± 91 mg g−1) and the tetraploid emmer (697 ± 94 mg g−1) did not differ significantly from those in the other species.
Alkylresorcinols are extracted by acetone, methanol, or mixture methanol/methyl-tert. butyl ether (MeOH/MTBE, 1:1, v/v), ethyl acetate or n-hexane [53]. Landberg [54] used diethyl ether and methanol, while Suzuki et al. [118] used 10% MeOH/CHCl3.
Righetti et al. [56] have suggested involvement of the lipophilic phenolic fraction in mycotoxin accumulation in wheat. The contamination, expressed as the sum of DON and deoxynivalenol 3-glucoside, was found to be significantly lower in common wheat and spelt than in emmer, durum wheat, and einkorn, while following the trend hexaploid < tetraploid < diploid species. The mycotoxins content negatively correlated with the total 5-n-alkylresorcinols, and the AR21:0/AR23:0 ratio (AR21:0 is 5-n-heneicosylresorcinol, where the saturated hydrocarbon chain attached to position 5 of resorcinol consists of 21 carbon atoms; AR23:0 is 5-n-tricosylresorcinol having 23 carbon atoms and no double bonds, Figure 4) was recently reported by Righetti et al. [56] as an indicator of antifungal activity. Their results suggest that only the lipophilic phenolic fraction in wheat exerts an inhibitory effect on mycotoxin accumulation [56].
4.2. Benzoxazinoids
The principal phytoanticipin in wheat and corn is 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA, Figure 5). For the extraction of benzoxazinoids, 70% methanol coupled with accelerated extraction system is generally used, as it is described by Kowalska and Kowalczyk [120]. DIMBOA accumulation is regulated by jasmonic acid in both the aboveground parts of wheat and the roots [121]. A recent study found that jasmonic acid signaling and DON detoxification have relevance for seedling resistance and that seedling development and root growth are jasmonic acid-controlled processes [122]. The results of this study confirm that development-specific determinants of resistance against Fusarium are more significant than are the organ-specific determinants, and suggest roots to be an important organ in studies of Fusarium–wheat interactions.
4.3. Volatile Organic Compounds
Pathogen infestation of vegetative tissues can induce volatile organic compounds (VOCs) production, which can in turn provide defensive functions to both injured and uninjured plants. In wheat, oats, and barley, the blend of VOCs induced after Fusarium spp. infestation was dominated by (Z)-hex-3-enal, (E)-hex-2-enal, (E)-hex-2-en-1-ol, (Z)-hex-3-enyl acetate, 1-hex-1-enyl acetate, β-linalool, and β -caryophyllene [70] (Figure 6). Buśko et al. [71] recently reported findings about VOCs contained in the grain of winter wheat varieties under controlled conditions after inoculation with F. culmorum. Among hydrocarbons, alcohols, aldehydes, ketones, aromatics, terpenes, and other components, terpenes were of particular importance [71] (Figure 6). Interestingly, the terpenes produced in wheat grains were further changed by F. culmorum into other compounds that were more toxic. Significantly large quantities of terpenes were observed in wheat grains inoculated with F. culmorum compared to uninoculated control samples. Trichodiene, thujopsene, and β-chamigrene were dominant in inoculated samples, while α-pinene, indane, and 3-carene dominated in control samples.
Nazareth et al. [123] used the volatile gaseous fumigant allyl isothiocyanate that is not contained in wheat (an antimicrobial organosulfur compound that can be obtained from mustard Brassica spp.) to restrict the production of beauvericin and enniatin produced by Fusarium poae in wheat flour. Synthesis of beauvericin was more inhibited than was that of enniatin.
4.4. Phytohormones
When studying the influence of phytohormones on the defense response of wheat against F. graminearum infection, Qi et al. [69] determined that infection of heads with F. graminearum induced accumulation of salicylic acid, jasmonic acid, abscisic acid, and indole acetic acid [69] (Figure 7). Small et al. [124] and Trapp et al. [125] reported the extraction of these phytohormones can be provided with methanol, ethyl acetate, mixture acetone-ethanol-water (1:1:2, v/v/v) or 100% cold methanol, dichlormethane, or isopropanol, respectively.
Jasmonic acid treatment reduced F. graminearum growth and FHB symptoms even as an increase in FHB was observed with abscisic acid [69]. After the application of some elicitors, including methyl jasmonate, on Fusarium verticillioides in corn, however, Small et al. [124] determined that these were not effective for reducing Fusarium ear rot and fumonisin contamination.
4.5. Carotenoids
The carotenoids are yellow pigments with antioxidant and photoprotective properties that belong to the terpenes, and their basic structure consists of eight isoprene units. Two classes of carotenoids can be distinguished: (1) carotenes are pure hydrocarbons, and (2) xanthophylls are derivatives containing one or more oxygen atoms. A wide range of carotenoids may be present in wheat grain, including lutein, β-carotene, β-cryptoxanthin, zeaxanthin, antheraxanthin, taraxanthin (lutein 5,6-epoxide), triticoxanthin, and flavoxanthin [51] (Figure 8). Carotenoids are efficiently extracted with mixture ethanol/acetone/hexane (1:1:2, v/v/v) [126]. In another study, extraction with hexane/ethyl acetate mixture (9:1, v/v) after incubation with KOH, 95% ethanol, NaCl (10 g L−1) and pyrogallol (60 g L−1 ethanol) has been applied [127]. Lutein is the most abundant carotenoid, followed by zeaxanthin, antheraxanthin, α-carotene, and β-carotene, while β-cryptoxanthin is a minor component or it occurs at non-detectable levels [51,126].
Bread wheat (Triticum aestivum L.) is poor in carotenoids, but durum wheat (Triticum durum Desf.) and other related species, such as einkorn (T. monococcum L.), showed higher carotenoid content and thereby potential as donors of useful traits [128]. Carotenoid content and color are influenced by intrinsic genotypic characteristics [51,129], and to a lesser extent by environmental conditions [62]. Delgado et al. [127] observed durum wheat cultivars to show greater lutein content than did common wheat cultivars. In their study, durum wheat was more susceptible to mycotoxin contamination than was common wheat. Positive correlations between the levels of lutein and mycotoxins in durum wheat cultivars were detected for the following mycotoxins: DON and its derivative DON-3-glucoside, moniliformin, as well as culmorin and its derivatives [127]. Martini et al. [60] observed stronger impact of genetic factors on the content of yellow (carotenoid) components and total antioxidant capacity in durum wheat, while content of total polyphenolics and phenolic acids was mostly affected by environmental conditions.
In wheat genotypes with higher levels of FHB resistance, the individual metabolites involved with particular efficiency in protection processes are represented in various proportions and they all contribute to final resistance. The degree of a particular genotype’s resistance will depend upon its genetic and enzymatic equipment for biosynthesis of the active metabolites and corresponds to the content of these compounds in the grain. Therefore, the representation of compounds with resistance activity in each genotype should be comprehensively determined and assessed.
5. Pigmentation of Grains and Fhb Resistance
The host deploys distinctive resistance mechanisms in different organs of wheat against F. graminearum [130,131]. Grain color and its relationship to resistance is the aspect most intensively studied. There exists various coloration of the grain in wheat due to levels of biologically active pigments possessing antioxidant capacity [51]. Descriptions of grain color in wheat are generally qualitative in nature: white, yellow, red, blue, or purple. Red pigmentation is associated with deposition of proanthocyanidins in the testa, whereas both blue and purple pigmentations derive from the accumulation of anthocyanins in the aleurone and the pericarp [132,133].
Anthocyanins can be synthesized in wheat genotypes in grains and in various organs, and they can be involved in the plant response to oxidative stress. Anthocyanins can be contained in the pericarp (purple coloration) or aleurone (blue coloration). When they are contained in both tissues, the color of the grains turns to a dark brown–black shade [134]. Hexaploid wheat varieties are being bred today with increased carotenoid content in the grain, and especially with higher lutein content. The highest carotenoid contents have been observed in yellow- and purple-grained genotypes [126].
In addition to the yellow grain color shades occurring due to carotenoids content, wheat varieties also exist that contain anthocyanins in the aleurone or pericarp layers causing blue and purple grain coloring [135].
6. Use of Antioxidants in Breeding for FHB Resistance
The best strategy for controlling FHB is to breed new varieties with reduced susceptibility. Colored-grain wheats are a potentially great alimentary source of other health-enhancing compounds, such as anthocyanins [51,136], tocols [137], and phenolic acids [88]. Expanding the breeding interest in the use of wheat forms with different grain color and plant organs can be a potential benefit for the creation of lines with increased resistance to various stresses. Spanić et al. [138] have demonstrated that differences in the antioxidant response of wheat varieties can be a valuable marker for the selection of FHB resistance. Rapid activation of the antioxidant system appears to be important in overcoming FHB, but the timing and type of antioxidant enzymes expressed are important. A large amount of variability in enzyme activity and H2O2 content exists within wheat varieties [138]. Measurements of ROS levels and the scavenging activities of antioxidant contents may be very useful for breeding programs to screen and select FHB-resistant varieties [41]. An example of a variety in which secondary metabolites have been implicated in FHB resistance is the most commonly used source of breeding material for FHB resistance, the cultivar Sumai 3 [113]. Gunnaiah and Kushalappa [113] report that several resistance-related metabolites produced in Sumai-3 can explain several mechanisms of resistance. Resistance in the Sumai-3 cultivar to FHB is mainly due to phenylpropanoid and flavonoid metabolites. Antimicrobial compounds and cell wall thickening by hydroxycinnamic acid amides in Sumai-3 also resist FHB [113].
Results obtained by Etzerodt et al. [49] could form a basis for choosing wheat cultivars using metabolite profiling as a marker for selecting wheat cultivars with improved resistance against FHB and accumulation of trichothecene toxins in wheat heads. They found that several phenolic acids, lutein, and β-carotene affected DON accumulation, but the effect varied for the two studied wheat types (spring versus winter wheat).
Furthermore, positive experiences in examining crops other than wheat have also been reported. In corn silk and kernels, induced expression of 3-deoxyanthocyanidins and flavan-4-ols imparted resistance to F. verticillioides and F. graminearum [40]. Expression data revealed that flavonoid pathway P1 and P2 genes were active during the early stages of silk development and PR-4 and PR-5 genes showed developmental and fungus-induced expression [40]. Anthocyanins can contribute to antioxidant properties of the polyphenolic complex, but they are unstable and can be easily degraded. Thus, their effects on fungi are not yet entirely clear. In their study of F. graminearum effect on wheat genotypes, Martin et al. [139] found no relationship with anthocyanin levels, which were affected more by environmental conditions. Meanwhile, Bernardi et al. [140] determined the red corn cultivar Rostrato Rosso having the greatest accumulation of anthocyanins to be highly resistant to the penetration and diffusion of F. verticillioides. Similarly, in a study by Lorenz-Kukuła et al. [141], expression of specific genes in flax increased resistance against Fusarium and resulted in a significant increase in the levels of anthocyanins and flavonoids and in their antioxidant capacity. In addition, metabolomic analysis of a red cotton mutant (S156) resistant to Verticillium dahliae showed enrichment of flavonoids and anthocyanins and upregulated expression of flavonoid biosynthesis genes [142].
On the other hand, it is known that there also exists varieties with colored grains that show susceptibility to FHB. An example is the variety Skorpion with blue grain. Although the anthocyanins which it contains are considered to offer health benefits due to their antioxidant effects, the variety shows susceptibility to FHB [90]. Thus, grain color alone cannot be taken as a marker to detect resistance. Moreover, for varieties with colored grain, it is always necessary to evaluate varietal resistance in trials through artificial infection.
7. Conclusions and Future Directions
In conclusion, many compounds like hydrophilic and lipophilic antioxidants (phenolic compounds such as phenolic acids, anthocyanins, flavonoids, and lipophilic carotenoids), alkylresorcinols, volatile organic compounds, phytohormones, and benzoxazinoids can be involved in protective mechanisms against FHB, the most common disease affecting wheat. However, these protective compounds affect Fusarium strains in varying degrees depending upon their antioxidant activity and different biochemical and cellular mechanisms. Complete resistance to F. graminearum is not detected in any host plant, and selection of FHB-resistant genotypes remains challenging. Therefore, considerable effort is needed to gain more in-depth insight into the genetics of the pathogen populations and to find novel and effective resistance markers in various hosts, as well as to identify the major components of cereals’ defense against the pathogen. It follows that more detailed studies are required to obtain a better understanding of the protective effects and modes of activity of these metabolites. Indirect selection for an antioxidant response associated with FHB resistance can be performed and the antioxidative mechanism plays a significant role against Fusarium biotic stress in wheat and other cereals. The efficient use of native resistance in the wheat gene pool, introgression of resistant alleles, and implementation of modern genotypic strategies to increase levels of native secondary metabolites with antifungal properties can enhance FHB resistance of new wheat varieties. A complex of secondary metabolites composed of individual antioxidants and compounds having antifungal efficiency, with their various contents and possible synergistic effects, can determine the resistance of wheat genotypes. In short, more detailed studies are warranted concerning new wheat genotypes, their native resistance metabolites, and the effects of these upon FHB.
Conceptualization, J.C., J.L., M.T. and P.M.; methodology, J.L. and M.O.; software, M.O.; validation, J.L., P.M. and J.C.; formal analysis, M.T.; investigation, J.L., M.O. and M.T.; resources, J.C.; data curation, J.L.; writing—original draft preparation, J.C. and J.L.; writing—review and editing, J.C.; visualization, J.L.; supervision, J.C.; project administration, M.T.; funding acquisition, P.M. All authors have read and agreed to the published version of the manuscript.
This research was funded by the Ministry of Agriculture of the Czech Republic, Project No. QK1910343.
Not applicable.
Not applicable.
The data that support the findings of this study are available from the corresponding authors upon reasonable request.
This research was supported by Project S grant of the Ministry of Education, Youth and Sports of the Czech Republic.
The authors declare no conflict of interest.
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Enlarge this image.Figure 3. Structure of (a) aglycones of flavonoids and (b) monolignols determined in wheat grains.
Enlarge this image.Figure 4. Structure of 5-n-Alkylresorcinols identified in wheat grains: 5-n-heptadecylresorcinol (C17:0), 5-n-nonadecylresorcinol (C19:0), 5-n-heneicosylresorcinol (C21:0), 5-n-tricosylresorcinol (C23:0), 5-pentacosylresorcinol (C25:0).
Enlarge this image.Figure 5. Structure of 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA) detected in wheat grains.
Enlarge this image.Figure 6. Structure of (a) terpenes and (b) volatile organic compounds determined in wheat grains.
Contents of bioactive antioxidant natural metabolites and phytochemicals in wheat (mg kg−1 dry matter [DM]).
| Compound | Content | Reference |
|---|---|---|
| Total 5-n-alkylresorcinols | 761 bread wheat, 743 spelt, 654 durum, 697 emmer, 737 einkorn |
[ |
| 5-n-Heptadecylresorcinol (C17:0) | 32–34 common wheat |
[ |
| 5-n-Nonadecylresorcinol (C19:0) | 250–272 common wheat |
[ |
| 5-n-Heneicosylresorcinol (C21:0) | 368–474 common wheat |
[ |
| 5-n-Tricosylresorcinol (C23:0) | 84–108 common wheat | [ |
| 5-n-Pentacosylresorcinol (C25:0) | 26–33 common wheat | [ |
| Total anthocyanins | 210 Pp grain; 430 Pp bran |
[ |
| Cyanidin-3-glucoside | Ba 3.07, Pp 10.34, R 4.02 | |
| Cyanidin-3-rutinoside | 8.42 Ba, Pp | |
| Delphinidin-3-glucoside | 13.68 Ba | |
| Delphinidin-3-rutinoside | 33.44 Ba | |
| Malvidin-3-glucoside | 12.04 Ba, 0.48 Pp, 0.22 R | |
| Peonidin-3-arabinoside | 2.22 Ba, Pp | |
| Peonidin-3-glucoside | 0.88 Pp | |
| Peonidin-3-galactoside | 1.94 Ba, 0.58 Pp, 0.33 R | |
| DIMBOA-glucoside | 18 common wheat | [ |
| Total carotenoids | 1.63–4.19 einkorn, 4.73–13.64 emmer, 2.69–8.38 durum, 1.62–2.98 spelt, 1.40–4.90 bread wheat |
[ |
| α-Carotene | 7.3–13.4 T. monococcum | [ |
| β-Carotene | 0.116 spring wheat, 0.195 einkorn | |
| Zeaxanthin | 0.144 spring wheat, 0.351 einkorn, 0.138 emmer wheat | |
| Lutein | 1.096 spring wheat, 5.246 einkorn, |
|
| Total phenolics | 1499; 1545.7 mg FAE kg−1 DM |
[ |
| Total flavonoids | 270.0, 236.2–319.3 mg RE kg−1 DM |
[ |
| Apigenin | 2.512 control, 104.565 inoculated with F. culmorum | [ |
| Kaempferol | 6.009 control, 124.739 inoculated with F. culmorum | |
| Luteolin | 7.117 control, 458.404 inoculated with F. culmorum | |
| Naringenin | 7.115 control, 127.787 inoculated with F. culmorum | |
| Quercetin | 6.958 control, 512.934 inoculated with F. culmorum | |
| Rutin | 13.764 control, 332.44 inoculated with F. culmorum | |
| Vitexin | 6.481 control, 148.256 inoculated with F. culmorum | |
| Total phenolic acids | 987.3; 4061.4 mg kg−1 DM | [ |
| Salicylic acid | < 0.3–0.8 > free salicylic acid in leaves | [ |
| Protocatechuic acid | < 6.8–13.3 > bran; 9.2 | [ |
| Ferulic acid | 270–1446; 3000 bran |
[ |
| 4-Hydroxybenzoic acid | 87.3 control, 87.3 infected | [ |
| Gallic acid | < 1–37 >; control 57, infected 77,3 | |
| Vanillic acid | < 30–70 >; control 26.7, infected 37.0 | |
| Syringic acid | < 1–62 >; control 30.7, infected 23 | |
| t-Cinnamic acid | < 3–83 >; control 127.0, infected 343.3 | |
| p-Coumaric acid | < 1–63 >; bran 90; control 45.7, infected 44.0 | |
| Caffeic acid | < 2–90 >; bran 38; control 40, infected 46.7 | |
| Sinapic acid | < 2–2017 >; bran 200; control 136.0, infected 360.0 | |
| Chlorogenic acid | < 10–69 >; control 38.0, infected 39.0 | |
| Abscisic acid | Increase from 86 to 154 ng g−1 DW after inoculation with F. graminearum | [ |
| Indol-3-acetic acid | Increase from 83 to 26 328 ng g−1 DW after inoculation with F. graminearum | |
| Jasmonic acid | Increase from 29 to 410 ng g−1 FW after inoculation with F. graminearum | |
| (-)-β-Caryophyllene | Increase from 9 to 104 ng sample−1 after inoculation with F. graminearum | [ |
| β-Linalool | Increase from 12 to 405 ng sample−1 after inoculation with F. graminearum | |
| (-)-Thujopsene | Increase from 0.005 to 0.018 ratio unit after inoculation with F. culmorum | [ |
| Trichodiene | Increase from 0.009 to 0.027 ratio unit after inoculation with F. culmorum | |
| (-)-β-Chamigrene | Increase from 0.003 to 0.012 ratio unit after inoculation with F. culmorum | |
| (Z)-hex-3-enal | Increase from 14 to 139 ng sample−1 after inoculation with F. graminearum | [ |
| (E)-hex-2-enal | Increase from 1 to 709 ng sample−1 after inoculation with F. graminearum | |
| (E)-hex-2-en-1-ol | Increase from 9 to 881 ng sample−1 after inoculation with F. graminearum | |
| (Z)-hex-3-en-1-yl acetate | Increase from 22 to 218 ng sample−1 after inoculation with F. graminearum | |
| Hex-1-en-1-yl acetate | Increase from 3 to 477 ng sample−1 after inoculation with F. graminearum |
Pp: purple pericarp; Ba: blue alerone, R: red grain colour; FAE: ferulic acid equivalent; GAE: gallic acid equivalent; RE: retinol equivalent; MR: moderately resistant; R: resistant; S: susceptible; DW: dry weight; DM: dry matter; FW: fresh weigh.
References
1. Mielniczuk, E.; Skwaryło-Bednarz, B. Fusarium Head Blight, Mycotoxins and Strategies for Their Reduction. Agronomy; 2020; 20, 509. [DOI: https://dx.doi.org/10.3390/agronomy10040509]
2. Zain, M.E. Impact of Mycotoxins on Humans and Animals. J. Saudi Chem. Soc.; 2011; 15, pp. 129-144. [DOI: https://dx.doi.org/10.1016/j.jscs.2010.06.006]
3. Pleadin, J. Mycotoxins in Grains and Feed—Contamination and Toxic Effect in Animals. Biotechnol. Anim. Husb.; 2015; 31, pp. 441-456. [DOI: https://dx.doi.org/10.2298/BAH1504441P]
4. Chrpová, J.; Šíp, V.; Štočková, L.; Milec, Z.; Bobková, L. Resistance of Winter Wheat Varieties Registered in the Czech Republic to Fusarium Head Blight in Relation to the Presence of Specific Rht alleles. Czech J. Genet. Plant Breed.; 2010; 46, pp. 122-134. [DOI: https://dx.doi.org/10.17221/74/2010-CJGPB]
5. Edwards, S. Investigation of Fusarium Mycotoxins in UK Wheat Production-Update. Society of Feed Technologists, Proceedings of the 2nd International Symposium on Fusarium Head Blight, Orlando, FL, USA, 11–15 December 2004; Society of Feed Technologists, Michigan State University: East Lansing, MI, USA, 2005; pp. 398-400.
6. Krska, R.; Baumgartner, S.; Josephs, R. The State-of-the-Art in the Analysis of Type-A and -B Trichothecene Mycotoxins in Cereals. Fresenius J. Anal. Chem.; 2001; 371, pp. 285-299. [DOI: https://dx.doi.org/10.1007/s002160100992]
7. Spanu, F.; Scherm, B.; Camboni, I.; Pani, G.; Oufensou, S.; Macciotta, N.; Pasquali, M.; Migheli, Q. FcRav2, a Gene with a ROGDI Domain Involved in Fusarium Head Blight and Crown Rot on Durum Wheat Caused by Fusarium culmorum. Mol. Plant Pathol.; 2018; 9, pp. 677-688. [DOI: https://dx.doi.org/10.1111/mpp.12551] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28322011]
8. Bilska, K.I.; Jurczak, S.; Kulik, T.; Ropelewska, E.; Olszewski, J.; Zelechowski, M.; Zapotoczny, P. Species Composition and Trichothecene Genotype Profiling of Fusarium Field Isolates Recovered from Wheat in Poland. Toxins; 2018; 10, 325. [DOI: https://dx.doi.org/10.3390/toxins10080325] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30103473]
9. Bilska, K.; Stuper-Szablewska, K.; Kulik, T.; Buśko, M.; Załuski, D.; Jurczak, S.; Perkowski, J. Changes in Phenylpropanoid and Trichothecene Production by Fusarium culmorum and F. graminearum Sensu Stricto via Exposure to Flavonoids. Toxins; 2018; 10, 110. [DOI: https://dx.doi.org/10.3390/toxins10030110]
10. Aoki, T.; Ward, T.J.; Kistlet, H.C.; O’Donnell, K. Systematics, Phylogeny and Trichothecene Mycotoxin Potential of Fusarium Head Blight Cereal Pathogens. JSM Mycotoxins; 2012; 62, pp. 91-102. [DOI: https://dx.doi.org/10.2520/myco.62.91]
11. Wagacha, J.M.; Muthomi, J.W. Fusarium culmorum: Infection Process, Mechanisms of Mycotoxin Production and Their Role in Pathogenesis in Wheat. J. Crop Prot.; 2007; 26, pp. 877-885. [DOI: https://dx.doi.org/10.1016/j.cropro.2006.09.003]
12. D’Mello, J.P.; Placinta, C.M.; Macdonald, A.M. Fusarium Mycotoxins: A Review of Global Implications for Animal Health, Welfare and Productivity. Anim. Feed Sci. Technol.; 1999; 80, pp. 183-205. [DOI: https://dx.doi.org/10.1016/S0377-8401(99)00059-0]
13. Buerstmayr, H.; Stierschneider, M.; Steiner, B.; Lemmens, M.; Griesser, M.; Nevo, E.; Fahima, T. Variation for Resistance to Head Blight Caused by Fusarium graminearum in Wild Emmer (Triticum dicoccoides) Originating from Israel. Euphytica; 2003; 130, pp. 17-23. [DOI: https://dx.doi.org/10.1023/A:1022324727780]
14. Pereyra, S.A.; Dill-Macky, R.; Sims, A.L. Survival and Inoculum Production of Gibberella zeae in Wheat Residue. Plant Dis.; 2004; 88, pp. 724-730. [DOI: https://dx.doi.org/10.1094/PDIS.2004.88.7.724] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30812483]
15. Liu, X.; Wang, J.; Xu, J.; Shi, J. FgIlv5 is Required for Branched-Chain Amino Acid Biosynthesis and Full Virulence in Fusarium graminearum. Microbiology; 2014; 160, pp. 692-702. [DOI: https://dx.doi.org/10.1099/mic.0.075333-0]
16. Sperschneider, J.; Gardiner, D.M.; Thatcher, L.F.; Lyons, R.; Singh, K.B.; Manners, J.M.; Taylor, J.M. Genome-Wide Analysis in Three Fusarium Pathogens Identifies Rapidly Evolving Chromosomes and Genes Associated with Pathogenicity. Genome Biol. Evol.; 2015; 7, pp. 1613-1627. [DOI: https://dx.doi.org/10.1093/gbe/evv092]
17. Dweba, C.C.; Figlan, S.; Shimelis, H.A.; Motaung, T.E.; Sydenham, S.; Mwadzingeni, L.; Tsilo, T.J. Fusarium Head Blight of Wheat: Pathogenesis and Control Strategies. Crop Prot.; 2017; 91, pp. 114-122. [DOI: https://dx.doi.org/10.1016/j.cropro.2016.10.002]
18. Khaledi, N.; Taheri, P.; Falahati-Rastegar, M. Identification, Virulence Factors Characterization, Pathogenicity and Aggressiveness Analysis of Fusarium spp., Causing Wheat Head Blight in Iran. Eur. J. Plant Pathol.; 2017; 147, pp. 897-918. [DOI: https://dx.doi.org/10.1007/s10658-016-1059-7]
19. Kikot, G.E.; Hours, R.A.; Alconada, T.M. Contribution of Cell Wall Degrading Enzymes to Pathogenesis of Fusarium graminearum: A Review. J. Basic Microbiol.; 2009; 49, pp. 231-241. [DOI: https://dx.doi.org/10.1002/jobm.200800231] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19025875]
20. Qin, J.; Wang, G.; Jiang, C.; Xu, J.R.; Wang, C. 1Fgk3 Glycogen Synthase Kinase is Important for Development, Pathogenesis, and Stress Responses in Fusarium graminearum. Sci. Rep.; 2015; 5, 8504. [DOI: https://dx.doi.org/10.1038/srep08504]
21. Wanyoike, W.M.; Kang, Z.; Buchenauer, H. Importance of Cell Wall Degrading Enzymes Produced by Fusarium graminearum During Infection of Wheat Head. Eur. J. Plant Pathol.; 2002; 108, pp. 803-810.
22. Feng, J.; Liu, G.; Selvaraj, G.; Hughes, G.R.; Wei, Y. A secreted Lipase Encoded by LIP1 is Necessary for Efficient Use of Saturated Triglyceride Lipids in Fusarium graminearum. Microbiology; 2005; 151, pp. 3911-3921. [DOI: https://dx.doi.org/10.1099/mic.0.28261-0]
23. Gao, S.; Glenn, A.E.; Blacutt, A.A.; Gold, S.E. Fungal Lactamases: Their Occurrence and Function. Front. Microbiol.; 2017; 8, E1775. [DOI: https://dx.doi.org/10.3389/fmicb.2017.01775]
24. Glenn, A.E.; Davis, C.B.; Gao, M.; Gold, S.E.; Mitchell, T.R.; Proctor, R.H.; Stewart, J.E.; Snook, M.E. Two Horizontally Transferred Xenobiotic Resistance Gene Cluster Associated with Detoxification of Benzoxazolinones by Fusarium Species. PLoS ONE; 2016; 11, e0147486. [DOI: https://dx.doi.org/10.1371/journal.pone.0147486]
25. Luz, C.; Saladino, F.; Luciano, F.; Mañes, J.; Meca, G. Occurrence, Toxicity, Bioaccessibility and Mitigation Strategies of Beauvericin, a Minor Fusarium Mycotoxin. Food Chem. Toxicol.; 2017; 107, pp. 430-439. [DOI: https://dx.doi.org/10.1016/j.fct.2017.07.032]
26. Kosová, K.; Chrpová, J.; Šíp, V. Cereal Resistance to Fusarium Head Blight and Possibilities of Its Improvement through Breeding. Czech J. Genet. Plant Breed.; 2009; 45, pp. 87-105. [DOI: https://dx.doi.org/10.17221/63/2009-CJGPB]
27. Bushnell, W.; Perkins-Veazie, P.; Russo, V.; Collins, J.; Seeland, T. Effects of Deoxynivalenol on Content of Chloroplast Pigments in Barley Leaf Tissues. Phytopathology; 2010; 100, pp. 33-41. [DOI: https://dx.doi.org/10.1094/PHYTO-100-1-0033] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19968547]
28. Cossette, F.; Miller, J.D. Phytotoxic Effect of Deoxynivalenol and Gibberella Ear Rot Resistance of Corn. Nat. Toxins; 1995; 3, pp. 383-388. [DOI: https://dx.doi.org/10.1002/nt.2620030510]
29. Wipfler, R.; Mc Cormick, S.P.; Proctor, R.H.; Teresi, J.M.; Hao, G.; Ward, T.J.; Alexander, N.J.; Vaughan, M.M. Synergistic Phytotoxic Effects of Culmorin and Trichothecene Mycotoxins. Toxins; 2019; 11, 555. [DOI: https://dx.doi.org/10.3390/toxins11100555] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31547160]
30. Lu, S.; Edwards, M.C. Genome Wide Analysis of Small Secreted Cysteine-Rich Proteins Identifies Candidate Effector Proteins Potentially Involved in Fusarium graminearum—Wheat Interactions. Phytopathology; 2016; 106, pp. 166-176. [DOI: https://dx.doi.org/10.1094/PHYTO-09-15-0215-R] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26524547]
31. Fabre, F.; Bormann, J.; Urbach, S.; Roche, S.; Langin, T.; Bonhommer, L. Unbalanced Roles of Fungal Aggressiveness and Host Cultivars in the Establishment of the Fusarium Head Blight in Bread Wheat. Front. Microbiol.; 2019; 10, 2857. [DOI: https://dx.doi.org/10.3389/fmicb.2019.02857] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31921038]
32. Ravensdale, M.; Rocheleau, H.; Wang, L.; Nasmith, C.; Ouellet, T.; Subramaniam, R. Components of Priming Induced Resistance to Fusarium Head Blight in Wheat Revealed by Two Distinct Mutants of Fusarium graminearum. Mol. Plant Pathol.; 2014; 15, pp. 948-956. [DOI: https://dx.doi.org/10.1111/mpp.12145]
33. Schroeder, H.W.; Christensen, J.J. Factors Affecting Resistance of Wheat to Scab by Gibberella zeae. Phytopathology; 1963; 53, pp. 831-838.
34. Miller, J.D.; Arnison, P.G. Degradation of Deoxynivalenol by Suspension Cultures of the Fusarium Head Blight Resistant Wheat Cultivar Frontana. Can. J. Plant Pathol.; 1986; 8, pp. 147-150. [DOI: https://dx.doi.org/10.1080/07060668609501818]
35. Spanic, V.; Marcek, T.; Abicic, I.; Sarkanj, B. Effects of Fusarium Head Blight on Wheat Grain and Malt Infected by Fusarium culmorum. Toxins; 2018; 10, 17. [DOI: https://dx.doi.org/10.3390/toxins10010017] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29280978]
36. Mesterházy, Á. Types and Components of Resistance to Fusarium Head Blight of Wheat. Plant Breed.; 1995; 114, pp. 377-386. [DOI: https://dx.doi.org/10.1111/j.1439-0523.1995.tb00816.x]
37. Mesterházy, Á. Theory and Practice of the Breeding for Fusarium Head Blight Resistance in Wheat. J. Appl. Gen.; 2002; 43A, pp. 289-302.
38. Malinovsky, F.G.; Fangel, J.U.; Willats, G.T. The Role of the Cell Wall in Plant Immunity. Front. Plant Sci.; 2014; 5, 178. [DOI: https://dx.doi.org/10.3389/fpls.2014.00178] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/24834069]
39. Miedes, E.; Vanholme, R.; Boerjan, W.; Molina, A. The Role of Secondary Cell Wall in Plant Resistance to Pathogens. Front. Plant Sci.; 2014; 5, 358. [DOI: https://dx.doi.org/10.3389/fpls.2014.00358]
40. Sekhon, R.S.; Kuldau, G.; Mansfield, M.; Chopra, S. Characterization of Fusarium-Induced Expression of Flavonoids and PR Genes in Maize. Physiol. Mol. Plant Pathol.; 2006; 69, pp. 109-117. [DOI: https://dx.doi.org/10.1016/j.pmpp.2007.02.004]
41. Khaledi, N.; Taheri, P.; Falahati-Rastegar, M. Reactive Oxygen Species and Antioxidant System Responses in Wheat Cultivars during Interaction with Fusarium Species. Austr. Plant Pathol.; 2016; 45, pp. 653-670. [DOI: https://dx.doi.org/10.1007/s13313-016-0455-y]
42. Ellinger, D.; Voigt, C.A. Callose Biosynthesis in Arabidopsis with a Focus on Pathogen Response: What We Have Learned Within the Last Decade. Ann. Bot.; 2014; 114, pp. 1349-1358. [DOI: https://dx.doi.org/10.1093/aob/mcu120] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/24984713]
43. Taheri, P. Cereal Diseases Caused by Fusarium graminearum: From Biology of the Pathogen to Oxidative Burst-Related Host Defense Responses. Eur. J. Plant Pathol.; 2018; 152, pp. 1-20. [DOI: https://dx.doi.org/10.1007/s10658-018-1471-2]
44. Khaledi, N.; Taheri, P.; Falahati-Rastegar, M. Evaluation of Resistance and the Role of Some Defense Responses in Wheat Cultivars to Fusarium Head Blight. J. Plant Protect. Res.; 2018; 57, pp. 205-217. [DOI: https://dx.doi.org/10.1515/jppr-2017-0054]
45. Boutigny, A.L.; Richard-Forget, F.; Barreau, C. Natural Mechanisms for Cereal Resistance to the Accumulation of Fusarium Trichothecenes. Eur. J. Plant Pathol.; 2008; 121, pp. 411-423. [DOI: https://dx.doi.org/10.1007/s10658-007-9266-x]
46. Jain, D.; Khurana, J.P. Role of Pathogenesis-Related (PR) Proteins in Plant Defense Mechanism. Molecular Aspects of Plant-Pathogen Interaction; Singh, A.; Singh, I. Springer: Singapore, 2018; pp. 265-281.
47. Ali, S.; Ganai, B.A.; Kamili, A.N.; Bhat, A.A.; Mir, Z.A.; Bhat, J.A.; Tyagi, A.; Islam, S.J.; Mushtaq, M.; Yadav, P. et al. Pathogenesis-Related Proteins and Peptides as Promising Tools for Engineering Plants with Multiple Stress Tolerance. Microbiol. Res.; 2018; 212–213, pp. 29-37. [DOI: https://dx.doi.org/10.1016/j.micres.2018.04.008] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29853166]
48. Sels, J.; Mathys, J.; De Coninck, B.M.; Cammue, B.P.; De Bolle, M.F. Plant Pathogenesis-Related (PR) Proteins: A Focus on PR Peptides. Plant Physiol. Biochem.; 2008; 46, pp. 941-950. [DOI: https://dx.doi.org/10.1016/j.plaphy.2008.06.011]
49. Etzerodt, T.; Gislum, R.; Laursen, B.B.; Heinrichson, K.; Gregersen, P.L.; Jørgensen, L.N.; Fomsgaard, I.S. Correlation of Deoxynivalenol Accumulation in Fusarium-Infected Winter and Spring Wheat Cultivars with Secondary Metabolites at Different Growth Stages. J. Agric. Food Chem.; 2016; 64, pp. 4545-4555. [DOI: https://dx.doi.org/10.1021/acs.jafc.6b01162] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27195655]
50. Boba, A.; Kulma, A.; Kostyn, K.; Starzycki, M.; Starzycka, E.; Szopa, J. The Influence of Carotenoid Biosynthesis Modification on the Fusarium culmorum and Fusarium oxysporum Resistance in Flax. Physiol. Mol. Plant Pathol.; 2011; 76, pp. 39-47. [DOI: https://dx.doi.org/10.1016/j.pmpp.2011.06.002]
51. Lachman, J.; Martinek, P.; Kotíková, Z.; Orsák, M.; Šulc, M. Genetics and Chemistry of Pigments in Wheat Grain—A Review. J. Cereal Sci.; 2017; 74, pp. 145-154. [DOI: https://dx.doi.org/10.1016/j.jcs.2017.02.007]
52. Pani, G.; Scherm, B.; Azara, E.; Balmas, V.; Jahanshiri, Z.; Carta, P.; Fabbri, D.; Dettori, M.A.; Fadda, A.; Dessi, A. et al. Natural and Natural-Like Phenolic Inhibitors of Type B Trichothecene In Vitro Production by the Wheat (Triticum sp.) Pathogen Fusarium culmorum. J. Agric. Food Chem.; 2014; 62, pp. 4969-4978. [DOI: https://dx.doi.org/10.1021/jf500647h]
53. Ziegler, J.U.; Steingass, C.B.; Longin, C.F.; Würschum, T.; Carle, R.; Schweiggert, R.M. Alkylresorcinol Composition Allows the Differentiation of Triticum spp. Having Different Degrees of Ploidy. J. Cereal Sci.; 2015; 65, pp. 244-251. [DOI: https://dx.doi.org/10.1016/j.jcs.2015.07.013]
54. Landberg, R. Alkylresorcinols as Biomarkers of Whole Grain Wheat and Rye Intake; Acta Universitatis Agriculturae Sueciae: Uppsala, Sweden, 2009.
55. Bordiga, M.; Locatelli, M.; Travaglia, F.; Arlorio, M.; Reyneri, A.; Blandino, M.; Coisson, J.D. Alkylresorcinol Content in Whole Grains and Pearled Fractions of Wheat and Barley. J. Cereal Sci.; 2016; 70, pp. 38-46. [DOI: https://dx.doi.org/10.1016/j.jcs.2016.05.017]
56. Righetti, L.; Cirlini, M.; Folloni, S.; Ranieri, R.; Galaverna, G.; Bertuzzi, T.; Dall’Asta, C.; Battilani, P.; Giorni, P. 5-n-Alkylresorcinols but Not Hydroxycinnamic Acids Are Directly Related to a Lower Accumulation of Deoxynivalenol and Its Glucoside in Triticum spp. Genotypes with Different Ploidity Levels. J. Cereal Sci.; 2019; 85, pp. 214-220. [DOI: https://dx.doi.org/10.1016/j.jcs.2018.11.011]
57. Abdel-Aal, E.S.; Hucl, P.; Rabalski, I. Compositional and Antioxidant Properties of Anthocyanin-Rich Products Prepared from Purple Wheat. Food Chem.; 2018; 254, pp. 13-19. [DOI: https://dx.doi.org/10.1016/j.foodchem.2018.01.170] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29548433]
58. Etzerodt, T.; Maeda, K.; Nakajima, Y.; Laursen, B.; Fomsgaard, I.S.; Kimura, M. 2,4-Dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (DIMBOA) Inhibits Trichothecene Production by Fusarium graminearum through Suppression of Tri6 Expression. Int. J. Food Microbiol.; 2015; 214, pp. 123-128. [DOI: https://dx.doi.org/10.1016/j.ijfoodmicro.2015.07.014]
59. Shewry, P.R.; Hey, S. Do “Ancient” Wheat Species Differ from Modern Bread Wheat in Their Contents of Bioactive Components?. J. Cereal Sci.; 2015; 65, pp. 236-243. [DOI: https://dx.doi.org/10.1016/j.jcs.2015.07.014]
60. Martini, D.; Taddei, F.; Ciccoritti, R.; Pasquini, M.; Nicoletti, I.; Corradini, D.; D´Egidio, M.G. Variation of Total Antioxidant Activity and of Phenolic Acid, Total Phenolics and Yellow Coloured Pigments in Durum Wheat (Triticum turgidum L. var. durum) as a Function of Genotype, Crop Year and Growing Area. J. Cereal Sci.; 2015; 65, pp. 175-185.
61. Ma, D.Y.; Sun, D.X.; Zuo, Y.; Wang, C.Y.; Zhu, Y.J.; Guo, T.C. Diversity of Antioxidant Content and Its Relationship to Grain Color and Morphological Characteristics in Winter Wheat Grains. J. Integr. Agric.; 2014; 13, pp. 1258-1267. [DOI: https://dx.doi.org/10.1016/S2095-3119(13)60573-0]
62. Lachman, J.; Hejtmánková, K.; Kotíková, Z. Tocols and Carotenoids of Einkorn, Emmer and Spring Wheat Varieties: Selection for Breeding and Production. J. Cereal Sci.; 2013; 57, pp. 207-214. [DOI: https://dx.doi.org/10.1016/j.jcs.2012.05.011]
63. Li, Y.G.; Ma, D.Y.; Sun, D.X.; Wang, C.Y.; Zhang, J.; Xie, Y.X.; Guo, T.C. Total Phenolic, Flavonoid Content, and Antioxidant Activity of Flour, Noodles, and Steamed Bread Made from Different Colored Wheat Grains by Three Milling Methods. J. Crop Prod.; 2015; 3, pp. 328-334. [DOI: https://dx.doi.org/10.1016/j.cj.2015.04.004]
64. Buśko, M.; Gòral, T.; Ostrowska, A.; Matysiak, A.; Walentyn-Gòral, D.; Perkowski, J. The Effect of Fusarium Fungicide Application on Concentrations of Flavonoids (Apigenin, Kaempferol, Luteolin, Naringenin, Quercetin, Rutin, Vitexin) in Winter Wheat Cultivars. Am. J. Sci.; 2014; 5, pp. 3727-3736. [DOI: https://dx.doi.org/10.4236/ajps.2014.525389]
65. Kovács, V.; Gondor, O.K.; Szalai, G.; Darkó, É.; Majláth, I.; Janda, T.; Pál, M. Synthesis and Role of Salicylic Acid in Wheat Varieties with Different Levels of Cadmium Tolerance. J. Hazard. Mater.; 2014; 280, pp. 12-19. [DOI: https://dx.doi.org/10.1016/j.jhazmat.2014.07.048]
66. Verma, B.; Hucl, P.; Chibbar, R.N. Phenolic Acid Composition and Antioxidant Capacity of Acid and Alkali Hydrolysed Bran Fractions. Food Chem.; 2009; 116, pp. 947-954. [DOI: https://dx.doi.org/10.1016/j.foodchem.2009.03.060]
67. Stuper-Szablewska, K.; Perkowski, J. Phenolic Acids in Cereals Grain: Occurrence, Metabolism and Role in Living Organisms. Crit. Rev. Food Sci. Nutr.; 2019; 59, pp. 664-675. [DOI: https://dx.doi.org/10.1080/10408398.2017.1387096] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28976227]
68. Martin, C. Resistance Elements of Small Grain Cereals against Fusarium Head Blight and Contribution of Health Promoting Compounds. Ph.D. Thesis; University of Neuchâtel: Neuchâtel, Switzerland, 2017.
69. Qi, P.F.; Balcerzak, M.; Rocheleau, H.; Leung, W.; Wei, Y.M.; Zheng, Y.L.; Ouellet, T. Jasmonic Acid and Abscisic Acid Play Important Roles in Host-Pathogen Interaction between Fusarium graminearum and Wheat during the Early Stages of Fusarium Head Blight. Physiol. Mol. Plant Pathol.; 2016; 93, pp. 39-48. [DOI: https://dx.doi.org/10.1016/j.pmpp.2015.12.004]
70. Piesik, D.; Pańka, D.; Delaney, K.J.; Skoczek, A.; Lamparski, R.; Weaver, D.K. Cereal Crop Volatile Organic Compound Induction After Mechanical Injury, Beetle Herbivory (Oulema spp.), or Fungal Infection (Fusarium spp.). J. Plant Physiol.; 2011; 168, pp. 878-886. [DOI: https://dx.doi.org/10.1016/j.jplph.2010.11.010]
71. Buśko, M.; Gòral, T.; Boczkowska, M.; Perkowski, J. Relationships between Volatile Organic Compounds with Emphasis on Terpene Compounds and Genetic Matrix in Inoculated and Non-inoculated Winter Wheat Cultivars. Chem. Ecol.; 2019; 35, pp. 971-986. [DOI: https://dx.doi.org/10.1080/02757540.2019.1668379]
72. Steiner, B.; Buerstmayr, M.; Michel, S.; Schweiger, W.; Lemmens, M.; Buerstmayr, H. Breeding Strategies and Advances in Line Selection for Fusarium Head Blight Resistance in Wheat. Trop. Plant Pathol.; 2017; 42, pp. 165-174. [DOI: https://dx.doi.org/10.1007/s40858-017-0127-7]
73. Jones, S.; Farooqi, A.; Foulkes, J.; Sparkes, D.L.; Linforth, R.; Ray, R.V. Canopy and Ear Traits Associated with Avoidance of Fusarium Head Blight in Wheat. Front. Plant Sci.; 2018; 9, 1021. [DOI: https://dx.doi.org/10.3389/fpls.2018.01021] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30108599]
74. Tessmann, E.W.; Van Sanford, D.A. Associations Between Morphological and FHB Traits in a Soft Red Winter Wheat Population. Euphytica; 2019; 215, 189. [DOI: https://dx.doi.org/10.1007/s10681-019-2509-z]
75. McCartney, C.A.; Brûlé-Babel, A.L.; Fedak, G.; Martin, R.A.; McCallum, B.D.; Gilbert, J.; Hiebert, C.W.; Pozniak, C.V. Fusarium Head Blight Resistance QTL in the Spring Wheat Cross Kenyon/86ISMN 2137. Front. Microbiol.; 2016; 7, 1542. [DOI: https://dx.doi.org/10.3389/fmicb.2016.01542]
76. Giancaspro, A.; Giove, S.L.; Zito, D.; Blanco, A.; Gadaleta, A. Mapping QTLs for Fusarium Head Blight Resistance in an Interspecific Wheat Population. Front. Plant Sci.; 2016; 7, 1381. [DOI: https://dx.doi.org/10.3389/fpls.2016.01381]
77. Haile, J.K.; N’Diaye, A.; Walkowiak, S.; Nilsen, K.T.; Clarke, J.M.; Kutcher, H.R.; Steiner, B.; Buerstmayr, H.; Pozniak, C.J. Fusarium Head Blight in Durum Wheat: Recent Status, Breeding Directions and Future Research Prospects. Phytopathology; 2019; 109, pp. 1664-1675. [DOI: https://dx.doi.org/10.1094/PHYTO-03-19-0095-RVW]
78. Buerstmayr, M.; Buerstmayr, H. The Semidwarfing Alleles Rht D1b and Rht B1b Show Marked Differences in Their Associations with Anther-Retention in Wheat Heads and with Fusarium Head Blight Susceptibility. Phytopathology; 2016; 106, pp. 1544-1552. [DOI: https://dx.doi.org/10.1094/PHYTO-05-16-0200-R] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27452901]
79. Giordano, D.; Beta, T.; Vanara, F.; Blandino, M. Influence of Agricultural Management on Phytochemicals of Colored Corn Genotypes (Zea mays L.). Part 1: Nitrogen Fertilization. J. Agric. Food Chem.; 2018; 66, pp. 4300-4308. [DOI: https://dx.doi.org/10.1021/acs.jafc.8b00325] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29641199]
80. Atanasova-Penichon, V.; Barreau, C.; Richard-Forget, F. Antioxidant Secondary Metabolites in Cereals: Potential Involvement in Resistance to Fusarium and Mycotoxin Accumulation. Front. Microbiol.; 2016; 7, 566. [DOI: https://dx.doi.org/10.3389/fmicb.2016.00566]
81. Žilič, S. Phenolic Compounds of Wheat: Their Content, Antioxidant Capacity and Bioaccessibility. MOJ Food Process. Technol.; 2016; 2, pp. 85-89. [DOI: https://dx.doi.org/10.15406/mojfpt.2016.02.00037]
82. Tian, S.; Sun, Y.; Chen, Z.; Zhao, R. Bioavailability and Bioactivity of Alkylresorcinols from Different Cereal Products. J. Food Qual.; 2020; 2020, 5781356. [DOI: https://dx.doi.org/10.1155/2020/5781356]
83. Niculaes, C.; Abramov, A.; Hannemann, L.; Frey, M. Plant Protection by Benzoazinoids—Recent Insights into Biosynthesis and Function. Agronomy; 2018; 8, 143. [DOI: https://dx.doi.org/10.3390/agronomy8080143]
84. Matsuura, T.; Mori, I.C.; Himi, E.E.; Hirayama, T. Plant Hormone Profiling in Developing Seeds of Common Wheat (Triticum aestivum L.). Breed. Sci.; 2019; 69, pp. 601-610. [DOI: https://dx.doi.org/10.1270/jsbbs.19030]
85. Wenda-Piesik, A.; Piesik, D.; Ligor, T.; Buszewski, B. Volatile Organic Compounds (VOCs) from Cereal Plants Infested with Crown Rot: Their Identity and Their Capacity for Inducing Production of VOCs in Uninfested Plants. Int. J. Pest Manag.; 2010; 4, pp. 377-383. [DOI: https://dx.doi.org/10.1080/09670874.2010.505668]
86. Nakabayashi, R.; Saito, K. Integrated Metabolomics for Abiotic Stress Responses in Plants. Curr. Opin. Plant Biol.; 2015; 24, pp. 10-16. [DOI: https://dx.doi.org/10.1016/j.pbi.2015.01.003] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25618839]
87. Santos-Sánchez, N.F.; Salas-Coronado, R.; Hernández-Carlos, B.; Villanueva-Cañongo, C. Shikimic Acid Pathway in Biosynthesis of Phenolic Compounds. Plant Physiological Aspects of Phenolic Compounds; Soto-Hernández, S.; García-Mateos, R.; Palma-Tenango, M. IntechOpen: London, UK, 2019; Chapter 3 pp. 35-50.
88. Paznocht, L.; Kotíková, Z.; Burešová, B.; Lachman, J.; Martinek, P. Phenolic Acids in Kernels of Different Coloured-Grain Wheat Genotypes. Plant Soil Environ.; 2020; 66, pp. 57-64. [DOI: https://dx.doi.org/10.17221/380/2019-PSE]
89. Chateigner-Boutin, A.L.; Lapierre, C.; Alvarado, C.; Yoshinaga, A.; Barron, C.; Bouchet, B.; Bakan, B.; Saulnier, L.; Devaux, M.F.; Girousse, C. et al. Ferulate and Lignin Cross-Links Increase in Cell Walls of Wheat Grain Outer Layers during Late Development. Plant Sci.; 2018; 276, pp. 199-207. [DOI: https://dx.doi.org/10.1016/j.plantsci.2018.08.022]
90. Martinek, P.; Škorpík, M.; Chrpová, J.; Fučík, P.; Schweiger, J. Development of the New Winter Wheat Variety Skorpion with Blue Grain. Czech J. Genet. Plant Breed.; 2013; 49, pp. 90-94. [DOI: https://dx.doi.org/10.17221/7/2013-CJGPB]
91. Gauthier, L.; Atanasova-Penichon, V.; Chéreau, S.; Richard-Forget, F. Metabolomics to Decipher the Chemical Defense of Cereals against Fusarium graminearum and Deoxynivalenol Accumulation. Int. J. Mol. Sci.; 2015; 6, pp. 24839-24872. [DOI: https://dx.doi.org/10.3390/ijms161024839]
92. Ponts, N.; Pinson-Gadais, L.; Barreau, C.; Richard-Forget, F.; Quellet, T. Exogenous H2O2 and Catalase Treatments Interfere with Tri Genes Expression in Liquid Cultures of Fusarium graminearum. FEBS Lett.; 2007; 581, pp. 443-447. [DOI: https://dx.doi.org/10.1016/j.febslet.2007.01.003] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17250833]
93. Schöneberg, T.; Kibler, K.; Sulyok, M.; Musa, T.; Bucheli, T.D.; Mascher, F.; Bertossa, M.; Foegele, R.T.; Vogelsang, S. Can Plant Phenolic Compounds Reduce Fusarium Growth and Mycotoxin Production in Cereals?. Food Addit. Contam. Part A; 2018; 35, pp. 2455-2470. [DOI: https://dx.doi.org/10.1080/19440049.2018.1538570]
94. Siranidou, E.; Kang, Z.; Buchenauer, H. Studies on Symptom Development, Phenolic Compounds and Morphological Defense Responses in Wheat Cultivars Differing in Resistance to Fusarium Head Blight. J. Phytopathol.; 2003; 150, pp. 200-208. [DOI: https://dx.doi.org/10.1046/j.1439-0434.2002.00738.x]
95. Gauthier, L.; Bonnin-Verdal, M.N.; Marchegay, G.; Pinson-Gadais, L.; Ducos, C.; Richard-Forget, F.; Atanasova-Penichon, V. Fungal Biotransformation of Chlorogenic and Caffeic Acids by Fusarium graminearum: New Insights in the Contribution of Phenolic Acids to Resistance to Deoxynivalenol Accumulation in Cereals. Int. J. Food Microbiol.; 2016; 221, pp. 61-68. [DOI: https://dx.doi.org/10.1016/j.ijfoodmicro.2016.01.005]
96. Giordano, D.; Beta, T.; Reyneri, A.; Blandino, M. Changes in the Phenolic Acid Content and Antioxidant Activity during Kernel Development in Corn (Zea mays L.) and Relationship with Mycotoxin Contamination. Cereal Chem.; 2017; 94, pp. 315-324. [DOI: https://dx.doi.org/10.1094/CCHEM-05-16-0155-R]
97. Sampietro, D.A.; Fauguel, C.M.; Vattuone, M.A.; Presello, D.A.; Catalán, C.A. Phenylpropanoids from Maize Pericarp: Resistance Factors to Kernel Infection and Fumonisin Accumulation by Fusarium verticillioides. Eur. J. Plant Pathol.; 2013; 135, pp. 105-113. [DOI: https://dx.doi.org/10.1007/s10658-012-0069-3]
98. Erayman, M.; Turktas, M.; Akdogan, G.; Gurkok, T.; Inal, B.; Ishakoglu, E.; Ilhan, E.; Unver, T. Transcriptome Analysis of Wheat Inoculated with Fusarium graminearum. Front. Plant Sci.; 2015; 6, 867. [DOI: https://dx.doi.org/10.3389/fpls.2015.00867] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26539199]
99. Rocheleau, H.; Al-Harthi, R.; Quellet, T. Degradation of Salicylic Acid by Fusarium graminearum. Fungal Biol.; 2019; 123, pp. 77-86. [DOI: https://dx.doi.org/10.1016/j.funbio.2018.11.002] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30654960]
100. Ponts, N.; Couedelo, L.; Pinson-Gadais, L.; Verdal-Bonnin, M.N.; Barreau, C.; Richard-Forget, F. Fusarium Response to by H2O2 is Trichothecene Chemotype-Dependent. FEMS Microbiol. Lett.; 2009; 293, pp. 255-262. [DOI: https://dx.doi.org/10.1111/j.1574-6968.2009.01521.x]
101. Ferrigo, D.; Raiola, A.; Bogialli, S.; Bortolini, C.; Tapparo, A.; Causin, R. In Vitro Production of Fumonisins by Fusarium verticillioides under Oxidative Stress Induced by H2O2. J. Agric. Food Chem.; 2015; 63, pp. 4879-4885. [DOI: https://dx.doi.org/10.1021/acs.jafc.5b00113] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25910187]
102. Steinkellner, S.; Mammerler, R. Effect of Flavonoids on the Development of Fusarium oxysporum f. sp. lycopersici. J. Plant Interact.; 2007; 2, pp. 17-23. [DOI: https://dx.doi.org/10.1080/17429140701409352]
103. Jimenez-Garcia, S.N.; Garcia-Mier, L.; Garcia-Trejo, J.F.; Ramirez-Gomez, X.S.; Guevara-Gonzalez, R.G.; Feregrino-Perez, A.A. Chapter 3. Fusarium Mycotoxins and Metabolites that Modulate Their Production. Fusarium Plant Diseases, Pathogen Diversity, Resistance and Molecular Markers; Askun, T. IntechOpen: London, UK, 2018; pp. 23-40.
104. Stuper-Szablewska, K.; Kurasiak-Popowska, D.; Nawracała, J.; Perkowski, J. Quantitative Profile of Phenolic Acids and Antioxidant Activity of Wheat Grain Exposed to Stress. Eur. Food Res. Technol.; 2019; 245, pp. 1595-1603. [DOI: https://dx.doi.org/10.1007/s00217-019-03262-8]
105. Pervaiz, T.; Songtao, J.; Faghihi, H.; Halder, M.S.; Fang, J. Naturally Occurring Anthocyanin, Structure, Functions and Biosynthetic Pathway in Fruit Plants. J. Plant. Physiol. Biochem.; 2017; 5, 187. [DOI: https://dx.doi.org/10.4172/2329-9029.1000187]
106. Shoeva, O.Y.; Gordeeva, E.I.; Arbuzova, V.S.; Khlestkina, E.K. Anthocyanins Participate in Protection of Wheat Seedlings from Osmotic Stress. Cereal Res. Commun.; 2017; 45, pp. 47-56. [DOI: https://dx.doi.org/10.1556/0806.44.2016.044]
107. Eliášová, M.; Kotíková, Z.; Lachman, J.; Orsák, M.; Martinek, P. Influence of Baking on Anthocyanin Content in Coloured-Grain Wheat Bread. Plant Soil Environ.; 2020; 66, pp. 381-383. [DOI: https://dx.doi.org/10.17221/210/2020-PSE]
108. Tyl, C.E.; Bunzel, M. Antioxidant Activity-Guided Fractionation of Blue Wheat (UC66049 Triticum aestivum L.). J. Agric. Food Chem.; 2012; 60, pp. 731-739. [DOI: https://dx.doi.org/10.1021/jf203648x] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/22225003]
109. Isah, T. Stress and Defense Responses in Plant Secondary Metabolites Production. Biol. Res.; 2019; 52, E39. [DOI: https://dx.doi.org/10.1186/s40659-019-0246-3] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31358053]
110. Wang, X.; Olsen, O.; Knudsen, S. Expression of Dihydroflavonol Reductase Gene in an Anthocyanin-Free Barley Mutant. Hereditas; 1993; 119, pp. 67-75. [DOI: https://dx.doi.org/10.1111/j.1601-5223.1993.00067.x]
111. Masisi, K.; Beta, T.; Moghadasian, M.H. Antioxidant Properties of Diverse Cereal Grains: A Review on In Vitro and In Vivo studies. Food Chem.; 2016; 196, pp. 90-97. [DOI: https://dx.doi.org/10.1016/j.foodchem.2015.09.021] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26593469]
112. Bollina, V.; Kushalappa, A.C. In Vitro Inhibition of Trichothecene Biosynthesis in Fusarium graminearum by Resistance-Related Endogenous Metabolites Identified in Barley. Mycology; 2011; 2, pp. 291-296.
113. Gunnaiah, R.; Kushalappa, A.C. Metabolomics Deciphers the Host Resistance Mechanisms in Wheat Cultivar Sumai-3, against Trichothecene Producing and Non-Producing Isolates of Fusarium graminearum. Plant Physiol. Biochem.; 2014; 83, pp. 40-50. [DOI: https://dx.doi.org/10.1016/j.plaphy.2014.07.002]
114. Durazzo, A.; Zaccaria, M.; Polito, A.; Maiani, G.; Carcea, M. Lignan Content in Cereals, Buckwheat and Derived Foods. Foods; 2013; 2, pp. 53-63. [DOI: https://dx.doi.org/10.3390/foods2010053] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28239096]
115. Peterson, J.; Dwyer, J.; Adlercreutz, H.; Scalbert, A.; Jacques, P.; McCullough, M.L. Dietary Lignans: Physiology and Potential for Cardiovascular Disease risk reduction. Nutr. Rev.; 2010; 68, pp. 571-603. [DOI: https://dx.doi.org/10.1111/j.1753-4887.2010.00319.x] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20883417]
116. Bagniewska-Zadworna, A.; Barakat, A.; Łakomy, P.; Smoliński, D.J.; Zadworny, M. Lignin and Lignans in Plant Defence: Insight from Expression Profiling of Cinnamyl Alcohol Dehydrogenase Genes during Development and Following Fungal Infection in Populus. Plant Sci. J.; 2014; 229, pp. 111-121. [DOI: https://dx.doi.org/10.1016/j.plantsci.2014.08.015]
117. Mattila, P.; Pihlava, J.M.; Hellstrom, J. Contents of Phenolic Acids, Alkyl- and Alkenylresorcinols, and Aventhramides in Commercial Grain Products. J. Agric. Food Chem.; 2005; 53, pp. 8290-8295. [DOI: https://dx.doi.org/10.1021/jf051437z] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16218677]
118. Suzuki, Y.; Kurano, M.; Esumi, Y.; Yamaguchi, I.; Yoshiharu, D. Biosynthesis of 5-alkylresorcinol in Rice: Icorporation of Putative Fatty Acid Unit in the 5-alkylresorcinol Carbon Chain. Bioorg. Chem.; 2003; 31, pp. 437-452. [DOI: https://dx.doi.org/10.1016/j.bioorg.2003.08.003]
119. Ross, A.B.; Kamal-Eldin, A.; Åman, P. Dietary Alkylresorcinols: Absorption, Bioactivities, and Possible Use as Biomarkers of Whole-Grain Wheat- and Rye-Rich Foods. Nutr. Rev.; 2004; 3, pp. 81-95. [DOI: https://dx.doi.org/10.1111/j.1753-4887.2004.tb00029.x] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/15098855]
120. Kowalska, I.; Kowalczyk, M. Determination of benzoxazinoids in Spring and Winter Varieties Using Ultra-Performance Liquid Chromatography Coupled with Mass Spectrometry. Acta Chromatogr.; 2019; 31, pp. 179-182. [DOI: https://dx.doi.org/10.1556/1326.2018.00418]
121. Meyer, J.; Murray, S.L.; Berger, D.K. Signals that Stop the Rot: Regulation of Secondary Metabolite Defences in Cereals. Physiol. Mol. Plant Pathol.; 2016; 94, pp. 156-166. [DOI: https://dx.doi.org/10.1016/j.pmpp.2015.05.011]
122. Wang, Q.; Shao, B.; Shaikh, F.I.; Friedt, W.; Gottwald, S. Wheat Resistances to Fusarium Root Rot and Head Blight Are Both Associated with Deoxynivalenol- and Jasmonate-Related Gene Expression. Phytopathology; 2018; 108, pp. 602-616. [DOI: https://dx.doi.org/10.1094/PHYTO-05-17-0172-R]
123. Nazareth, T.M.; Bordin, K.; Manyes, L.; Meca, G.; Mañes, J.; Luciano, F.B. Gaseous Allyl Isothiocyanate to Inhibit the Production of Aflatoxins, Beauvericin and Enniatins by Aspergillus parasiticus and Fusarium poae in Wheat Flour. Food Control; 2016; 62, pp. 317-321. [DOI: https://dx.doi.org/10.1016/j.foodcont.2015.11.003]
124. Small, I.M.; Flett, B.C.; Marasas, W.F.; McLeod, A.; Stander, M.A.; Viljoen, A. Resistance in Maize Inbred Lines to Fusarium verticillioides and Fumonisin Accumulation in South Africa. Plant Dis.; 2012; 96, pp. 881-888. [DOI: https://dx.doi.org/10.1094/PDIS-08-11-0695]
125. Trapp, M.A.; De Souza, G.D.; Rodrigues-Filho, E.; Boland, W.; Mithöfer, A. Validated Method for Quantification in Plants. Front. Plant Sci.; 2014; 5, 417.
126. Paznocht, L.; Kotíková, Z.; Šulc, M.; Lachman, J.; Orsák, M.; Eliášová, M.; Martinek, P. Free and Esterified Carotenoids in Pigmented Wheat, Tritordeum and Barley Grains. Food Chem.; 2018; 240, pp. 670-678. [DOI: https://dx.doi.org/10.1016/j.foodchem.2017.07.151] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28946328]
127. Delgado, R.M.; Sulyok, M.; Jirsa, O.; Spitzer, T.; Krska, R.; Polišenská, I. Relationship between Lutein and Mycotoxin Content in Durum Wheat. Food Addit. Contam. Part A; 2014; 31, pp. 1274-1283. [DOI: https://dx.doi.org/10.1080/19440049.2014.925589] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/24844356]
128. Hidalgo, A.; Fongaro, L.; Brandolini, A. Colour Screening of Whole Meal Flours and Discrimination of Seven Triticum Subspecies. J. Cereal Sci.; 2017; 77, pp. 9-16. [DOI: https://dx.doi.org/10.1016/j.jcs.2017.07.006]
129. Colasuonno, P.; Lozito, M.L.; Marcotuli, I.; Nigro, D.; Giancaspro, A.; Mangini, G.; De Vita, P.; Mastrangelo, A.M.; Pecchini, N.; Houston, K. et al. The Carotenoid Biosynthetic and Catabolic Genes and Their Association with Yellow Pigments. BMC Genet.; 2017; 18, 122. [DOI: https://dx.doi.org/10.1186/s12864-016-3395-6]
130. Golkari, S.; Gilbert, J.; Prashar, S.; Procunier, J.D. Microarray Analysis of Fusarium graminearum-Induced Wheat Genes: Identification of Organ-Specific and Differentially Expressed Genes. Plant Biotechnol. J.; 2007; 5, pp. 38-49. [DOI: https://dx.doi.org/10.1111/j.1467-7652.2006.00213.x]
131. Gunnaiah, R.; Kushalappa, A.C.; Duggavathi, R.; Fox, S.; Somers, D.J. Integrated Metabolo-Proteomic Approach to Decipher the Mechanisms by Which Wheat QTL (Fhb1) Contributes to Resistance against Fusarium graminearum. PLoS ONE; 2012; 7, e40695. [DOI: https://dx.doi.org/10.1371/journal.pone.0040695]
132. Zykin, P.A.; Andreeva, E.A.; Lakholay, A.N.; Tsvetkova, N.V.; Voloylokov, A.V. Anthocyanin Composition and Content in Rye Plants with Different Grain Color. Molecules; 2018; 23, 948. [DOI: https://dx.doi.org/10.3390/molecules23040948] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29671758]
133. Gordeeva, E.I.; Shoeva, O.Y.; Khlestkina, E.K. Marker-Assisted Development of Bread Wheat Near-Isogenic Lines Carrying Various Combinations of Purple Pericarp (Pp) Alleles. Euphytica; 2015; 203, pp. 469-476. [DOI: https://dx.doi.org/10.1007/s10681-014-1317-8]
134. Syed Jaafar, S.N.; Baron, J.; Siebenhandl-Ehn, S.; Rosenau, T.; Böhmdorfer, S.; Grausgruber, H. Increased Anthocyanin Content in Purple Pericarp x Blue Aleurone Wheat Crosses. Plant Breed.; 2013; 132, pp. 48-58. [DOI: https://dx.doi.org/10.1111/pbr.12090]
135. Francavilla, A.; Joye, I. Anthocyanins in Whole Grain Cereals and Their Potential Effect on Health. Nutrients; 2020; 12, 2922. [DOI: https://dx.doi.org/10.3390/nu12102922]
136. Paznocht, L.; Burešová, B.; Kotíková, Z.; Martinek, P. Carotenoid Content of Extruded and Puffed Products Made of Colored-Grain Wheats. Food Chem.; 2021; 340, 127951. [DOI: https://dx.doi.org/10.1016/j.foodchem.2020.127951]
137. Lachman, J.; Hejtmánková, A.; Orsák, M.; Popov, M.; Martinek, P. Tocotrienols and Tocopherols in Colored-Grain Wheat, Tritordeum and Barley. Food Chem.; 2018; 240, pp. 725-735. [DOI: https://dx.doi.org/10.1016/j.foodchem.2017.07.123] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28946335]
138. Spanić, V.; Viljevać Vuletić, M.; Abicić, I.; Marček, T. Early Response of Wheat Antioxidant System with Special Reference to Fusarium Head Blight Stress. Plant Physiol. Biochem.; 2017; 115, pp. 34-43. [DOI: https://dx.doi.org/10.1016/j.plaphy.2017.03.010] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28319793]
139. Martin, C.; Schöneberg, T.; Vogelsang, S.; Vincenti, J.; Bertossa, M.; Mauch-Mani, B.; Masher, F. Factors of Wheat Grain Resistance to Fusarium Head Blight. Phytopathol. Mediterr.; 2017; 56, pp. 154-166.
140. Bernardi, J.; Stagnati, L.; Lucini, L.; Rocchetti, G.; Lanubil, A.; Cortellini, C.; De Poli, G.; Busconi, M.; Marocco, A. Phenolic Profile and Susceptibility to Fusarium Infection of Pigmented Maize Cultivars. Front. Plant Sci.; 2018; 9, 1189. [DOI: https://dx.doi.org/10.3389/fpls.2018.01189]
141. Lorenz-Kukuła, K.; Wróbel-Kwiatkowska, M.; Starzycki, M.; Szopa, J. Engineering Flax with Increased Flavonoid Content and thus Fusarium Resistance. Physiol. Mol. Plant Pathol.; 2007; 70, pp. 38-48. [DOI: https://dx.doi.org/10.1016/j.pmpp.2007.05.005]
142. Long, L.; Liu, J.; Gao, Y.; Xu, F.C.; Zhao, J.R.; Li, B.; Gao, W. Flavonoid Accumulation in Spontaneous Cotton Mutant Results in Red Coloration and Enhanced Disease Resistance. Plant Physiol. Biochem.; 2019; 143, pp. 40-49. [DOI: https://dx.doi.org/10.1016/j.plaphy.2019.08.021] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31479881]
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