1. Types of Mycotoxins and Current Status of Feed Contamination
Mycotoxins, which are toxic compounds produced by specific fungi, pose a serious threat of contamination to a wide range of food sources. In agricultural products, molds are capable of producing more than 300 types of mycotoxins, many of which are considered major threats to human and animal health, with toxic and carcinogenic effects on the immune system, liver, kidneys, genes, and reproductive system [1]. The presence of these toxins in feed involves multiple complex steps, including fungal growth, toxin production, contamination pathways, absorption, distribution, and ultimate toxic effects. Ranging from hepatotoxicity to immunotoxicity, these toxins severely impact animal health, and due to their thermal stability, they can survive during feed processing, posing a persistent threat to animal productivity (Table 1). Therefore, a deep understanding of the mechanism of action of mycotoxins is crucial for developing effective prevention and control strategies to mitigate their polluting impact. Against this backdrop, measures for the prevention and control of mycotoxins are vital, and post-contamination detoxification technologies are equally critical. Recently, plant extracts containing flavonoids, terpenoids, and phenolics have become the focus of research on mycotoxin control and detoxification, with the potential of these natural compounds lying in their ability to interfere with the absorption and bioavailability of toxins, potentially reducing the toxicity of mycotoxins [2].
1.1. Types and Chemical Stability of Mycotoxins
Most mycotoxins are produced by toxigenic molds, such as Aspergillus, Penicillium, Fusarium, Claviceps, and Grapevine, and certain species of endophytic fungi. At present, more than 300 kinds of mycotoxins are known, among which aflatoxins (AFs), deoxynivalenol (DON), zearalenone (ZEA), fumonisins (FBs), and ochratoxin-A (OTA) are serious hazards to animal husbandry. They are widely distributed in cereals, such as maize and rice, and nuts, such as pistachios. These mycotoxins have stable physical and chemical properties and are resistant to high temperatures during conventional feed processing (including heating). For example, aflatoxin B1 (AFB1) is stable at most feed processing temperatures and has a boiling point of 268 °C [3]. DON remains chemically stable through processing, storage, and even cooking, which makes it difficult to eliminate [4].
Table 1Five common mycotoxins in feed and their mechanisms of toxicology.
Mycotoxin Types | Sources | Toxicity Characteristics | Mechanisms | Reference |
---|---|---|---|---|
AFs | Aspergillus flavus and Aspergillus parasiticus | Highly toxic, hepatotoxic and carcinogenic | Inhibits protein synthesis, causes cell apoptosis, and increases the risk of hepatic carcinogenesis | [5] |
DON | Fusarium graminearum | Food refusal, vomiting, growth retardation, and immunosuppression | Activates the intracellular stress response, leading to apoptosis | [6] |
ZEA | Fusarium graminearum and Fusarium rhubarb | Simulating estrogen, pseudopregnancy, vaginitis, and infertility | Activates estrogen receptors and affects the development of reproductive organs | [7] |
FBs | Fusarium sp. | Neurotoxicity, liver and kidney injuries, immunosuppression, and reproductive disorders | Inhibits sphingolipid biosynthesis and disrupts cell membrane structure | [8] |
OTA | Aspergillus spp. and Penicillium spp. | Kidney injury, immunosuppression, and growth retardation | Inhibits protein synthesis and causes cell death | [9] |
1.2. Widespread Occurrence of Mycotoxin Contamination
Mycotoxin contamination is a major challenge to feed safety globally, affecting 60–80% of agriculture products. The prevalence, co-occurrence patterns, and regulatory exceedances are listed in Table 2. A quarter of the world’s food and feed crops are susceptible to mycotoxins, according to the FAO (The Food and Agriculture Organization). The European survey in 2021 showed that 98.5% of nearly 1200 feed samples contained at least one mycotoxin, 86.1% contained two or more mycotoxins, and 77% of cereals such as wheat and barley were detected with novel mycotoxins [10]. AFs are widely present in the feed of Indian dairy cattle, with AFs detected in 59% of concentrated feeds, 44% exceeding the US limit of 20 μg/kg, and 58% exceeding the EU limit of 5 μg/kg [11]. The study conducted by Zhao et al. in China from 2018 to 2020 found that the average content of AFB1 in feed and whole feed was 1.2–27.4 μg/kg, the incidence rate was 81.9–100%, and 0.9% of the raw materials were contaminated with AFB1 exceeding the Chinese safety standard concentration [12]. Wei Hao et al. ’s study, covering 9392 feed samples in China from 2017 to 2021, found that trichothecene B and FB contamination were the most common in new season maize, with detection rates as high as 84.04% and 87.16%, respectively [13]. Zhang Yong and his colleagues analyzed 1025 feed samples and found that the detection rates of AFB1, ZEN, and DON reached 95.99%, 98.54%, and 100%, respectively. Particularly striking, 89.85% of the samples contained these three mycotoxins, revealing a widespread problem of multiple contamination in 2021 [14]. Cargill Animal Nutrition analyzed over 350,000 results from 145,000 raw material samples collected from more than 150 feed mills, farms, and raw material storage sites in 2023, which indicated that the top three in terms of prevalence and risk level were DON, FBs, and ZEA [15]. Based on a globally extensive survey, it has been revealed that climate is a crucial factor in determining the areas contaminated by mycotoxins. In several regions of South Asia, Sub-Saharan Africa, and Southeast Asia, rainfall or significant temperature variations during the critical period of grain development are the decisive factors for the concentration of mycotoxin contamination. A large number of samples (64%) were co-contaminated by ≥two types of mycotoxins [16]. A study examined data from 717 wheat fields across Norway, Sweden, Finland, and the Netherlands. The observational data included details on flowering dates, the length of time between flowering and harvest, the resistance of wheat to Fusarium infection, and the concentration of deoxynivalenol (DON) in relation to various climate variables critical to wheat cultivation, such as relative humidity, temperature, and rainfall. The findings highlighted that the pattern of DON contamination in wheat in Northwestern Europe is influenced by climatic changes [17]. Taken together, mycotoxin contamination poses a global challenge that requires continuous surveillance.
Table 2Mycotoxin contamination in feed: prevalence, co-occurrence patterns, and regulatory exceedances.
Mycotoxin Type | Country/Region | Study Period/Year | Sample Size/Scope | Contamination Levels | Detection Rate (%) | Exceedance of Limits |
---|---|---|---|---|---|---|
Multiple mycotoxins | Europe | 2021 | ~1200 feed samples | 98.5% with ≥1 mycotoxin; 86.1% with ≥2 mycotoxins; 77% cereals with novel mycotoxins | 98.5 (any) | - |
AFs | India | - | Dairy cattle feed | AF detected in 59% of concentrated feeds | 59 | 44% exceeded US limit (20 μg/kg); 58% exceeded EU limit (5 μg/kg) |
AFB1 | China | 2018–2020 | Various feeds | Average content: 1.2–27.4 μg/kg; incidence: 81.9–100% | 81.9–100 | 0.9% of materials exceeded the Chinese safety standard |
Trichothecene B and FBs | China | 2017–2021 | 9392 feed samples | Most common in new season maize | 84.04 (trichothecene B); 87.16 (FBs) | - |
AFB1, ZEN, and DON | China | 2021 | 1025 feed samples | Co-contamination prevalence | 95.99 (AFB1); 98.54 (ZEN); 100 (DON) | 89.85% of samples contained all three mycotoxins |
DON, FBs, and ZEN | Global (Cargill data) | 2023 | >145,000 samples from 150+ sites | Top 3 prevalent mycotoxins by risk level | - | Global contamination patterns observed |
1.3. Effects and Toxicology of Five Common Mycotoxin Contaminants on Livestock and Poultry
Ingestion of feed contaminated with these mycotoxins commonly induces poisoning in animals. Low concentrations impair animal growth performance and immune function, resulting in liver and kidney dysfunctions, intestinal syndrome, digestive tract inflammation, and reproductive dysfunction, while high concentrations cause acute death in animals [18,19]. In addition, the residues of mycotoxins in meat, eggs, milk, and other products have become a major hazard to the safety of animal-derived food [20]. The effective management and mitigation of mycotoxin contamination in food and feed play a crucial role in improving animal performance and ensuring the safety of the human food chain. The pathological characteristics of different animals exposed to these five common mycotoxins in diets are listed in Table 3.
AFs, as a high-risk and prevalent mycotoxin, pose significant threats to livestock health and productivity [21]. Aflatoxin mainly affects the livers of animals, and chronic exposure can cause fatty liver degeneration and liver tissue necrosis. The characteristics of poisoning include depression, loss of appetite, weight loss, stagnating movement, and decreased immunity. Liver damage was particularly significant, which was manifested as liver enlargement, fragile texture, and brown color and, in severe cases, accompanied by liver fibrosis and pathological structural changes [22,23,24,25]. Although pigs are slightly less sensitive to aflatoxin than birds, their liver damage is more serious, and the ingestion of contaminated feed by sows can be transmitted to piglets through milk, leading to growth retardation or death [26,27]. In addition, the ingestion of aflatoxin-contaminated diets by cows can destroy their intestinal barrier function, affect their immune response, and weaken their defense against pathogens while impairing their cellular and humoral immune mechanisms and reducing their resistance to viral infections and parasites [28].
ZEA, as a kind of estrogen substance, mainly affects the function of the reproductive system and can cause estrogen hyperemia in animals. The intake of ZEA during pregnancy can cause abortion, stillbirths, and malformation and has negative effects on the central nervous system, such as nausea, chills, headache, confusion, and coordination disorders [7]. Gilts are particularly sensitive to ZEA, and the typical characteristic of poisoning is vulvovaginitis with abnormal mammary gland development, while boars show decreased libido, testicular atrophy, and decreased semen quality [29]. Compared with swine, poultry has a higher tolerance to ZEA due to its efficient hepatic and intestinal circulation, rapid excretion capacity, and specific physiological characteristics, such as microbial transformation, differential enzyme activities, and low estrogen receptor binding capacity [30]. Ruminants are less susceptible to ZEA, which may be attributed to their rumen microorganisms degrading ZEA.
Table 3Pathological characteristics of different animals exposed to five common mycotoxins in diets.
Mycotoxin Types | Effects on Monogastric Animal | Effects on Poultry | Effects on Ruminants | Effects on Aquatic Livestock |
---|---|---|---|---|
AFs | Growth retardation, decreased feed utilization, depression, anorexia, acute liver disease, and immunosuppression | Subcutaneous hemorrhage, smaller eggs, reduced yolk weight, and reduced fertilization and hatching rate | Reduced resistance of cows to viruses and parasites | Liver necrosis, decreased feed intake, and weight loss were observed |
ZEA | Pseudoestrus, vaginitis, abortion, stillbirth in gilts, testicular atrophy in boars, and decreased semen quality in gilts | The ovaries were atrophic, the egg production rate was decreased, and the fertilization rate of breeding eggs was decreased | The rumen degrades 90% of ZEA and generates the more toxic zearalenol | Decreased fecundity, ovulation disorders, and infertility |
DON | Decreased feed intake, intestinal damage, vomiting, and food refusal | Invasion of the digestive tract, decreased feed intake, food refusal, and reduced egg production rate | Under stress, the risk of poisoning is increased | Destroying the integrity of the gill structure |
FBs | Growth arrest, liver tissue damage, reproductive impairment, and immunosuppression | Reduced egg production, poor feather growth, oral ulcers, and neurological disorders | Weight loss, immunosuppression, and liver toxicity | Inhibit growth and cause pathological damage |
OTA | Weight loss, growth retardation, and liver and kidney lesions | Incomplete eggshell calcification, high rate of egg breaking, and subcutaneous hemorrhage | Anorexia, diarrhea, difficulty gaining weight, and decreased milk production | Nervous system and respiratory toxicities |
DON has been identified as one of the most dangerous natural food contaminants by the FAO and WHO. After the ingestion of feed contaminated with DON, livestock will show signs of anorexia, vomiting, diarrhea, fever, dyskinesia, and delayed response. In severe cases, it can lead to blood system damage and even death [31]. Pigs are the most sensitive to DON, showing obvious loss of appetite, food refusal, vomiting, and intestinal damage. Every 1 mg/kg of DON in the diet can reduce the weight gain of pigs by 8% [32]. Moreover, 2 mg/kg of DON in the diet significantly decreased the digestibility of essential amino acids, impaired the absorption of nutrients, and reduced the utilization rate of energy and nutrition [33]. Birds have a high tolerance to DON; however, high doses of DON also reduce their feed intake and growth performance [34,35]. Ruminants show a high tolerance to DON; likewise, beef cattle and sheep can tolerate up to 21 mg/kg of DON intake [36,37,38].
FBs commonly cause pulmonary edema; damage the liver, kidneys, and intestine; affect the reproductive health of boars; reduce sperm quality; and interfere with the ovarian function of sows [39,40,41,42]. For example, 2 μg/kg injection of FB1 into the air cell of chicken eggs can significantly reduce the number of chicken embryos and cause bleeding [43]. The air chamber experiment of chicken embryos incubated for 72 h after injection of different doses of FB1 showed that the mortality rate of chicken embryos was up to 100% [44].
The action mechanism of OTA on ruminants and monogastric animals is different: the former is degraded by microorganisms in the rumen, while the latter is absorbed directly in the intestine [45]. OTA mainly attacks the kidney, showing nephrotoxicity in all monogastric animals, resulting in kidney atrophy, enlargement, and pallor [46]. Experiments have shown that piglets fed rice cultures contaminated with OTA (0.2 to 0.6 mg/kg body weight per day) or pure toxin (2.0 or 1.0 mg/kg body weight per day) suddenly develop depression and reduced feed intake, resulting in weight loss, followed by diarrhea, anorexia, and dehydration [47]. After consuming OTA-contaminated feed, 65% of OTA was absorbed in the GI tract, and the remaining OTA was deposited in the kidney, resulting in weight loss, low feed efficiency, and weight gain [48]. Physiological symptoms of OTA toxicity in poultry include fatigue, reduced feed consumption, developmental delay, poor oviposition, reduced plumage, and extreme mortality at high dietary concentrations, with weight gain reduced in a dose-dependent manner when infected at rates of 0.5 to 29.4 mg/kg for 7 to 60 days in experimental studies. Reduced feed intake was observed between 21 and 60 days of 0.5–4 mg/kg OTA feeding, whereas egg production, hatchability, shell thickness, and egg production were severely affected between 28 and 84 days of 0.5–4 mg/kg OTA feeding in the diet [48,49]. In cattle, microbes in the rumen degrade low doses of OTA to nontoxic forms. Higher doses of OTA ingestion by cattle cause anorexia, diarrhea, difficulty gaining weight, and rapid loss of milk production [50].
In conclusion, different types of mycotoxins have different hazards to different livestock and poultry, and prevention and control can be focused according to the category of livestock and poultry.
2. Mechanisms and Targets of Feed Mycotoxins That Harm the Health and Growth of Livestock and Poultry
2.1. AFs
AFs are the most frequent mycotoxins in human food and animal feed. Their fat-soluble properties promote AFs to invade organisms through the skin, respiratory tract, and digestive tract, especially the digestive tract is the main pathway for the absorption of feed mycotoxins [51,52]. According to a previous study, about half of AFB1 from feed is absorbed in the duodenum and then transported to the target tissues through the blood circulation and lymphatic system [53].
The liver plays a central role in the biotransformation of AFs, in which AFB1 undergoes hydroxylation, epoxidation, hydration, and α-dimethylation catalyzed by the reductase system in the liver microsome and cytoplasm to be converted to less toxic derivatives. This conversion process includes reversible and irreversible reaction types [54,55,56].
Aflatoxin B1 is converted to a more active B1–8, 9-epoxide catalyzed by the hepatic microsomal P450 enzyme system. This epoxide can form stable adducts to DNA and proteins, for example, by covalent bonding at position C8 to DNA guanine N7 and binding to lysine residues, interfering with genetic information transmission and protein synthesis. It can induce genetic mutations, malformations, and carcinogenic effects [57,58].
By promoting the high-frequency mutation of the p53 gene, aflatoxin B1 not only eliminates its tumor suppressor function, but also activates the anti-apoptotic pathway, drives cell proliferation disorders, and then causes tumor formation, showing the typical characteristics of oncogenes. These mutant p53 proteins also tend to build stable complexes with oncogenic proteins, prolong their intracellular stability and over-express, and accelerate the process of cell carcinogenesis [59].
As a powerful immunosuppressant, aflatoxin has multiple effects, not only hindering the normal development of immune organs but also weakening host defense by inhibiting humoral and cellular immune mechanisms and increasing the sensitivity to bacterial, viral, and parasitic infections [60,61]. Aflatoxin also inhibits protein synthesis through DNA/RNA binding, resulting in thymic degeneration, the depletion of lymphocytes, and the impairment of liver and macrophage functions, accompanied by the suppression of complement C4 and T-lymphokine production [62,63]. At the level of humoral immunity, aflatoxin interferes with the activity of RNA polymerase and the synthesis of immunoglobulin, thus showing immunotoxicity [52]. In terms of cellular immunity, aflatoxin B1 further weakened the cellular immune response by downregulating the mRNA expression of IL-2 and IFN-γ in hepatocytes [64].
2.2. ZEA
The absorption and biotransformation sites of ZEA are the gastrointestinal tract and liver. Its metabolic pathway can be summarized as a two-stage process: The first stage involves the hydroxylation reaction. Under the catalysis of steroid hydrogenase and 3α/3β-hydroxysteroid deoxy enzyme, ZEA undergoes ketone group reduction at the C-6 position to produce α- and β-ZEA isomers and then undergoes double-bond reduction at the C11-C12 position to form α- and β- ZEA. In the second stage, uridine diphosphate glucuronosyltransferase (UDP-glucuronosyltransferase) catalyzes glucuronic acid conjugation of these compounds, resulting in the resultant conjugates being cleared from the body through different excretion pathways [65,66,67].
Studies have shown that ZEA and its derivatives ZOL and ZEL can specifically and competitively bind to the ERα and ERβ isoforms of the ER (estrogen receptor) in the cytoplasm, mimicking the mechanism of 17-β-estradiol. The structure of the phenolic ring in ZEA and its derivatives ZOL and ZEL show consistency with the binding domain of the A ring of estradiol in the active site. Notably, as a full agonist of ERα and a partial agonist of ERβ, the modulatory effects of ZEA on estrogenic activity are mainly mediated through ERα. After binding, the ER-ZEA complex is transported into the nucleus and interacts with estrogen response elements (EREs) to regulate target gene transcription and protein synthesis, interfere with cell proliferation and growth, and display typical estrogen-like activities [68,69,70].
The mechanism by which ZEA promotes ROS production may involve structural changes in mitochondria. As the main source of ROS, ZEA can reduce mitochondrial membrane potential, mitochondrial membrane damage, permeability transition, and cytochrome c oxidase inactivation in a dose-dependent manner. The inhibition of immunoglobulin secretion may result from the direct inhibition of B cells, reducing immunoglobulin production, given that plasma cells are responsible for immunoglobulin secretion after differentiation from B cells upon antigen stimulation [71,72].
2.3. DON
DON is absorbed primarily in the duodenum, which, thanks to its small-molecule properties, allows for passive transport into the osmotic bloodstream. Generally, DON interferes with the function of 5-hydroxytryptamine and catecholamine receptors in the small intestine and interferes with the normal peristaltic rhythm, resulting in a series of digestive disorders, such as nausea, vomiting, loss of appetite, and diarrhea [73].
Studies have shown that DON can reduce the transepithelial electrical resistance (TEER) of intestinal epithelial cell monolayer in a dose-dependent manner. In addition, DON downregulated the expression of tight junction proteins (ZO-1, E-cadherin, Occludin, and Claudin) in the intestinal epithelium both in vitro and in vivo, which may be regulated by the activation of the MAPK pathway [74,75]. DON has also been found to significantly increase the expressions of TNF-α, IL-1β, IFN-γ, IL-6, and other pro-inflammatory factors in the jejunums and ilea of piglets, affect cytokine and immune function, and damage the intestinal mucosal barrier [76]. Additionally, DON affects mucosal SIgA secretion and further damages the host defense against pathogens, indicating the adverse effects of DON on intestinal mucosal immunity [77].
2.4. FBs
The gastrointestinal absorption of FBs in pigs is limited, and the absorption rate of fumonisin-B1 (FB1) is only about 4%. The accumulation of FB1 was mainly distributed in the liver, kidneys, and spleen in pigs, and its distribution pattern was significantly affected by the dose and duration of exposure [78]. Specifically, during low-dose, long-term exposure, FB1 accumulated the most in the lungs, followed by the liver and kidneys. On the other hand, when a high dose was taken for a short period, the accumulation of the toxin in the liver was the first, followed by the kidneys, heart, and lungs, showing the regulation of the dose and time on the distribution of the toxin [79].
FB1, which is structurally similar to sphingosine, can inhibit the activity of N-acyltransferase, thereby interfering with sphingomyelin synthesis [80]. Sphingolipids, as a key component of the cell membrane, are involved in the regulation of cell life activities. FB competes with sphingosine N-2 acyltransferase due to its structural similarity, hindering sphingolipid metabolism and causing cell damage [81]. In addition, by interfering with sphingolipid-mediated cell signaling, FB1 can affect the activities of protein kinase C, phosphorylase D, and AP-1 transcription factors and interfere with cell adhesion, differentiation, proliferation, and even carcinogenesis [82,83].
Several studies have suggested that FB1 may mediate toxicity and carcinogenicity through oxidative stress. For example, when HepG2 cells were treated with 50 μM FB1 for 0, 12, and 24 h, the ROS content in treated cells was significantly higher than that in blank cells [42]. When 2.5 mg/kg FB 1 was exposed to the colon of mice, antioxidant enzymes such as SOD-1, SOD-2, GR, and GADPH in the FB 1-treated group were significantly lower than those in the control group. The contents of CYTP450, TRX, HSP70, and HSP90 were significantly higher than those in the control group [84].
2.5. OTA
OTA is mainly absorbed in the small intestine segment and undergoes a biotransformation process in the liver and kidneys of pigs [85]. After entering the blood, the OTA binds serum proteins in a bivalent form and maintains its long-term toxic effect through interaction with biomacromolecules and reabsorption in the kidneys and hepatic–intestinal circulation [86].
OTA inhibits protein synthesis by competitively binding to tRNA synthesis sites and affects phenylalanine access, thereby inhibiting t-RNA function [87]. Its promotion of lipid peroxidation may be related to the activation of NADPH and the enhancement of ascorbate-dependent lipid peroxidation, leading to the accumulation of malondialdehyde [88]. In the main target organ, the kidneys, OTA inhibits renal enzyme activity through the phenylalanine group, affecting renal function. OTA can also cause liver peroxidation, leading to hepatocyte apoptosis and dysfunction [89]. Its cytotoxic mechanism may involve competitive inhibition of mitochondrial carrier proteins, blocking mitochondrial phosphate transport and the respiratory chain and affecting mitochondrial function. In addition, OTA inhibits protein synthesis, reduces immunoglobulin secretion, reduces the activity of immune factors, and inhibits the proliferation and apoptosis of immune cells [90].
3. Study on the Application of Plant Extracts in Mycotoxin Poisoning
3.1. The Development Potential of Plant Extracts
Since ancient times, plants have played a central role in the prevention and treatment of diseases, a tradition that continues to this day. Despite the remarkable advances in modern medicine, many people in developing regions still rely on traditional remedies to cope with health problems, both for cultural heritage, economic, and efficacy reasons [91]. According to the World Health Organization, about 80% of the world’s population relies on traditional medicine for their basic medical needs, demonstrating the universal value of plant medicine [92]. Recent studies have witnessed a resurgence of interest in medicinal products derived from plants in both developed and developing societies, highlighting the vast resources and geographical diversity of plants for medicinal use, as well as the translation of traditional wisdom into modern medicines derived from plants [93].
3.2. Source and Composition of Plant Extracts
Plant extracts are the products of physical extraction or biological fermentation of the whole or parts of one or more natural plants as raw materials. They are usually derived from the roots, stems, leaves, flowers, fruits, or seeds of plants and contain a variety of phytochemicals. According to the main active ingredients, they can be divided into alkaloids, glycosides, flavonoids, organic acids, polysaccharides, polyphenols, and volatile oils [94]. Saponins are widely distributed in higher plant kingdoms and play important roles in Chinese herbal medicine, such as ginseng, Astragalus membranaceus, Panax notoginseng, and jujube seed. They show a variety of pharmacological activities, including anti-cancer, anti-tumor, antipyretic, detoxification, etc., which can play a beneficial role in the immunity, antioxidant digestive, and metabolic functions of livestock and poultry, thereby improving the performance of livestock and poultry [95]. Flavonoids, which are widely distributed in plants, play key roles in plant growth and development and have antibacterial and disease-prevention functions [96]. As widely distributed non-amino acid compounds, organic acids are widely present in plants with acidic characteristics, especially in fruits. Su Hong et al. used the Box–Behnkenken design to optimize the compound biological preservative of citric acid, thymol, and sodium alginate and provided a natural and efficient microbial inhibition scheme [97]. Polysaccharides are mainly distributed in plants, microorganisms, and marine organisms, especially in plant tissues. ZHAI et al. showed that pomegranate peel polysaccharides can significantly improve the activity of antioxidant enzymes in mice with CCI4-induced liver damage, suggesting their protective effect [98]. Hu Aijun’s team extracted polysaccharides from chickpeas with the assistance of ultrasound, which proved that both non-starchy and acidic polysaccharides had free radical scavenging ability, emphasizing the potential of polysaccharides in biological protection and treatment [99]. Polyphenols are a class of secondary metabolites that are widely present in plants, and most representatives of these compounds are characterized by interactions with reactive oxygen species [100]. In summary, the active components of the plant extracts were proven to have significant antioxidative and tissue-protective effects, showing potential to ameliorate mycotoxin-induced damage. Polyphenolic compounds, flavonoids, and other bioactive components in plant extracts can prevent the absorption of mycotoxins or reduce their biological activity by binding to mycotoxin molecules. Phenolics from beetroot may interfere with the absorption and bioavailability of mycotoxins in the gastrointestinal tract, potentially reducing their toxicity [101]. Pumpkin extract plays a significant role in mitigating the toxic effects of aflatoxin B1 and Ochratoxin A on neuronal differentiation. Specifically, the addition of pumpkin extract in contaminated breads significantly reduced the bio-accessibility of aflatoxin B1 and Ochratoxin A [102]. Moreover, some extracts can enhance the detoxification capacity in animals by regulating the activities of detoxifying enzymes. This study indicates that the phenolic compounds in algal extracts can aid in the detoxification of rats damaged by AFB1 [103].
3.3. Application of Plant Extracts
Plant extracts are rich in bioactive components with anti-mutagenic, antioxidant, and anti-cancer properties, which may effectively reduce the toxicity of mycotoxins. Their antioxidant mechanism involves scavenging free radicals, protecting cell membranes and macromolecules from free radical damage, and maintaining cell integrity [104]. Experimental research has substantiated that the elevated polyphenol content found in edamame and various common bean varieties enhances their antioxidant characteristics. The bioactive compounds present in these beans have exhibited potent antifungal and antitoxic properties, suggesting the capacity of legumes to counteract aflatoxin contamination by leveraging the antioxidative attributes of phenolic compounds [105]. Mutagenicity resistance is reflected in reducing gene variation induced by mutagens and maintaining genetic stability [106]. This study highlights the antioxidant and anti-mutagenic potential of Piper nigrum. The ability of phytocompounds to interact with DNA might reduce the interaction of mutagens and could be one of the possible mechanisms of the anti-mutagenic activity of P. nigrum extract [107]. On the anti-cancer side, plant extracts can activate and induce detoxification enzymes, interfere with key oncogenic signaling pathways (such as PI3K/Akt and Raf/MEK/ERK), and suppress tumor progression [108].
Interestingly, bioactive compounds in plants have been used as additives to prevent fungal growth and mycotoxin contamination in food and feed, thereby reducing the risk of mutagenicity and carcinogenicity of mycotoxins (Table 4). For instance, the potent inhibitory effect of essential oil on a variety of molds, including Aspergillus flavus and Aspergillus niger, and their toxins has been verified. Kocic-Tanackov et al. further demonstrated that a high concentration of Carum carvi L. essential oil treatment can completely block the production of aflatoxin [109]. It has also been reported that calabash extract, especially the polar extract with a high ferulic acid composition, has shown potential in inhibiting toxigenic fungi and reducing mycotoxin accumulation [110]. In addition, the high efficiency of plant-derived phenols such as chlorophyll in limiting the proliferation of Fusarium verticillioides and the production of its toxin, FB1, provides a solid theoretical basis for the development of biosafety strategies to prevent the penetration of harmful mycotoxins into the food chain [111]. Phenolic substances contained in soybeans have been proven to strengthen the defense system of antifungals and inhibit the formation of aflatoxin [112]. Shah Zaman conducted experimental tests to demonstrate the potential resistance of certain plant species (C. cyminum). The findings revealed a statistically significant and robust negative correlation between average mycotoxins and phytochemical concentrations [113].
Table 4Overview of studies on the reduction of mycotoxin toxicity by a compound.
Plant Extract | Classification | Experimental Subject | Mechanism | References |
---|---|---|---|---|
Curcumin | Polyphenol | DucksMice | Increased jejunal tight junction protein mRNA and protein levels to protect the intestinal barrier and mitochondria from OTA-induced damageRegulation of Nrf2/p53-mediated apoptosis pathway and NF-kB/MLCK-mediated TJ pathway alleviates intestinal epithelial barrier damage induced by DON in mice | [114,115] |
Resveratrol | Polyphenol | Intestinal cells | Activation of the protein kinase-dependent pathway regulates IL-6 and IL-8 secretion to promote the assembly of claudin-4 in tight junction complexes to prevent DON-induced barrier dysfunction | [116] |
Dihydromyricetin | Flavone | IPEC-J2 | Alleviates cell damage caused by DON through its antioxidant activity, anti-inflammatory activity, or regulation of metabolic pathways | [117] |
Grape seed proanthocyanidin extract | Glycoside | Rats | GSPE can alleviate the oxidative stress induced by AFB1 and significantly improve the immune damage induced by AFB1 in mice | [118] |
Red orange and lemon extract | Glycoside | Rats | RLE attenuates OTA kidney injury caused by oxidative stress | [119] |
Flavonoid-rich fractions from Chromolena odorata | Flavone | Rats | Afb1-induced liver and intestinal injuries were ameliorated by changing the levels of pro-inflammatory cytokines, TNF-α, and IL-1β | [120] |
Ferulic acid | Organic acid | Rats | Upregulation of tight junction proteins, downregulation of ROCK, competition for CYP450 enzyme, and activation of GST attenuate AFB1-induced duodenal barrier injury in rats | [121] |
Quercetin | Polyphenol | Mice | Quercetin alleviates intestinal injury induced by DON in mice by inhibiting the TLR4/NF-κB signaling pathway and ferroptosis | [122] |
Hericium mushroom polysaccharide | Polysaccharide | IPEC-J2 | It can significantly protect IPEC-J2 cells from DON-induced oxidative stress, inhibit DON-induced apoptosis, and reduce the production of reactive oxygen species (ROS) | [123] |
Theophylline | Alkaloid | Piglets | To improve the intestinal barrier function and reduce inflammation, immunosuppression, and oxidative stress in piglets challenged with DON by regulating NF-κB/MAPK signaling pathway | [124] |
Melaleuca alternifolia | Essential oil | Silver catfish | Elevated levels of ROS, LOOH, and PC in plasma and liver were avoided; in addition, TTO treatment attenuated aflatoxin-related liver injury | [125] |
Studies have also found that phenol-rich ginger extract (GE) can effectively reduce oxidative stress and liver injury caused by AFB1, and this protective effect may be related to the activation of the Nrf2/HO-1 signaling pathway [126]. A study demonstrated the protective effect of Tunisian radish extract (TRE) against immunosuppression induced by aflatoxin ZEN in Balb/c mice by quantifying flavonoids and isothiocyanates in TRE and measuring its antioxidant capacity [127]. Subsequently, onion, garlic extract, and eugenol were found to have significant effects on the growth and toxin synthesis of aflatoxin, especially the excellent toxin inhibition performance of onion extract [128]. In addition, carnosic acid (CA), a key polyphenol in rosemary, shows a powerful free radical scavenging effect and effectively alleviates AFB1-induced cytotoxicity and oxidative stress at the cellular level [129]. In addition, the antioxidant mechanism of total curcumin (TCMN) has been verified to significantly improve the adverse effects of AFB1 on broking chickens, restore serum biochemical indicators, and enhance the antioxidant capacity of the body, providing scientific evidence for the biological activities of the above plant extracts [130].
Scutellaria baicalensis root extract has been verified to specifically block the metabolic pathway of AFB1 in rat and human liver microsomes and reduce the generation of harmful metabolites by inhibiting CYP1A1/2 enzyme activity [131]. FWGE showed an efficient effect on alleviating the oxidative stress caused by DON and T-2 toxin in IPEC-J2 cells, reflecting its cytoprotective performance [132]. The ability of green tea extract to inhibit AFB1-induced transformation of liver cancer was confirmed across models, highlighting the value of anti-cancer components in water-soluble and ethanol extracts [133]. Agave plant extracts, especially flower parts, can significantly inhibit the production of aflatoxin and cyclopidonic acid [134]. The study of Capsantal and its mixture (Capsantal FS-30-NT) revealed its complex regulatory effects on the growth and toxin production of aflatoxin, and a low temperature was identified as the key intervention point [135]. In addition, studies have revealed that green tea extract and coumarins can regulate AFB1 metabolism in piglets and enhance detoxification, highlighting the positive utility of antioxidants in this process [136].
Currently, plant extracts have also achieved good application effects as alternatives in antimicrobial and detoxifying medications, such as common Chinese herbal medicines like licorice, bupleurum, coptis, balloon flower, isatis root, pulsatilla, and forsythia. A mixture of oregano and thyme, along with two commercial inoculants, was fermented. After 90 days of fermentation, it was indicated that the herbal extracts of oregano and thyme could be used to reduce the mycotoxin concentrations and improve the hygienic quality of corn silage [137]. The extract of Houttuynia cordata has been proven to completely replace certain antibiotics in animal diets, such as colistin sulfate or doxycycline calcium, and has been applied in large- and medium-sized enterprises for several years [138].
4. Limitations and Prospects
The increasing demand for plant extracts and their compounds has raised concerns about the safety, toxicity, and quality of these products. Therefore, a thorough screening of their toxicological properties is necessary. Future applications of plant extracts against mycotoxins should prioritize the development of techniques for producing safe and stable extracts. This includes comparing the similarities and differences among the active constituents of plant extracts that demonstrate effective detoxification properties and validating their precise detoxification mechanisms. Additionally, research should investigate the use of material coatings to deliver the extracts to targeted sites of action. It is also essential to determine the optimal concentrations for the application of these extracts under different conditions to minimize costs.
Research on plant extracts in the field of anti-mycotoxins has shown potential, but there are still several key gaps:
(1). Most studies focus on superficial effects, such as antioxidation and anti-inflammation, but there is insufficient analysis of the molecular targets for detoxification, such as key enzyme inhibition and signaling pathway regulation, as well as the toxin metabolism pathways. There is a lack of systematic validation at the multi-omics level.
(2). Active components (such as polyphenols and flavonoids) are prone to degradation under the influence of light, heat, and pH, and some extracts may cause unknown toxicities or interact with feed components. A long-term toxicological evaluation system needs to be established.
(3). The extracts have low absorption rates and rapid metabolisms in animals, making it difficult to target the sites of toxin action (such as the intestines and liver). There is an urgent need to develop encapsulation technologies (such as nanocarriers) to improve delivery efficiency.
(4). Existing research mostly focuses on single toxins, whereas actual contamination often involves multiple mycotoxins coexisting. The synergistic detoxification effects and mechanisms of plant extracts on complex contamination have not yet been clarified.
(5). The extraction process of high-purity active components is complex and costly, and it is limited by the regional and seasonal availability of plant resources. There is a need to optimize low-cost, sustainable industrial production schemes.
(6). There are no uniform quality control standards for the active components of different extracts, and there is a lack of research on the dose-effect relationship between active ingredients and detoxification effects, which affects the reliability of practical applications.
In the future, it will be necessary to combine metabolomics, targeted delivery technologies, and interdisciplinary collaboration to break through the aforementioned bottlenecks and promote the transformation of plant extracts from basic research to industrial application.
Conceptualization, X.Z., K.Y. and Q.J.; investigation, X.Z., J.C., X.M., X.T. and Q.J.; methodology, X.Z., P.L., K.Y. and Q.J.; visualization, X.Z., P.L., K.Y. and Q.J.; project administration, J.C., X.M., X.T., B.T., P.L., K.Y. and Q.J.; writing—original draft, X.Z. and Q.J.; writing—review and editing, X.Z., J.C., X.M., X.T., B.T., P.L., K.Y. and Q.J.; funding acquisition, P.L., K.Y. and Q.J. All authors have read and agreed to the published version of the manuscript.
Not applicable.
Not applicable.
No new data were created or analyzed in this study.
The authors declare no competing interests.
Footnotes
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1. Khan, R. Mycotoxins in food: Occurrence, health implications, and control strategies-A comprehensive review. Toxicon; 2024; 248, 108038. [DOI: https://dx.doi.org/10.1016/j.toxicon.2024.108038]
2. Makhuvele, R.; Naidu, K.; Gbashi, S.; Thipe, V.C.; Adebo, O.A.; Njobeh, P.B. The use of plant extracts and their phytochemicals for control of toxigenic fungi and mycotoxins. Heliyon; 2020; 6, e05291. [DOI: https://dx.doi.org/10.1016/j.heliyon.2020.e05291] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/33134582]
3. Raters, M.; Matissek, R. Thermal stability of aflatoxin B1 and ochratoxin A. Mycotoxin Res.; 2008; 24, pp. 130-134. [DOI: https://dx.doi.org/10.1007/BF03032339] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23604747]
4. Li, Y.; Gao, H.; Wang, R.; Xu, Q. Deoxynivalenol in food and feed: Recent advances in decontamination strategies. Front. Microbiol.; 2023; 14, 1141378. [DOI: https://dx.doi.org/10.3389/fmicb.2023.1141378]
5. Awuchi, C.G.; Ondari, E.N.; Nwozo, S.; Odongo, G.A.; Eseoghene, I.J.; Twinomuhwezi, H.; Ogbonna, C.U.; Upadhyay, A.K.; Adeleye, A.O.; Okpala, C.O.R. Mycotoxins’ Toxicological Mechanisms Involving Humans, Livestock and Their Associated Health Concerns: A Review. Toxins; 2022; 14, 167. [DOI: https://dx.doi.org/10.3390/toxins14030167]
6. Murtaza, B.; Wang, L.; Li, X.; Nawaz, M.Y.; Saleemi, M.K.; Khatoon, A.; Yongping, X. Recalling the reported toxicity assessment of deoxynivalenol, mitigating strategies and its toxicity mechanisms: Comprehensive review. Chem.-Biol. Interact.; 2024; 387, 110799. [DOI: https://dx.doi.org/10.1016/j.cbi.2023.110799]
7. Lv, Q.; Xu, W.; Yang, F.; Wei, W.; Chen, X.; Zhang, Z.; Liu, Y. Reproductive Toxicity of Zearalenone and Its Molecular Mechanisms: A Review. Molecules; 2025; 30, 505. [DOI: https://dx.doi.org/10.3390/molecules30030505]
8. Kamle, M.; Mahato, D.K.; Devi, S.; Lee, K.E.; Kang, S.G.; Kumar, P. Fumonisins: Impact on Agriculture, Food, and Human Health and their Management Strategies. Toxins; 2019; 11, 328. [DOI: https://dx.doi.org/10.3390/toxins11060328]
9. Banahene, J.C.M.; Ofosu, I.W.; Odai, B.T.; Lutterodt, H.E.; Agyemang, P.A.; Ellis, W.O. Ochratoxin A in food commodities: A review of occurrence, toxicity, and management strategies. Heliyon; 2024; 10, e39313. [DOI: https://dx.doi.org/10.1016/j.heliyon.2024.e39313]
10. Zhang, Z.; McCullough, C. Survey on the Content of Mycotoxins in Newly Harvested Feeds and Forages in Europe, 2021. Today Pig Ind.; 2022; 1, pp. 66-68.
11. Patyal, A.; Gill, J.P.S.; Bedi, J.S.; Aulakh, R.S. Assessment of aflatoxin contamination in dairy animal concentrate feed from Punjab, India. Environ. Sci. Pollut. Res. Int.; 2021; 28, pp. 37705-37715. [DOI: https://dx.doi.org/10.1007/s11356-021-13321-x] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/33723771]
12. Zhao, L.; Zhang, L.; Xu, Z.; Liu, X.; Chen, L.; Dai, J.; Karrow, N.A.; Sun, L. Occurrence of Aflatoxin B(1), deoxynivalenol and zearalenone in feeds in China during 2018–2020. J. Anim. Sci. Biotechnol.; 2021; 12, 74. [DOI: https://dx.doi.org/10.1186/s40104-021-00603-0]
13. Hao, W.; Guan, S.; Li, A.; Wang, J.; An, G.; Hofstetter, U.; Schatzmayr, G. Mycotoxin Occurrence in Feeds and Raw Materials in China: A Five-Year Investigation. Toxins; 2023; 15, 63. [DOI: https://dx.doi.org/10.3390/toxins15010063] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/36668883]
14. Zhang, Y.; Yang, Y.; Qi, S.; Zhou, J.; Wang, C.; Zheng, W.; Lei, Y.; Ji, C. Survey on the Mycotoxin Contamination in Domestic Feed. and Feed. Ingredients in 2021. Feed. Ind.; 2022; 43, pp. 55-58. [DOI: https://dx.doi.org/10.13302/j.cnki.fi.2022.15.011]
15. Cargill’s 2023 Global Mycotoxin Report. Available online: https://mycotoxins.com/home (accessed on 6 February 2024).
16. Gruber-Dorninger, C.; Jenkins, T.; Schatzmayr, G. Global Mycotoxin Occurrence in Feed: A Ten-Year Survey. Toxins; 2019; 11, 375. [DOI: https://dx.doi.org/10.3390/toxins11070375]
17. van der Fels-Klerx, H.J.; Goedhart, P.W.; Elen, O.; Börjesson, T.; Hietaniemi, V.; Booij, C.J. Modeling deoxynivalenol contamination of wheat in northwestern Europe for climate change assessments. J. Food Prot.; 2012; 75, pp. 1099-1106. [DOI: https://dx.doi.org/10.4315/0362-028x.Jfp-11-435] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/22691478]
18. Tian, M.; Feng, Y.; He, X.; Zhang, D.; Wang, W.; Liu, D. Mycotoxins in livestock feed in China—Current status and future challenges. Toxicon; 2022; 214, pp. 112-120. [DOI: https://dx.doi.org/10.1016/j.toxicon.2022.05.041]
19. Yang, C.; Song, G.; Lim, W. Effects of mycotoxin-contaminated feed on farm animals. J. Hazard. Mater.; 2020; 389, 122087. [DOI: https://dx.doi.org/10.1016/j.jhazmat.2020.122087]
20. Ivanovics, B.; Gazsi, G.; Reining, M.; Berta, I.; Poliska, S.; Toth, M.; Domokos, A.; Nagy, B., Jr.; Staszny, A.; Cserhati, M.
21. Mahato, D.K.; Lee, K.E.; Kamle, M.; Devi, S.; Dewangan, K.N.; Kumar, P.; Kang, S.G. Aflatoxins in Food and Feed: An Overview on Prevalence, Detection and Control Strategies. Front. Microbiol.; 2019; 10, 2266. [DOI: https://dx.doi.org/10.3389/fmicb.2019.02266]
22. Liu, X.; Kumar Mishra, S.; Wang, T.; Xu, Z.; Zhao, X.; Wang, Y.; Yin, H.; Fan, X.; Zeng, B.; Yang, M.
23. Loi, M.; Fanelli, F.; Liuzzi, V.C.; Logrieco, A.F.; Mulè, G. Mycotoxin Biotransformation by Native and Commercial Enzymes: Present and Future Perspectives. Toxins; 2017; 9, 111. [DOI: https://dx.doi.org/10.3390/toxins9040111] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28338601]
24. Wu, F.; Groopman, J.D.; Pestka, J.J. Public health impacts of foodborne mycotoxins. Annu. Rev. Food Sci. Technol.; 2014; 5, pp. 351-372. [DOI: https://dx.doi.org/10.1146/annurev-food-030713-092431]
25. Benkerroum, N. Chronic and Acute Toxicities of Aflatoxins: Mechanisms of Action. Int. J. Environ. Res. Public Health; 2020; 17, 423. [DOI: https://dx.doi.org/10.3390/ijerph17020423] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31936320]
26. Rawal, S.; Kim, J.E.; Coulombe, R., Jr. Aflatoxin B1 in poultry: Toxicology, metabolism and prevention. Res. Vet. Sci.; 2010; 89, pp. 325-331. [DOI: https://dx.doi.org/10.1016/j.rvsc.2010.04.011]
27. Silvotti, L.; Petterino, C.; Bonomi, A.; Cabassi, E. Immunotoxicological effects on piglets of feeding sows diets containing aflatoxins. Vet. Rec.; 1997; 141, pp. 469-472. [DOI: https://dx.doi.org/10.1136/vr.141.18.469]
28. Jiang, Y.; Ogunade, I.M.; Vyas, D.; Adesogan, A.T. Aflatoxin in Dairy Cows: Toxicity, Occurrence in Feedstuffs and Milk and Dietary Mitigation Strategies. Toxins; 2021; 13, 283. [DOI: https://dx.doi.org/10.3390/toxins13040283] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/33920591]
29. Tassis, P.D.; Reisinger, N.; Nagl, V.; Tzika, E.; Schatzmayr, D.; Mittas, N.; Basioura, A.; Michos, I.; Tsakmakidis, I.A. Comparative Effects of Deoxynivalenol, Zearalenone and Its Modified Forms De-Epoxy-Deoxynivalenol and Hydrolyzed Zearalenone on Boar Semen In Vitro. Toxins; 2022; 14, 497. [DOI: https://dx.doi.org/10.3390/toxins14070497]
30. Wu, K.; Ren, C.; Gong, Y.; Gao, X.; Rajput, S.A.; Qi, D.; Wang, S. The insensitive mechanism of poultry to zearalenone: A review. Anim. Nutr. (Zhongguo Xu Mu Shou Yi Xue Hui); 2021; 7, pp. 587-594. [DOI: https://dx.doi.org/10.1016/j.aninu.2021.01.002]
31. Hooft, J.M.; Bureau, D.P. Deoxynivalenol: Mechanisms of action and its effects on various terrestrial and aquatic species. Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc.; 2021; 157, 112616. [DOI: https://dx.doi.org/10.1016/j.fct.2021.112616]
32. Dersjant-Li, Y.; Verstegen, M.W.; Gerrits, W.J. The impact of low concentrations of aflatoxin, deoxynivalenol or fumonisin in diets on growing pigs and poultry. Nutr. Res. Rev.; 2003; 16, pp. 223-239. [DOI: https://dx.doi.org/10.1079/NRR200368] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19087391]
33. Holanda, D.M.; Yiannikouris, A.; Kim, S.W. Investigation of the Efficacy of a Postbiotic Yeast Cell Wall-Based Blend on Newly-Weaned Pigs under a Dietary Challenge of Multiple Mycotoxins with Emphasis on Deoxynivalenol. Toxins; 2020; 12, 504. [DOI: https://dx.doi.org/10.3390/toxins12080504]
34. Metayer, J.P.; Travel, A.; Mika, A.; Bailly, J.D.; Cleva, D.; Boissieu, C.; Guennec, J.L.; Froment, P.; Albaric, O.; Labrut, S.
35. Kim, J.H.; Park, G.H.; Han, G.P.; Kil, D.Y. Effect of feeding corn distillers dried grains with solubles naturally contaminated with deoxynivalenol on growth performance, meat quality, intestinal permeability, and utilization of energy and nutrients in broiler chickens. Poult. Sci.; 2021; 100, 101215. [DOI: https://dx.doi.org/10.1016/j.psj.2021.101215] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/34171654]
36. Dong, J.N.; Zhao, Z.K.; Wang, Z.Q.; Li, S.Z.; Zhang, Y.P.; Sun, Z.; Qin, G.X.; Zhang, X.F.; Zhao, W.; Aschalew, N.D.
37. Loh, Z.H.; Ouwerkerk, D.; Klieve, A.V.; Hungerford, N.L.; Fletcher, M.T. Toxin Degradation by Rumen Microorganisms: A Review. Toxins; 2020; 12, 664. [DOI: https://dx.doi.org/10.3390/toxins12100664]
38. Wang, G.; Du, Y. The Impact of Vomitoxin on Ruminant Animals. Feed. Ind.; 2016; 37, pp. 58-61. [DOI: https://dx.doi.org/10.13302/j.cnki.fi.2016.20.013]
39. Li, W.; He, Y.; Zhao, H.; Peng, L.; Li, J.; Rui, R.; Ju, S. Grape Seed Proanthocyanidin Ameliorates FB(1)-Induced Meiotic Defects in Porcine Oocytes. Toxins; 2021; 13, 841. [DOI: https://dx.doi.org/10.3390/toxins13120841] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/34941679]
40. Gbore, F.A. Reproductive organ weights and semen quality of pubertal boars fed dietary fumonisin B1. Anim. Int. J. Anim. Biosci.; 2009; 3, pp. 1133-1137. [DOI: https://dx.doi.org/10.1017/S1751731109004467]
41. Wang, Y.; Quan, H.; Li, X.; Li, Q.; Haque, M.A.; Shi, Q.; Fu, Q.; He, C. Contamination With Fumonisin B and Deoxynivalenol Is a Threat to Egg Safety and Contributes to Gizzard Ulcerations of Newborn Chickens. Front. Microbiol.; 2021; 12, 676671. [DOI: https://dx.doi.org/10.3389/fmicb.2021.676671]
42. Singh, M.P.; Kang, S.C. Endoplasmic reticulum stress-mediated autophagy activation attenuates fumonisin B1 induced hepatotoxicity in vitro and in vivo. Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc.; 2017; 110, pp. 371-382. [DOI: https://dx.doi.org/10.1016/j.fct.2017.10.054] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29097114]
43. Henry, M.H.; Wyatt, R.D. The toxicity of fumonisin B1, B2, and B3, individually and in combination, in chicken embryos. Poult. Sci.; 2001; 80, pp. 401-407. [DOI: https://dx.doi.org/10.1093/ps/80.4.401]
44. Zacharias, C.; van Echten-Deckert, G.; Wang, E.; Merrill, A.H., Jr.; Sandhoff, K. The effect of fumonisin B1 on developing chick embryos: Correlation between de novo sphingolipid biosynthesis and gross morphological changes. Glycoconj. J.; 1996; 13, pp. 167-175. [DOI: https://dx.doi.org/10.1007/BF00731491]
45. Denli, M.; Perez, J.F. Ochratoxins in feed, a risk for animal and human health: Control strategies. Toxins; 2010; 2, pp. 1065-1077. [DOI: https://dx.doi.org/10.3390/toxins2051065]
46. Tao, Y.; Xie, S.; Xu, F.; Liu, A.; Wang, Y.; Chen, D.; Pan, Y.; Huang, L.; Peng, D.; Wang, X.
47. Stoev, S.D.; Paskalev, M.; MacDonald, S.; Mantle, P.G. Experimental one year ochratoxin A toxicosis in pigs. Exp. Toxicol. Pathol. Off. J. Ges. Fur Toxikol. Pathol.; 2002; 53, pp. 481-487. [DOI: https://dx.doi.org/10.1078/0940-2993-00213] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/11926291]
48. Liu, W.C.; Pushparaj, K.; Meyyazhagan, A.; Arumugam, V.A.; Pappuswamy, M.; Bhotla, H.K.; Baskaran, R.; Issara, U.; Balasubramanian, B.; Mousavi Khaneghah, A. Ochratoxin A as an alarming health threat for livestock and human: A review on molecular interactions, mechanism of toxicity, detection, detoxification, and dietary prophylaxis. Toxicon; 2022; 213, pp. 59-75. [DOI: https://dx.doi.org/10.1016/j.toxicon.2022.04.012] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/35452686]
49. Murugesan, G.R.; Ledoux, D.R.; Naehrer, K.; Berthiller, F.; Applegate, T.J.; Grenier, B.; Phillips, T.D.; Schatzmayr, G. Prevalence and effects of mycotoxins on poultry health and performance, and recent development in mycotoxin counteracting strategies. Poult. Sci.; 2015; 94, pp. 1298-1315. [DOI: https://dx.doi.org/10.3382/ps/pev075]
50. Mobashar, M.; Hummel, J.; Blank, R.; Südekum, K.H. Ochratoxin A in ruminants—A review on its degradation by gut microbes and effects on animals. Toxins; 2010; 2, pp. 809-839. [DOI: https://dx.doi.org/10.3390/toxins204809]
51. Kumar, V.; Bahuguna, A.; Ramalingam, S.; Dhakal, G.; Shim, J.J.; Kim, M. Recent technological advances in mechanism, toxicity, and food perspectives of enzyme-mediated aflatoxin degradation. Crit. Rev. Food Sci. Nutr.; 2022; 62, pp. 5395-5412. [DOI: https://dx.doi.org/10.1080/10408398.2021.2010647]
52. Jaćević, V.; Dumanović, J.; Alomar, S.Y.; Resanović, R.; Milovanović, Z.; Nepovimova, E.; Wu, Q.; Franca, T.C.C.; Wu, W.; Kuča, K. Research update on aflatoxins toxicity, metabolism, distribution, and detection: A concise overview. Toxicology; 2023; 492, 153549. [DOI: https://dx.doi.org/10.1016/j.tox.2023.153549] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/37209941]
53. Kumagai, S. Intestinal absorption and excretion of aflatoxin in rats. Toxicol. Appl. Pharmacol.; 1989; 97, pp. 88-97. [DOI: https://dx.doi.org/10.1016/0041-008x(89)90057-4]
54. Min, L.; Fink-Gremmels, J.; Li, D.; Tong, X.; Tang, J.; Nan, X.; Yu, Z.; Chen, W.; Wang, G. An overview of aflatoxin B1 biotransformation and aflatoxin M1 secretion in lactating dairy cows. Anim. Nutr. (Zhongguo Xu Mu Shou Yi Xue Hui); 2021; 7, pp. 42-48. [DOI: https://dx.doi.org/10.1016/j.aninu.2020.11.002]
55. Deng, J.; Zhao, L.; Zhang, N.Y.; Karrow, N.A.; Krumm, C.S.; Qi, D.S.; Sun, L.H. Aflatoxin B(1) metabolism: Regulation by phase I and II metabolizing enzymes and chemoprotective agents. Mutat. Res. Rev. Mutat. Res.; 2018; 778, pp. 79-89. [DOI: https://dx.doi.org/10.1016/j.mrrev.2018.10.002] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30454686]
56. Wang, L.; Huang, Q.; Wu, J.; Wu, W.; Jiang, J.; Yan, H.; Huang, J.; Sun, Y.; Deng, Y. The metabolism and biotransformation of AFB(1): Key enzymes and pathways. Biochem. Pharmacol.; 2022; 199, 115005. [DOI: https://dx.doi.org/10.1016/j.bcp.2022.115005]
57. Rushing, B.R.; Selim, M.I. Aflatoxin B1: A review on metabolism, toxicity, occurrence in food, occupational exposure, and detoxification methods. Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc.; 2019; 124, pp. 81-100. [DOI: https://dx.doi.org/10.1016/j.fct.2018.11.047]
58. Eaton, D.L.; Williams, D.E.; Coulombe, R.A. Species Differences in the Biotransformation of Aflatoxin B1: Primary Determinants of Relative Carcinogenic Potency in Different Animal Species. Toxins; 2025; 17, 30. [DOI: https://dx.doi.org/10.3390/toxins17010030]
59. Su, J.J.; Ban, K.C.; Li, Y.; Qin, L.L.; Wang, H.Y.; Yang, C.; Ou, C.; Duan, X.X.; Lee, Y.L.; Yang, R.Q. Alteration of p53 and p21 during hepatocarcinogenesis in tree shrews. World J. Gastroenterol.; 2004; 10, pp. 3559-3563. [DOI: https://dx.doi.org/10.3748/wjg.v10.i24.3559] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/15534906]
60. Saha Turna, N.; Comstock, S.S.; Gangur, V.; Wu, F. Effects of aflatoxin on the immune system: Evidence from human and mammalian animal research. Crit. Rev. Food Sci. Nutr.; 2024; 64, pp. 9955-9973. [DOI: https://dx.doi.org/10.1080/10408398.2023.2219336]
61. He, X.N.; Zeng, Z.Z.; Wu, P.; Jiang, W.D.; Liu, Y.; Jiang, J.; Kuang, S.Y.; Tang, L.; Feng, L.; Zhou, X.Q. Dietary Aflatoxin B1 attenuates immune function of immune organs in grass carp (Ctenopharyngodon idella) by modulating NF-κB and the TOR signaling pathway. Front. Immunol.; 2022; 13, 1027064. [DOI: https://dx.doi.org/10.3389/fimmu.2022.1027064]
62. Lyman, B.A.; Erki, L.; Biedrzycka, D.W.; Devlin, T.M.; Ch’ih, J.J. Modification of protein synthetic components by aflatoxin B1. Biochem. Pharmacol.; 1988; 37, pp. 1481-1486. [DOI: https://dx.doi.org/10.1016/0006-2952(88)90009-3] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/3128983]
63. Pai, M.R.; Bai, N.J.; Venkitasubramanian, T.A. Aflatoxin induced inhibition of protein synthesis. Toxicon; 1978; 16, pp. 283-287. [DOI: https://dx.doi.org/10.1016/0041-0101(78)90089-2]
64. Han, S.H.; Jeon, Y.J.; Yea, S.S.; Yang, K.H. Suppression of the interleukin-2 gene expression by aflatoxin B1 is mediated through the down-regulation of the NF-AT and AP-1 transcription factors. Toxicol. Lett.; 1999; 108, pp. 1-10. [DOI: https://dx.doi.org/10.1016/S0378-4274(99)00008-9]
65. Yang, S.; Zhang, H.; Sun, F.; De Ruyck, K.; Zhang, J.; Jin, Y.; Li, Y.; Wang, Z.; Zhang, S.; De Saeger, S.
66. Pfeiffer, E.; Kommer, A.; Dempe, J.S.; Hildebrand, A.A.; Metzler, M. Absorption and metabolism of the mycotoxin zearalenone and the growth promotor zeranol in Caco-2 cells in vitro. Mol. Nutr. Food Res.; 2011; 55, pp. 560-567. [DOI: https://dx.doi.org/10.1002/mnfr.201000381]
67. Ropejko, K.; Twarużek, M. Zearalenone and Its Metabolites-General Overview, Occurrence, and Toxicity. Toxins; 2021; 13, 35. [DOI: https://dx.doi.org/10.3390/toxins13010035]
68. Tatay, E.; Espín, S.; García-Fernández, A.J.; Ruiz, M.J. Estrogenic activity of zearalenone, α-zearalenol and β-zearalenol assessed using the E-screen assay in MCF-7 cells. Toxicol. Mech. Methods; 2018; 28, pp. 239-242. [DOI: https://dx.doi.org/10.1080/15376516.2017.1395501]
69. Zhou, J.; Zhao, L.; Huang, S.; Liu, Q.; Ao, X.; Lei, Y.; Ji, C.; Ma, Q. Zearalenone toxicosis on reproduction as estrogen receptor selective modulator and alleviation of zearalenone biodegradative agent in pregnant sows. J. Anim. Sci. Biotechnol.; 2022; 13, 36. [DOI: https://dx.doi.org/10.1186/s40104-022-00686-3]
70. Takemura, H.; Shim, J.Y.; Sayama, K.; Tsubura, A.; Zhu, B.T.; Shimoi, K. Characterization of the estrogenic activities of zearalenone and zeranol in vivo and in vitro. J. Steroid Biochem. Mol. Biol.; 2007; 103, pp. 170-177. [DOI: https://dx.doi.org/10.1016/j.jsbmb.2006.08.008]
71. Fan, W.; Shen, T.; Ding, Q.; Lv, Y.; Li, L.; Huang, K.; Yan, L.; Song, S. Zearalenone induces ROS-mediated mitochondrial damage in porcine IPEC-J2 cells. J. Biochem. Mol. Toxicol.; 2017; 31, e21944. [DOI: https://dx.doi.org/10.1002/jbt.21944]
72. Feng, Y.Q.; Zhao, A.H.; Wang, J.J.; Tian, Y.; Yan, Z.H.; Dri, M.; Shen, W.; De Felici, M.; Li, L. Oxidative stress as a plausible mechanism for zearalenone to induce genome toxicity. Gene; 2022; 829, 146511. [DOI: https://dx.doi.org/10.1016/j.gene.2022.146511] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/35447234]
73. Gershon, M.D. 5-Hydroxytryptamine (serotonin) in the gastrointestinal tract. Curr. Opin. Endocrinol. Diabetes Obes.; 2013; 20, pp. 14-21. [DOI: https://dx.doi.org/10.1097/MED.0b013e32835bc703]
74. Li, E.; Horn, N.; Ajuwon, K.M. Mechanisms of deoxynivalenol-induced endocytosis and degradation of tight junction proteins in jejunal IPEC-J2 cells involve selective activation of the MAPK pathways. Arch. Toxicol.; 2021; 95, pp. 2065-2079. [DOI: https://dx.doi.org/10.1007/s00204-021-03044-w] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/33847777]
75. Zhao, X.; Dong, B.; Friesen, M.; Liu, S.; Zhu, C.; Yang, C. Capsaicin Attenuates Lipopolysaccharide-Induced Inflammation and Barrier Dysfunction in Intestinal Porcine Epithelial Cell Line-J2. Front. Physiol.; 2021; 12, 715469. [DOI: https://dx.doi.org/10.3389/fphys.2021.715469]
76. Gao, H.; Liu, L.; Zhao, Y.; Hara, H.; Chen, P.; Xu, J.; Tang, J.; Wei, L.; Li, Z.; Cooper, D.K.C.
77. Macpherson, A.J.; Geuking, M.B.; Slack, E.; Hapfelmeier, S.; McCoy, K.D. The habitat, double life, citizenship, and forgetfulness of IgA. Immunol. Rev.; 2012; 245, pp. 132-146. [DOI: https://dx.doi.org/10.1111/j.1600-065X.2011.01072.x] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/22168417]
78. Fodor, J.; Balogh, K.; Weber, M.; Miklós, M.; Kametler, L.; Pósa, R.; Mamet, R.; Bauer, J.; Horn, P.; Kovács, F.
79. Szabó, A.; Szabó-Fodor, J.; Kachlek, M.; Mézes, M.; Balogh, K.; Glávits, R.; Ali, O.; Zeebone, Y.Y.; Kovács, M. Dose and Exposure Time-Dependent Renal and Hepatic Effects of Intraperitoneally Administered Fumonisin B1 in Rats. Toxins; 2018; 10, 465. [DOI: https://dx.doi.org/10.3390/toxins10110465]
80. Chen, J.; Wen, J.; Tang, Y.; Shi, J.; Mu, G.; Yan, R.; Cai, J.; Long, M. Research Progress on Fumonisin B1 Contamination and Toxicity: A Review. Molecules; 2021; 26, 5238. [DOI: https://dx.doi.org/10.3390/molecules26175238]
81. Li, H.; Wang, M.; Kang, W.; Lin, Z.; Gan, F.; Huang, K. Non-cytotoxic dosage of fumonisin B1 aggravates ochratoxin A-induced nephrocytotoxicity and apoptosis via ROS-dependent JNK/MAPK signaling pathway. Toxicology; 2021; 457, 152802. [DOI: https://dx.doi.org/10.1016/j.tox.2021.152802]
82. Burgess, K.M.; Renaud, J.B.; McDowell, T.; Sumarah, M.W. Mechanistic Insight into the Biosynthesis and Detoxification of Fumonisin Mycotoxins. ACS Chem. Biol.; 2016; 11, pp. 2618-2625. [DOI: https://dx.doi.org/10.1021/acschembio.6b00438] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27444057]
83. Hannun, Y.A.; Obeid, L.M. Sphingolipids and their metabolism in physiology and disease. Nat. Rev. Mol. Cell Biol.; 2018; 19, pp. 175-191. [DOI: https://dx.doi.org/10.1038/nrm.2017.107] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29165427]
84. Kim, S.H.; Singh, M.P.; Sharma, C.; Kang, S.C. Fumonisin B1 actuates oxidative stress-associated colonic damage via apoptosis and autophagy activation in murine model. J. Biochem. Mol. Toxicol.; 2018; 32, e22161. [DOI: https://dx.doi.org/10.1002/jbt.22161]
85. Schrenk, D.; Bignami, M.; Bodin, L.; Chipman, J.K.; Del Mazo, J.; Grasl-Kraupp, B.; Hogstrand, C.; Hoogenboom, L.R.; Leblanc, J.C.; Nielsen, E.
86. Hagelberg, S.; Hult, K.; Fuchs, R. Toxicokinetics of ochratoxin A in several species and its plasma-binding properties. J. Appl. Toxicol. JAT; 1989; 9, pp. 91-96. [DOI: https://dx.doi.org/10.1002/jat.2550090204]
87. Creppy, E.E.; Størmer, F.C.; Kern, D.; Röschenthaler, R.; Dirheimer, G. Effects of ochratoxin A metabolites on yeast phenylalanyl-tRNA synthetase and on the growth and in vivo protein synthesis of hepatoma cells. Chem.-Biol. Interact.; 1983; 47, pp. 239-247. [DOI: https://dx.doi.org/10.1016/0009-2797(83)90160-6]
88. Huang, X.; Gao, Y.; Li, S.; Wu, C.; Wang, J.; Zheng, N. Modulation of Mucin (MUC2, MUC5AC and MUC5B) mRNA Expression and Protein Production and Secretion in Caco-2/HT29-MTX Co-Cultures Following Exposure to Individual and Combined Aflatoxin M1 and Ochratoxin A. Toxins; 2019; 11, 132. [DOI: https://dx.doi.org/10.3390/toxins11020132]
89. Al-Anati, L.; Petzinger, E. Immunotoxic activity of ochratoxin A. J. Vet. Pharmacol. Ther.; 2006; 29, pp. 79-90. [DOI: https://dx.doi.org/10.1111/j.1365-2885.2006.00718.x]
90. Aleo, M.D.; Wyatt, R.D.; Schnellmann, R.G. Mitochondrial dysfunction is an early event in ochratoxin A but not oosporein toxicity to rat renal proximal tubules. Toxicol. Appl. Pharmacol.; 1991; 107, pp. 73-80. [DOI: https://dx.doi.org/10.1016/0041-008x(91)90332-9]
91. Sofowora, A.; Ogunbodede, E.; Onayade, A. The role and place of medicinal plants in the strategies for disease prevention. Afr. J. Tradit. Complement. Altern. Med. AJTCAM; 2013; 10, pp. 210-229. [DOI: https://dx.doi.org/10.4314/ajtcam.v10i5.2]
92. Mumtaz, A.; Ashfaq, U.A.; Ul Qamar, M.T.; Anwar, F.; Gulzar, F.; Ali, M.A.; Saari, N.; Pervez, M.T. MPD3: A useful medicinal plants database for drug designing. Nat. Prod. Res.; 2017; 31, pp. 1228-1236. [DOI: https://dx.doi.org/10.1080/14786419.2016.1233409] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27681445]
93. Pandita, D.; Pandita, A.; Wani, S.H.; Abdelmohsen, S.A.M.; Alyousef, H.A.; Abdelbacki, A.M.M.; Al-Yafrasi, M.A.; Al-Mana, F.A.; Elansary, H.O. Crosstalk of Multi-Omics Platforms with Plants of Therapeutic Importance. Cells; 2021; 10, 1296. [DOI: https://dx.doi.org/10.3390/cells10061296]
94. Sarker, S.D.; Nahar, L. An introduction to natural products isolation. Methods Mol. Biol.; 2012; 864, pp. 1-25. [DOI: https://dx.doi.org/10.1007/978-1-61779-624-1_1] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/22367891]
95. Rao, A.V.; Gurfinkel, D.M. The bioactivity of saponins: Triterpenoid and steroidal glycosides. Drug Metab. Drug Interact.; 2000; 17, pp. 211-235. [DOI: https://dx.doi.org/10.1515/DMDI.2000.17.1-4.211]
96. Cao, Y.; Xie, L.; Liu, K.; Liang, Y.; Dai, X.; Wang, X.; Lu, J.; Zhang, X.; Li, X. The antihypertensive potential of flavonoids from Chinese Herbal Medicine: A review. Pharmacol. Res.; 2021; 174, 105919. [DOI: https://dx.doi.org/10.1016/j.phrs.2021.105919] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/34601080]
97. Su, H.; Shen, L.; Bi, S.; Zhang, X.; Guo, R.; Liu, H. The Preservation Effect of Composite Biopreservatives Combined with Ice Temperature Storage on Redfin Tetrodotoxin. J. Fish. Sci.; 2019; 43, pp. 688-696.
98. Zhai, X.; Zhu, C.; Zhang, Y.; Sun, J.; Alim, A.; Yang, X. Chemical characteristics, antioxidant capacities and hepatoprotection of polysaccharides from pomegranate peel. Carbohydr. Polym.; 2018; 202, pp. 461-469. [DOI: https://dx.doi.org/10.1016/j.carbpol.2018.09.013]
99. Hu, A.; Li, Y.; Li, Z.; Wang, H.; Zhao, C.; Ma, L. Ultrasonic Extraction of Non-starch Polysaccharides from Chickpeas and Their Antioxidant Activities. China Food Addit.; 2018; 6, pp. 133-138.
100. Bolat, E.; Sarıtaş, S.; Duman, H.; Eker, F.; Akdaşçi, E.; Karav, S.; Witkowska, A.M. Polyphenols: Secondary Metabolites with a Biological Impression. Nutrients; 2024; 16, 2550. [DOI: https://dx.doi.org/10.3390/nu16152550]
101. Paula, L.; Ana, J.G.; Hannu, P.; Carlos, M.J.; Eeva-Riikka, V.; Cristina, J. Role of red beetroot in bread for reducing mycotoxin risks: Bioavailability of beetroot polyphenols and betalains with ochratoxin a, aflatoxin B1 and zearalenone in Caco-2 cells. Food Chem.; 2025; 465, 142036. [DOI: https://dx.doi.org/10.1016/j.foodchem.2024.142036]
102. Frangiamone, M.; Alonso-Garrido, M.; Font, G.; Cimbalo, A.; Manyes, L. Pumpkin extract and fermented whey individually and in combination alleviated AFB1- and OTA-induced alterations on neuronal differentiation invitro. Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc.; 2022; 164, 113011. [DOI: https://dx.doi.org/10.1016/j.fct.2022.113011]
103. Marrez, D.A.; Badr, A.N.; El-Bahrawy, A.; Naeem, M.A. Algal extracts evaluation as an Antitoxicity sustainable solution against aflatoxin B(1) toxicity in rat tissues. Toxicon; 2024; 250, 108098. [DOI: https://dx.doi.org/10.1016/j.toxicon.2024.108098] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/39284454]
104. Ahmad Nejhad, A.; Alizadeh Behbahani, B.; Hojjati, M.; Vasiee, A.; Mehrnia, M.A. Identification of phytochemical, antioxidant, anticancer and antimicrobial potential of Calotropis procera leaf aqueous extract. Sci. Rep.; 2023; 13, 14716. [DOI: https://dx.doi.org/10.1038/s41598-023-42086-1] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/37679486]
105. León-Cortés, D.; Arce-Villalobos, K.; Bogantes-Ledezma, D.; Irías-Mata, A.; Chaves-Barrantes, N.; Vinas, M. Anti-aflatoxin potential of phenolic compounds from common beans (Phaseolus vulgaris L.). Food Chem.; 2025; 469, 142597. [DOI: https://dx.doi.org/10.1016/j.foodchem.2024.142597]
106. Makhafola, T.J.; Elgorashi, E.E.; McGaw, L.J.; Verschaeve, L.; Eloff, J.N. The correlation between antimutagenic activity and total phenolic content of extracts of 31 plant species with high antioxidant activity. BMC Complement. Altern. Med.; 2016; 16, 490. [DOI: https://dx.doi.org/10.1186/s12906-016-1437-x]
107. Zahin, M.; Bokhari, N.A.; Ahmad, I.; Husain, F.M.; Althubiani, A.S.; Alruways, M.W.; Perveen, K.; Shalawi, M. Antioxidant, antibacterial, and antimutagenic activity of Piper nigrum seeds extracts. Saudi J. Biol. Sci.; 2021; 28, pp. 5094-5105. [DOI: https://dx.doi.org/10.1016/j.sjbs.2021.05.030]
108. Manogaran, P.; Beeraka, N.M.; Paulraj, R.S.; Sathiyachandran, P.; Thammaiappa, M. Impediment of Cancer by Dietary Plant-derived Alkaloids Through Oxidative Stress: Implications of PI3K/AKT Pathway in Apoptosis, Autophagy, and Ferroptosis. Curr. Top. Med. Chem.; 2023; 23, pp. 860-877. [DOI: https://dx.doi.org/10.2174/1568026623666230111154537]
109. Maurya, A.; Kumar, S.; Singh, B.K.; Chaudhari, A.K.; Dwivedy, A.K.; Prakash, B.; Dubey, N.K. Mechanistic investigations on antifungal and antiaflatoxigenic activities of chemically characterised Carum carvi L. essential oil against fungal infestation and aflatoxin contamination of herbal raw materials. Nat. Prod. Res.; 2022; 36, pp. 4569-4574. [DOI: https://dx.doi.org/10.1080/14786419.2021.1994566]
110. Abdel-Razek, A.G.; Badr, A.N.; Alharthi, S.S.; Selim, K.A. Efficacy of Bottle Gourd Seeds’ Extracts in Chemical Hazard Reduction Secreted as Toxigenic Fungi Metabolites. Toxins; 2021; 13, 789. [DOI: https://dx.doi.org/10.3390/toxins13110789]
111. Beekrum, S.; Govinden, R.; Padayachee, T.; Odhav, B. Naturally occurring phenols: A detoxification strategy for fumonisin B1. Food Addit. Contam.; 2003; 20, pp. 490-493. [DOI: https://dx.doi.org/10.1080/0265203031000098678]
112. Silva, B.; Souza, M.M.; Badiale-Furlong, E. Antioxidant and antifungal activity of phenolic compounds and their relation to aflatoxin B1 occurrence in soybeans (Glycine max L.). J. Sci. Food Agric.; 2020; 100, pp. 1256-1264. [DOI: https://dx.doi.org/10.1002/jsfa.10137] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31710698]
113. Zaman, S.; Khan, N.; Zahoor, M.; Ullah, R.; Bari, A.; Sohail,. Phytochemical-mediated regulation of aflatoxigenic fungi contamination in a shifting climate and environment. Environ. Geochem. Health; 2024; 46, 272. [DOI: https://dx.doi.org/10.1007/s10653-024-02045-9] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/38958785]
114. Ruan, D.; Wang, W.C.; Lin, C.X.; Fouad, A.M.; Chen, W.; Xia, W.G.; Wang, S.; Luo, X.; Zhang, W.H.; Yan, S.J.
115. Cao, Z.; Gao, J.; Huang, W.; Yan, J.; Shan, A.; Gao, X. Curcumin mitigates deoxynivalenol-induced intestinal epithelial barrier disruption by regulating Nrf2/p53 and NF-κB/MLCK signaling in mice. Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc.; 2022; 167, 113281. [DOI: https://dx.doi.org/10.1016/j.fct.2022.113281]
116. Ling, K.H.; Wan, M.L.; El-Nezami, H.; Wang, M. Protective Capacity of Resveratrol, a Natural Polyphenolic Compound, against Deoxynivalenol-Induced Intestinal Barrier Dysfunction and Bacterial Translocation. Chem. Res. Toxicol.; 2016; 29, pp. 823-833. [DOI: https://dx.doi.org/10.1021/acs.chemrestox.6b00001] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27058607]
117. Long, H.; Xin, Z.; Zhang, F.; Zhai, Z.; Ni, X.; Chen, J.; Yang, K.; Liao, P.; Zhang, L.; Xiao, Z.
118. Long, M.; Zhang, Y.; Li, P.; Yang, S.H.; Zhang, W.K.; Han, J.X.; Wang, Y.; He, J.B. Intervention of Grape Seed Proanthocyanidin Extract on the Subchronic Immune Injury in Mice Induced by Aflatoxin B1. Int. J. Mol. Sci.; 2016; 17, 516. [DOI: https://dx.doi.org/10.3390/ijms17040516]
119. Damiano, S.; Iovane, V.; Squillacioti, C.; Mirabella, N.; Prisco, F.; Ariano, A.; Amenta, M.; Giordano, A.; Florio, S.; Ciarcia, R. Red orange and lemon extract prevents the renal toxicity induced by ochratoxin A in rats. J. Cell. Physiol.; 2020; 235, pp. 5386-5393. [DOI: https://dx.doi.org/10.1002/jcp.29425]
120. Akinrinmade, F.J.; Akinrinde, A.S.; Amid, A. Changes in serum cytokine levels, hepatic and intestinal morphology in aflatoxin B1-induced injury: Modulatory roles of melatonin and flavonoid-rich fractions from Chromolena odorata. Mycotoxin Res.; 2016; 32, pp. 53-60. [DOI: https://dx.doi.org/10.1007/s12550-016-0239-9]
121. Wang, X.; Yang, F.; Na, L.; Jia, M.; Ishfaq, M.; Zhang, Y.; Liu, M.; Wu, C. Ferulic acid alleviates AFB1-induced duodenal barrier damage in rats via up-regulating tight junction proteins, down-regulating ROCK, competing CYP450 enzyme and activating GST. Ecotoxicol. Environ. Saf.; 2022; 241, 113805. [DOI: https://dx.doi.org/10.1016/j.ecoenv.2022.113805]
122. Ye, Y.; Jiang, M.; Hong, X.; Fu, Y.; Chen, Y.; Wu, H.; Sun, Y.; Wang, X.; Zhou, E.; Wang, J.
123. Qin, T.; Liu, X.; Luo, Y.; Yu, R.; Chen, S.; Zhang, J.; Xu, Y.; Meng, Z.; Huang, Y.; Ren, Z. Characterization of polysaccharides isolated from Hericium erinaceus and their protective effects on the DON-induced oxidative stress. Int. J. Biol. Macromol.; 2020; 152, pp. 1265-1273. [DOI: https://dx.doi.org/10.1016/j.ijbiomac.2019.10.223]
124. Tang, M.; Yuan, D.; Liao, P. Berberine improves intestinal barrier function and reduces inflammation, immunosuppression, and oxidative stress by regulating the NF-κB/MAPK signaling pathway in deoxynivalenol-challenged piglets. Environ. Pollut.; 2021; 289, 117865. [DOI: https://dx.doi.org/10.1016/j.envpol.2021.117865] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/34358871]
125. de Freitas Souza, C.; Baldissera, M.D.; Descovi, S.; Zeppenfeld, C.; Eslava-Mocha, P.R.; Gloria, E.M.; Zanette, R.A.; Baldisserotto, B.; Schafer da Silva, A. Melaleuca alternifolia essential oil abrogates hepatic oxidative damage in silver catfish (Rhamdia quelen) fed with an aflatoxin-contaminated diet. Comp. Biochem. Physiol. Toxicol. Pharmacol. CBP; 2019; 221, pp. 10-20. [DOI: https://dx.doi.org/10.1016/j.cbpc.2019.03.007]
126. Vipin, A.V.; Rao, R.; Kurrey, N.K.; KA, A.A.; Venkateswaran, G. Protective effects of phenolics rich extract of ginger against Aflatoxin B(1)-induced oxidative stress and hepatotoxicity. Biomed. Pharmacother. Biomed. Pharmacother.; 2017; 91, pp. 415-424. [DOI: https://dx.doi.org/10.1016/j.biopha.2017.04.107]
127. Ben Salah-Abbès, J.; Abbès, S.; Houas, Z.; Abdel-Wahhab, M.A.; Oueslati, R. Zearalenone induces immunotoxicity in mice: Possible protective effects of radish extract (Raphanus sativus). J. Pharm. Pharmacol.; 2008; 60, pp. 761-770. [DOI: https://dx.doi.org/10.1211/jpp.60.6.0012]
128. Bilgrami, K.S.; Sinha, K.K.; Sinha, A.K. Inhibition of aflatoxin production & growth of Aspergillus flavus by eugenol & onion & garlic extracts. Indian. J. Med. Res.; 1992; 96, pp. 171-175.
129. Costa, S.; Utan, A.; Speroni, E.; Cervellati, R.; Piva, G.; Prandini, A.; Guerra, M.C. Carnosic acid from rosemary extracts: A potential chemoprotective agent against aflatoxin B1. An in vitro study. J. Appl. Toxicol. JAT; 2007; 27, pp. 152-159. [DOI: https://dx.doi.org/10.1002/jat.1186]
130. Gowda, N.K.; Ledoux, D.R.; Rottinghaus, G.E.; Bermudez, A.J.; Chen, Y.C. Antioxidant efficacy of curcuminoids from turmeric (Curcuma longa L.) powder in broiler chickens fed diets containing aflatoxin B1. Br. J. Nutr.; 2009; 102, pp. 1629-1634. [DOI: https://dx.doi.org/10.1017/s0007114509990869]
131. Kim, B.R.; Kim, D.H.; Park, R.; Kwon, K.B.; Ryu, D.G.; Kim, Y.C.; Kim, N.Y.; Jeong, S.; Kang, B.K.; Kim, K.S. Effect of an extract of the root of Scutellaria baicalensis and its flavonoids on aflatoxin B1 oxidizing cytochrome P450 enzymes. Planta Medica; 2001; 67, pp. 396-399. [DOI: https://dx.doi.org/10.1055/s-2001-15810]
132. Pomothy, J.M.; Pászti-Gere, E.; Barna, R.F.; Prokoly, D.; Jerzsele, Á. The Impact of Fermented Wheat Germ Extract on Porcine Epithelial Cell Line Exposed to Deoxynivalenol and T-2 Mycotoxins. Oxidative Med. Cell. Longev.; 2020; 2020, 3854247. [DOI: https://dx.doi.org/10.1155/2020/3854247] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/33456669]
133. Qin, G.Z. Effects of green tea extract on the development of aflatoxin B1-induced precancerous enzyme-altered hepatocellular foci in rats. Zhonghua Yu Fang Yi Xue Za Zhi Chin. J. Prev. Med.; 1991; 25, pp. 332-334.
134. Sánchez, E.; Heredia, N.; García, S. Inhibition of growth and mycotoxin production of Aspergillus flavus and Aspergillus parasiticus by extracts of Agave species. Int. J. Food Microbiol.; 2005; 98, pp. 271-279. [DOI: https://dx.doi.org/10.1016/j.ijfoodmicro.2004.07.009] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/15698688]
135. Santos, L.; Kasper, R.; Sardiñas, N.; Marín, S.; Sanchis, V.; Ramos, A.J. Effect of Capsicum carotenoids on growth and aflatoxins production by Aspergillus flavus isolated from paprika and chilli. Food Microbiol.; 2010; 27, pp. 1064-1070. [DOI: https://dx.doi.org/10.1016/j.fm.2010.07.010]
136. Tulayakul, P.; Dong, K.S.; Li, J.Y.; Manabe, N.; Kumagai, S. The effect of feeding piglets with the diet containing green tea extracts or coumarin on in vitro metabolism of aflatoxin B1 by their tissues. Toxicon; 2007; 50, pp. 339-348. [DOI: https://dx.doi.org/10.1016/j.toxicon.2007.04.005]
137. Vaičiulienė, G.; Bakutis, B.; Jovaišienė, J.; Falkauskas, R.; Gerulis, G.; Bartkienė, E.; Klupšaitė, D.; Klementavičiūtė, J.; Baliukonienė, V. Effects of Ethanol Extracts of Origanum vulgare and Thymus vulgaris on the Mycotoxin Concentrations and the Hygienic Quality of Maize (Zea mays L.). Silage. Toxins; 2022; 14, 298. [DOI: https://dx.doi.org/10.3390/toxins14050298]
138. Jin, L.; Yang, J. Research Progress on the Antioxidant Properties of Plant Extracts and Their Application in Antibiotic-Free Animal Feed. China Anim. Husb. Mag.; 2020; 56, pp. 29-34. [DOI: https://dx.doi.org/10.19556/j.0258-7033.20200309-06]
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1 Animal Nutritional Genome and Germplasm Innovation Research Center, College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China; [email protected] (X.Z.); [email protected] (J.C.); [email protected] (X.M.); [email protected] (X.T.); [email protected] (B.T.), Yuelushan Laboratory, Changsha 410128, China, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China; [email protected]
2 Animal Nutritional Genome and Germplasm Innovation Research Center, College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China; [email protected] (X.Z.); [email protected] (J.C.); [email protected] (X.M.); [email protected] (X.T.); [email protected] (B.T.), Yuelushan Laboratory, Changsha 410128, China
3 Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China; [email protected]