霉菌毒素是由子囊菌的许多丝状真菌产生的有毒次级代谢产物 [ 1 ]。霉菌毒素污染是一个持续存在的全球性问题，不可避免且不可预测。霉菌毒素的产生受周围环境的影响；即使是良好的生长和储存环境也不能完全阻止霉菌毒素的产生[ 2 ]。伏马菌素是继黄曲霉毒素后对食品和动物健康构成重大威胁的一组毒素。伏马菌素毒性大，常与黄曲霉毒素毒性同时出现。它们给畜禽养殖业造成巨大的经济损失，威胁人类健康[ 3 , 4 ]]。因此，一些研究一直在探索控制和减轻伏马菌素毒性的方法。伏马菌素很容易污染玉米、大米和其他谷物，对以这些谷物为食的几种动物的肝脏和肾脏造成损害，甚至引起肿瘤问题 [ 5 , 6 ]。此外，伏马菌素的毒性与引起人类食管癌和神经管缺损病有关[ 7、8 ] ，因此伏马菌素逐渐成为继黄曲霉毒素之后的研究热点。

伏马菌素是一种水溶性次生代谢产物，主要由轮枝镰刀菌、增殖镰刀菌和其他镰刀菌属物种产生 [ 9 ]。它存在于多种基质上，主要存在于玉米等谷物上，也存在于以谷物为原料制造的产品中 [ 5 ]。伏马菌素可分为四类：A、B、C 和 P，包括 28 种结构类似物：FA _1、 FA _2、 FA _3、 PHFA _3a、 PHFA _3b、 HFA _3、 FAK _1、 FBK _1、 FB _1、 Iso- FB _1,PHFB _1a、 PHFB _1b、 HFB _1、 FB _2、 FB _3、 FB _4、 FB _5、 FC _1、 N-乙酰基-FC _1、 Iso-FC _1、 N-乙酰基-iso-FC _1、 OH-FC _1、 N-乙酰基-OH-FC _1、 FC _3、 FC _4、 FP _1、 FP ₂和 FP ₃。值得注意的是，伏马菌素 B 家族是主要且毒性最强的家族。伏马菌素B ₁ (FB ₁ ) 和伏马菌素 B ₂ (FB ₂) 是天然污染玉米的最丰富和毒性最大的变体，占伏马菌素总数的 70-80% 和 15-25% [ 10 , 11 ]。

世界卫生组织（2001 年）将伏马菌素的临时最高每日耐受水平设定为 2 μg/kg-BW（体重），因为其浓度高且毒性高 [ 12 ]。欧盟委员会（2006 年和 2007 年）将未加工玉米的伏马菌素最高水平设定为 4000 μg/kg，人类玉米类食品的 FB 为 1000 μg/kg，玉米早餐谷物和零食为 800 μg/kg，以及 200 μg /kg 以玉米为基础的婴儿食品 [ 13 , 14 ]。国际癌症研究机构 (IARC) 将伏马菌素分类为 2B 组，由于其有害影响，这可能是人类致癌物 [ 15 ]。因此，降低食品中伏马菌素的含量和解毒作用就显得尤为重要。

伏马菌素易溶于水，热稳定性强，在各种条件下化学性质稳定。因此，将它们从普通谷物加工中去除以满足正常食用标准是一项挑战[ 16 ]。物理和化学方法不能有效去除谷物中的伏马菌素等有毒物质。研究报告称，生物方法可以有效去除农作物中的伏马菌素。因此，研究广泛探讨了通过生物控制和生物降解来抑制伏马菌素生产菌株的生长和降解[ 17 , 18 ]。

姜黄素是从姜科和其他植物的根茎中提取的一种天然多酚类化合物[ 56 ]。值得注意的是，姜黄素通过刺激神经酰胺的从头合成、激活中性鞘磷脂酶和抑制鞘磷脂合酶的活性来增加神经酰胺浓度 [ 57 ]。劳埃德-埃文斯等人。观察到姜黄素通过恢复细胞内钙含量来减少 So、鞘磷脂、鞘糖脂和胆固醇的细胞内积累。这些特征是 Niemann-PicktypeC1 病的主要特征 [ 58]，以及伏马菌素中毒的特征。用添加600 mg/kg伏马菌素和10 mg/kg姜黄素的姜黄素纳米胶囊喂养雏鸡，表现出对肝脏的保护作用和抗氧化作用，并降低了ROS中硫代巴比妥酸活性物质的水平，提高了鸡的增重。小鸡与对照组相比 [ 59 ]。此外，姜黄素可减少体外 PK-15 的死亡。_{施用用 50 μM FB 1}预处理的姜黄素 PK-15 细胞显示细胞存活率从 53.7% 提高到 77%，细胞内 ROS 含量从 97.4% 降低到 75.5% [ 60]。水飞蓟素 (SIL) 也是一种多酚，其作用与姜黄素相似。Sozmen 等人。报道在用 100 mg/kg FB ₁和 1.5 mg/kg SIL处理的 BALB/c 小鼠中，SIL 显着降低肝细胞凋亡 ( p < 0.0001) 并上调 Caspase-8 和 TNF-α 的表达 ( p < 0.0001)体内 [ 61 ]。此外，Ledur 等人。观察到，对用 2.5 μM SIL 预处理的 PK-15 细胞施用 50 μM FB ₁可使细胞存活率从 53.7% 提高到 89.2%，并将细胞内 ROS 含量从 97.4% 降低到 34.2% [ 60 ]。此外，Marnewick 等人。据报道，茶多酚可减轻 FB _{1 引起的肝毒性。}例如，雄性 Fischer 大鼠在发酵前后给予 250 mg/kg FB ₁和 rooibos ( Aspalathus linearis )、honeybush ( Cyclopia intermedia )、草本茶和绿茶 ( Camellia sinensis ) 的水提取物显示出显着的效果。增加小鼠肝细胞对自由基的清除能力。此外，发酵的凉茶和未发酵的蜜树显着降低了 FB ₁诱导的肝脏脂质过氧化。此外，三种茶提取物都不同程度地提高了 CAT、GPx 和 GR 的活性 [ 62]。绿原酸对产生伏马菌素的菌株也有抑制作用。绿原酸是一种常见的膳食多酚，具有显着的生物活性。给予绿原酸后对伏马菌素产生菌株的抑制率高达70%[ 63 ]。

Hassan et al. explored the protective effect of ginseng extract (PGE) on mice exposed to FB₁, as PGE contains a lot of sterols such as ginsenosides. The findings indicated that PGE reduced fragmentation of DNA in the liver and kidney after the administration of 20 mg/kg-BW of PGE and 100 μg/kg-BW FB₁ to male mice at the same time. Moreover, PGE alleviated LP changes in the liver and kidney, increased GSH level, and upregulated GPx, SOD1, and CAT mRNA expression. In addition, the GPx, SOD1, and CAT mRNA expression levels of mice in the PGE group treated with 20 mg/kg-BW of FB₁ were significantly higher relative to the expression levels of mice in the blank control group [64]. Additionally, Abdel-Wahhab et al. explored the effect of red ginseng on FB₁ toxicity in Sprague-Dawley rats and reported consistent findings [65]. The root extract of Panax notoginseng has an inhibitory effect on the carcinogenicity of FB₁. Takao et al. administered FB₁ and acetone to female SENCAR mice through a skin smear to stimulate papilloma formation. The treatment group was administered with Panax notoginseng acetone extract 1 h before each administration of FB₁. The findings showed that 100% of the mice in the control group developed papilloma after 12 weeks of FB₁ and acetone skin smearing, whereas only about 20% and 50% of the mice in the treatment group developed papilloma after 12 and 15 weeks, respectively [66]. Moreover, daily consumption of ginseng may have a preventive or detoxifying effect on fumonisin toxicity.

Ferulic acid is a phenyl propionic acid compound derived from Ferula feruloides (Steudel) Korovin and other plants. Ferulic acid at 10–25 mM significantly decreased the growth rate of Fusarium oxysporum compared with the control group (p < 0.001). In addition, fumonisin production was inhibited to a certain extent [67]. Ferulic acid can be extracted from cheap agricultural by-products, therefore, the extraction of ferulic acid from low-cost agricultural by-products can be an important source in controlling the production of fumonisins in plants [68,69].

Vitamin E is an important antioxidant. Pretreatment of mice with 25 µM vitamin E (tocopherol) for 24 h before 18 µM FB₁ treatment significantly reduces FB₁-induced DNA damage and apoptosis [70,71]. In addition, vitamin E can be combined with selenium, CoQ10, and L-carnitine to prepare a compound with synergistic effects. In a previous study, mice were pretreated with vitamin E (30 IU/kg), selenium (1 mg/kg), CoQ10 (30 mg/kg), and L-L-carnitine (2.8 mg/kg), then intravenously administered with 1.55 mg/kg-BW FB₁. The results indicated that a combination of these antioxidants alleviated DNA damage and increased the activities of aspartate aminotransferase and alanine aminotransferase by 18% and 18%, respectively, compared with the level of mice not exposed to FB₁ [33]. Oginni et al. administered juvenile catfish with vitamin E and vitamin C at the same time and observed that the decrease in nutrient content in juvenile catfish induced by FB₁ was improved. Notably, the crude protein content in juvenile catfish was higher compared with that of the FB₁ group (p < 0.05) [72]. Furthermore, folic acid has a protective effect on cytotoxicity induced by fumonisins. Sadler et al. reported that folic acid reduced the toxic effect of FB₁ on mouse embryos and improved the growth of mouse embryos after culturing embryos with a mixture of 10 mM folic acid and 2 µM FB₁, indicating that folic acid improves the toxic effect of fumonisins, however, the change was not significant [73].

Essential oils are unique aromatic substances extracted from plants, mainly containing alcohols, aldehydes, phenols, acetones, terpenes, and other volatile secondary metabolites synthesized by plants [74,75]. Several types of essential oils such as Litsea cubeba, cinnamon, and ginger have been reported, and most have an inhibitory effect on bacterial growth. Pante et al. conducted an in vitro experiment and reported that Litsea cubeba essential oil inhibited mycelial development of Furium verticillioides and synthesis of FB₁ and FB₂. The minimum inhibitory concentration of Fusarium verticillioides was 125 µg/mL and the inhibitory effect was dose dependent. The antioxidant effect of Litsea cubeba essential oil was evaluated by DPPH and ABTS methods, showing excellent antioxidant activity [76]. Bomfim et al. reported that Rosmarinus officinalis L. essential oil (REO) had a similar effect. Administration of 300 µg/mL REO caused significant morphological changes such as bacterial cell wall rupture and cell content flow out in a dose-dependent manner [77]. In addition, Zingiber officinale essential oil (GEO) inhibits the growth of fumonisin-producing bacteria and fumonisin production. Notably, administration of 2000 µg/mL GEO and 4000 µg/mL GEO significantly inhibits the production of FB₁ and FB₂. The inhibition rates of ergosterol biosynthesis after administration of 4000 µg/mL and 5000 µg/mL GEO were 57% and 100%, respectively [78]. Ergosterol modulates the activity of several membrane binding enzymes [79], and the reduction of ergosterol activity could result in membrane synthesis disorders, thus exhibiting a bacteriostatic effect. Castro et al. reported similar results with minimum inhibitory concentrations of Cinnamomum zeylanicum and Cymbopogon martinii essential oils to Fusarium verticillioides at 250, 250, and 500 µg/mL, respectively [80]. Plant essential oils inhibit the growth of fumonisin-producing bacteria and fumonisin production, as well as reduce or prevent toxicity caused by fumonisins. Essential oils have a strong smell and react with some drugs, thus, embedding technology is commonly used to embed essential oils. Cinnamon essential oil embedded with whey protein effectively improved the serum levels of ALT, AST, ALP, Urea, and Uric acid, and restored the normal levels in male Sprague-Dawley male rats treated with 100 mg/kg-BW FB_1. Furthermore, testosterone levels in rats were restored to normal values thus reducing reproductive toxicity. Lipid peroxidation and tumor marker TNF-α in liver and kidney tissues were improved to some extent but were not restored to normal levels [74]. Studies report that the cinnamon extract glycerol monolaurate (GML) has similar effects. The levels of serum triglyceride, globulin, cholesterol, liver lipid peroxidation, SOD, and serum reactive oxygen species were restored to normal or below normal levels after chicks were fed with 400 µg/kg fumonisins and GML coated with 8 mg/kg nanomaterials. However, the body weight of chicks was not improved indicating that GML does not reduce the oxidative stress caused by fumonisins to a minimum. However, it alleviates oxidative stress caused by fumonisins and enhances the activity of glutathione S-transferase which is the enzyme responsible for liver detoxification [81].

In addition to the above-mentioned antioxidants, several other types of antioxidants have been reported in previous studies. Domijan et al. reported that sodium copper chlorophyllin (CHL) had a protective effect on FB₁-induced cell and DNA damage after administration of 100 µg/mL (CHL) in combination with 20 µg/mL of FB₁. Oxidative stress is the main cause of DNA damage caused by FB₁, thus CHL indirectly prevented FB₁-induced cell death, DNA damage, and possible carcinogenesis by preventing oxidative stress [82]. Zhao et al. conducted a study whereby indole glucosinolates (IGS) were infiltrated into wild-type Col-0 plants followed by a 10 µM FB₁ solution into the wild-type IGS plants and compared the results with the administration of only the FB₁ solution. The findings showed that IGS inhibited FB₁-induced apoptosis. IGS decomposition products produced through the action of β-glucosinolase effectively reduce the accumulation of ROS, increase the activity of antioxidant enzymes, and improve ROS scavenging ability, thus reducing FB₁-induced oxidative stress and apoptosis [83]. CHL and IGS are widely distributed in green leafy vegetables, thus eating more green leafy vegetables may have a preventive effect on fumonisins toxicity.

In addition to single-component antioxidants, several compound antioxidants have been reported. Hassan et al. observed that all biochemical and cytogenetic test parameters and histological images of liver tissue were significantly improved after feeding mice with an ethanol extract of Aquilegia vulgaris L. at 10 mg/kg-BW and 200 mg/kg voronisin [84]. Gbore et al. reported that the food intake of female rabbits approached the normal level after administration of Moringa leaf meal (MLM) in combination with FB₁ and the effect of MLM was dose dependent. The antioxidant effect of MLM improved the adverse effects of FB₁ on nutrient utilization and growth performance of female rabbits. Notably, MLM is a cheaper alternative compared with commercial antioxidants. MLM can be used as an antidote in traditional feed to reduce the harmful effects of FB₁ on domestic animal production [85].

此外，昆虫产品具有抗氧化作用。一些蜜蜂产品是天然抗氧化剂的潜在来源，可以抵消由各种疾病引起的氧化应激的影响 [ 86 ]。蜂王浆（RJ）含有多种生物活性物质和酚类化合物，主要包括黄酮类和茴香酸，具有抗氧化活性。与单独喂食 FB ₁的小鼠相比，当雄性 Sprague-Dawley 大鼠联合 200 mg/kg 伏马菌素和 150 mg/kg-BW RJ 给药时，肝脏和肾脏指数显着改善。肝肾指标也恢复到正常水平，说明RJ对伏马菌素毒性有保护作用。值得注意的是，保护作用是剂量依赖性的 [ 87 ]。