黄曲霉毒素抑制剂及其作用机理研究进展

    Research Progress on Aflatoxin Inhibitors and Their Mechanisms of Action

    • 摘要: 黄曲霉毒素是由黄曲霉菌、寄生曲霉菌等真菌产生的次级代谢产物,具有强致癌性和毒性。长期低剂量摄入黄曲霉毒素可导致肝脏损伤、免疫抑制和生长迟缓,高剂量暴露则可引发急性中毒甚至死亡,严重危害人畜健康。源头抑制黄曲霉毒素的合成是防控毒素污染的重要手段,因此近年来毒素抑制剂被广泛研究。该文系统总结近10年不同类型黄曲霉毒素抑制剂的研究进展,主要包括三大类别:(1)植物源抑制剂,包括植物精油类、黄酮类物质和多酚类物质;(2)微生物源抑制剂,涵盖乳酸菌、芽孢杆菌、酵母菌和非产毒曲霉菌等;(3)化学合成抑制剂,如硫代半卡巴肼类化合物、有机酸及其衍生物和抗菌肽等。抑制剂主要通过以下5种机制发挥作用:(1)干扰黄曲霉菌的细胞膜结构完整性和线粒体呼吸链功能,破坏细胞基本生理结构;(2)调控毒素合成基因簇中关键基因的表达,抑制聚酮合酶、单加氧酶等关键酶活性,直接阻断毒素生物合成途径;(3)调节细胞内活性氧水平和抗氧化酶系统,维持氧化还原平衡;(4)抑制真菌发育分化过程,包括菌核形成、无性生殖和孢子萌发等关键阶段;(5)通过物理吸附、生物降解和化学转化等方式促进已产生毒素的解毒。基于机理分析,进一步探讨靶向黄曲霉毒素合成的潜在靶标,并对未来黄曲霉毒素控制策略的发展方向进行展望,以期为开发有效的黄曲霉毒素控制方法提供理论指导和实践依据。

       

      Abstract: Aflatoxins (AF) are secondary metabolites produced by fungi such as Aspergillus flavus, A. parasiticus, and other related species, possessing strong carcinogenic and toxic properties. Long-term exposure to low doses of aflatoxins can cause liver damage, immunosuppression, and growth retardation, while high-dose exposure can lead to acute poisoning or even death, seriously endangering the health of both humans and animals. Inhibiting aflatoxin biosynthesis at source is a crucial approach for controlling aflatoxin contamination, which has led to extensive research on aflatoxin inhibitors in recent years. This review systematically summarizes the research progress of different types of aflatoxin inhibitors over the past decade, primarily including three major categories: (1) Plant-derived inhibitors, encompassing essential oils, flavonoids, and polyphenolic compounds. (2) Microbial-derived inhibitors, covering lactic acid bacteria, Bacillus species, yeasts, and non-aflatoxigenic Aspergillus strains. (3) Chemically synthesized inhibitors, such as thiosemicarbazone compounds, organic acids and their derivatives, and antimicrobial peptides. Further analysis reveals that inhibitors function through five major mechanisms: (1) Disrupting cell membrane structural integrity and mitochondrial respiratory chain function in A. flavus, destroying fundamental cellular physiological structures. (2) Regulating the expression of key genes in the aflatoxin biosynthesis gene cluster and inhibiting activities of key enzymes such as polyketide synthase and monooxygenases, directly blocking aflatoxin biosynthetic pathway. (3) Modulating intracellular reactive oxygen species levels and antioxidant enzyme systems to maintain redox balance. (4) Inhibiting fungal development and differentiation processes, including key stages such as sclerotia formation, asexual reproduction, and spore germination. (5) Promoting detoxification of produced aflatoxins through physical adsorption, biodegradation, and chemical transformation. Based on mechanistic analysis, the review further explores potential targets for aflatoxin biosynthesis inhibition and provides perspectives on future directions for aflatoxin control strategies, aiming to provide theoretical guidance and a practical basis for developing effective control methods.

       

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