Dihydromyricetin switches pyroptosis to apoptosis during Aeromonas hydrophila infection in Mylopharyngodon piceus

IF 4.1 2区农林科学 Q1 FISHERIES

Fish & shellfish immunology Pub Date : 2025-05-27 DOI:10.1016/j.fsi.2025.110460

Jingjing Xu , Can Yang , Jing Xiang , Rui Song , Dongsheng Ou , Ruozhong Wang

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引用次数: 0

Abstract

Ampelopsis grossedentata is a traditional Chinese medicine used to treat fever, anti-inflammatory and parasitic infections. Dihydromyricetin is one of the flavonoids with high content, which has been proved to have certain antibacterial and anti-inflammatory effects. However, its antibacterial mechanism is still unclear. In this study, the mechanisms by which A. grossedentata extract and dihydromyricetin promote the organism's defence against A. hydrophila were investigated. The results showed that both A. grossedentata grape extract and dihydromyricetin (DMY) promoted the expression of IL1β in MPK cells. A. hydrophila infection resulted in a significant increase in the expression of caspase1, IL1β, and GSDME, and a significant enhancement of IL1β and LDH release, which were slowed down by DMY. Differently, on the basis of the up-regulation of A. hydrophila, DMY treatment further enhanced the expression of caspase3 and BAX and the activity of caspase3 resulting in stronger apoptosis. And at the same time, the titer of A. hydrophila was decreased by DMY treatment. In black carp (Mylopharyngodon piceus), injections of A. grossedentata extract and DMY also significantly reduced the lethality of A. hydrophila. The up-regulation of the expression of genes associated with pyroptosis due to A. hydrophila infection in splenocytes was attenuated by dihydromyricetin treatment, whereas the expression of apoptosis-associated genes was significantly enhanced. Tissue sections showed significant damage to splenic tissue following A. hydrophila infection, whereas splenic damage was alleviated and its apoptosis-associated DNA breaks were enhanced by dihydromyricetin injection. DMY may regulate multiple modes of cell death in cells. Further studies revealed that TBK1 may be a molecular target of DMY because of their high structural binding potential and as well as functional synergy and relevance. Therefore, these data implied that DMY potentially regulates TBK1 to transform A. hydrophila-induced pyroptosis into apoptosis. This provides a theoretical basis for the application of dihydromyricetin as an antibiotic alternative and feed additive in aquaculture.

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在青鱼嗜水气单胞菌感染过程中，二氢杨梅素将热亡转换为细胞凋亡

蛇耳藤是一种用于治疗发烧、消炎和寄生虫感染的中药。二氢杨梅素是含量较高的黄酮类化合物之一，已被证明具有一定的抗菌和抗炎作用。然而，其抗菌机制尚不清楚。本研究探讨了大叶茅提取物和二氢杨梅素促进嗜水单胞菌防御的作用机制。结果表明，葡萄提取物和二氢杨梅素均能促进MPK细胞中il - 1β的表达。嗜水单胞菌感染后，caspase1、il - 1β和GSDME的表达显著升高，il - 1β和LDH的释放显著增强，DMY减缓了这一过程。不同的是，DMY处理在上调嗜水螅的基础上，进一步增强了caspase3和BAX的表达以及caspase3的活性，导致更强的凋亡。同时，DMY处理使嗜水单胞菌滴度降低。在青鱼（Mylopharyngodon piceus）中，注射大叶刺槐提取物和DMY也显著降低了嗜水刺槐的致死率。二氢杨梅素处理后，嗜水单胞菌感染引起的脾细胞焦亡相关基因的表达上调明显减弱，而凋亡相关基因的表达明显增强。组织切片显示嗜水单胞菌感染后脾脏组织明显损伤，而注射二氢杨梅素可减轻脾损伤，并增强其凋亡相关DNA断裂。DMY可能调控细胞内多种细胞死亡模式。进一步的研究表明TBK1可能是DMY的分子靶点，因为它们具有高的结构结合潜力以及功能协同和相关性。因此，这些数据表明DMY可能调节TBK1将嗜水草诱导的焦亡转化为细胞凋亡。这为二氢杨梅素作为抗生素替代品和饲料添加剂在水产养殖中的应用提供了理论依据。

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来源期刊

Fish & shellfish immunology 农林科学-海洋与淡水生物学

CiteScore

7.50

自引率

19.10%

发文量

750

审稿时长

68 days

期刊介绍： Fish and Shellfish Immunology rapidly publishes high-quality, peer-refereed contributions in the expanding fields of fish and shellfish immunology. It presents studies on the basic mechanisms of both the specific and non-specific defense systems, the cells, tissues, and humoral factors involved, their dependence on environmental and intrinsic factors, response to pathogens, response to vaccination, and applied studies on the development of specific vaccines for use in the aquaculture industry.