Xu Jingjing, Yang Can, Xiang Jing, Song Rui, Ou Dongsheng, Wang Ruozhong
College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, 410128, China.
Hunan Fisheries Science Institute, Hunan Academy of Agricultural Sciences, Changsha, 410153, China.
Fish Shellfish Immunol. 2025 Oct;165:110460. doi: 10.1016/j.fsi.2025.110460. Epub 2025 May 27.
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.
显齿蛇葡萄是一种用于治疗发热、抗炎和寄生虫感染的传统中药。二氢杨梅素是其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，其抗菌机制仍不清楚。在本研究中，研究了显齿蛇葡萄提取物和二氢杨梅素促进机体抵御嗜水气单胞菌的机制。结果表明，显齿蛇葡萄提取物和二氢杨梅素（DMY）均能促进MPK细胞中IL1β的表达。嗜水气单胞菌感染导致caspase1、IL1β和GSDME的表达显著增加，以及IL1β和LDH释放显著增强，而DMY减缓了这些变化。不同的是，在嗜水气单胞菌上调的基础上，DMY处理进一步增强了caspase3和BAX的表达以及caspase3的活性，导致更强的细胞凋亡。同时，DMY处理降低了嗜水气单胞菌的滴度。在草鱼中，注射显齿蛇葡萄提取物和DMY也显著降低了嗜水气单胞菌的致死率。二氢杨梅素处理减弱了嗜水气单胞菌感染导致的脾细胞中与焦亡相关基因表达的上调，而凋亡相关基因的表达显著增强。组织切片显示嗜水气单胞菌感染后脾组织有明显损伤，而注射二氢杨梅素可减轻脾损伤并增强其凋亡相关的DNA断裂。DMY可能调节细胞中的多种细胞死亡模式。进一步研究表明，TBK1可能是DMY的分子靶点，因为它们具有较高的结构结合潜力以及功能协同性和相关性。因此，这些数据表明DMY可能通过调节TBK1将嗜水气单胞菌诱导的焦亡转化为凋亡。这为二氢杨梅素作为水产养殖中抗生素替代品和饲料添加剂的应用提供了理论依据。
