Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin, 300384, China.
Parasit Vectors. 2024 Aug 15;17(1):342. doi: 10.1186/s13071-024-06426-y.
Artemisinin (ART) analogs, such as dihydroartemisinin, arteether, artemether, and artesunate, all featuring an endoperoxide bridge, have demonstrated efficacy against schistosomiasis. Artemisitene (ATT), which contains an additional α, β-unsaturated carbonyl structure, has shown enhanced biological activities. This study aims to evaluate the anti-schistosomaiasis japonica activity of ATT and compare it with ART.
We assessed liver inflammation and fibrosis in mice using hematoxylin and eosin staining and Sirius red staining, respectively. RNA sequencing analyzed transcriptomics in female and male Schistosoma japonicum (S. japonicum) adult worms and mice livers, with cytokine profiling and flow cytometry to study immune responses under ART or ATT treatment.
ATT exhibits a marked reduction in female S. japonicum adult worms and egg numbers, damaging the adult worms' surface. It also influences the transcription of genes related to cellular anatomical structures. Notably, ATT treatment resulted in significant reductions in liver granuloma size and collagen area, alongside lowering serum levels of glutamic pyruvic and glutamic oxaloacetic transaminase more effectively than ART. Both ART and ATT markedly decreased neutrophil frequency in the liver and elevated eosinophil counts. However, only ATT treatment significantly reduced the M1/M2 and Th1/Th2 indices, indicating a pronounced shift in immune response profiles. ATT-affected host immunity correlated with the extent of liver fibrosis and the count of single males more strongly than ART.
ATT, as a novel preventive strategy for schistosomiasis japonica in mice, significantly outperforms ART.
青蒿素（ART）类似物，如双氢青蒿素、青蒿琥酯、蒿甲醚和青蒿琥酯，都具有一个内过氧化物桥，对血吸虫病都显示出疗效。青蒿烯（ATT）含有额外的α，β-不饱和羰基结构，显示出增强的生物活性。本研究旨在评估 ATT 对日本血吸虫的抗血吸虫病活性，并与 ART 进行比较。
我们分别通过苏木精和伊红染色和天狼猩红染色评估小鼠的肝炎症和纤维化。RNA 测序分析雌性和雄性日本血吸虫（S. japonicum）成虫和小鼠肝脏的转录组学，细胞因子谱和流式细胞术研究 ART 或 ATT 治疗下的免疫反应。
ATT 明显减少了雌性日本血吸虫成虫和虫卵的数量，破坏了成虫的表面。它还影响与细胞解剖结构相关的基因的转录。值得注意的是，ATT 治疗导致肝肉芽肿大小和胶原面积显著减少，同时比 ART 更有效地降低血清谷氨酸丙酮酸和谷氨酸草酰乙酸转氨酶水平。ART 和 ATT 都显著降低了肝中性粒细胞的频率，并增加了嗜酸性粒细胞的计数。然而，只有 ATT 治疗显著降低了 M1/M2 和 Th1/Th2 指数，表明免疫反应谱发生了明显的转变。ATT 影响的宿主免疫与肝纤维化程度和单雄虫计数的相关性比 ART 更强。
ATT 作为一种新型的预防日本血吸虫病的策略，在小鼠中显著优于 ART。
