背景:青蒿素(ART)类似物,比如双氢青蒿素,arteether,蒿甲醚,还有青蒿琥酯,都有一个内过氧化物桥,已证明对血吸虫病有效。青蒿属(ATT),它包含一个额外的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的抗日本血吸虫病活性,并与ART进行比较。
方法:我们使用苏木精和伊红染色和天狼星红染色评估小鼠肝脏炎症和纤维化,分别。RNA测序分析了雌性和雄性日本血吸虫的转录组学(S.日本)成虫和小鼠肝脏,用细胞因子谱分析和流式细胞术研究ART或ATT治疗下的免疫反应。
结果:ATT显示雌性日本血吸虫成虫和卵数显著减少,破坏成虫的表面。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,同时降低谷丙转氨酶和谷草转氨酶的血清水平比ART更有效。ART和ATT均显着降低了肝脏中的中性粒细胞频率,并升高了嗜酸性粒细胞计数。然而,仅ATT治疗显着降低M1/M2和Th1/Th2指数,表明免疫反应谱发生了明显的变化。与ART相比,受ATT影响的宿主免疫与肝纤维化程度和单身男性的数量密切相关。
结论:ATT,作为一种新的预防小鼠日本血吸虫病的策略,明显优于ART。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: ATT, as a novel preventive strategy for schistosomiasis japonica in mice, significantly outperforms ART.