巴黎多叶茎草中的巴黎皂苷I、II和VII是三种重要的成分，已被广泛研究作为肿瘤细胞毒药物，但它们在体内的安全性尚未报告。因此，本研究在斑马鱼模型基础上评价了这些药物的安全性。首先，确定了三种皂苷的致死曲线和半数致死率，结果显示巴黎皂苷I、II和VII的LC50值分别为122.2、210.7和566.2 ng/ml。然后，我们的数据显示，巴黎皂苷I、II和VII具有明显的肝毒性，这表现为斑马鱼肝脏区域和荧光强度的显著降低。此外，巴黎皂苷I影响了斑马鱼的心率，表明其具有心血管毒性。随后，我们发现巴黎皂苷I和VII减少了斑马鱼肾脏区域和荧光强度，并具有轻度的肾毒性。当斑马鱼接受巴黎皂苷I治疗时，肝组织的病理切片显示空泡，肝细胞严重坏死，然后通过TUNEL染色可观察到肝细胞凋亡。最终，我们发现在巴黎皂苷I给药组中，p53、Bax和β-catenin等基因的表达发生了显著变化。总之，我们的研究证明了巴黎皂苷I是三种皂苷中最具毒性的，并且最明显的毒性靶点是肝脏和心血管。进一步推断，巴黎皂苷I的肝毒性可能与p53通路和Wnt通路的调节有关。以上结果显示，在斑马鱼中三种皂苷的毒性，提示在未来应更加注意它们的安全性。版权所有©2023 Elsevier Ltd.

Paris saponin I, II, and VII are three important components in Paris polyphylla, which have been widely studied as tumor cytotoxic drugs, but their safety in vivo has not been reported. Therefore, this study evaluated the safety of these three drugs based on the zebrafish model. Firstly, the lethality curves and half lethal rates of the three saponins were determined and the results showed the values of LC50 of Paris saponin I, II, and VII were 122.2, 210.7, 566.2 ng/ml, respectively. And then our data revealed that Paris saponin I, II and VII had definite hepatotoxicity, as shown by their significant reduction in the liver area and fluorescence intensity of zebrafish. Besides, Paris saponin Ⅰ affected the heart rate of zebrafish obviously, suggesting its cardiovascular toxicity. Afterwards, we found Paris saponin Ⅰ and Ⅶ reduced the area and fluorescence intensity of kidney in zebrafish, and had mild nephrotoxicity. And when treated with Paris saponin I, the pathological section of liver tissue in zebrafish showed vacuoles, severe necrosis of hepatocytes, and then the apoptosis of hepatocytes could be observed by TUNEL staining. Eventually, we found that the genes expression of p53, Bax and β-catenin changed significantly in the administration group of Paris saponin I. In general, our study proved Paris saponin Ⅰ was the most toxic of the three saponins, and the most definite toxic target sites were liver and cardiovascular. And it was further inferred that the hepatotoxicity of Paris saponin Ⅰ may be related to the regulation of p53 pathway and Wnt pathway. These results above showed the toxicity of the three saponins in zebrafish, suggesting their safety should be paid more attention in the future.Copyright © 2023. Published by Elsevier Ltd.