Ageratina adenophora (A. adenophora), one of the prominent invasive plants in the Asian continent has shown toxicity in animals. However, studies examining the gene expression and metabolic profiles of animals that ingest A. adenophora have not yet been reported in the literature. Therefore, considering the wide distribution of A. adenophora, it is necessary to elucidate the toxic mechanisms of A. adenophora via multiomics approach. In this study, we identified and evaluated the toxic mechanisms of action associated with bioactive compounds in A. adenophora by using network toxicology studies combined with metabolomics and transcriptomics and found that 2-deoxo-2-(acetyloxy)− 9-oxoageraphorone, 10Hβ-9-oxo-agerophorone, 10Hα-9-oxo-agerophorone, nerolidol, 9-oxo-10,11-dehydro-agerophorone were the main active toxic compounds in A. adenophora. In addition, using metabolomics approach we identified differential metabolites such as L-pyroglutamic acid, 1-methylhistidine, prostaglandin F2alpha and hydrocortisone from A. adenophora and these metabolites were involved in amino acid metabolism, lipid metabolism and signal conducting media regulation. Based on network toxicological analysis, we observed that, A. adenophora can affect the Ras signaling, Phospholipase D signaling and MAPK signaling pathways by regulating EGFR, PDGFRB, KIT and other targets. From the results of this study we concluded that A. adenophora induces liver inflammatory damage by activating the EGFR expression and Ras/Raf/MEK/ERK signaling pathways as well as affect nutrients metabolism and neuron conduction.

紫茎泽兰( A. adenphora ) 是亚洲大陆主要的入侵植物之一，已对动物表现出毒性。然而，文献中尚未报道对摄入紫茎泽兰的动物的基因表达和代谢谱进行检查的研究。因此，考虑到紫茎泽兰分布广泛，有必要通过多组学方法阐明紫茎泽兰的毒性机制。在本研究中，我们通过网络毒理学研究结合代谢组学和转录组学，鉴定并评估了紫茎泽兰中生物活性化合物的毒性作用机制，发现2-deoxo-2-(乙酰氧基)− 9-oxoageraphorone, 10Hβ- 9-氧代香叶佛尔酮、10Hα-9-氧代香叶佛尔酮、橙花叔醇、9-氧代-10,11-脱氢香叶佛尔酮是紫茎泽兰中的主要活性有毒化合物。此外，利用代谢组学方法，我们鉴定了紫茎泽兰中的差异代谢物，如L-焦谷氨酸、1-甲基组氨酸、前列腺素F2α和氢化可的松，这些代谢物参与氨基酸代谢、脂质代谢和信号传导介质调节。基于网络毒理学分析，我们观察到紫茎泽兰可以通过调节EGFR、PDGFRB、KIT等靶点影响Ras信号、磷脂酶D信号和MAPK信号通路。根据本研究的结果，我们得出结论，紫茎泽兰通过激活 EGFR 表达和 Ras/Raf/MEK/ERK 信号通路诱导肝脏炎症损伤，并影响营养物质代谢和神经元传导。