附子（附子，FZ）是临床上常用的中药（TCM）。但其毒副作用特别是心脏损伤明显，使用前需进行处理。为了研究吸收成分引起的毒性机制以及加工后的 FZ 的缓解作用，我们建立了一种结合血清药物化学和网络药理学方法的综合方法。血浆中总共鉴定出 31 种化学成分，在处理过的 FZ 中观察到这些成分的响应强度普遍下降。随后，选择四种成分进行网络药理学分析。该分析揭示了 150 个药物作用目标并确定了 1162 个心脏毒性目标。通过交叉分析，确定了 41 个与心脏毒性相关的关键靶标，以及 9 个重要的京都基因和基因组百科全书 (KEGG) 通路。确定的最关键目标是 AKT1、MTOR 和 PARP1。所涉及的关键生物学途径是心肌细胞中的肾上腺素信号传导、癌症中的蛋白聚糖以及钙信号传导途径。 FZ处理后大鼠心脏组织的组织学染色和生化指标有显着差异，表明处理确实可以降低其心脏毒性。事实上，本文为阐明有毒中药的毒性机制提供了一个有价值的策略。© 2024 John Wiley

Aconiti Lateralis Radix Praeparata (Fuzi, FZ) is a frequently utilized traditional Chinese medicine (TCM) in clinical settings. However, its toxic and side effects, particularly cardiac injury, are apparent, necessitating processing before use. To investigate the mechanism of toxicity induced by absorbed components and the mitigating effect of processed FZ, we established a comprehensive method combining serum pharmacochemistry and a network pharmacology approach. In total, 31 chemical components were identified in the plasma, with a general decrease in response intensity observed for these components in processed FZ. Subsequently, four components were selected for network pharmacology analysis. This analysis revealed 150 drug action targets and identified 1162 cardiac toxicity targets. Through intersection analysis, 41 key targets related to cardiac toxicity were identified, along with 9 significant Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The most critical targets identified were AKT1, MTOR, and PARP1. The key biological pathways implicated were adrenergic signaling in cardiomyocytes, proteoglycans in cancer, and the calcium signaling pathway. Significant differences were observed in histological staining and biochemical indicators in the cardiac tissue of rats treated with FZ, indicating that processing could indeed reduce its cardiotoxicity. Indeed, this article presents a valuable strategy for elucidating the toxification mechanism of toxic TCM.© 2024 John Wiley & Sons Ltd.