State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Molecules. 2023 Jun 28;28(13):5045. doi: 10.3390/molecules28135045.
The root bark of Turcz is a traditional Chinese medicine, Dictamni Cortex (DC), which is mainly used in the clinical treatment of skin inflammation, eczema, rubella, rheumatism, and gynecological inflammation. Unexpectedly, there are some cases of liver injury after the administration of DC. However, the mechanism of hepatotoxicity remains ambiguous. The aim of this study was to explore the mechanism and substance bases of DC hepatotoxicity based on network pharmacology and molecular docking, verified through pharmacological experiments. Partial prototype components and metabolites in vivo of quinoline alkaloids from DC were selected as candidate compounds, whose targets were collected from databases. Network pharmacology was applied to study the potential hepatotoxic mechanism after correlating the targets of candidate compounds with the targets of hepatotoxicity. Molecular docking was simulated to uncover the molecular mechanism. Furthermore, the hepatotoxicity of the extract and its constituents from DC was evaluated in vivo and in vitro. We constructed the "potential toxic components-toxic target-toxic pathway" network. Our results showed that the targets of DC included CYP1A2 and GSR, participating in heterologous steroid metabolism, REDOX metabolism, drug metabolism, heterocyclic metabolic processes, the synthesis of steroid hormone, cytochrome P450 metabolism, chemical carcinogens and bile secretion pathways. In vitro and in vivo experiments displayed that DC could result in a decrease in GSH-Px and oxidative stress, simultaneously inhibiting the expression of CYP1A2 and inducing hepatotoxicity. These results further indicated the mechanism of hepatotoxicity induced by , providing a basic theory to explore and prevent hepatotoxicity in the clinical usage of
Turcz 的根皮是一种传统的中药，白鲜皮（DC），主要用于治疗皮肤炎症、湿疹、风疹、风湿和妇科炎症。但令人意外的是，在使用 DC 后会出现一些肝损伤的病例。然而，其肝毒性的机制仍不清楚。本研究旨在基于网络药理学和分子对接技术，探索 DC 肝毒性的机制和物质基础，并通过药理实验进行验证。选择 DC 中的喹啉生物碱的部分原型成分和代谢物作为候选化合物，从数据库中收集其靶标。网络药理学用于研究候选化合物的靶标与肝毒性靶标相关联后的潜在肝毒性机制。分子对接用于揭示分子机制。此外，还评估了 DC 提取物及其成分的体内和体外肝毒性。我们构建了“潜在毒性成分-毒性靶标-毒性途径”网络。研究结果表明，DC 的靶标包括 CYP1A2 和 GSR，参与异源甾体代谢、氧化还原代谢、药物代谢、杂环代谢过程、甾体激素合成、细胞色素 P450 代谢、化学致癌物质和胆汁分泌途径。体内和体外实验显示，DC 可导致 GSH-Px 减少和氧化应激，同时抑制 CYP1A2 的表达并诱导肝毒性。这些结果进一步表明了, 引起肝毒性的机制，为临床应用中探索和预防肝毒性提供了基本理论。
