Abstract：
BACKGROUND: Radix Aconiti Lateralis (Fuzi), a mono-herbal preparation of Aconitum herbs in the genus Aconitum, is commonly used in traditional Chinese medicine (TCM) to treat critical illnesses. The curative effect of Fuzi is remarkable. However, the toxic effects of Fuzi are still a key clinical focus, and the substances inducing nephrotoxicity are still unclear. Therefore, this study proposes a research model combining \"in vitro and in vivo component mining-virtual multi-target screening-active component prediction-literature verification\" to screen potential nephrotoxic substances rapidly.
METHODS: The UHPLC-Q-Exactive-Orbitrap MS analysis method was used for the correlation analysis of Fuzi\'s in vitro-in vivo chemical substance groups. On this basis, the key targets of nephrotoxicity were screened by combining online disease databases and a protein-protein interaction (PPI) network. The computer screening technique was used to verify the binding mode and affinity of Fuzi\'s components with nephrotoxic targets. Finally, the potential material basis of Fuzi-induced nephrotoxicity was screened.
RESULTS: Eighty-one Fuzi components were identified. Among them, 35 components were absorbed into the blood. Based on the network biology method, 21 important chemical components and three potential key targets were screened. Computer virtual screening revealed that mesaconine, benzoylaconine, aconitine, deoxyaconitine, hypaconitine, benzoylhypaconine, benzoylmesaconine, and hypaconitine may be potential nephrotoxic substances of Fuzi.
CONCLUSIONS: Fuzi may interact with multiple components and targets in the process of inducing nephrotoxicity. In the future, experiments can be designed to explore further. This study provides a reference for screening Fuzi nephrotoxic components and has certain significance for the safe use of Fuzi.
METHODS: The UHPLC-Q-Exactive-Orbitrap MS analysis method was used for the correlation analysis of Fuzi\'s in vitro-in vivo chemical substance groups. On this basis, the key targets of nephrotoxicity were screened by combining online disease databases and a protein-protein interaction (PPI) network. The computer screening technique was used to verify the binding mode and affinity of Fuzi\'s components with nephrotoxic targets. Finally, the potential material basis of Fuzi-induced nephrotoxicity was screened.
RESULTS: Eighty-one Fuzi components were identified. Among them, 35 components were absorbed into the blood. Based on the network biology method, 21 important chemical components and three potential key targets were screened. Computer virtual screening revealed that mesaconine, benzoylaconine, aconitine, deoxyaconitine, hypaconitine, benzoylhypaconine, benzoylmesaconine, and hypaconitine may be potential nephrotoxic substances of Fuzi.
CONCLUSIONS: Fuzi may interact with multiple components and targets in the process of inducing nephrotoxicity. In the future, experiments can be designed to explore further. This study provides a reference for screening Fuzi nephrotoxic components and has certain significance for the safe use of Fuzi.
摘要：
背景:附子,乌头属乌头草本植物的单一草药制剂，常用于中医治疗危重症。附子疗效显著。然而,附子的毒性作用仍是临床重点,诱导肾毒性的物质仍不清楚。因此,本研究提出了一种结合“体外和体内成分挖掘-虚拟多靶标筛选-活性成分预测-文献验证”的研究模型，以快速筛选潜在的肾毒性物质。
方法：采用UHPLC-Q-Exactive-OrbitrapMS分析方法对附子体内外化学物质组进行相关性分析。在此基础上,通过结合在线疾病数据库和蛋白质-蛋白质相互作用(PPI)网络筛选肾毒性的关键靶标.计算机筛选技术用于验证附子成分与肾毒性靶标的结合模式和亲和力。最后,筛选附子肾毒性的潜在物质基础。
结果：鉴定出81个附子成分。其中,35种成分被吸收到血液中。基于网络生物学方法，筛选了21个重要化学成分和3个潜在关键靶标。计算机虚拟筛查显示，苯甲酰乌头，乌头碱,脱氧乌头碱,次乌头碱,苯甲酰基hypaconine,苯甲酰基美松碱，次乌头碱可能是附子的潜在肾毒性物质。
结论：附子在诱导肾毒性的过程中可能与多种成分和靶标相互作用。在未来,可以设计实验来进一步探索。本研究为进一步筛选附子肾毒性成分提供了参考,对附子的安全使用具有一定的指导意义。
方法：采用UHPLC-Q-Exactive-OrbitrapMS分析方法对附子体内外化学物质组进行相关性分析。在此基础上,通过结合在线疾病数据库和蛋白质-蛋白质相互作用(PPI)网络筛选肾毒性的关键靶标.计算机筛选技术用于验证附子成分与肾毒性靶标的结合模式和亲和力。最后,筛选附子肾毒性的潜在物质基础。
结果：鉴定出81个附子成分。其中,35种成分被吸收到血液中。基于网络生物学方法，筛选了21个重要化学成分和3个潜在关键靶标。计算机虚拟筛查显示，苯甲酰乌头，乌头碱,脱氧乌头碱,次乌头碱,苯甲酰基hypaconine,苯甲酰基美松碱，次乌头碱可能是附子的潜在肾毒性物质。
结论：附子在诱导肾毒性的过程中可能与多种成分和靶标相互作用。在未来,可以设计实验来进一步探索。本研究为进一步筛选附子肾毒性成分提供了参考,对附子的安全使用具有一定的指导意义。
