In Vitro Nephrotoxicity Induced by Herb-Herb Interaction between Radix Glycyrrhizae and Radix Euphorbiae Pekinensis
In Vitro Nephrotoxicity Induced by Herb-Herb Interaction between Radix Glycyrrhizae and Radix Euphorbiae Pekinensis
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DOI：
10.1155/2020/6894751
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发表时间：
2020-04-28
影响因子：
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通讯作者：
Wang, Rufeng
中科院分区：
文献类型：
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作者：
Chen, Meng;Geng, Di;Wang, Rufeng
甘草-大戟根(RG)-大戟根(REP)是18种配伍药物中具有代表性的配伍配伍，在临床应用中长期存在争议。本研究以马丁达比犬肾(MDCK)细胞系为研究对象，采用细胞毒试验、细胞凋亡检测、细胞周期测定、活性氧(ROS)测定、高含量分析(HCA)结合高效液相(HPLC)指纹图谱比对等方法，从细胞毒性的角度阐明RG和REP能否同时使用，并对RG和REP的主要相关化合物进行研究，探讨其可能的作用机制。结果表明，REP与RG以1：1的比例配伍使用，可显著增强REP的毒性，并随RG比例的增加而减弱。3，3‘-二-O-甲基纤维素酸-4’-O-β-D-二甲基吡喃糖苷(DEAX)和3，3‘-二-O-甲基纤维素酸(DEA)是REP和RG合用引起的毒性的主要原因。RG-rep煎剂和上述两种化合物均能促进细胞凋亡、细胞形态改变、ROS积聚和线粒体膜电位的破坏。总之，由于RG的双向调节作用，RG和rep的不相容使用是有条件的，导致RG-rep不相容的主要化合物是DEAX和DEA，它们通过激活ROS产生增加而诱导的线粒体依赖的细胞凋亡而产生毒性。这项研究为理解RG和REP的不相容用法以及EIM理论提供了基础。
Radix Glycyrrhizae (RG)-Radix Euphorbiae Pekinensis (REP) is a representative incompatible herbal pair of Eighteen Incompatible Medicaments (EIM) and has been disputed in clinical application for a long time. The present study was performed with the Madin-Darby canine kidney (MDCK) cell line using cell cytotoxicity assay, apoptosis detection, cell cycle measurement, reactive oxygen species (ROS) determination, and high content analysis (HCA) in combination with high-performance liquid chromatography (HPLC) fingerprint comparison to clarify whether RG and REP can be concomitantly used from the perspective of cytotoxicity, investigate the major correlated compounds, and elucidate the underlying mechanisms. The results showed that the toxicity of REP could be significantly enhanced through its concomitant use with RG in the ratio of 1 : 1, and this increased toxicity could be weakened with the further increased proportion of RG. 3,3 '-di-O-methylellagic acid-4 '-O-beta-D-xylopyranoside (DEAX) and 3,3 '-di-O-methylellagic acid (DEA) were shown to be mainly responsible for the toxicity induced by concomitant use of REP and RG. Both RG-REP decoctions and the above two compounds boosted cell apoptosis, cellular morphological change, ROS accumulation, and mitochondrial membrane potential (MMP) disruption. In conclusion, the incompatible use of RG and REP is conditionally established because of the bidirectional regulatory effect of RG, and the major compounds responsible for RG-REP incompatibility are DEAX and DEA, which result in toxicity through activation of mitochondria-dependent apoptosis induced by increased ROS production. This study provided a basis for understanding the incompatible use of RG and REP and the EIM theory.