Abstract
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-β-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.
Highlights
Drug-drug interaction is a very important aspect in the clinical practice and is a focus of medical research
The results obtained from the MTT assay showed that the inhibition rate of the Radix Glycyrrhizae (RG) decoction on Madin-Darby canine kidney (MDCK) cells was decreased even though without significant difference compared with that of the Dulbecco’s modified Eagle’s medium (DMEM) control group, suggesting RG was nontoxic to MDCK cells
The 3 : 1 RG-Radix Euphorbiae Pekinensis (REP) decoction provided significant protective effect on the cells compared with the REP decoction and the 1 : 1 RG-REP decoction
Summary
Drug-drug interaction is a very important aspect in the clinical practice and is a focus of medical research. A book entitled Variorum of Shennong’s Herbal Classic authored by Hongjing Tao, who was a Chinese pharmacologist in the Northern and Southern Dynasties, listed the incompatible herbal drug pairs including those mentioned above These incompatible herbal drug pairs have been avoided as much as possible by TCM practitioners since ancient times, the experience of concomitant use of these pairs has been accumulated, and the treatment cases of the rare and intractable diseases using them have been recorded and [1,2,3]. Pharmacologists possess different viewpoints on this concept and have not yet come to Oxidative Medicine and Cellular Longevity an agreement [4, 5] This theory has been observed and disputed by Chinese pharmacologists since ancient times, and it is still an interesting question whether EIM should be absolutely avoided in the clinical practice and whether there has been scientific basis to support this occult theory
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
