An integrated metabolomics strategy to reveal dose-effect relationship and therapeutic mechanisms of different efficacy of rhubarb in constipation rats

Publication date: Available online 26 August 2019Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Jia-Qian Chen, Yan-Yan Chen, Hui-Juan Tao, Zong-Jin Pu, Xu-Qin Shi, Jing Zhang, Ya-Jie Tan, Shi-Jun Yue, Gui-Sheng Zhou, Er-Xin Shang, Yu-Ping Tang, Jin-Ao DuanAbstractThe ambiguity of dose-effect relationship of many traditional Chinese medicines (TCMs) has always influenced their rational use in TCM clinic. Rhubarb, a preferred representative of cathartic TCM, is currently widely used that results in a diversity of its dosage. The aim of this study was to use an integrated metabolomics strategy to simultaneously reveal dose-effect relationship and therapeutic mechanisms of different efficacy of rhubarb in constipation rats. Six doses of rhubarb (0.135, 0.27, 0.81, 1.35, 4.05, and 8.1 g/kg) were examined to elucidate the laxative and fire-purging effects by pathological sections and UPLC-Q-TOF/MSE. The results showed that there existed serious lesions in the stomach and colon of model rats. And conditions were basically improved to some extent in rhubarb-treated groups. Through relative distance calculation based on metabolomics score plots, it suggested that the effective dose threshold (EC20˜EC80 range) of rhubarb was from 0.31 to 4.5 g/kg (corresponding to 3.44˜50.00 g in the clinic) in rat serum and 0.29˜2.1 g/kg (corresponding to 3.22˜23.33 g in the clinic) in feces. Then, 33 potential biomarkers were identified in total. Functional pathway ...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research