摘要
Tanreqing(TRQ), a traditional Chinese medicine(TCM) formula, can alleviate liver injury and improve liver function. Its pharmacological mechanisms of actions are still unclear due to its complex components and multi-target natures. Metabolomic study is an effective approach to investigating drug pharmacological actions, new diagnostic markers, and potential mechanisms of actions. In the present study, a new strategy was used to evaluate the protective effect of TRQ capsule against carbon tetrachloride(CCl_4)-induced hepatotoxicity in rats, by analyzing metabolic profiling of endogenous bile acids(BAs) along with biochemical and histological analyses. BAs concentrations were determined by ultra-performance liquid chromatography coupled with quadrupole mass spectrometry(UPLC-MS). Principal component analysis and partial least squares discriminant analysis were then employed to analyze the UPLC-MS results and compare the hepatoprotective effect of TRQ capsule in different groups at the doses of 0.36, 1.44, and 2.88 g·kg^(-1) body weight, respectively. Moreover, our results suggested that taurocholic acid(TCA) and taurohyodesoxycholic acid(THDCA) were the most important biochemical markers, which were indicative of CCl_4-induced acute hepatic damage and hepatoprotective effect of TRQ capsule. Therefore, this new strategy would be an excellent alternative method for evaluating hepatoprotective effect and proposing potential mechanisms of action for other drugs as well.
Tanreqing（TRQ）, a traditional Chinese medicine（TCM） formula, can alleviate liver injury and improve liver function. Its pharmacological mechanisms of actions are still unclear due to its complex components and multi-target natures. Metabolomic study is an effective approach to investigating drug pharmacological actions, new diagnostic markers, and potential mechanisms of actions. In the present study, a new strategy was used to evaluate the protective effect of TRQ capsule against carbon tetrachloride（CCl_4）-induced hepatotoxicity in rats, by analyzing metabolic profiling of endogenous bile acids（BAs） along with biochemical and histological analyses. BAs concentrations were determined by ultra-performance liquid chromatography coupled with quadrupole mass spectrometry（UPLC-MS）. Principal component analysis and partial least squares discriminant analysis were then employed to analyze the UPLC-MS results and compare the hepatoprotective effect of TRQ capsule in different groups at the doses of 0.36, 1.44, and 2.88 g·kg^-1 body weight, respectively. Moreover, our results suggested that taurocholic acid（TCA） and taurohyodesoxycholic acid（THDCA） were the most important biochemical markers, which were indicative of CCl_4-induced acute hepatic damage and hepatoprotective effect of TRQ capsule. Therefore, this new strategy would be an excellent alternative method for evaluating hepatoprotective effect and proposing potential mechanisms of action for other drugs as well.
基金
supported by the National Natural Science Foundation of China(No.81403089)
the China Postdoctoral Science Foundation(No.2012M520920)
