Investigation of the detoxification effect of licorice on Semen Strychni-induced acute toxicity in rats using a HPLC-Q-TOF/MS-based metabolomics approach

Semen Strychni, a traditional Chinese medicine (TCM), has been widely used to treat paraplegia, facial nerve palsy and myasthenia gravis. However, its clinical application is greatly limited due to its fatal toxicity. To investigate the acute toxicity of Semen Strychni and the detoxification effect of licorice, a high-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF/MS) based urinary metabolomics method was developed in this study. After intraperitoneal injection to rats with Semen Strychni extract, the serum biochemical indexes were changed significantly, the liver and kidney showed severe necrosis and edema. Then the poisoned rat model was subsequently used for metabolomics research. Through principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA), we finally identified 19 endogenous differential metabolites involved in amino acid metabolism, glycerophospholipid metabolism, tricarboxylic acid (TCA) cycle, oxidative stress and energy metabolism. In addition, 4 exogenous compounds from Semen Strychni (3 prototypes and 1 metabolite) were also identified in the present study. Results showed that the alterations of 23 compounds caused by Semen Strychni were significantly reversed after licorice treatment, which indicated that restoring the endogenous metabolic disorder and accelerating the metabolism of the main toxic components might be the possible detoxification mechanisms of licorice. This study may provide an integral understanding for the acute toxicity of Semen Strychni and the detoxification effect of licorice, thereby contributing to the clinical use of Semen Strychni and licorice.