A metabolic profiling analysis of the acute hepatotoxicity and nephrotoxicity of Zhusha Anshen Wan compared with cinnabar in rats using 1H NMR spectroscopy

Zhusha Anshen Wan (ZSASW), a traditional Chinese medicine (TCM) prescription, composed of cinnabar (cinnabaris), Coptidis Rhizoma (Coptis chinensis French.), Angelicae Sinensis Radix (Angelica sinensis (oliv.) Diels), uncooked Rehmanniae Radix (Rehmannia glutinosa Libosch.), honey fried Glycyrrhizae Radix Et Rhizoma (Glycyrrhiza uralensis Fisch.), has been widely used for sedative therapy. Cinnabar, the chief component of ZSASW, has been proved to possess the toxicities.In this study, a metabonomics approach based on high-resolution (1)H nuclear magnetic resonance spectroscopy was applied to investigate the protective effects of ZSASW on the toxic effects induced by cinnabar alone.Male Wistar rats were divided into three groups: control group, ZSASW group and cinnabar group. Partial least squares-discriminant analysis (PLS-DA) was performed to identify different metabolic profiles of urine and serum from rats. Liver and kidney histopathology examinations and serum clinical chemistry analysis were also performed.The significant difference in metabolic profiling of urine and serum of the rats was observed between cinnabar treated group, control group, and the changes of endogenous metabolites related to the toxicities were identified. The results were also certified by the liver and kidney histopathology examinations and biochemical analysis of blood.Our results suggested that the four combined herbal medicines of ZSASW had the effects of protecting from the toxicity induced by cinnabar alone. This work showed that the NMR-based metabonomics approach might be a promising approach to study detoxification of Chinese medicines and reasonable combination of TCM prescriptions.