A plasma untargeted metabolomic study of Chinese medicine Zhi-Zi-Da-Huang decoction intervention to alcohol-induced hepatic steatosis

Zhi-Zi-Da-Huang decoction (ZZDHD) is a classical traditional Chinese medicine (TCM) prescription that has been widely used to treat alcoholic liver disease over a millennium in China. However, the hepatoprotective mechanism of ZZDHD remains obscure. In this work, an untargeted metabolomic study based LC-TOF/MS and LC-QqQ/MS was conducted to explore plasma metabolic changes of ZZDHD intervention to alcohol-induced hepatic steatosis (AHS). The XCMS Online platform was used for nonlinear alignment of the data in the time domain, metabolite feature annotation and extraction of the peak intensities. Principal component analysis (PCA) and orthogonal projection to latent structures discriminant analysis (OPLS-DA) were used to examine the data in a multivariate setting. The observations in control, AHS and ZZDHD-dosed groups could be clearly distinguished by PCA and the ZZDHD-dosed group displayed a distinct returning trend to the control group. 16 potential biomarkers which contribute to the therapeutic mechanism of ZZDHD on AHS rats were screened by OPLS-DA. These potential biomarkers mainly involved in the metabolism of amino acids, phospholipids, fatty acids, cholesterols and sphingolipid, which could be useful to further investigate the characteristics of AHS and the hepatoprotective effects of ZZDHD. This study also illustrates that the untargeted metabolomic method is a promising method to identify candidate metabolic biomarkers and understand the mechanism of TCM.