Botanicals have earned widespread application in the world, and the value of dietary supplement/wellness has increased from $9.4 billion (1994) to $36.7 billion (2014, US) (Navarro et al., 2017). Over past few decades, the consumption of herbal ingredients of dietary supplements (HDS), such as traditional Chinese medicine (TCM), has grown tremendously. However, the applications of HDS have been accompanied by a growth in HDS-related complications, especially for drug-induced liver injury (DILI) (Roytman et al., 2018). DILI can be induced by a variety of prescription or non-prescription drugs, such as chemical drugs, HDS, etc (Yu et al., 2017; Chalasani et al., 2014). Researchers have found that HDS-induced hepatic injury has been the new factor in acute hepatic injury requiring hepatic transplantation (Wong et al., 2017). Navarro et al. revealed that there was an overall 7–20 % increase in the number of DILI cases caused by HDS. Over the 10 years, the growth in non-building HDS cases was dramatically increased from 5 % to 12 % (2004 – 2012) (Navarro et al., 2014). Thus, it is essential to reveal the mechanism of TCM-induced liver injury.

Sophorae tonkinensis Radix et Rhizoma (STR), the dried roots of Sophora tonkinensis Gagnep (http://www.theplantlist.org), is mainly distributed in Guangxi and Guangdong provinces of China. STR has been applied in the treatment of swollen sore throats, clearing heat-toxin in clinical (Tang et al., 2013 ; Chinese Pharmacopoeia Commission, 2020). Moreover, STR has a variety of biological activities, including anti-tumor, anti-inflammation, and antioxidant, etc. (Chui et al., 2005; Chae et al., 2016). Notably, STR is a typical TCM with some well-known side-effects, such as DILI and neurological toxicity (Liu et al., 2017). So far, the mechanism of SILI remains unclear and needed to be conducted in order to improve the ational applications of STR.

Nowadays, ultra-performance liquid chromatography coupled quadrupole -time-of-flight mass spectrometry (UPLC-Q/TOF MS), with higher sensitivity and resolution than traditional methods, is widely used to profile the chemical components in herbs or TCM (Zhang et al., 2016b; Chen et al., 2021). Meanwhile, network pharmacology can effectively reveal the relationship between drugs and targets and predict their pharmacological mechanism, such as the potential anti-influenza mechanism of Lonicerae japonicae flos. (Zhang et al., 2021), the mechanism of Panax notoginseng against myocardial fibrosis (Han et al., 2022), etc. Moreover, the“omics” technologies were treated as effective strategies in hepatotoxicity research (Jiang et al., 2019a; Rao et al., 2022; Zeki et al., 2020), such as transcriptomics (Kohonen et al., 2017; Wetmore et al., 2010), metabolomics (Fan et al., 2016), or proteomic (Thongboonkerd et al., 2014) are frequently applied to predict the mechanism and biomarkers of DILI. Thus, the omics approach coupled chemical profiling and network pharmacology may be a powerful tool to explore the prospective mechanisms of TCM-induced liver injury.

In this work, “multi-omics” strategy combined with network pharmacology and chemical profiling was used to explore the mechanisms of SILI in vivo. This study provides new insights to explore the mechanisms of other herbs induced liver injury.