Target RNA expression omics approach to reveal the liver detoxification effect induced by Chinese medicine prescription Niu Huang Jie Du against realgar overexposure to mice

Niu Huang Jie Du prescription (NHJD) is a traditional Chinese medicine (TCM) widely used in patients suffering from excessive inner fire toxin (Huo Du Nei Sheng) syndrome, such as sore throat, gingival swelling, and pain, mouth and tongue sores, etc. This formula contains realgar (As4S4) which is one of the 28 toxic medicinal materials promulgated by the Chinese Ministry of Health. Many studies reported its toxicity on the liver and kidney, and the detoxification effect of NHJD. However, its detoxification mechanism is still unclear.To clarify the detoxification mechanism of NHJD to realgar, this study evaluated the detoxification effect of NHJD on realgar exposure in mice, and analyzed differences in mRNA expression profiles in liver tissues and associated functional predictions.ICR mice were administered with NHJD, realgar, and CMC-Na as blank control for 12 weeks, respectively. Liver injury was evaluated by histopathologic examination and liver mRNA gene were sequenced by Illumina. Differentially expressed gene, functionally enrichment and protein association network analysis were conducted.43 genes were screened out, among which 15 genes in the realgar group were decreased, but the extent of the decline has been restored in the NHJD group. The remaining 28 genes have exactly the opposite trends. Functional module analysis revealed that those detoxification function-related genes were primarily for positive regulation of glutathione metabolism, P450 on the metabolism of exogenous compounds, oxidative stress and immune-related, etc. CONCLUSIONS: The results indicated that realgar mainly causes liver damage by changing the common enzymes of drug metabolism, especially the expression of genes related to CYPs, GSTs family, oxidative stress, and complement immunity, while the TCM prescription NHJD has a regulatory effect on the abnormal expression of corresponding genes. Our results will provide some clues for the detoxification mechanism of arsenic-containing TCM prescriptions.