Potential biomarkers screening of Polygonum multiflorum radix-induced liver injury based on metabonomics analysis of clinical samples

Ethnopharmacological relevance: Polygonum multiflorum Radix (PMR) is the dried root tuber of Polygonum mul-tiflorum Thunb., which has been used in the clinic for a variety of pharmacological activities. However, Polyg-onum multiflorum Radix-induced liver injury (PMR-ILI) has been reported in recent years, which has limited its clinical use to some extent. The occurrence of PMR-ILI is not universal, so finding the different metabolic characteristics between PMR-ILI and Polygonum multiflorum Radix-tolerance group (PMR-T) is very important for the PMR rational clinical application and PMR-ILI early clinical diagnosis. Methods: In this study, 6 clinical plasma samples of PMR-ILI and 13 PMR-T were collected and analyzed by high -resolution liquid chromatography-mass spectrometry. Firstly, the differential metabolites of the two groups were screened by conventional screening methods such as multivariate statistical analysis. Secondly, the characteristic metabolites with greater contribution, correlation with liver injury and high sensitivity were screened by cor-relation analysis with clinical liver injury indicators, random forest analysis, and receiver operating character-istic curve (ROC). Results: After multivariate statistical analysis and screening analysis, 29 differential metabolites were identified. Compared with PMR-T group, the metabolism of glycerol and phospholipid, glutamine and glutamate, phenyl-alanine, sphingolipid and tryptophan in PMR-ILI group were disturbed. After correlation analysis with liver injury indexes and random forest screening, 8 potential biomarkers closely related to clinical liver injury were obtained. Finally, 3 potential biomarkers with high expression in PMR-ILI, hypoxanthine, LysoPC(P-16:0/0:0) and taurochenodesoxycholic acid, were screened out through the analysis of ROC, which can provide a basis for the early clinical diagnosis. Conclusion: Based on the analysis of the PMR-ILI and PMR-T plasma samples by LC-MS, three biomarkers of clinical liver injury of Polygonum multiflorum Radix were selected: hypoxanthine, LysoPC(P-16:0/0:0) and taurochenodeoxycholic acid.