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Rhizoma Paridis  is a traditional Chinese medicine commonly used in the clinical treatment of gynecological diseases. Previous studies have shown that aqueous extracts of  Rhizoma Paridis  exhibit some hepatotoxicity to hepatocytes. Here, using lipidomics analysis, we investigated the potential hepatotoxicity of  Rhizoma Paridis  and its possible mechanism. The hepatic damaging of different solvent extracts of  Rhizoma Paridis  on zebrafish larvae were determined by a combination of mortality dose, biochemical, morphological, and functional tests. We found that ethyl acetate extracts (AcOEtE) were the most toxic fraction. Notably, lipidomic responsible for the pharmacological effects of AcOEtE were investigated by Q-Exactive HF-X mass spectrometer (Thermo Scientific high-resolution) coupled in tandem with a UHPLC system. Approximately 1958 unique spectral features were detected, of which 325 were identified as unique lipid species. Among these lipid species, phosphatidylethanolamine cardiolipin Ceramide (Cer), lysophosphatidylinositol sphingosine (Sph), etc., were significantly upregulated in the treated group. Pathway analysis indicates that  Rhizoma Paridis  may cause liver damage  via  interfering with the glycerophospholipid metabolism. Collectively, this study has revealed previously uncharacterized lipid metabolic disorder involving lipid synthesis, metabolism, and transport that functionally determines hepatic fibrosis procession.

Lipidomics Indicates the Hepatotoxicity Effects of EtOAc Extract of Rhizoma Paridis