[Hepatotoxicity and renotoxicity of different processed products of Strychnos nux-vomica seeds based on serum metabolomics and their mechanisms of action].

This study investigated the toxicological mechanisms of different processed products of Strychnos nux-vomica seeds using serum metabolomics analysis. Seventy-two female KM mice were randomly divided into six groups(n=12 per group): control, raw seeds, vinegar-processed seeds, urine-soaked seeds, sand-roasted seeds, and oil-fried seeds. Each processed preparation group received an aqueous decoction of the original herb at the same concentration for 7 days. Hepatic and renal coefficients were measured in each group, and the levels of hepatic and renal injury markers, including aspartate transaminase(AST), alanine transaminase(ALT), blood urea nitrogen(BUN), and creatinine(CRE) were determined using a fully automated biochemical analyzer. Hematoxylin-eosin(HE) staining was used for histopathological examination of the liver and kidney. Liquid chromatography-mass spectrometry(LC-MS/MS) combined with multivariate statistical analysis was employed to screen for differential serum metabolites across groups. Metabolic pathway enrichment analysis of the selected differential markers was performed using the Human Metabolome Database(HMDB) and MetaboAnalyst 6.0. All processed S. nux-vomica seed products increased hepatic and renal coefficients and elevated hepatic and renal injury markers(AST, ALT, BUN, CRE), although these effects were reduced to varying degrees compared to the raw product. Overall, vinegar processing exhibited the most significant detoxification effect, followed by oil-fried>sand-roasted≈urine-soaked>raw seeds. Metabolomic analysis identified 14 differential metabolites across the groups, primarily including sphingolipids, glycerophospholipids, and vitamin-related compounds. Five significantly perturbed metabolic pathways were identified: sphingolipid metabolism, glycerophospholipid metabolism, α-linolenic acid metabolism, lipoic acid metabolism, and linoleic acid metabolism, with sphingolipid and glycerophospholipid metabolism common to all groups. In conclusion, processing of S. nux-vomica seeds reduced hepatorenal toxicity to varying degrees, and its toxic mechanisms may primarily involve disturbances in sphingolipid and glycerophospholipid metabolism.