[Differences in toxicity and serum metabolomics of ethyl acetate fraction of Euphorbiae Pekinensis Radix before and after vinegar processing]

This study aimed to investigate the toxicity differences of the ethyl acetate fraction of Euphorbiae Pekinensis Radix before and after vinegar processing and explore the detoxification mechanism of vinegar processing using non-targeted metabolomics. The changes in terpenoid components in the ethyl acetate fraction before and after vinegar processing were analyzed using UFLC-Q-TOF-MS. Normal rats were orally administered the raw and vinegar-processed ethyl acetate fractions of Euphorbia Pekinensis Radix. The toxicity differences in ethyl acetate fractions of Euphorbia Pekinensis Radix before and after vinegar processing were evaluated by pathological morphology, serum liver and kidney function, oxidative damage, and inflammatory injury indicators, and apoptosis factors. Serum metabolomics technology was utilized to identify changes in endogenous metabolites. Principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) were employed to identify differential metabolites and metabolic pathways related to the detoxification of vinegar-processed Euphorbia Pekinensis Radix. The content of terpenoid components in the ethyl acetate fraction of Euphorbia Pekinensis Radix significantly decreased after vinegar processing. Histopathological sections and various indicators revealed that both the raw and vinegar-processed ethyl acetate fractions of Euphorbia Pekinensis Radix could induce toxicity in the liver, stomach, and intestine, with a reduction after vinegar processing. The toxicity was associated with oxidative damage, inflammatory injury, and apoptosis. A total of 13 differential metabolites and 5 main metabolic pathways related to Euphorbia Pekinensis Radix toxicity were identified by serum metabolomics. PCA and PLS-DA score plots indicated that both the raw and vinegar-processed ethyl acetate fractions disrupted the endogenous metabolic profiles in rats, mainly concentrating on lipid metabolism, primary bile acid biosynthesis, and arachidonic acid metabolism, with vinegar processing alleviating these metabolic disruptions. Therefore, the ethyl acetate fraction of Euphorbia Pekinensis Radix possesses liver, stomach, and intestinal toxicity, and vinegar processing reduces its toxicity by decreasing the content of terpenoid components. The detoxification mechanism may be related to alleviating oxidative damage, inflammatory injury, apoptosis, and improving lipid metabolism.