Comprehensive Metabolic Profiling of Brucea javanica Oil Oral Emulsion in Rat Serum by Ultrahigh Performance Liquid Chromatography Time‐of‐Flight Mass Spectrometry and Its Correlation With Anti‐Glioblastoma Activity

ABSTRACT Brucea javanica oil oral emulsion (BJOE) serves as an adjunctive therapeutic agent for glioblastoma multiforme (GBM); however, the inhibitory effects of its serum metabolites remain unexplored. In this study, ultrahigh performance liquid chromatography‐quadrupole‐time‐of‐flight mass spectrometry (UHPLC‐Q‐TOF‐MS/MS) was employed to analyze serum metabolites in rats following BJOE administration. The inhibitory effects of the serum on GBM were assessed using U251 cell bioassays, and the relationship between serum metabolites and cellular inhibitory activity was examined. Six prototype components and six metabolites were identified in the serum, including linoleic acid, linoleic acid‐M1, linoleic acid‐M2, linoleic acid‐M3, oleic acid, oleic acid‐M1, oleic acid‐M2, oleic acid‐M3, sphingosine, palmitoleic acid, oleamide, and 1‐stearoyl‐rac‐glycerol. Rat serum collected 2 h postdosing significantly inhibited U251 cell proliferation. Gray relationship analysis indicated that oleic acid, oleic acid‐M1, linoleic acid, linoleic acid‐M1, linoleic acid‐M2, sphingosine, palmitoleic acid, oleamide, and 1‐stearoyl‐rac‐glycerol were highly correlated with the inhibition rate of U251 cell proliferation, with oleic acid‐M1 showing the highest correlation coefficient (0.9806). These findings suggest that BJOE and its metabolites may possess therapeutic potential against GBM, particularly in inhibiting glioma cell proliferation, with oleic acid and its metabolites likely playing a significant role.