Abstract
Non-targeted metabonomics was used to investigate the metabolite changes in the glioblastoma orthotopic tumor-bearing mice after timosaponin AⅢ(TIA) intervention to explore the metabolic relevant mechanism of glioblastoma and TIA intervention. The mice were randomly divided into a blank group, a model group, and a TIA group. HPLC-LTQ-Orbitrap Elite liquid chromatography-mass spectrometry was used to detect the metabolite changes in the serum of rats in the three groups after treatment for 4 weeks. Principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) were performed on the metabolites, and the differential metabolites were selected based on VIP values and P values(P<0.05). The results showed that TIA significantly inhibited the in vivo glioblastoma growth, but it had limited influence on body weight. Serum samples were clearly distinguishable among groups. As compared with the blank group, six metabolites including ceramide, succinic acid, α-ketoglutarate acid(αKG), citric acid, indophenol sulfate, and 3 a, 6 b, 7 b-trihydroxy-5 b-cholic acid in the model group significantly decreased. As compared with the model group, five metabolites except phenol sulfate, PC[20:4(5Z,7E,11Z,14Z)-OH(9)/diMe(9,3)], o-palmitoyl carnitine, α-ketoglutarate acid, and citric acid in the TIA group significantly increased. According to the MetaboAnalyst enrichment analysis, the metabolic pathways were enriched in the tricarboxylic acid cycle, and alanine, aspartic acid, and glutamate metabolism. These results show that during the glioblastoma growth process, the metabolites including αKG and citric acid are down-regulated, and TIA exerts the anti-glioblastoma growth effect through the regulation of tricarboxylic acid cycle, and alanine, aspartic acid, and glutamate metabolism to elevate the levels of αKG, citric acid, and other metabolites.
Published Version
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