1H NMR-Based Metabolomics Reveals the Antitumor Mechanisms of Triptolide in BALB/c Mice Bearing CT26 Tumors

Triptolide, the main active ingredient in Tripterygium wilfordii Hook. f. (Celastraceae), has shown promising effects against a variety of tumors. However, the molecular pharmacological mechanisms explaining the action of triptolide remain unknown. In this study, the CT26 colon tumor cell line was inoculated subcutaneously into BALB/c mice, and plasma samples were subjected to H-1 NMR metabolomics analysis. The metabolic signature identified five metabolites whose levels were lower and 15 whose levels were higher in CT26 tumor-bearing mice than in normal control mice. Triptolide treatment significantly reversed the levels of nine of these metabolites, including isoleucine, glutamine, methionine, proline, 3-hydroxybutyric acid, 2-hydroxyisovalerate, 2-hydroxyisobutyrate, and low-density lipoprotein/very low-density lipoprotein. Based on the identities of these potential biomarkers, we conclude that the antitumor mechanism of triptolide might rely on correcting perturbations in branched-chain amino acid metabolism, serine/glycine/methionine biosynthesis, and ketone bodies metabolism.

雷公藤甲素是雷公藤（卫矛科）的主要活性成分，已显示出对多种肿瘤有良好的疗效。然而，解释雷公藤甲素作用的分子药理机制仍然未知。在本研究中，将CT26结肠肿瘤细胞系皮下接种到BALB/c小鼠体内，并对血浆样本进行氢 - 1核磁共振代谢组学分析。代谢特征显示，与正常对照小鼠相比，CT26荷瘤小鼠体内有5种代谢物水平较低，15种代谢物水平较高。雷公藤甲素治疗显著逆转了其中9种代谢物的水平，包括异亮氨酸、谷氨酰胺、蛋氨酸、脯氨酸、3 - 羟基丁酸、2 - 羟基异戊酸、2 - 羟基异丁酸以及低密度脂蛋白/极低密度脂蛋白。基于这些潜在生物标志物的特性，我们得出结论：雷公藤甲素的抗肿瘤机制可能依赖于纠正支链氨基酸代谢、丝氨酸/甘氨酸/蛋氨酸生物合成以及酮体代谢的紊乱。