Department of Chemistry, Capital Normal University, No. 105 Xisanhuanbeilu, Haidian District, Beijing 100048, China.
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16 Nanxiaojie, Dongzhimennei, Beijing 100700, China.
Eur J Pharmacol. 2019 Jan 5;842:10-19. doi: 10.1016/j.ejphar.2018.10.025. Epub 2018 Oct 21.
Jolkinolide B (JB), which is isolated from the dried root of Euphorbia fischeriana Steud., has been reported to possess various therapeutic effects, such as treatment of edema and abdominal distention and protection against acute lung injury, and it has also been reported to have anti-inflammatory even antitumor properties. Thus, JB has always been considered a promising anticancer drug candidate. In the current work, a cellular metabolomics evaluation based on the nuclear magnetic resonance (NMR) approach was applied to investigate the mechanism of JB in HepG2 cells. In addition, biological assays such as the MTT assay, DAPI staining and the Annexin V-FITC/PI assay were implemented to evaluate cell viability and apoptosis in JB-treated cells. Subsequently, we used multivariate statistical analyses, such as principal component analysis (PCA) and orthogonal projection to latent structure with discriminant analysis (OPLS-DA) to identify metabolic biomarkers. In total, 36 metabolites in the cell extract samples and 30 metabolites in the cell culture media samples were clearly identified to be altered after the treatment. Variations in the specific metabolites suggested that HepG2 cells that were exposed to JB displayed the disordered effects in multiple metabolic pathways, such as the tricarboxylic acid cycle, amino acid metabolism, GSH synthesis and pyruvate metabolism. NMR-based cell metabolomics provided a holistic method for the identification of JB's antitumor mechanisms and the exploration of its potential applications in preclinical and clinical studies.
京尼平苷 B（JB）是从大戟Euphorbia fischeriana Steud. 的干根中分离出来的，已被报道具有多种治疗作用，例如治疗水肿和腹胀以及预防急性肺损伤，并且还具有抗炎甚至抗肿瘤的特性。因此，JB 一直被认为是一种很有前途的抗癌药物候选物。在目前的工作中，应用基于核磁共振（NMR）方法的细胞代谢组学评估来研究 JB 在 HepG2 细胞中的作用机制。此外，还实施了诸如 MTT 测定、DAPI 染色和 Annexin V-FITC/PI 测定等生物测定，以评估 JB 处理细胞中的细胞活力和细胞凋亡。随后，我们使用多元统计分析，如主成分分析（PCA）和正交偏最小二乘判别分析（OPLS-DA）来鉴定代谢生物标志物。总共鉴定出 JB 处理后细胞提取物样品中的 36 种代谢物和细胞培养物样品中的 30 种代谢物发生了明显改变。特定代谢物的变化表明，暴露于 JB 的 HepG2 细胞在多个代谢途径中表现出紊乱的效应，例如三羧酸循环、氨基酸代谢、GSH 合成和丙酮酸代谢。基于 NMR 的细胞代谢组学为鉴定 JB 的抗肿瘤机制以及探索其在临床前和临床研究中的潜在应用提供了一种整体方法。
