Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav St, 1000, Sofia, Bulgaria.
Department of Infectious Microbiology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 26 Akad. G. Bonchev Str, 1113, Sofia, Bulgaria.
Food Chem Toxicol. 2019 Nov;133:110777. doi: 10.1016/j.fct.2019.110777. Epub 2019 Aug 28.
Glucuronide Oleanane-type Triterpenoid Carboxylic Acid 3,28-Bidesmosides (GOTCAB) are accumulated in Gypsophila L. roots. In the study we aimed at investigating the possible synergistic effects of Gypsophila trichotoma GOTCABs and cytostatic etoposide towards the Hodgkin lymphoma cell line HD-MY-Z. The combination effects with etoposide were evaluated using the symbolic mathematical software MAPLE. Liquid chromatography-mass spectrometry allowed the identification or tentative assignment of 28 core GOTCAB structures together with 6 monodesmosides in the root extract. Tested gypsogenin-based saponins possessed C-28 ester-bonded chain substituted with acetyl, cis/trans methoxycinnamoyl and both acetyl and sulfate groups. No cytotoxic effect was observed up to 20 μg/mL on normal mice fibroblasts (CCL-1 cell line) and lymphoma cells. Etoposide alone exerted IC 93 μg/mL. In the presence of acetylated saponins (20 μg/mL), a strong synergism (Fa = 0.8, CI = 0.1) was observed with IC 11 μg/mL. The combination induced apoptosis witnessed by caspase activation, elevated levels of cytosolic mono- and oligonucleosomes, and nuclear fragmentation together with discernible increase in ROS generation. The results emphasize the arabinose in the C-3 chain and acetylation pattern of the C-28 chain of the saponins as important structural features for cytotoxicity enhancing activity. Triterpenoid saponins are a valuable tool to improve the efficacy of cytostatics.
毛茛泽泻型五环三萜羧酸 3,28-双糖基昔（GOTCAB）在丝石竹属植物的根部积累。在本研究中，我们旨在研究毛茛泽泻 GOTCABs 和细胞毒药物依托泊苷对霍奇金淋巴瘤细胞系 HD-MY-Z 可能的协同作用。使用符号数学软件 MAPLE 评估与依托泊苷的组合效应。液相色谱-质谱允许鉴定或暂定分配 28 个核心 GOTCAB 结构以及根提取物中的 6 个单糖昔。测试的毛茛皂昔基皂昔具有 C-28 酯键连接的链取代乙酰基、顺/反甲氧基肉桂酰基和乙酰基和硫酸盐基。在 20μg/mL 及以下浓度下，对正常小鼠成纤维细胞（CCL-1 细胞系）和淋巴瘤细胞没有细胞毒性作用。依托泊苷单独作用的 IC 93μg/mL。在乙酰化皂昔（20μg/mL）存在的情况下，观察到强烈的协同作用（Fa=0.8，CI=0.1），IC 11μg/mL。组合诱导细胞凋亡，通过半胱天冬酶激活、细胞质中单核小体和寡核小体水平升高以及核片段化以及可识别的 ROS 生成增加来证明。结果强调了 C-3 链上的阿拉伯糖和 C-28 链上的乙酰化模式是增强细胞毒性活性的重要结构特征。三萜皂昔是提高细胞毒药物疗效的有价值工具。
