Gevrenova R, Joubert O, Mandova Tsv, Zaiou M, Chapleur Y, Henry M
Department of Pharmacognosy, Faculty of Pharmacy, Medical University-Sofia , Sofia , Bulgaria .
Pharm Biol. 2014 Jul;52(7):919-25. doi: 10.3109/13880209.2013.868492. Epub 2014 May 27.
Saponins have been reported to possess antitumor properties, to inhibit angiogenesis and to induce tumor apoptosis.
To test the possible cytotoxic effect of crude extracts from four Caryophyllaceae species including Gypsophila paniculata L., Gypsophila trichotoma Wend., Saponaria officinalis L., and Dianthus sylvestris Wulffen on cultured monocyte/macrophage cell lines.
After acid hydrolysis of the methanol-aqueous extracts, two representative prosaponins of the Caryophyllaceae, gypsogenin 3-O-glucuronide and quillaic acid 3-O-glucuronide were purified using solid-phase extraction (SPE), then identified by ultra-performance liquid chromatography-electrospray/mass spectrometry (UPLC-ESI/MS). Cytotoxic activity of the crude extracts at concentrations ranging from 0.1 to 200 µg/ml was evaluated on rat alveolar macrophage NR8383 and human monocytic THP-1 cell lines. Apoptosis was determined by measuring caspase-3 activity.
Quantitative analysis by reversed-phase high-performance liquid chromatography (RP-HPLC) revealed a high content of gypsogenin 3-O-glucuronide in Gypsophila species roots (0.52-1.13% dry weight). At a concentration ≥10 µg/ml of crude extracts, a significant reduction of NR8383 and THP-1 cell lines viability was evidenced using the Trypan blue exclusion test. D. sylvestris extract exhibited the highest toxicity against THP-1 cells. Caspase-3 activation was evidenced after 4 and 24 h incubation of macrophages with 100 µg/ml of S. officinalis and G. trichotoma extracts, indicating apoptosis induction.
Crude extracts from the assayed species revealed cytotoxic effects toward macrophage cell lines. In Gypsophila species, gypsogenin 3-O-glucuronide derivatives could be responsible for the observed cytotoxicity. Therefore, crude extract of Caryophyllaceae is worth investigating for the potential development of agents against cancer cells.
据报道，皂苷具有抗肿瘤特性、抑制血管生成和诱导肿瘤细胞凋亡的作用。
检测包括满天星、细裂叶丝石竹、肥皂草和森林石竹在内的四种石竹科植物的粗提物对培养的单核细胞/巨噬细胞系的潜在细胞毒性作用。
甲醇-水提取物经酸水解后，采用固相萃取（SPE）法纯化石竹科两种具有代表性的原皂苷——gypsogenin 3-O-葡萄糖醛酸苷和齐墩果酸3-O-葡萄糖醛酸苷，然后通过超高效液相色谱-电喷雾/质谱联用仪（UPLC-ESI/MS）进行鉴定。在0.1至200µg/ml浓度范围内，评估粗提物对大鼠肺泡巨噬细胞NR8383和人单核细胞THP-1细胞系的细胞毒性活性。通过测量半胱天冬酶-3活性来确定细胞凋亡情况。
反相高效液相色谱（RP-HPLC）定量分析显示，满天星属植物根中gypsogenin 3-O-葡萄糖醛酸苷含量较高（干重的0.52 - 1.13%）。使用台盼蓝排斥试验证明，当粗提物浓度≥10µg/ml时，NR8383和THP-1细胞系的活力显著降低。森林石竹提取物对THP-1细胞表现出最高毒性。巨噬细胞与100µg/ml的肥皂草和细裂叶丝石竹提取物孵育4小时和24小时后，半胱天冬酶-3被激活，表明诱导了细胞凋亡。
所检测植物的粗提物显示出对巨噬细胞系的细胞毒性作用。在满天星属植物中，gypsogenin 3-O-葡萄糖醛酸苷衍生物可能是观察到的细胞毒性的原因。因此，石竹科植物的粗提物在抗癌药物的潜在开发方面值得研究。
