Horgan Mark James, Sigg Ines, Poulopoulou Ioanna, Rodriguez-Mejias Francisco J, Albertini Eva, Fusani Pietro, Fischer Florian, Martinidou Eftychia, Schuster Daniela, Martens Stefan, Dürr Pidder Jansen, Gauly Matthias, Stuppner Hermann, Weiss Alexander, Temml Veronika, Siewert Bianka
Institute of Pharmacy/Pharmacognosy, Center for Chemistry and Biomedicine, University of Innsbruck, 6020, Innsbruck, Austria.
Research Institute for Biomedical Aging Research, University of Innsbruck, 6020, Innsbruck, Austria.
Sci Rep. 2025 Feb 3;15(1):4108. doi: 10.1038/s41598-024-73958-9.
The alpine plant Cicerbita alpina (L.) Wallr., when grown as a sprout, is known as a bitter-tasting culinary delicacy. Recently it has also been reported to have anthelmintic activity, prompting further investigation into its mechanism of action. Liquid-liquid fractions were prepared from a methanolic extract of the aerial parts and were submitted in parallel to embryo development (ED), worm motility (WMT), and cytotoxicity assays for anthelmintic and toxicity evaluations. The anthelminthic assays revealed the more polar fractions to be most active against Ascaridia galli embryos (BuOH | 68% ED | c = 500 µg/ml and EtOAc | 65% ED | c = 500 µg/ml) and Caenorhabditis elegans adult worms (BuOH | 49% WMT | c = 150 µg/ml and EtOAc | 74% WMT | c = 150 µg/ml) suggesting the fraction's constituents possess dual anthelmintic activity against multiple life-cycle stages (i.e., eggs, worms) of helminths. Additionally, the BuOH fraction was non-cytotoxic to human cell-lines. Subsequent FCC and SEC derived subfractions were submitted to the anthelmintic assay workflow and the enriched subfractions B1 and E3.8, phytochemically assigned as 11-β,13-dihydrolactucin and luteolin, demonstrated bioactivity against the embryo phenotype (B1 | 58% ED | c = 1.8 µM and E3.8 | 46% ED | c = 1.7 µM) within range of the flubendazole control. Furthermore, luteolin was found to inhibit C. elegans egg hatching (luteolin | 65% EH | c = 10 µM | t = 10 h) within the range of the control albendazole. Both identified anthelmintic phytochemicals were found to affect tubulin polymerisation at a concentration of c = 50 µM. Together with in silico virtual screening studies, these results suggest microtubule stabilisation as a possible anthelmintic target and mechanism of action. This work effectively advocates the consideration of C. alpina extracts and fractions for the development of herbal therapeutics against parasitic helminths.
高山植物高山苦苣菜（Cicerbita alpina (L.) Wallr.），作为芽苗菜种植时，是一种味道苦涩的烹饪佳肴。最近也有报道称其具有驱虫活性，这促使人们进一步研究其作用机制。从地上部分的甲醇提取物中制备液 - 液馏分，并同时进行胚胎发育（ED）、蠕虫运动性（WMT）和细胞毒性测定，以进行驱虫和毒性评估。驱虫试验表明，极性较强的馏分对鸡蛔虫胚胎（正丁醇 | 68% ED | c = 500 µg/ml 和乙酸乙酯 | 65% ED | c = 500 µg/ml）和秀丽隐杆线虫成虫（正丁醇 | 49% WMT | c = 150 µg/ml 和乙酸乙酯 | 74% WMT | c = 150 µg/ml）最具活性，这表明该馏分的成分对蠕虫的多个生命周期阶段（即卵、成虫）具有双重驱虫活性。此外，正丁醇馏分对人细胞系无细胞毒性。随后，将通过快速柱色谱（FCC）和尺寸排阻色谱（SEC）得到的亚馏分进行驱虫试验流程，富集的亚馏分B1和E3.8，经植物化学鉴定为11-β,13 - 二氢莴苣内酯和木犀草素，在氟苯达唑对照范围内表现出对胚胎表型的生物活性（B1 | 58% ED | c = 1.8 µM 和 E3.8 | 46% ED | c = 1.7 µM）。此外，发现木犀草素在阿苯达唑对照范围内抑制秀丽隐杆线虫卵孵化（木犀草素 | 65% EH | c = 10 µM | t = 10 h）。两种已鉴定的驱虫植物化学物质在浓度为c = 50 µM时均被发现影响微管蛋白聚合。结合计算机虚拟筛选研究，这些结果表明微管稳定可能是一种驱虫靶点和作用机制。这项工作有效地倡导考虑将高山苦苣菜提取物和馏分用于开发抗寄生蠕虫的草药疗法。
