Microtubule inhibition as a proposed mechanism for the anthelmintic effect of phytochemicals isolated from Cicerbita alpina
Abstract 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...
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Nature Portfolio
2025-02-01
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| Online Access: | https://doi.org/10.1038/s41598-024-73958-9 |
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| author | Mark James Horgan Ines Sigg Ioanna Poulopoulou Francisco J. Rodriguez-Mejias Eva Albertini Pietro Fusani Florian Fischer Eftychia Martinidou Daniela Schuster Stefan Martens Pidder Jansen Dürr Matthias Gauly Hermann Stuppner Alexander Weiss Veronika Temml Bianka Siewert |
| author_facet | Mark James Horgan Ines Sigg Ioanna Poulopoulou Francisco J. Rodriguez-Mejias Eva Albertini Pietro Fusani Florian Fischer Eftychia Martinidou Daniela Schuster Stefan Martens Pidder Jansen Dürr Matthias Gauly Hermann Stuppner Alexander Weiss Veronika Temml Bianka Siewert |
| author_sort | Mark James Horgan |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-d9a3e66b785c49e1ac4923557a69ff73 |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-02-01 |
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| spelling | doaj-art-d9a3e66b785c49e1ac4923557a69ff732025-02-09T12:28:22ZengNature PortfolioScientific Reports2045-23222025-02-0115111510.1038/s41598-024-73958-9Microtubule inhibition as a proposed mechanism for the anthelmintic effect of phytochemicals isolated from Cicerbita alpinaMark James Horgan0Ines Sigg1Ioanna Poulopoulou2Francisco J. Rodriguez-Mejias3Eva Albertini4Pietro Fusani5Florian Fischer6Eftychia Martinidou7Daniela Schuster8Stefan Martens9Pidder Jansen Dürr10Matthias Gauly11Hermann Stuppner12Alexander Weiss13Veronika Temml14Bianka Siewert15Institute of Pharmacy/Pharmacognosy, Center for Chemistry and Biomedicine, University of InnsbruckInstitute of Pharmacy/Pharmacognosy, Center for Chemistry and Biomedicine, University of InnsbruckFaculty of Agricultural, Environmental and Food Sciences, Free University of BolzanoInstitute of Pharmacy/Pharmacognosy, Center for Chemistry and Biomedicine, University of InnsbruckResearch Institute for Biomedical Aging Research, University of InnsbruckCentro Di Ricerca Foreste E Legno, Consiglio Per La Ricerca in Agricoltura E L’analisi Dell’economia AgrariaInstitute of Pharmacy, Department of Pharmaceutical and Medicinal Chemistry and Research and Innovation Center for Novel Therapies and Regenerative Medicine, Paracelsus Medical University SalzburgResearch and Innovation Center, Edmund Mach FoundationInstitute of Pharmacy, Department of Pharmaceutical and Medicinal Chemistry and Research and Innovation Center for Novel Therapies and Regenerative Medicine, Paracelsus Medical University SalzburgResearch and Innovation Center, Edmund Mach FoundationResearch Institute for Biomedical Aging Research, University of InnsbruckFaculty of Agricultural, Environmental and Food Sciences, Free University of BolzanoInstitute of Pharmacy/Pharmacognosy, Center for Chemistry and Biomedicine, University of InnsbruckResearch Institute for Biomedical Aging Research, University of InnsbruckInstitute of Pharmacy, Department of Pharmaceutical and Medicinal Chemistry and Research and Innovation Center for Novel Therapies and Regenerative Medicine, Paracelsus Medical University SalzburgInstitute of Pharmacy/Pharmacognosy, Center for Chemistry and Biomedicine, University of InnsbruckAbstract 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.https://doi.org/10.1038/s41598-024-73958-9 |
| spellingShingle | Mark James Horgan Ines Sigg Ioanna Poulopoulou Francisco J. Rodriguez-Mejias Eva Albertini Pietro Fusani Florian Fischer Eftychia Martinidou Daniela Schuster Stefan Martens Pidder Jansen Dürr Matthias Gauly Hermann Stuppner Alexander Weiss Veronika Temml Bianka Siewert Microtubule inhibition as a proposed mechanism for the anthelmintic effect of phytochemicals isolated from Cicerbita alpina Scientific Reports |
| title | Microtubule inhibition as a proposed mechanism for the anthelmintic effect of phytochemicals isolated from Cicerbita alpina |
| title_full | Microtubule inhibition as a proposed mechanism for the anthelmintic effect of phytochemicals isolated from Cicerbita alpina |
| title_fullStr | Microtubule inhibition as a proposed mechanism for the anthelmintic effect of phytochemicals isolated from Cicerbita alpina |
| title_full_unstemmed | Microtubule inhibition as a proposed mechanism for the anthelmintic effect of phytochemicals isolated from Cicerbita alpina |
| title_short | Microtubule inhibition as a proposed mechanism for the anthelmintic effect of phytochemicals isolated from Cicerbita alpina |
| title_sort | microtubule inhibition as a proposed mechanism for the anthelmintic effect of phytochemicals isolated from cicerbita alpina |
| url | https://doi.org/10.1038/s41598-024-73958-9 |
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