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Identification of compounds responsible for the anthelmintic effects of chicory (Cichorium intybus) by molecular networking and bio-guided fractionation.
Int J Parasitol Drugs Drug Resist. 2021 04; 15:105-114.IJ

Abstract

Increasing resistance towards anthelmintic drugs has necessitated the search for alternative treatments for the control of gastrointestinal nematode parasites. Animals fed on chicory (Cichorium intybus L.), a temperate (pasture) crop, have reduced parasite burdens, hence making C. intybus a potentially useful source for novel anthelmintic compounds or a diet-based preventive/therapeutic option. Here, we utilized in vitro bioassays with the parasitic nematode Ascaris suum and molecular networking techniques with five chicory cultivars to identify putative active compounds. Network analysis predicted sesquiterpene lactones (SL) as the most likely group of anthelmintic compounds. Further bioassay-guided fractionation supported these predictions, and isolation of pure compounds demonstrated that the SL 8-deoxylactucin (8-DOL) is the compound most strongly associated with anti-parasitic activity. Furthermore, we showed that 8-DOL acts in a synergistic combination with other SL to exert the anti-parasitic effects. Finally, we established that chicory-derived extracts also showed activity against two ruminant nematodes (Teladorsagia circumcincta and Cooperia oncophora) in in vitro assays. Collectively, our results confirm the anti-parasitic activity of chicory against a range of nematodes, and pave the way for targeted extraction of active compounds or selective breeding of specific cultivars to optimize its future use in human and veterinary medicine.

Authors+Show Affiliations

Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.Sensus b.v., Oostelijke Havendijk 15, 4704, RA Roosendaal, the Netherlands.Section for Clinical Mass Spectrometry, Danish Center for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.Instituto de Farmacología y Morfofisiología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads 223, 2800, Kongens Lyngby, Denmark.Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.Instituto de Ganadería de Montaña, CSIC-Universidad de León, Department of Animal Health, 24346, Grulleros. León, Spain.Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163, Berlin, Germany.Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163, Berlin, Germany.Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads 223, 2800, Kongens Lyngby, Denmark.Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark. Electronic address: arw@sund.ku.dk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33618233

Citation

Valente, Angela H., et al. "Identification of Compounds Responsible for the Anthelmintic Effects of Chicory (Cichorium Intybus) By Molecular Networking and Bio-guided Fractionation." International Journal for Parasitology. Drugs and Drug Resistance, vol. 15, 2021, pp. 105-114.
Valente AH, de Roode M, Ernst M, et al. Identification of compounds responsible for the anthelmintic effects of chicory (Cichorium intybus) by molecular networking and bio-guided fractionation. Int J Parasitol Drugs Drug Resist. 2021;15:105-114.
Valente, A. H., de Roode, M., Ernst, M., Peña-Espinoza, M., Bornancin, L., Bonde, C. S., Martínez-Valladares, M., Ramünke, S., Krücken, J., Simonsen, H. T., Thamsborg, S. M., & Williams, A. R. (2021). Identification of compounds responsible for the anthelmintic effects of chicory (Cichorium intybus) by molecular networking and bio-guided fractionation. International Journal for Parasitology. Drugs and Drug Resistance, 15, 105-114. https://doi.org/10.1016/j.ijpddr.2021.02.002
Valente AH, et al. Identification of Compounds Responsible for the Anthelmintic Effects of Chicory (Cichorium Intybus) By Molecular Networking and Bio-guided Fractionation. Int J Parasitol Drugs Drug Resist. 2021;15:105-114. PubMed PMID: 33618233.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of compounds responsible for the anthelmintic effects of chicory (Cichorium intybus) by molecular networking and bio-guided fractionation. AU - Valente,Angela H, AU - de Roode,Matthew, AU - Ernst,Madeleine, AU - Peña-Espinoza,Miguel, AU - Bornancin,Louis, AU - Bonde,Charlotte S, AU - Martínez-Valladares,María, AU - Ramünke,Sabrina, AU - Krücken,Jürgen, AU - Simonsen,Henrik T, AU - Thamsborg,Stig M, AU - Williams,Andrew R, Y1 - 2021/02/11/ PY - 2020/10/26/received PY - 2021/02/03/revised PY - 2021/02/03/accepted PY - 2021/2/23/pubmed PY - 2021/10/12/medline PY - 2021/2/22/entrez KW - Anthelmintic KW - Chicory KW - Parasite KW - Sesquiterpene lactones SP - 105 EP - 114 JF - International journal for parasitology. Drugs and drug resistance JO - Int J Parasitol Drugs Drug Resist VL - 15 N2 - Increasing resistance towards anthelmintic drugs has necessitated the search for alternative treatments for the control of gastrointestinal nematode parasites. Animals fed on chicory (Cichorium intybus L.), a temperate (pasture) crop, have reduced parasite burdens, hence making C. intybus a potentially useful source for novel anthelmintic compounds or a diet-based preventive/therapeutic option. Here, we utilized in vitro bioassays with the parasitic nematode Ascaris suum and molecular networking techniques with five chicory cultivars to identify putative active compounds. Network analysis predicted sesquiterpene lactones (SL) as the most likely group of anthelmintic compounds. Further bioassay-guided fractionation supported these predictions, and isolation of pure compounds demonstrated that the SL 8-deoxylactucin (8-DOL) is the compound most strongly associated with anti-parasitic activity. Furthermore, we showed that 8-DOL acts in a synergistic combination with other SL to exert the anti-parasitic effects. Finally, we established that chicory-derived extracts also showed activity against two ruminant nematodes (Teladorsagia circumcincta and Cooperia oncophora) in in vitro assays. Collectively, our results confirm the anti-parasitic activity of chicory against a range of nematodes, and pave the way for targeted extraction of active compounds or selective breeding of specific cultivars to optimize its future use in human and veterinary medicine. SN - 2211-3207 UR - https://www.unboundmedicine.com/medline/citation/33618233/Identification_of_compounds_responsible_for_the_anthelmintic_effects_of_chicory__Cichorium_intybus__by_molecular_networking_and_bio_guided_fractionation_ DB - PRIME DP - Unbound Medicine ER -