Anti-protozoal activity and metabolomic analyses of Cichorium intybus L. against Trypanosoma cruzi
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Anti-protozoal activity and metabolomic analyses of Cichorium intybus L. against Trypanosoma cruzi. / Peña-Espinoza, Miguel; Romero-Uzqueda, Yeambell; Valente, Angela H.; de Roode, Matthew; Simonsen, Henrik T.; Thamsborg, Stig M.; Williams, Andrew R.; López-Muñoz, Rodrigo.
In: International Journal for Parasitology: Drugs and Drug Resistance, Vol. 20, 2022, p. 43-53.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Anti-protozoal activity and metabolomic analyses of Cichorium intybus L. against Trypanosoma cruzi
AU - Peña-Espinoza, Miguel
AU - Romero-Uzqueda, Yeambell
AU - Valente, Angela H.
AU - de Roode, Matthew
AU - Simonsen, Henrik T.
AU - Thamsborg, Stig M.
AU - Williams, Andrew R.
AU - López-Muñoz, Rodrigo
N1 - Publisher Copyright: © 2022 The Authors
PY - 2022
Y1 - 2022
N2 - Chagas disease, caused by the protozoa Trypanosoma cruzi, is a potentially life-threatening parasitic zoonosis infecting 6–7 million people worldwide, mainly in Latin America. Due to the limited numbers of drugs available against this neglected disease and their frequent adverse effects, novel anti-chagasic agents are urgently needed. Cichorium intybus L. (chicory) is a bioactive plant with potent activity against parasitic nematodes, but its effects on protozoans are poorly known and no studies have explored its trypanocidal potential. Here, we investigated the activity of C. intybus against extracellular and intracellular stages of T. cruzi, including the prediction of trypanocidal compounds by metabolomic analyses and bioactivity-based molecular networking. Purified C. intybus extracts were prepared from leaves and roots of five C. intybus cultivars (cv. ‘Benulite’, ‘Goldine’, ‘Larigot’, ‘Maestoso’ and ‘Spadona’). All C. intybus extracts induced concentration-dependent effects against T. cruzi trypomastigotes. C. intybus leaf extracts had higher trypanocidal selectivity and lower cytotoxicity on mammalian cells than root extracts. The leaf extract of C. intybus cv. Goldine also significantly reduced the number of mammalian cells infected with T. cruzi amastigotes. Metabolomic and bioactivity-based molecular networking analyses revealed 11 compounds in C. intybus leaves strongly linked with activity against trypomastigotes, including the sesquiterpene lactone lactucin, and flavonoid- and fatty acid-derivatives. Furthermore, seven distinct C. intybus molecules (including two sesquiterpene lactone-derivatives) were predicted to be involved in reducing the number of mammalian cells infected with amastigotes. This is the first report of the anti-protozoal activity of C. intybus against trypanosomatid parasites and expands our understanding of the anti-parasitic effects of this plant and its bioactive metabolites. Further studies to elucidate the anti-protozoal compound(s) in C. intybus and their mode(s) of action will improve our knowledge of using this bioactive plant as a promising source of novel broad-spectrum anti-parasitic compounds with associated health benefits and biomedical potential.
AB - Chagas disease, caused by the protozoa Trypanosoma cruzi, is a potentially life-threatening parasitic zoonosis infecting 6–7 million people worldwide, mainly in Latin America. Due to the limited numbers of drugs available against this neglected disease and their frequent adverse effects, novel anti-chagasic agents are urgently needed. Cichorium intybus L. (chicory) is a bioactive plant with potent activity against parasitic nematodes, but its effects on protozoans are poorly known and no studies have explored its trypanocidal potential. Here, we investigated the activity of C. intybus against extracellular and intracellular stages of T. cruzi, including the prediction of trypanocidal compounds by metabolomic analyses and bioactivity-based molecular networking. Purified C. intybus extracts were prepared from leaves and roots of five C. intybus cultivars (cv. ‘Benulite’, ‘Goldine’, ‘Larigot’, ‘Maestoso’ and ‘Spadona’). All C. intybus extracts induced concentration-dependent effects against T. cruzi trypomastigotes. C. intybus leaf extracts had higher trypanocidal selectivity and lower cytotoxicity on mammalian cells than root extracts. The leaf extract of C. intybus cv. Goldine also significantly reduced the number of mammalian cells infected with T. cruzi amastigotes. Metabolomic and bioactivity-based molecular networking analyses revealed 11 compounds in C. intybus leaves strongly linked with activity against trypomastigotes, including the sesquiterpene lactone lactucin, and flavonoid- and fatty acid-derivatives. Furthermore, seven distinct C. intybus molecules (including two sesquiterpene lactone-derivatives) were predicted to be involved in reducing the number of mammalian cells infected with amastigotes. This is the first report of the anti-protozoal activity of C. intybus against trypanosomatid parasites and expands our understanding of the anti-parasitic effects of this plant and its bioactive metabolites. Further studies to elucidate the anti-protozoal compound(s) in C. intybus and their mode(s) of action will improve our knowledge of using this bioactive plant as a promising source of novel broad-spectrum anti-parasitic compounds with associated health benefits and biomedical potential.
KW - Anti-protozoal
KW - Chagas disease
KW - Cichorium intybus
KW - Metabolomics
KW - Sesquiterpene lactones
KW - Trypanosoma cruzi
U2 - 10.1016/j.ijpddr.2022.08.002
DO - 10.1016/j.ijpddr.2022.08.002
M3 - Journal article
C2 - 36037562
AN - SCOPUS:85136598910
VL - 20
SP - 43
EP - 53
JO - International Journal for Parasitology
JF - International Journal for Parasitology
SN - 0020-7519
ER -
ID: 319162876