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Planta Med 2020; 86(02): 121-131
DOI: 10.1055/a-1023-8918
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Centaurium Erythraea Extracts Exert Vascular Effects through Endothelium- and Fibroblast-dependent Pathways

Alae Chda
1   Laboratory Bioactives Molecules, Faculty of Sciences and Techniques, University Sidi Mohamed Ben Abdellah, Fes, Morocco
2   Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
,
Mohamed El Kabbaoui
1   Laboratory Bioactives Molecules, Faculty of Sciences and Techniques, University Sidi Mohamed Ben Abdellah, Fes, Morocco
,
Paula Fresco
2   Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
,
Dany Silva
2   Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
,
Jorge Gonçalves
2   Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
3   I₃ S Institute for Research and Innovation in Health Sciences, University of Porto, Porto, Portugal
,
Andreia P. Oliveira
4   REQUIMTE/LAQV, Laboratory of Pharmacognosy, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
,
Paula B. Andrade
4   REQUIMTE/LAQV, Laboratory of Pharmacognosy, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
,
Patrícia Valentão
4   REQUIMTE/LAQV, Laboratory of Pharmacognosy, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
,
Abdelali Tazi
1   Laboratory Bioactives Molecules, Faculty of Sciences and Techniques, University Sidi Mohamed Ben Abdellah, Fes, Morocco
,
Kaouakib El Abida
1   Laboratory Bioactives Molecules, Faculty of Sciences and Techniques, University Sidi Mohamed Ben Abdellah, Fes, Morocco
,
Rachid Bencheikh
1   Laboratory Bioactives Molecules, Faculty of Sciences and Techniques, University Sidi Mohamed Ben Abdellah, Fes, Morocco
› Institutsangaben Acknowledgements: We are grateful to Professor Amina Bari (Department of Biology, FSDM, University sidi Mohamed Ben Abdellah, Fez, Maroc) for botanical identification, to M. Céu Pereira (Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Portugal) for technical support, and to Professor Paulo Correia-de-Sá (Laboratory of Pharmacology, ICBAS, University of Porto, Portugal) for the generous gift of fibroblast cells. AC received a scholarship from Erasmus+ International Credit Mobility – MARE NOSTRUM Consortium to support his stay, as a visiting Ph.D. student, in Porto, Portugal. This work was supported by UID/QUI/50006/2019 with funding from FCT/MCTES through national funds, by Programa de Cooperación Interreg V-A España – Portugal (POCTEP) 2014 – 2020 (project 0377_IBERPHENOL_6_E), and by REQUIMTE through the APO research contract (DL57/2016/CP1346/CT0015).
Weitere Informationen

Publikationsverlauf

received 28. Mai 2019
revised 30. September 2019

accepted 03. Oktober 2019

Publikationsdatum:
23. Oktober 2019 (online)

   Lizenzen und Reprints

Abstract

Centaurium erythraea is a plant used in traditional medicine for several cardiovascular disorders, namely hypertension, but there is no scientific evidence able to provide a molecular basis for its claimed antihypertensive effects. After a preliminary screen of extracts obtained from sequential extraction of C. erythraea aerial parts, effects of the methanolic fraction (MFCE) on changes in perfusion pressure of isolated rat mesenteric vascular bed (MVB) and in rat cardiac fibroblasts proliferation were investigated, gathering information on the mechanisms involved in endothelium-dependent effects and their dependence on a pro-proliferative stimulus. The HPLC-DAD determination of the phenolics content of MFCE revealed the presence of 22 phenolic compounds. MFCE reduced (63.3 ± 3.9%; n = 4) perfusion pressure in MVB and almost completely abrogated the Ang II-induced increase in cardiac fibroblasts proliferation. Reduction of the perfusion pressure caused by MFCE was endothelium-dependent and occurred in parallel with an increase in NO release. These effects were inhibited by muscarinic receptor antagonists, by L-NAME (a NO synthase inhibitor), and by ODQ (a soluble guanylate cyclase inhibitor). Experiments revealed that effects required the involvement of K+ channels, being inhibited by tetraethylamonium (TEA; a Ca2+ activated K+ channels inhibitor) and by glibenclamide (an ATP-sensitive K+ channels inhibitor). In conclusion, extracts from C. erythraea, particularly the compounds present in the MFCE, induce endothelium-dependent vasodilation and prevent fibroblast proliferation induced by angiotensin II, which can account for the claimed antihypertensive effects of C. erythraea in traditional medicine.

Key words

Centaurium erythraea - Gentianaceae - hypertension - endothelium-dependent relaxation - cholinomimetic effects - K⁺ channel mediated hyperpolarization - fibroblast proliferation - phenolic composition

Supporting Information

    Additional evidence for involvement of muscarinic receptors and NO release on the effects of MFCE was gathered by investigating the effects of MFCE on isolated rat ileum contractions and on NO release in breast cancer MCF-7 cells, using DAF-FM DA, a highly sensitive and selective fluorescent NO probe.

  • Supporting Information
 

  • References

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