| Autor: |
Giménez-Bastida JA; Laboratory of Food & Health, Research Group on Quality, Safety and Bioactivity of Plant Foods, CEBAS-CSIC, Murcia, Spain. jgbastida@cebas.csic.es., Ávila-Gálvez MÁ; Laboratory of Food & Health, Research Group on Quality, Safety and Bioactivity of Plant Foods, CEBAS-CSIC, Murcia, Spain. jgbastida@cebas.csic.es.; NOVA Medical School|Faculdade de Ciências Médicas, NMS|FCM, Universidade NOVA de Lisboa, Lisboa, Portugal., Martínez-López A; Center for Biomedical Research in Rare Diseases Network (CIBERER), Carlos III Health Institute, 28029, Madrid, Spain.; Biomedical Research Institute of Murcia (IMIB)-Pascual Parrilla, 30120, Murcia, Spain., García-Moreno D; Center for Biomedical Research in Rare Diseases Network (CIBERER), Carlos III Health Institute, 28029, Madrid, Spain.; Biomedical Research Institute of Murcia (IMIB)-Pascual Parrilla, 30120, Murcia, Spain., Espín JC; Laboratory of Food & Health, Research Group on Quality, Safety and Bioactivity of Plant Foods, CEBAS-CSIC, Murcia, Spain. jgbastida@cebas.csic.es., González-Sarrías A; Laboratory of Food & Health, Research Group on Quality, Safety and Bioactivity of Plant Foods, CEBAS-CSIC, Murcia, Spain. jgbastida@cebas.csic.es. |
| Abstrakt: |
Current knowledge indicates that the consumption of isoflavone-rich foodstuffs can have a beneficial impact on cardiovascular health. To what extent these isoflavones act as the main actors of that benefit is less clear. Genistein (GEN), daidzein (DAZ), and the DAZ-derived microbial metabolite equol (Eq) exhibit antiangiogenic effects in vitro , but their low bloodstream concentrations make it difficult to rationalize the in vivo effects. Their derived phase-II metabolites (glucuronides and sulfates) are major metabolites found in plasma, but their role as antiangiogenic molecules remains unexplored. We aimed here to first assess the anti-angiogenic activities of the main circulating isoflavone metabolites (glucuronides and sulfates) and compare them with their corresponding free forms at physiological concentrations (0.1-10 μM). The effects of the conjugated vs. free forms on tubulogenesis, cell migration, and VEGF-induced signalling were investigated in primary human aortic endothelial cells (HAECs). While ( R , S )-equol 7-β-D-glucuronide (Eq 7-glur) exerted dose-dependent inhibition of tubulogenesis and endothelial migration comparable to that exerted by the free forms (GEN, DAZ, and Eq), the rest of the phase-II conjugates exhibited no significant effects. The underlying molecular mechanisms were independent of the bFGF but related to the modulation of the VEGF pathway. Besides, the observed dissimilar cellular metabolism (conjugation/deconjugation) places the phase-II metabolites as precursors of the free forms; however, the question of whether this metabolism impacts their biological activity requires additional studies. These new insights suggest that isoflavones and their circulating metabolites, including Eq 7-glur, may be involved in cardiovascular health ( e.g. , targeting angiogenesis). |
