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Novel Insights into the Mode of Action of Vasorelaxant Synthetic Polyoxygenated Chalcones.

ABSTRACT: Polyphenols consumption has been associated with a lower risk of cardiovascular diseases (CVDs) notably through nitric oxide (NO)- and estrogen receptor ? (ER?)-dependent pathways. Among polyphenolic compounds, chalcones have been suggested to prevent endothelial dysfunction and hypertension. However, the involvement of both the NO and the ER? pathways for the beneficial vascular effects of chalcones has never been demonstrated. In this study, we aimed to identify chalcones with high vasorelaxation potential and to characterize the signaling pathways in relation to ER? signaling and NO involvement. The evaluation of vasorelaxation potential was performed by myography on wild-type (WT) and ER? knock-out (ER?-KO) mice aorta in the presence or in absence of the eNOS inhibitor N?-nitro-L-arginine methyl ester (L-NAME). Among the set of chalcones that were synthesized, four (3, 8, 13 and 15) exhibited a strong vasorelaxant effect (more than 80% vasorelaxation) while five compounds (6, 10, 11, 16, 17) have shown a 60% relief of the pre-contraction and four compounds (12, 14, 18, 20) led to a lower vasorelaxation. We were able to demonstrate that the vasorelaxant effect of two highly active chalcones was either ER?-dependent and NO-independent or ER?-independent and NO-dependent. Thus some structure-activity relationships (SAR) were discussed for an optimized vasorelaxant effect.

SUBMITTER: Legeay S

PROVIDER: S-EPMC7084244 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Novel Insights into the Mode of Action of Vasorelaxant Synthetic Polyoxygenated Chalcones.

Legeay Samuel S Trân Kien K Abatuci Yannick Y Faure Sébastien S Helesbeux Jean-Jacques JJ

International journal of molecular sciences 20200226 5

Polyphenols consumption has been associated with a lower risk of cardiovascular diseases (CVDs) notably through nitric oxide (NO)- and estrogen receptor α (ERα)-dependent pathways. Among polyphenolic compounds, chalcones have been suggested to prevent endothelial dysfunction and hypertension. However, the involvement of both the NO and the ERα pathways for the beneficial vascular effects of chalcones has never been demonstrated. In this study, we aimed to identify chalcones with high vasorelaxat ...[more]

PMID: 32111098

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Novel Insights into the Mode of Action of Vasorelaxant Synthetic Polyoxygenated Chalcones.

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Novel Insights into the Mode of Action of Vasorelaxant Synthetic Polyoxygenated Chalcones.

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