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 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 vasorelaxation potential and to characterize the signaling pathways in relation to ERα signaling and NO involvement. The evaluation of vasorelaxation potential was performed by myography on wild-type (WT) and ERα knock-out (ERα-KO) mice aorta in the presence or in absence of the eNOS inhibitor Nω-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 ERα-dependent and NO-independent or ERα-independent and NO-dependent. Thus some structure-activity relationships (SAR) were discussed for an optimized vasorelaxant effect.

Exploration of Lamiaceae in Cardio Vascular Diseases and Functional Foods: Medicine as Food and Food as Medicine

“…Vasorelaxants are drugs that can cause dilation of blood vessels that ensure the flow of blood through the vessels at ease—most of these cause relaxation of vascular smooth muscles—the most common method of treatment used for hypertension ( Herradón et al, 2007 ). It has been reported that plant-based compounds like chalcones inhibit angiotensin-converting exam (ACE) through nitric oxide (NO)- and estrogen receptor α (ERα)-dependent pathways to bring about vasorelaxation and lower the risk of CVDs ( Legeay et al, 2020 ). Agastache mexicana (Kunth.)…”