Relaxation to Flavones and Flavonols in Rat Isolated Thoracic Aorta: Mechanism of Action and Structure-Activity Relationships

Abstract

The mechanism of the relaxant action and the structure-activity relation of flavonols (fisetin, quercetin, and 3,3',4'-trihydroxyflavone) and flavones (apigenin, chrysin, and luteolin) were examined in rat isolated thoracic aorta. The control responses to flavonols and flavones were compared with responses observed after the removal of the endothelium or in the presence of the L-type Ca2+ channel blocker, nifedipine (10(-7) M). The effects of flavonoids on contraction caused by the influx of extracellular Ca2+ and agonist-induced release of intracellular Ca2+ also were investigated. The flavones exhibited endothelium-independent vasorelaxation, whereas the removal of the endothelium significantly decreased the sensitivity of the relaxant responses to the flavonols without affecting the maximal relaxation. In the presence of nifedipine, the responses to apigenin, luteolin, and quercetin were significantly inhibited, but relaxation to chrysin, fisetin, and 3,3',4'-trihydroxyflavone was unaffected. All flavonols and flavones caused concentration-dependent inhibition of the contractile responses to exogenous application of Ca2+ and the release of intracellular Ca2+ stimulated by phenylephrine. Of the six flavonoids examined, 3,3',4'-trihydroxyflavone was the most potent when causing vasorelaxation or inhibition of contraction caused by the influx or release of Ca2+. In conclusion, these studies provide evidence that the hydroxyl substitution in the carbon 3 position that characterizes the flavonols is important in stimulating endothelium-dependent vasorelaxation, and the absence of hydroxyl substitution on the A phenolic ring enhances the relaxant action.

ALPHA ANTIADRENERGIC EFFECT OF Achyrocline bogotensis EXTRACT (“Vira Vira”) IN ISOLATED RAT AORTIC RING

“…This flavone could also play a pivotal role in the smooth muscle relaxant effects of A. bogotensis. It fulfills the criteria proposed for displaying relaxant effects according to structure-activity relationships studied for flavonoid compounds, particularly due to hydroxyl substitution of the B phenolic ring and the absence of these substitutions on the A phenolic ring (29,30). This conformation would belong to the group of flavone compounds with the 2-phenyl-1,4-benzopyrone backbone.…”

Flavone Attenuates Vascular Contractions by Inhibiting RhoA/Rho Kinase Pathway

“…In many studies, the relaxant actions of the flavonoids involve other mechanisms, including the inhibition of Ca 2＋ release from intracellular stores (Ko et al, 1991;Chan et al, 2000). 17β-Estradiol also inhibits vascular contractions in a Ca 2＋ -dependent manner (Lee et al, 2005) whereas flavone inhibits vascular contractions, even in the absence of Ca 2＋ (Ajay et al, 2003).…”

Antibacterial and Antifungal Evaluation of Chloroflavones

“…They are found in fruits, vegetables, nuts, seeds and flowers as well as in teas and wines and are important constituent of human diet [3]. These products have been demonstrated to possess many biological and pharmacological activities such as antioxidant [4], anti-inflammatory [5], antimutagenic, antiallergic activities, and inhibitory activities on several enzymes [6,7]. Synthesis of these compounds has attracted considerable attention for their significant biocidal [8] and pharmaceutical [9,10] effects.…”