Flavonoid metabolite 3-(3-hydroxyphenyl)propionic acid formed by human microflora decreases arterial blood pressure in rats

Scope: A number of studies have suggested that higher flavonoid intake is associated with lower cardiovascular mortality. The direct vasodilatory potential of flavonoids is one proposed mechanism for this link. However, the bioavailability of flavonoid aglycones is low. The metabolites of flavonoids could therefore explain/contribute to the effect. Methods and results: We tested a series of quercetin metabolites formed by both human enzymes and colon microflora. In vitro, a number of these metabolites resulted in vasodilation of isolated rat aortic rings, precontracted with norepinephrine. However, 3-(3-hydroxyphenyl)propionic acid (3HPPA) was clearly the most potent with an effect of about one order better than quercetin or its close methylderivatives isorhamnetin and tamarixetin. In contrast, quercetin-3-O-glucuronide was void of any effect. The vasodilatory activity of 3HPPA was confirmed by in vivo experiments on both normotensive and spontaneously hypertensive rats. Subsequent experiments showed that the arterial blood pressure decrease found after 3HPPA was associated with the peripheral action of the compound on vascular beds and was NO-based. Conclusion: This is the first study showing that a metabolite of flavonoids formed by human microflora has haemodynamic effects.