Structure-activity relationships of flavonoids for vascular relaxation in porcine coronary artery.

Flavonoids are polyphenolic compounds that are widespread in the plant kingdom, and structure-activity relationships (SAR) for vascular relaxation effects were examined for 17 of them using porcine coronary arteries. Density functional theory was employed to calculate the chemical parameters of these compounds. The order of potency for vascular relaxation was as follows: flavones (apigenin and luteolin) >or= flavonols (kaempferol and quercetin)>isoflavones (genistein and daidzein)>flavanon(ol)es (naringenin)>chalcones (phloretin)>anthocyanidins (pelargonidin)>flavan(ol)es ((+)-catechin and (-)-epicatechin). SAR analysis revealed that for good relaxation activity, the 5-OH, 7-OH, 4'-OH, C2=C3 and C4=O functionalities were essential. Comparison of rutin with quercetin, genistin with genistein, and puerarin with daidzein demonstrated that the presence of a glycosylation group greatly reduced relaxation effect. Total energy and molecular volume were also predictive of their relaxation activities. Our findings indicated that the most effective relaxing agents are apigenin, luteolin, kaempferol and genistein. These flavonoids possess the key chemical structures demonstrated in our SAR analysis.

Kaempferol enhances endothelium-independent and dependent relaxation in the porcine coronary artery.

The vascular effects of kaempferol were investigated in isolated porcine coronary artery rings. U46619 (9,11-dideoxy-9alpha, 11alpha-methanoepoxy prostaglandin F2alpha, 30 nM) was used to contract porcine coronary arterial rings. Concentration relaxation curve of kaempferol (1 nM - 100 microM) was constructed and kaempferol demonstrated significant relaxation at high concentrations. At low concentration with no significant effect on relaxation, kaempferol (10 microM) enhanced relaxation produced by bradykinin, the calcium ionophore A23187, isoproterenol and sodium nitroprusside in endothelium-intact porcine coronary arteries. In endothelium-disrupt rings, kaempferol (10 microM) also enhanced the relaxation caused by isoproterenol, sodium nitroprusside, levcromakalim and nifedipine. On the other hand, antioxidant agents did not affect bradykinin-induced relaxation or the enhancement effect of kaempferol. In summary, a low concentration of kaempferol (10 microM), devoid of significant vascular effect, has the ability to enhance endothelium-dependent and endothelium-independent relaxations. This action of kaempferol is unrelated to its antioxidant property.