Structural requirements of flavonoids for increment of ocular blood flow in the rabbit and retinal function recovery in rat eyes.

Abstract

We have recently reported that the effect of a flavonoid on ocular blood flow depends upon the number of hydroxy (OH) groups in its backbone structure. To elucidate the structural features on the number and type of functional groups present in the flavonoid molecule plus the number of OH groups, flavonoids with four to five OH groups, with or without methoxy groups, were studied on their effects to affect the ocular blood flow and the retinal function recovery. A colored microsphere technique was used to determine the ocular blood flow in albino rabbit eyes and electroretinography was used to measure the retinal function recovery. Flavonols with four free OH groups produced no effects on the ocular blood flow (fisetin, kaempferol), whereas flavanone and flavones with four free OH groups and without the C2-C3 double bond produced the rapid increment on ocular blood flow (dihydrofisetin and luteolin, respectively). Similarly, flavonols with five free OH groups produced no effects on the ocular blood flow (morin, quercetin). Yet, flavanone with five free OH groups and without the C2-C3 double bond produced the rapid increment on ocular blood flow (dihydroquercetin). Flavanols with five free OH groups and without the C2-C3 double bond and the carbonyl group produced no effects on the ocular blood flow (catechin). Flavonols with four free OH groups and a methoxy group on the 7 position produced no effects on the ocular blood flow (Rhamnetin). Flavonols with four free OH groups and a methoxy group at the 5 (5-methylquercetin) or 3' position (isorhamnetin) produced positive effects on the ocular blood flow also. Flavonol with five methoxy groups but no OH group produced positive effects on the ocular blood flow (pentamethylquercetin). Flavonols with an excessive number of OH groups, having both a catechol-like structure in the C ring and a catechol at the B ring, produced no effect on the ocular blood flow (rhamnetin, quercetin). Parallel results were obtained on retinal function recovery after ischemic insult. The presence of OH groups at certain positions and the double bond at C2-C3 in the flavonoid molecules, which produces lipophilic action, can affect the increment on ocular blood flow and retinal function recovery. O-methylation can increase ocular blood flow and retinal function recovery as well.