Rolipram has high (PDE4
H) and low (PDE4
L) affinities for phosphodiesterase (PDE)-4, respectively. In general, it is believed that inhibitions by PDE4
H and PDE4
L are respectively associated with an adverse response and with anti-inflammatory and bronchodilating effects. This has provided a rational basis for designing new compounds with high PDE4
H/PDE4
L ratios. In the present study, we attempted to determine the PDE4
H/PDE4
L ratios of quercetin (
1), qercetin-3-
O-methylether (3-MQ,
2), quercetin-3,7,4′-
O-trimethylether (ayanin,
3), quercetin-3,7,3′,4′-
O- tetramethylether (QTME,
4), quercetin-3,5,7,3′,4′-
O-petamethylether (QPME,
5), quercetin-3,5,7,3′,4′-
O-pentaacetate (QPA,
6), and quercetin-3-
O-methyl-5,7,3′,4′-
O-tetraacetate (QMTA,
7). The activities of PDE1∼5, which were partially separated from homogenates of guinea pig lungs and hearts, were measured by a two-step procedure using adenosine 3',5'-cyclic monophosphate (cAMP) with [
3
H]-cAMP or guanosine 3',5'-cyclic monophosphate (cGMP) with [
3
H]-cGMP as substrates. The IC
50 values of all of these compounds except quercetin (
1), 3-MQ (
2), and QMTA (
7) on PDE1∼5 inhibition were determined. The anti-inflammatory effects of PDE4 inhibitors were reported to be associated with inhibition of PDE4 catalytic activity. Therefore, these IC
50 values for PDE4 inhibition were taken as the PDE4
L values. The effective concentration (EC
50), at which one half of the [
3
H]-rolipram bound to high-affinity rolipram binding sites (HARBSs) of brain cell membranes was replaced, was defined as the PDE4
H value. In the present results, the PDE4
H/PDE4
L ratios of quercetin (
1), ayanin (
3), and QPME (
5) were >30, >19, and 11, respectively (Table
1), which are higher than or equal to that of AWD12-281, the selective PDE4 inhibitor with the greatest potential currently undergoing clinical trials for treating asthma and chronic obstructive pulmonary disease.