Vasorelaxant effect of new neo-clerodane diterpenoids isolated from Croton schiedeanus.

The vasorelaxant effect of two new neo-clerodane diterpenoids, (12R)-12-hydroxycascarillone and 5beta-hydroxy-cis-dehydrocrotonin, in addition to the known cis-dehydrocrotonin and trans-dehydrocrotonin, all them previously isolated by us from Croton schiedeanus Schlecht, was studied in isolated aorta rings contracted by high K+ (80 mM) or phenylephrine (1 microM). According to their IC50 values to KCl induced contraction, the potency order was (12R)-12-hydroxycascarillone > cis-dehydrocrotonin > 5beta-hydroxy-cis-dehydrocrotonin > trans-dehydrocrotonin (0.3, 1.5, 96 and >100 mM, respectively). The possible cooperativity between diterpenoid compounds and the predominant flavonoid (ayanin) was studied. The vasorelaxant activity of cis-dehydrocrotonin and ayanin was increased when both compounds were incorporated simultaneously to the aortic rings precontracted with phenylephrine. These results suggest that Croton schiedeanus induces its effects via the synergistic actions of several vasodilator substances, among which neo-clerodane diterpenoids play an important role.