Characterisation of marrubenol, a diterpene extracted from Marrubium vulgare, as an L-type calcium channel blocker

1 The objective of the present study was to investigate the mechanism of the relaxant activity of marrubenol, a diterpenoid extracted from Marrubium vulgare. In rat aorta, marrubenol was a more potent inhibitor of the contraction evoked by 100 mM KCl (IC50: 11.8+/-0.3 muM, maximum relaxation: 93 +/- 0.6%) than of the contraction evoked by noradrenaline (maximum relaxation: 30 +/- 1.5%). 2 In fura-2-loaded aorta, marrubenol simultaneously inhibited the Ca2+ signal and the contraction evoked by 100 rum KCl, and decreased the quenching rate of fura-2 fluorescence by Mn2+. 3 Patch-clamp data obtained in aortic smooth muscle cells (A7r5) indicated that marrubenol inhibited Ba2+ inward current in a voltage-dependent manner (K-D: 8+/-2 and 40+/-6 muM at holding potentials of -50 and -100 mV, respectively). 4 These results showed that marrubenol inhibits smooth muscle contraction by blocking L-type calcium channels.