Abstract
The sesquiterpene zerumbone, isolated from the rhizome of Zingiber zerumbet Sm., besides its widespread use as a food flavouring and appetiser, is also recommended
in traditional medicine for the treatment of several ailments. It has attracted great
attention recently for its effective chemopreventive and therapeutic effects observed
in various models of cancer. To assess the zerumbone safety profile, a pharmacology
study designed to flag any potential adverse effect on vasculature was performed.
Zerumbone was tested for vasorelaxing activity on rat aorta rings and for L-type Ba2+ current blocking activity on single myocytes isolated from the rat-tail artery. The
spasmolytic effect of zerumbone was more marked on rings stimulated with 60 mM than
with 30 mM K+ (IC50 values of 16 µM and 102 µM, respectively). In the presence of 60 mM K+, zerumbone concentration-dependently inhibited the contraction induced by the cumulative
additions of Ca2+, this inhibition being inversely related to the Ca2+ concentration. Phenylephrine-induced contraction was inhibited by the drug, though
less efficiently and independently of the presence of an intact endothelium, without
affecting Ca2+ release from the intracellular stores. Zerumbone inhibited the L-type Ba2+ current (estimated IC50 value of 458.7 µM) and accelerated the kinetics of current decay. In conclusion,
zerumbone showed an overall weak in vitro vasodilating activity, partly attributable to the blocking of the L-type Ca2+ channel, which does not seem to represent, however, a serious threat to its widespread
use.
Key words
Zingiber zerumbet
- Zingiberaceae - zerumbone - L-type Ca
2+ channel - whole-cell patch-clamp - vascular smooth muscle
