Vasorelaxant effects of cardamonin and alpinetin from Alpinia henryi K. Schum.

The vascular effects of cardamonin and alpinetin from Alpinia henryi K. Schum. were examined in the rat isolated mesenteric arteries. ¹H and ¹³C nuclear magnetic resonance spectra showed that cardamonin is present in trans-form, and single-crystal radiographic structure revealed that alpinetin is present in S configuration. Both cardamonin and alpinetin produced a rightward shift in the concentration-response curve for phenylephrine in a noncompetitive manner, and they induced relaxation of phenylephrine-preconstricted arteries with respective mean inhibitory concentrations (IC₅₀) of 9.3 ± 0.6 μM and 27.5 ± 2.8 μM. Both compounds also relaxed arteries preconstricted by endothelin I or U46619. Their relaxant effects were decreased in endothelium-removed rings. Pretreatment with N^G-nitro-L-arginine methyl ester or methylene blue inhibited relaxation induced by both agents, and pretreatment with L-arginine reversed the effect of N^G-nitro-L-arginine methyl ester on cardamonin-induced endothelium-dependent relaxation. The relaxant effects of cardamonin and alpinetin were unaffected by indomethacin (3 μM). Cardamonin and alpinetin inhibited 60 mM K⁺-induced contraction with respective IC⁵⁰ of 11.5 ± 0.3 μM and 37.9 ± 3.6 μM. In addition, both agents inhibited the transient contraction induced by 3 μM phenylephrine or by 10 mM caffeine in Ca²⁺-free Krebs solution. Finally, these two agents also concentration dependently relax the arteries preconstricted by 1 μM phorbol 12,13-diacetate in Ca²⁺-free Krebs solution. These results indicate that purified cardamonin and alpinetin from A. henryi K. Schum. relaxed rat mesenteric arteries through multiple mechanisms. They induced both endothelium-dependent and -independent relaxation; the former is likely mediated by nitric oxide whereas the latter is probably mediated through nonselective inhibition of Ca²⁺ influx and intracellular Ca²⁺ release and inhibition of the protein kinase C-dependent contractile mechanism.