The main active components of saffron are crocin, crocetin, picrocrocin, and safranal. There are many studies on their cardioprotective effects, but their cardiotoxicities have not been reported. The human ether-a-go-go-related gene (hERG) K+ channels are of considerable pharmaceutical interest as the target responsible for acquired long QT syndromes. The aim of this study is to explore the effects of crocin, crocetin, picrocrocin, and safranal on the K+ channels encoded by hERG. The interaction of these components with the rapid delayed rectification of K+ currents (I-Kr) were studied using the perforated patch recording technique. Crocin and picrocrocin had no significant effects on I-Kr, but crocetin and safranal inhibited hERG K+ currents in a concentration-dependent manner, with IC50 values of 36.35 mu M and 37.86 mu M, respectively. The maximum inhibitory effects were 37.74 +/- 4.14% and 33.74 +/- 4.81%, respectively, and the effects were reversible upon washout. The results demonstrate that crocetin and safranal significantly inhibit hERG K+ current, but crocin and picrocrocin do not. This suggests that crocetin and safranal may increase the risk of cardiac arrhythmias by inhibiting I-Kr.