Baifuzi reduces transient ischemic brain damage through an interaction with the STREX domain of BK(Ca) channels

Stroke is a long-term disability and one of the leading causes of death. However, no successful therapeutic intervention is available for the majority of stroke patients. In this study, we explored a traditional Chinese medicine Baifuzi (Typhonium giganteum Engl.). We show, at first, that the ethanol extract of Baifuzi exerts neuroprotective effects against brain damage induced by transient global or focal cerebral ischemia in rats and mice. Second, the extract activated large-conductance Ca(2+)-activated K(+) channel (BK(Ca)) channels, and BK(Ca) channel blockade suppressed the neuroprotection of the extract, suggesting that the BK(Ca) is the molecular target of Baifuzi. Third, Baifuzi cerebroside (Baifuzi-CB), purified from its ethanol extract, activated BK(Ca) channels in a manner similar to that of the extract. Fourth, the stress axis hormone-regulated exon (STREX) domain of the BK(Ca) channel directly interacted with Baifuzi-CB, and its deletion suppressed channel activation by Baifuzi-CB. These results indicate that Baifuzi-CB activated the BK(Ca) channel through its direct interaction with the STREX domain of the channel and suggests that Baifuzi-CB merits exploration as a potential therapeutic agent for treating brain ischemia.