Baifuzi reduces transient ischemic brain damage through an interaction with the STREX domain of BKCa channels

Abstract

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 Ca2+-activated K+ channel (BKCa) channels, and BKCa channel blockade suppressed the neuroprotection of the extract, suggesting that the BKCa is the molecular target of Baifuzi. Third, Baifuzi cerebroside (Baifuzi-CB), purified from its ethanol extract, activated BKCa channels in a manner similar to that of the extract. Fourth, the stress axis hormone-regulated exon (STREX) domain of the BKCa channel directly interacted with Baifuzi-CB, and its deletion suppressed channel activation by Baifuzi-CB. These results indicate that Baifuzi-CB activated the BKCa 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.

BK Channels in the Central Nervous System

“…Increased BK channel activity also mediates the neuroprotective effect of the traditional Chinese medicine Baifuzi and the antipsychotic chlorpromazine in rodent models of cerebral ischemia (Chi et al, 2010; Li, Zhang, et al, 2014), as well as the neuroprotective effect of resveratrol and estrogen receptor activators in hippocampal slices deprived from oxygen and glucose (Zhang et al, 2008, 2009). Interestingly, Baifuzi promotes BK channel activation via a direct interaction with the STREX insert of BK α, a domain that also mediates BK channel sensitivity to hypoxia (Chi et al, 2010; McCartney et al, 2005).…”

“…Interestingly, Baifuzi promotes BK channel activation via a direct interaction with the STREX insert of BK α, a domain that also mediates BK channel sensitivity to hypoxia (Chi et al, 2010; McCartney et al, 2005). BK channel activation also contributes to the neuroprotective effect of mitochondrial division inhibitor mdivi-1 in a model of spinal cord ischemia–reperfusion injury (Liu et al, 2015).…”

Ethanol but not Aqueous Extracts of Tubers of Sauromatum Giganteum(Engl.) Cusimano and Hett Inhibit Cancer Cell Proliferation

“…) Cusimano and Hett, a synonym is Typhonium giganteum Engl., the dried root tuber of which is named Baifuzi in Chinese and recorded in Chinese pharmacopoeia as a traditional Chinese medicine (Gao et al, 2007;Chi et al, 2010). It has the effect of "dispelling wind-phelgm" and has been used for the folklore treatment of cancer for a long time in Northeast of China.…”

BKCachannel is a molecular target of vitamin C to protect against ischemic brain stroke

“…Details on the number of the rats in each experiment were shown in the corresponding figures. The transient middle cerebral artery occlusion (MCAO) was induced by using intraluminal filament insertion technique as previously described (Chi et al, 2010). Briefly, the filament thread (with a blunt tip of 0.36 ± 0.02 mm in diameter, type 2636-A3, Beijing Cinontech, China) was inserted through the left common carotid artery and advanced into the internal carotid artery to occlude the origin of the middle cerebral artery (approximately 18-20 mm) for 24 hours.…”