Hyperforin, a lipophilic constituent of medicinal herb St John's wort, has been identified as the main active ingredient of St John's wort extract for
antidepressant action by experimental and clinical studies.
Hyperforin is currently known to activate transient receptor potential canonical (subtype) 6 (
TRPC6) channel, increase the phosphorylated CREB (p-CREB), and has
N-methyl-D-aspartate receptor-antagonistic effect that convert potential
neuroprotective effects in vitro. However, the protective effects of
hyperforin on
ischemic stroke in vivo remain controversial and its neuroprotective mechanisms are still unclear. This study was designed to examine the effects of intracerebroventricular (i.c.v.) injection of
hyperforin on transient focal
cerebral ischemia in rats.
Hyperforin, when applied immediately after
middle cerebral artery occlusion (MCAO) onset, significantly reduced
infarct volumes and apoptotic cells, and also increased neurologic scores at 24 hours after reperfusion accompanied by elevated
TRPC6 and p-CREB activity and decreased SBDP145 activity. When
MEK or CaMKIV activity was specifically inhibited, the
neuroprotective effect of
hyperforin was attenuated, and we observed a correlated decrease in CREB activity. In conclusion, our results clearly showed that i.c.v. injection of
hyperforin immediately after MCAO onset blocked
calpain-mediated
TRPC6 channels degradation, and then to stimulate the Ras/
MEK/ERK and CaMKIV pathways that converge on CREB activation, contributed to neuroprotection.