Hyperforin, the main active ingredient of the medicinal plant Hypericum perforatum, has been shown to be neuroprotective against
acute ischemic stroke. However, the long-term actions of
hyperforin on the post-
stroke functional recovery and underlying mechanisms have not been investigated. C57BL/6 wild-type mice or
interleukin (IL)-17A knock-out mice underwent
middle cerebral artery occlusion (60min) followed by reperfusion for 28 days. Here, we found that
delayed treatment with
hyperforin significantly promoted functional recovery and increased
IL-17A expression in the ischemic hemisphere at 28 days post-
ischemia (dpi).
IL-17A knock-out or anti-IL-17A
monoclonal antibody (mAb) treatment significantly attenuated the promoting effects of
hyperforin on functional recovery. After screening for
neurotrophic factors, we revealed that blocking
IL-17A significantly decreased, whereas recombinant mouse
IL-17A (rIL-17A) treatment significantly increased
vascular endothelial growth factor (
VEGF) expression. Our data also showed that rIL-17A treatment significantly increased CD34 expression and promoted functional recovery at 28dpi, and the promoting effects were attenuated by
VEGF neutralizing antibody treatment. Furthermore,
hyperforin treatment significantly increased the expression of
VEGF and CD34 in the ischemic hemisphere at 28dpi, and the effects were attenuated by blocking
IL-17A. Furthermore,
VEGF neutralizing antibody significantly attenuated the promoting role of
hyperforin on the cerebral CD34 expression. Thus, our results suggest that, in addition to the acute neuroprotection when delivered immediately after
ischemic stroke,
hyperforin could also promote functional recovery when delivered in the later phases of
stroke recovery. Our results also reveal a previously uncharacterized property of IL-17A/
VEGF signaling-induced angiogenesis in
hyperforin-mediated functional recovery.