The present study assessed whether
baicalein (5,6,7-trihydroxyflavone), a polyphenolic
antioxidant 12/
15-lipoxygenase inhibitor would attenuate oxidative cell death in vitro using a mouse hippocampal HT22 cell assay. Moreover, we determined if
baicalein would be useful to attenuate behavioral deficits associated with multiple
infarct ischemic events in vivo using a rabbit small clot
embolic stroke model (RSCEM). Using HT22 cell in vitro,
baicalein was shown to significantly promote cell survival with an estimated dose for 50% cell survival of 2 muM following incubation in the presence of
iodoacetic acid (20 muM), an irreversible inhibitor of the glycolytic pathway that results in the
free radical production, lipid peroxidation and cell death. Since
baicalein was neuroprotective and attenuated
iodoacetic acid (IAA) toxicity in vitro, we studied its effects in vivo in an
embolic stroke model using behavioral measures as the endpoint. Quantal analysis for each treatment in the
embolism model identifies the quantity of microclots (mg) that produce
neurologic dysfunction in 50% of a group of animals (P(50)), with intervention considered neuroprotective if it increases the P(50) compared with controls.
Baicalein (100 mg/kg, s.c.) injected 5 and 60 min post-embolization significantly (P<0.05) improved behavioral function. The calculated P(50) values were 2.85+/-0.64 mg (n=21) and 2.15+/-0.12 mg (n=14), respectively compared with 1.37+/-0.20 mg (n=23) for the control group. In conclusion, we have shown that
baicalein effectively attenuated cell death in vitro using HT22 cells and also significantly reduced behavioral deficits in rabbits when given up to 1 h following an
embolic stroke. The results suggest that
baicalein, or derivatives of
baicalein with multiple pharmacological activities may be useful to develop as novel treatments for
acute ischemic stroke.