Ischemic stroke is a devastating disease with a complex pathophysiology.
Galangin is a natural
flavonoid isolated from the rhizome of Alpina officinarum Hance, which has been widely used as an
antioxidant agent. However, its effects against
ischemic stroke have not been reported and its related neuroprotective mechanism has not really been explored. In this study, neurological behavior,
cerebral infarct volumes and the improvement of the regional cortical blood flow (rCBF) were used to evaluate the
therapeutic effect of
galangin in rats impaired by
middle cerebral artery occlusion (MCAO)-induced focal
cerebral ischemia. Furthermore, the determination of mitochondrial function and Western blot of apoptosis-related
proteins were performed to interpret the neuroprotective mechanism of
galangin. The results showed that
galangin alleviated the neurologic impairments, reduced
cerebral infarct at 24 h after MCAO and exerted a protective effect on the mitochondria with decreased production of mitochondrial
reactive oxygen species (ROS). These effects were consistent with improvements in the membrane potential level (Dym), membrane fluidity, and degree of mitochondrial swelling in a dose-dependent manner. Moreover,
galangin significantly improved the reduced rCBF after MCAO. Western blot analysis revealed that
galangin also inhibited apoptosis in a dose-dependent manner concomitant with the up-regulation of Bcl-2 expression, down-regulation of Bax expression and the Bax/Bcl-2 ratio, a reduction in
cytochrome c release from the mitochondria to the cytosol, the reduced expression of activated
caspase-3 and the cleavage of
poly(ADP-ribose) polymerase (PARP). All these data in this study demonstrated that
galangin might have therapeutic potential for
ischemic stroke and play its protective role through the improvement in rCBF, mitochondrial protection and inhibiting
caspase-dependent mitochondrial cell death pathway for the first time.