Recently, the treatment of
stroke has focused on
antioxidant therapies, where oxidative stress is implicated. The preventive and therapeutic potential of plant compounds on
ischemic stroke has been intensively studied because many of them contain
antioxidant properties.
Genistein, one of the active ingredients in soybean, possesses many bioactivities. In this study, we investigated the potential
neuroprotective effects of
genistein and its possible mechanism of action in a
cerebral ischemia mouse model. Mice were pretreated with
genistein (2.5, 5, and 10mg/kg) or vehicle orally once daily for 14 consecutive days before transient
middle cerebral artery occlusion was performed.
Genistein at doses of 2.5-10mg/kg significantly reduced the
infarct volume, improved the neurological deficit and prevented cell apoptosis after
ischemia. In addition,
genistein pretreatment was shown to inhibit the
ischemia-induced
reactive oxygen species (ROS) production, enhance the activities of
antioxidant enzymes superoxide dismutase (SOD) and
glutathione peroxidase (GPx), and decrease levels of
malondialdehyde (MDA) in
stroke mice. Moreover,
genistein reversed the
mitochondria dysfunction after
ischemia, as evidenced by decreasing mitochondria ROS levels, preventing
cytochrome C release to the cytoplasm and inhibiting
caspase-3 activation. Western blotting showed
ischemia activated the ROS-dependent nuclear factor-κB (NF-κB) signaling pathway, and
genistein suppressed phosphorylation and activation of the NF-κB p65 subunit, as well as the phosphorylation and degradation of the inhibitor
protein of κBα (IκBα). Our findings suggested that
genistein has a
neuroprotective effect in transient focal
ischemia, which may involve regulation of mitochondria-dependent apoptosis pathways and suppression of ROS-induced NF-κB activation.