It is believed that ROS-induced oxidative stress triggers numerous signaling pathways which are involved in
neurodegenerative diseases, including
Alzheimer's disease. To find the effective drugs for
neurodegenerative diseases, the deep delve into molecular mechanisms underlie these diseases is necessary. In the current study, we investigated the effects of
flavonoid baicalein on H(2)O(2)-induced oxidative stress and cell death in SK-N-MC cells. Our results revealed that the treatment of SK-N-MC cells with H(2)O(2) led to a decrease in cell viability through phosphorylation and activation of
extracellular signal-regulated kinases (ERKs) and c-Jun N-terminal
kinases (JNKs) pathways followed by increase in Bax/Bcl2 ratio and initiation of
caspase-dependent apoptotic pathways. In addition, our results showed that the exposure of SK-N-MC cells to H(2)O(2) ended up in reduction of
glutathione (GSH) levels of SK-N-MC cells via JNK/ERK-mediated down-regulation of γ-glutamyl-
cysteine synthetase (γ-GCS) expression. Our results demonstrated that
flavonoid baicalein protected against H(2)O(2)-induced cell death by inhibition of JNK/ERK pathways activation and other key molecules in apoptotic pathways, including blockage of Bax and
caspase-9 activation, induction of Bcl-2 expression and prevention of cell death.
Baicalein supported intracellular defense mechanisms through maintaining GSH levels in SK-N-MC cells by the removal of inhibition effects of JNK/ERK pathways from γ-GCS expression. In addition,
baicalein attenuated
lipid and
protein peroxidation and intracellular
reactive oxygen species in SK-N-MC cells. In accordance with these observations,
baicalein can be a promising candidate in
antioxidant therapy and designing of natural-based
drug for ROS-induced
neurodegenerative disorders.