It is believed that ROS-induced oxidative stress triggers numerous signaling pathways which are involved in neurodegenerative diseases including Alzheimer\'s disease (AD). In order to find the effective drugs for neurodegenerative diseases, the deep delve into molecular mechanisms underlies these diseases are necessary. In the current study, we investigated the effects of flavonoid baicalein on H₂O₂-induced oxidative stress and cell death in SK-N-MC cells. Our results revealed that treatment of SK-N-MC cells with H₂O₂ led to 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. Also, our results showed that exposure of SK-N-MC cells to H₂O₂, ended up in reduction of glutathione (GSH) levels of SK-N-MC cells via JNK/ERK-mediated down-regulation of γ-GCS expression. Our results demonstrated that flavonoid baicalein protected against H₂O₂-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. Also, 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.

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