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Flavonoid baicalein modulates H2O2-induced mitogen-activated protein kinases activation and cell death in SK-N-MC
Maryam Moslehi1, Azadeh Meshkini, Razieh Yazdanparast
1Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
Abstract:
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.
Insights
Flavonoid baicalein protects against oxidative stress and cell death in neurodegenerative disease models. It maintains glutathione levels and reduces harmful reactive oxygen species, showing potential for antioxidant therapies.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Oxidative stress from reactive oxygen species (ROS) is implicated in neurodegenerative diseases like Alzheimer's.
- Understanding molecular mechanisms is crucial for developing effective treatments for neurodegenerative disorders.
Purpose of the Study:
- To investigate the protective effects of the flavonoid baicalein against hydrogen peroxide (H2O2)-induced oxidative stress and cell death in SK-N-MC cells.
- To elucidate the molecular pathways involved in baicalein's neuroprotective action.
Main Methods:
- SK-N-MC cells were treated with H2O2 to induce oxidative stress.
- The effects of baicalein on cell viability, apoptosis-related proteins (Bax, Bcl-2, caspase-9), signaling pathways (ERK, JNK), glutathione (GSH) levels, and γ-glutamyl-cysteine synthetase (γ-GCS) expression were analyzed.
Main Results:
- H2O2 treatment decreased cell viability by activating ERK and JNK pathways, increasing the Bax/Bcl-2 ratio, and initiating apoptosis.
- H2O2 reduced GSH levels by down-regulating γ-GCS expression via JNK/ERK pathways.
- Baicalein protected cells by inhibiting JNK/ERK activation, blocking Bax and caspase-9, up-regulating Bcl-2, and maintaining GSH levels.
- Baicalein also reduced lipid peroxidation, protein peroxidation, and intracellular ROS.
Conclusions:
- Baicalein demonstrates significant neuroprotective effects against H2O2-induced oxidative stress and apoptosis in neuronal cells.
- Baicalein acts by modulating key apoptotic pathways and enhancing cellular antioxidant defense mechanisms, particularly GSH levels.
- Baicalein is a promising candidate for antioxidant therapy and the development of natural-based drugs for ROS-induced neurodegenerative disorders.
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