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.

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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