2. Academic Validation
  3. Neuroprotection against 6-OHDA-induced oxidative stress and apoptosis in SH-SY5Y cells by 5,7-Dihydroxychromone: Activation of the Nrf2/ARE pathway

Neuroprotection against 6-OHDA-induced oxidative stress and apoptosis in SH-SY5Y cells by 5,7-Dihydroxychromone: Activation of the Nrf2/ARE pathway

  • Life Sci. 2015 Jun 1;130:25-30. doi: 10.1016/j.lfs.2015.02.026.
Dong-Woo Kim 1,  Kyoung-Tae Lee 2,  Jaeyoung Kwon 3,  Hak Ju Lee 2,  Dongho Lee 4,  Woongchon Mar 5
Affiliations

Affiliations

  • 1 Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
  • 2 Division of Wood Chemistry & Microbiology, Department of Forest Products, Korea Forest Research Institute, Seoul 130-712, Republic of Korea.
  • 3 Department of Biosystems and Biotechnology, Korea University, Seoul 136-713, Republic of Korea.
  • 4 Department of Biosystems and Biotechnology, Korea University, Seoul 136-713, Republic of Korea. Electronic address: [email protected].
  • 5 Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: [email protected].
PMID: 25818191 DOI: 10.1016/j.lfs.2015.02.026
Abstract

Aims: The aim of this study was to prove the neuroprotective effect of 5,7-Dihydroxychromone (DHC) through the Nrf2/ARE signaling pathway. To elucidate the mechanism, we investigated whether 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in SH-SY5Y cells could be attenuated by DHC via activating the Nrf2/ARE signal and whether DHC could down-regulate 6-OHDA-induced excessive ROS generation

Main methods: To evaluate the neuroprotective effect of DHC against 6-OHDA-induced Apoptosis, FACS analysis was performed using PI staining. The inhibitory effect of DHC against 6-OHDA-induced ROS generation was evaluated by DCFH-DA staining assay. Additionally, translocation of Nrf2 to the nucleus and increased Nrf2/ARE binding activity, which subsequently resulted in the up-regulation of the Nrf2-dependent antioxidant gene expressions including HO-1, NQO1, and GCLc, were evaluated by Western blotting and EMSA.

Key findings: Pre-treatment of DHC, one of the constituents of Cudrania tricuspidata, significantly protects 6-OHDA-induced neuronal cell death and ROS generation. Also, DHC inhibited the expression of activated Caspase-3 and caspase-9 and cleaved PARP in 6-OHDA-induced SH-SY5Y cells. DHC induced the translocation of Nrf2 to the nucleus and increased Nrf2/ARE binding activity which results in the up-regulation of the expression of Nrf2-dependent antioxidant genes, including HO-1, NQO1, and GCLc. The addition of Nrf2 siRNA abolished the neuroprotective effect of DHC against 6-OHDA-induced neurotoxicity and the expression of Nrf2-mediated antioxidant genes.

Significance: Activation of Nrf2/ARE signal by DHC exerted neuroprotective effects against 6-OHDA-induced oxidative stress and Apoptosis. This finding will give an insight that activating Nrf2/ARE signal could be a new potential therapeutic strategy for neurodegenerative disease.

Keywords

5,7-Dihydroxychromone; 6-OHDA; Cudrania tricuspidata; Neuroprotection; Nrf2/ARE pathway; Oxidative stress.

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