1. Academic Validation
  2. Tricetin protects against 6-OHDA-induced neurotoxicity in Parkinson's disease model by activating Nrf2/HO-1 signaling pathway and preventing mitochondria-dependent apoptosis pathway

Tricetin protects against 6-OHDA-induced neurotoxicity in Parkinson's disease model by activating Nrf2/HO-1 signaling pathway and preventing mitochondria-dependent apoptosis pathway

  • Toxicol Appl Pharmacol. 2019 Sep 1;378:114617. doi: 10.1016/j.taap.2019.114617.
Jie Ren 1 Ling Yuan 2 Wenbin Wang 2 Meiju Zhang 2 Qun Wang 2 Simin Li 2 Ling Zhang 2 Kun Hu 3
Affiliations

Affiliations

  • 1 School of Pharmaceutical Engineering & Life Science, Changzhou University, Changzhou, Jiangsu 213164, People's Republic of China. Electronic address: renjie@cczu.edu.cn.
  • 2 School of Pharmaceutical Engineering & Life Science, Changzhou University, Changzhou, Jiangsu 213164, People's Republic of China.
  • 3 School of Pharmaceutical Engineering & Life Science, Changzhou University, Changzhou, Jiangsu 213164, People's Republic of China. Electronic address: hukun@cczu.edu.cn.
Abstract

Apoptosis of DA neurons is a contributing cause of disability and death for Parkinson's disease (PD). In this experiment, the neuroprotective effect of Tricetin was examined in PD models both in vitro and in vivo. The results suggested that 6-OHDA-induced cytotoxicity was accompanied by an increase in ROS generation, an increase in Caspase-3 protein activity, an increase in Lactate Dehydrogenase (LDH) release and an increase in the ratio of Bax/Bcl-2, but the pretreatment with Tricetin significantly improved cell viability and suppressed mitochondria-mediated Apoptosis. Moreover, Tricetin also induced the protein expression of Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its transcriptional activation, resulting in the up-regulated expression of heme oxygenase-1 (HO-1), which conferred neuroprotection against 6-OHDA-induced oxidative damage. Results from molecular docking indicated that Tricetin could be a potent competitive inhibitor of the Keap1-Nrf2 Protein Protein Interaction (PPI). Finally, in vivo findings were confirmed in the 6-OHDA-PD C. elegans model. Thus, Tricetin may be an attractive therapeutic candidate for the neuroprotection.

Keywords

Apoptosis; C. elegans; Nrf2; Oxidative stress; Parkinson's disease; Tricetin.

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