Research Paper Volume 13, Issue 8 pp 11738—11751

Administration of quercetin improves mitochondria quality control and protects the neurons in 6-OHDA-lesioned Parkinson's disease models

Wen-Wen Wang1, *, , Ruiyu Han4, *, , Hai-Jun He1,2, , Jia Li2, , Si-Yan Chen2, , Yingying Gu3, &, , Chenglong Xie2, ,

  • 1 The Center of Traditional Chinese Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China
  • 2 Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
  • 3 Department of Psychiatry, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
  • 4 NHC Key Laboratory of Family Planning and Healthy, Hebei Key Laboratory of Reproductive Medicine, Hebei Research Institute for Family Planning Science and Technology, Shijiazhuang 050071, Hebei, China
* Equal contribution

Received: November 16, 2020       Accepted: March 14, 2021       Published: April 20, 2021
How to Cite

Copyright: © 2021 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Mounting evidence suggests that mitochondrial dysfunction and impaired mitophagy lead to Parkinson’s disease (PD). Quercetin, one of the most abundant polyphenolic flavonoids, displays many health-promoting biological effects in many diseases. We explored the neuroprotective effect of quercetin in vivo in the 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD and in vitro in 6-OHDA-treated PC12 cells. In vitro, we found that quercetin (20 μM) treatment improved mitochondrial quality control, reduced oxidative stress, increased the levels of the mitophagy markers PINK1 and Parkin and decreased α-synuclein protein expression in 6-OHDA-treated PC12 cells. Moreover, our in vivo findings demonstrated that administration of quercetin also relieved 6-OHDA-induced progressive PD-like motor behaviors, mitigated neuronal death and reduced mitochondrial damage and α-synuclein accumulation in PD rats. Furthermore, the neuroprotective effect of quercetin was suppressed by knockdown of either Pink1 or Parkin.


6-OHDA: 6-hydroxydopamine; PD: Parkinson’s disease; PINK1: PTEN-induced kinase 1; L-dopa: Levodopa; LIDs: L-dopa induced dyskinesias; α-syn: a-synuclein; ROS: reactive oxygen species; Nrf2: nuclear erythroid 2-related factor 2; HO-1: heme oxygenase-1; Akt: Protein kinase B; mTOR: The mechanistic target of rapamycin; HIF-1a: hypoxia-induced factor 1α; STAT3: Signal transducer and activator of transcription 3; Bcl-2: B-cell lymphoma 2; MMP: mitochondrial membrane potential; ATP: Adenosine Triphosphate; DMEM: Dulbecco's modified Eagle medium; FBS: fetal bovine serum; CCK-8: Cell Counting Kit-8; GFP: Green fluorescent protein; RFP: red fluorescent protein; SD: Sprague-Dawley; AAV: Adeno-associated viruses; MDA: Malondialdehyde; SOD: Superoxide Dismutase; TH: Tyrosine Hydroxylase; TBK1: TANK-binding kinase 1; ULK1: Unc-51 like autophagy activating kinase; ANOVA: one-way analysis of variance; NMN: nicotinamide mononucleotide; SN: substantia nigra; OMM: outer mitochondrial membrane; TNF-α: Tumor necrosis factor alpha; IL: Interleukin; BBB: Blood Brain Barrier.