Silibinin attenuates motor dysfunction in a mouse model of Parkinson's disease by suppression of oxidative stress and neuroinflammation along with promotion of mitophagy

Xiumin Liu, Weiwei Liu, Chenkang Wang, Yinzhe Chen, Panwen Liu, Toshihiko Hayashi, Kazunori Mizuno, Shunji Hattori, Hitomi Fujisaki, Takashi Ikejima*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

Silybum marianum (L.) Gaertn has been widely used to obtain a drug for the treatment of hepatic diseases. Silibinin (silybin), a flavonoid extracted and isolated from the fruit of S. marianumis investigated in our study to explore its motor protective potential on Parkinson's disease (PD) model mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). PD is a neurodegenerative disease that causes a debilitating movement disorder, characterized by a progressive loss of nigrostriatal (substantia nigra and striatum) dopaminergic neurons. Several studies have proven that neurodegeneration is aggravated by neuroinflammation, oxidative stress and/or the presence of α-synuclein (α-syn) aggregation. Essentially no causal therapy for PD exists at present. Our results demonstrate that silibinin significantly attenuates MPTP-induced movement disorder in behavioral tests. Immunohistochemical analysis shows that MPTP injection results in the loss of dopaminergic neurons in the substantia nigra, and the decrease of the striatal tyrosine hydroxylase. However, MPTP-injected mice were protected against dopaminergic neuronal loss by oral administration of silibinin (280 mg/kg) that increased expressions of PTEN-induced putative kinase 1 (PINK1) and Parkin, suggesting mitophagy activation. The neuroprotective mechanism of silibinin involves not only reduction of mitochondrial damage by repressing proinflammatory response and α-syn aggregation, but also enhancement of oxidative defense system. Namely, protection of dopaminergic nerves is due to promotion of mitophagy, leading to clearance of the toxic effects of damaged mitochondria. These findings suggest that silibinin has a potential to be further developed as a therapeutic candidate for PD.

Original languageEnglish
Article number113510
JournalPhysiology and Behavior
Volume239
DOIs
Publication statusPublished - 1 Oct 2021
Externally publishedYes

Keywords

  • Inflammatory response
  • Mitophagy
  • Motor dysfunction
  • Oxidative stress
  • Silibinin
  • α-Synuclein

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