Silymarin Protects Against Impaired Autophagy Associated with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Parkinsonism.
J Mol Neurosci. 2019 Nov 15. Epub 2019 Nov 15. PMID: 31732923
Manish Kumar Tripathi
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exacerbates mitochondrial impairment andα-synuclein expression leading to Parkinsonism. Impaired mitochondria and over-expressed α-synuclein are degraded and eliminated via macroautophagy and chaperone-mediated autophagy. Owing to multiple properties, silymarin protects from oxidative stress-mediated cellular injury. However, its effecton MPTP-induced changes in autophagy is not yet known. The study aimed to decipher the effect of silymarin on MPTP-induced changes in autophagy. Male mice (20-25 g) were treated with silymarin (intraperitoneally, daily, 40 mg/kg) for 2 weeks. On day 7, a few animals were also administered with MPTP(intraperitoneally, 20 mg/kg, 4 injections at 2-h interval) along with vehicles. Striatal dopamine content was determined. Western blot analysis was done to assess α-synuclein, beclin-1, sequestosome, phosphorylated 5' adenosine monophosphate-activated protein kinase (p-AMPK), lysosome-associatedmembrane protein-2 (LAMP-2), heat shock cognate-70 (Hsc-70), LAMP-2A, phosphorylated unc-51-like autophagy activating kinase (p-Ulk1), and phosphorylated mechanistic target of rapamycin (p-mTOR) levels in the nigrostriatal tissue. Silymarin rescued from MPTP-induced increase in beclin-1, sequestosome, p-AMPK, and p-Ulk1 and decrease in LAMP-2, p-mTOR, and LAMP-2A levels. Silymarin defended against MPTP-induced increase in α-synuclein and reduction in dopamine content. The results demonstrate that silymarin protects against MPTP-induced changes in autophagy leading to Parkinsonism.