Neuroprotective effect of silymarin in a MPTP mouse model of Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disease secondary to the loss of dopaminergic neurons in the substantia nigra. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces in mice and primates histopathological changes similar to PD in humans. A common feature of PD and MPTP models is neuronal death and dopamine depletion. Silymarin is a complex of flavonolignans derived from the seeds of the plant Silybum marianum and has mainly antioxidant, anti-inflammatory, cytoprotective and neuroprotective effects. In order to explore whether silymarin has a neuroprotective effects in a mouse model of PD we determined the concentration of striatal dopamine by HPLC, the number of apoptotic cells by in situ Tunel assay and the number of tyrosine hydroxylase positive neurons by immunohistochemistry in substantia nigra of vehicle-treated, silymarin-treated, MPTP-intoxicated and MPTP-silymarin treated C57BL/6J male mice. MPTP (30 mg/kg) and silymarin doses (25, 50, 100, 200, 250, 300 or 400mg/kg) were administered intraperitoneally once daily for five consecutive days. Silymarin treatment showed a non-monotonic dose-response curve and only 50 and 100mg/kg doses preserved dopamine levels (62% and 69%, respectively) after MPTP intoxication. Additionally, 100mg/kg silymarin treatment significantly diminished the number of apoptotic cells and preserved dopaminergic neurons in the substantia nigra of MPTP-intoxicated mice. These results show the neuroprotective properties of 100mg/kg silymarin and may be of interest in the treatment of PD.