الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 165 |  |  |
| | | from | 165 | | |
Abstract
Parkinson’s disease (PD) is a prevalent neurodegenerative disorder, characterized by motor and psychological dysfunction. Palliative treatment and dopamine replenishment therapy are the only available therapeutic options. Calcium channel blockers (CCBs) have been reported to protect against several neurodegenerative disorders. Moreover, phytoestrogens have shown significant potential in neuroprotection, particularly in protecting against neurodegeneration. The current study was designed to evaluate the neuroprotective impact of Felodipine (10 mg/kg, orally) as a CCB and Calycosin (30 mg/kg, orally) as a phytoestrogen on motor and biochemical dysfunction associated with experimentally induced PD using rotenone (2.5 mg/kg, IP) and to investigate the underlying mechanisms. Rotenone induced deleterious neuromotor outcomes, typical of those associated with PD. The striatum revealed increased oxidative burden and NO levels with decreased antioxidant capacity. Nrf2 content significantly decreased with the accumulation of α-synuclein and tau proteins in both the substantia nigra and striatum. These observations significantly improved with felodipine and calycosin treatment. Of note, felodipine and calycosin increased dopamine levels in the substantia nigra and striatum as confirmed by the suppression of inflammation and the significant reduction in striatal NF-𝞳B and TNF-α contents. Moreover, felodipine and calycosin enhanced mitophagy, as confirmed by a significant increase in mitochondrial Parkin and suppression of LC3a/b and SQSTM1/p62. In conclusion, felodipine and calycosin restored dopamine synthesis, attenuated oxidative stress, inflammation, and mitochondrial dysfunction, and improved the mitophagy process resulting in improved PD-associated motor impairment.