Neuroprotective and Partial Agonistic Effect of 4-(2-phenyl-6, 7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl) morpholine (PP-43) in Rotenone-Induced Parkinson’s Disease in mice

This study investigates the neuroprotective and partial agonistic effects of PP-43 against rotenone-induced Parkinson’s disease using C57BL6/J mice. PP-43 Administration of PP-43 (10 mg/kg and 20 mg/kg) significantly attenuated neurotoxicity by improving behavioural performance and reducing oxidative stress markers. Treated mice exhibited reduced cataleptic behaviour, enhanced motor coordination, and increased locomotor activity. Biochemical analysis revealed that PP-43 elevated dopamine and glutathione levels while decreasing neuroinflammatory markers, including MPO, IL-1β, and IL-6. Additionally, PP-43 minimized lipid peroxidation and acetylcholine dysregulation, preserving neuronal integrity. Histopathological assessments confirmed reduced glial cell congestion and neuronal damage in PP-43-treated groups. While levodopa showed stronger neuroprotective effects, PP-43 effectively alleviated Parkinsonian symptoms and neuroinflammation. Observations of pyknotic nuclei in rotenone-treated mice further indicated dopaminergic neuronal apoptosis. These findings suggest that PP-43 holds promise as a neuroprotective agent for Parkinson’s disease, warranting further research to elucidate its precise mechanism and therapeutic potential.