Neuroprotective Effect of Delicaflavone in Rotenone-induced Parkinson's Disease in Rats: Role of Nrf2/HO-1, NF-κB and PI3K/Akt/mTOR Pathways.

Parkinson's disease is a progressive neurodegenerative disease characterized by degeneration of dopaminergic neurons in the substantia nigra, reduced striatal dopamine levels, mitochondrial dysfunction, oxidative stress, and neuroinflammation. Delicaflavone, a natural biflavonoid, possesses antioxidant, anti-inflammatory, and neuroprotective effects; however, its neuroprotective potential against rotenone-induced Parkinson's disease warrants exploration. To induce Parkinson's disease in rats, 0.5 mg/kg of rotenone was administered subcutaneously for 28 days, and delicaflavone was administered orally at different doses (10, 20, and 40 mg/kg). In addition to behavioral tests, neurochemical parameters, oxidative stress, mitochondrial function, inflammatory cytokines, and apoptosis were assessed. Delicaflavone treatment increased square-crossed activity and rotarod performance and reduced catalepsy time. It was also found to positively affect neurochemical parameters, activate antioxidant enzymes, and support neuronal survival by inhibiting apoptosis. In addition to suppressing inflammatory parameters, it reduced pro-inflammatory cytokines and increased anti-inflammatory cytokines. Delicaflavone ameliorates rotenone-induced Parkinson's disease in rats via alteration of Nrf2/HO-1, NF-κB mediated inflammatory pathway and PI3K/Akt/mTOR survival signaling pathway.