Delicaflavone mitigates rotenone-induced Parkinson's disease in rats by modulating Nrf2/HO-1, NF-κB, and PI3K/Akt/mTOR pathways

Parkinson's disease (PD) is a debilitating neurodegenerative disorder marked by the progressive degeneration of dopaminergic neurons in the substantia nigra, leading to reduced striatal dopamine levels. This neuronal loss is exacerbated by mitochondrial dysfunction, oxidative stress, and neuroinflammation. Current treatments primarily manage symptoms, highlighting an urgent need for neuroprotective strategies that address these underlying pathological mechanisms. Natural compounds like delicaflavone, a biflavonoid with known antioxidant and anti-inflammatory properties, offer a promising avenue for exploring such neuroprotective potential.

Researchers induced Parkinson's disease in rats by administering 0.5 mg/kg of rotenone subcutaneously for 28 days. Following this, delicaflavone was administered orally at doses of 10, 20, and 40 mg/kg daily. The study assessed behavioral improvements using square-crossed activity and rotarod performance tests, and measured catalepsy time. Neurochemical parameters, markers of oxidative stress, mitochondrial function, inflammatory cytokines, and apoptosis were also evaluated to understand the compound's mechanism of action.

Delicaflavone treatment significantly improved motor function in rotenone-induced PD rats. Animals receiving delicaflavone showed increased square-crossed activity and enhanced rotarod performance, while catalepsy time was reduced. The compound positively affected neurochemical parameters, indicating a protective effect on dopaminergic systems. Furthermore, delicaflavone activated antioxidant enzymes, bolstering the cellular defense against oxidative stress, and supported neuronal survival by inhibiting apoptosis. It also demonstrated potent anti-inflammatory effects: > Delicaflavone suppressed overall inflammatory parameters, reducing pro-inflammatory cytokines and increasing anti-inflammatory cytokines. Mechanistically, delicaflavone was found to ameliorate rotenone-induced Parkinson's disease by altering the Nrf2/HO-1 pathway, modulating the NF-κB mediated inflammatory pathway, and activating the PI3K/Akt/mTOR survival signaling pathway.