Neuroprotective Effects of 3,6-Dihydroxyflavone in LPS-Stimulated BV-2 Microglial Cells and an MPTP-Induced Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is a leading neurodegenerative disorder and is triggered by genetic mutations, environmental toxins, and aging, with limited available treatments. 3, 6-dihydroxyflavone is a flavonoid with antioxidant, anti-apoptotic, and neuroprotective properties. However, the neuroprotective effect of 3,6-DHF on MPTP-induced oxidative stress and neuroinflammation in a PD mouse model has not yet been investigated. In this study, we investigated whether 3,6-dihydroxyphenylhydrazine (3,6-DHF) is protective against MPTP-induced oxidative stress and neuroinflammation and explored its potential neuroprotective mechanism. 3,6-DHF was administered orally at doses of 5, 10, and 20 mg/kg/day for 7 days. MPTP was administered at 30 mg/kg/day via intraperitoneal injection, once daily, for 4 consecutive days, from day 4 to day 7. In vitro, 3,6-DHF enhanced cell survival and suppressed inflammatory markers and NF-κB/MAPK signaling pathways associated with microglial activation in LPS-stimulated BV-2 cells. In the in vivo study, 3,6-DHF reduced PD motor deficits and enhanced motor performance in the open field test, beam walking, rotarod, pole, and grip strength tests. 3,6-DHF significantly reduced neuronal oxidative stress by decreasing lipid peroxidation, which in turn helped restore impaired antioxidant enzyme activity, while also enhancing the expression of Nrf2 and HO-1 proteins. It also increased the expression levels of the TH protein, reduced the expression of inflammatory mediators, and inhibited the activation of microglia and astrocytes induced by MPTP. These results suggest that 3,6-DHF effectively modulates neuroprotective, antioxidant, and neuroinflammatory processes and improves motor functions, highlighting its potential for further exploration in PD treatment.