6-Aminoflavone Activates Nrf2 to Inhibit the Phospho-JNK/TNF- Signaling Pathway to Reduce Amyloid Burden in an Aging Mouse Model

In the current study, we examined the antioxidant activityandanti-amyloidogenic potential of 6-aminoflavone in an adult mice modelof d-galactose-induced aging. Male albino eight-week-oldmice were assigned into four groups: 1. the control group (saline-treated),2. d-galactose-treatedmice (100 mg/kg/day, intravenously) for eight weeks, 3. d-galactose-treated mice (100 mg/kg/day, intravenously for eight weeks)and 6-AF-treated mice (30 mg/kg/day, intravenously for the final fourweeks), and 4. 6-AF-treated mice (30 mg/kg/day i.p. for four weeks).We conducted many assays for antioxidant enzymes, including lipidperoxidation, catalase, glutathione (GSH), peroxidase (POD), and sulfoxidedismutase (SOD) (LPO). Western blotting was used to assess proteinexpression while the Morris water maze (MWM) and Y-maze (YM) wereused to study behavior. The findings show that 6-AF greatly improvedneuronal synapse and memory impairment brought on by d-galactoseand it significantly inhibited BACE1 to reduce the amyloidogenic pathwayof A (both amyloid & beta; production and aggregation) by upregulatingNrf2 proteins (validated through molecular docking studies) and suppressingphosphorylated JNK and TNF-& alpha; proteins in adult albino mice'sbrain homogenates. These findings suggest that 6-AF, through the Nrf2/p-JNK/TNF-& alpha;signaling pathway, can diminish the oxidative stress caused by d-galactose, as well as the amyloidogenic route of A formationand memory impairment.