6-Aminoflavone Activates Nrf2 to Inhibit the Phospho-JNK/TNF-α Signaling Pathway to Reduce Amyloid Burden in an Aging Mouse Model.
Shakeel AhmadShahid Ali ShahUmar NishanNaeem KhanMikhlid Hammad AlmutairiFozia FoziaNargis JamilaBader O AlmutairiZia UllahPublished in: ACS omega (2023)
In the current study, we examined the antioxidant activity and anti-amyloidogenic potential of 6-aminoflavone in an adult mice model of d-galactose-induced aging. Male albino eight-week-old mice were assigned into four groups: 1. the control group (saline-treated), 2. d-galactose-treated mice (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 four weeks), and 4. 6-AF-treated mice (30 mg/kg/day i.p. for four weeks). We conducted many assays for antioxidant enzymes, including lipid peroxidation, catalase, glutathione (GSH), peroxidase (POD), and sulfoxide dismutase (SOD) (LPO). Western blotting was used to assess protein expression while the Morris water maze (MWM) and Y-maze (YM) were used to study behavior. The findings show that 6-AF greatly improved neuronal synapse and memory impairment brought on by d-galactose and it significantly inhibited BACE1 to reduce the amyloidogenic pathway of A (both amyloid β production and aggregation) by upregulating Nrf2 proteins (validated through molecular docking studies) and suppressing phosphorylated JNK and TNF-α proteins in adult albino mice's brain homogenates. These findings suggest that 6-AF, through the Nrf2/p-JNK/TNF-α signaling pathway, can diminish the oxidative stress caused by d-galactose, as well as the amyloidogenic route of A formation and memory impairment.
Keyphrases
- cell death
- oxidative stress
- signaling pathway
- high fat diet induced
- molecular docking
- rheumatoid arthritis
- mouse model
- atrial fibrillation
- induced apoptosis
- type diabetes
- clinical trial
- pi k akt
- insulin resistance
- epithelial mesenchymal transition
- risk assessment
- newly diagnosed
- working memory
- cell proliferation
- gestational age
- climate change
- human health
- subarachnoid hemorrhage
- endothelial cells
- endoplasmic reticulum stress
- ischemia reperfusion injury
- risk factors
- preterm birth
- cerebral ischemia
- single cell
- functional connectivity