Influence of Chrysin on D-galactose induced-aging in mice: Up regulation of AMP kinase/liver kinase B1/Peroxisome proliferator-activated receptor-γ coactivator 1-α signaling pathway.

AMP kinase (AMPK)/liver kinase B1 (LKB1)/Peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC 1α) pathway has a vital role in regulating age-related diseases. It controls neurogenesis, cell proliferation, axon outgrowth and cellular energy homeostasis. AMPK pathway, also, regulates mitochondrial synthesis. The current study evaluated the effect of chrysin on D-galactose (D-gal) induced-aging, neuron degeneration, mitochondrial dysfunction, oxidative stress and neuroinflammation in mice. The mice were allocated randomly into four groups (10 each): Group 1: Normal control group. Group 2: D-gal group, Groups 3& 4: Chrysin (125 & 250 mg/kg). Groups 2-4 were injected with D-gal (200 mg/kg/day; s.c) for 8 weeks to induce aging. Group 3 & 4 were orally gavaged every day concurrent with D-gal. At the end of experiment, behavioral, brain biochemical and histopathological changes were monitored. Chrysin administration elevated discrimination ratio in object recognition, Y Maze percentage alternation, locomotor activity and brain contents of AMPK, LKB1, PGC1α, NAD (P)H quinone oxidoreductase 1 (NQO1), Heme oxygenase 1 (HO-1), nerve growth factor (neurotrophin-3; NT-3), seretonin as well as reduced brain contents of tumor necrosis factor-alpha (TNF-α), nuclear factor kabba B (NF-κB), advanced glycation endproducts (AGEs) and glial fibrillary acidic protein (GFAP) compared to D-gal-treated mice. Chrysin, also, alleviated cerebral cortex and white matter neurons degeneration. Chrysin protects against neurodegeneration, improves mitochondrial autophagy and biogenesis as well as activates antioxidant genes expression. In addition, chrysin ameliorates neuroinflammation and stimulates the release of nerve growth factor and serotonin neurotransmitter. So, chrysin has a neuroprotective effect in D-gal induced-aging in mice.