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.

Adenosine monophosphate kinase/liver kinase B1/peroxisome proliferator‐activated receptor‐γ coactivator 1‐α (AMPK/LKB1/PGC1α) 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): Group 1: normal control group, Group 2: D‐gal group, Groups 3 and 4: chrysin (125 and 250 mg/kg, respectively). Groups 2–4 were injected with D‐gal (200 mg/kg/day; s.c) for 8 weeks to induce aging. Groups 3 and 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 (NGF) (neurotrophin‐3; NT‐3), and seretonin as well as reduced brain contents of tumor necrosis factor‐alpha (TNF‐α), nuclear factor kappa B (NF‐κB), advanced glycation end products (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 NGF and serotonin neurotransmitter. So, chrysin has a neuroprotective effect in D‐gal induced‐aging in mice. [ABSTRACT FROM AUTHOR]