Chrysin ameliorates D-galactose-induced liver aging in mice: the impact of targeting Nrf2/AKT and CXCL1/TNF-α/P53 signaling pathways

Liver aging is a major cause of death all over the world. D-galactose (D-gal) induces liver aging via inflammatory pathways in Kupffer cells. Chrysin (CHR) is a flavonoid having anti-inflammatory and antioxidant effects that can protect liver from aging responses. This study aimed to clarify the hepatoprotective activity of CHR in D-gal-induced liver aging. Four groups of male mice (10 mice each) were used in the study: normal control group, D-gal (200 mg/kg/day) group, D-gal group + 25 mg/kg/day CHR, and D-gal group + 50 mg/kg/day CHR. Treatment continued for 8 weeks. Elevation in cytochrome P2E1 (CYP2E1) enzyme, the chemokine (C-X-C motif) ligand-1 (CXCL-1), the cell surface adhesion receptor CD44, and tumor necrosis factor (TNF)-α occurred in D-gal group. Oxidative stress was evident through downregulation of catalase enzymes, nuclear factor erythroid 2-related factor 2 (Nrf2) and protein kinase B (AKT), and an increasing nitric oxide (NO) levels. Consequently, liver injury was evident with elevation of ALT and AST levels. These responses affected the morphology of the hepatic tissues. CHR managed to prevent these pathways and preserved normal morphology of the hepatic tissues. Our study revealed that CHR prevents D-gal-induced liver aging through its anti-inflammatory and antioxidant effects.