Leonurine ameliorates D-galactose-induced aging in mice through activation of the Nrf2 signalling pathway

Aging is a complex physiological phenomenon associated with oxidative stress damage. The objective of this study was to investigate the potential effects of leonurine on D-galactose-induced aging in mice and its possible mechanisms. In this study, we first tested the antioxidant activity of leonurine in vitro. A subcutaneous injection of D-galactose in mice for 8 weeks was used to establish the aging model to evaluate the protective effects of leonurine. The results showed that treatment with 150 mg·kg^-1 leonurine could improve the mental condition, organic index, and behavioural impairment; significantly increase the activities of antioxidative enzymes including SOD, CAT, and T-AOC; and ameliorate the advanced glycation end product (AGE) level and histopathological injury. Furthermore, the Western blotting data revealed that leonurine supplementation noticeably modulated the suppression of the Nrf2 pathway and upregulated the downstream expression of HO-1 and NOQ1 in aging mice. Additionally, leonurine treatment activated Nrf2 nuclear translocation in both aging mice and normal young mice, and the expression levels of Nrf2 in normal young mice was higher than those in naturally aging mice. In conclusion, our findings suggest that leonurine is a promising agent for attenuating the aging process, and the underlying molecular mechanisms depend on activating the Nrf2 pathway.