Abstract: Objective: To explore the effect of alkaloids from mulberry leaves on improving oxidative protein damage in mice and the underlying mechanism for the purpose of providing a theoretical basis for the development and utilization of alkaloids from mulberry leaves. Methods: A mouse model of oxidative damage was induced by D-galactose (D-Gal) and administered with different doses of mulberry leaf alkaloids. At the end of the 8th week, the contents of protein carbonyl (PCO), advanced oxidation protein products (AOPP) and 3-nitrotyrosine (3-NT), and the enzyme activity levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and NAD(P)H quinine oxidoreductase 1 (NQO1) in plasma were measured. The mRNA expression of SOD, GSH-Px, NQO1, nuclear erythroid related factor 2 (Nrf2) and Kelch-like ECH-associated protein-1 (Keap1) in liver tissues were also detected by real-time polymerase chain reaction (qPCR). Results: Compared with the model control group, the plasma PCO, AOPP and 3-NT levels of mice decreased by 36.43%, 61.81% and 58.13%, respectively after intragastric administration of high-dose mulberry leaf alkaloids (200 mg/kg mb) (P < 0.01). However, the activity of SOD, GSH-Px and NQO1 in plasma increased by 48.89%, 167.17% and 85.12% (P < 0.01). Meanwhile, high-dose mulberry leaf alkaloids also increased the mRNA expression of SOD1, SOD2, GSH-Px, NQO1 and Nrf2 in the liver by 96.96%, 94.26%, 116.71%, 101.51% and 63.01%, respectively (P < 0.01), but decreased the mRNA level of Keap1 by 33.54% (P < 0.01). Conclusion: Mulberry leaf alkaloids have a protective effect on D-Gal-induced oxidative protein damage in mice via adjusting Keap1/Nrf2 signal pathway.

Key words: mulberry leaf alkaloids; D-galactose; protein; oxidative damage; nuclear erythroid related factor 2/Kelch-like ECH-associated protein-1 signaling pathway