Abstract: Objective: To investigate the improving effect of mulberry leaf alkaloid (MLA) on D-galactose (D-Gal)-induced oxidative damage in mice, and to illustrate its underlying mechanism from the perspective of the animal’s own antioxidant defense system. Methods: An oxidative stress model was induced by D-Gal. Ten normal mice were served as the normal control. The model mice were randomly divided into model control, positive control (glutathione at 200 mg/kg mb) and low-, medium- and high-dose MLA treatment groups (50, 100, and 200 mg/kg mb). After intragastric administration for 4 consecutive weeks, body mass, food intake and food utilization of the mice were measured. The levels of 8-iso-prostaglandin F2α (8-iso-PGF2α), protein carbonyl (PCO), advanced oxidation protein products (AOPP), 3-nitrotyrosine (3-NT), 8-hydroxy-2’-desoxyguanosine (8-OH-dG), 5-hydroxy-2’-deoxycotosine (5-OH-dC) in plasma were measured by enzyme-linked immunosorbent assay test kit. The activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px), and the levels of metallothionein (MT) and thioredoxin (Trx), as well as total antioxidant capacity (TAC) in plasma were measured by using commercial test kits. Results: Compared with the model control group, body mass, food intake and food utilization of mice in the high-dose MLA group were significantly increased. The plasma contents of 8-iso-PGF2α, PCO, AOPP, 3-NT, 8-OH-dG, and 5-OH-dC in the medium- and high-dose MAL groups were significantly decreased (P < 0.05), and the activities of T-SOD and GSH-Px, the contents of MT and Trx, and TAC value were significantly increased (P < 0.05); all these effects were dose-dependent. In the high-dose group, the contents of 8-iso-PGF2α, PCO, AOPP, 3-NT, 8-OH-dG, and 5-OH-dC were significantly reduced by 83.46%, 35.43%, 61.70%, 63.65%, 65.02%, and 57.90%, respectively (P < 0.05). In addition, T-SOD, GSH-Px, MT, Trx, and TAC increased by 1.47, 2.96, 1.74, 1.37 and 1.63 times, respectively (P < 0.05), all of which reached the normal levels (P > 0.05). Conclusion: Mulberry leaf alkaloid can effectively improve lipid, DNA and protein oxidative damage in mice. The underlying mechanism may be related to regulating antioxidant enzyme activities and non-enzyme antioxidant contents, and enhancing the antioxidant defense system.

Key words: mulberry leaf alkaloid, D-galactose, biomacromolecule, oxidative damage