Abstract: Objective: The purpose of this study was to explore the effects of mulberry leaf alkaloids on the improvement of D-galactose-induced intestinal flora imbalance in mice, so as to provide a basis for the development and utilization mulberry leaf alkaloids. Methods: D-galactose was used to establish a mouse model of oxidative damage, and then the mice were administered intragastrically with mulberry leaf alkaloids at low (50 mg/kg mb), medium (100 mg/kg mb) and high (200 mg/kg mb) doses. After 45 days of administration, the levels of reactive oxygen species (ROS), superoxide dismutase (SOD) and thioredoxin-1 (Trx-1) in small intestine tissue were measured, and high-throughput sequencing was used to analyze the changes of α-diversity, β-diversity and bacterial composition in the cecum contents of mice. Results: Compared with the model group, the level of ROS in the high-dose mulberry leaf alkaloid group was reduced by 30.34% (P < 0.05), and the activity of SOD and the content of Trx-1 were increased by 63.59% and 123.75%, respectively (P < 0.05). Mulberry leaf alkaloids significantly improved intestinal flora diversity, adjust the ratio of Firmicutes/Bacteroides, decrease the relative abundance of potentially harmful bacteria such as Lachnospiraceae_NK4A136_group, Helicobacter and Mucispirillum, and increase the abundance of potentially beneficial bacteria like Lactobacillus and Bifidobacterium. Among the three doses of mulberry leaf alkaloids, the high dose was the most effective. In conclusion, mulberry leaf alkaloids can effectively improve the diversity reduction and structural disorders of intestinal flora caused by oxidative stress, which may be related to the antioxidant properties of mulberry leaf alkaloids.

Key words: mulberry leaf alkaloid; antioxidant; D-galactose; intestinal flora