Abstract: Objective: Our aim was to study the ameliorative effect of mulberry leaf alkaloids on intestinal barrier damage in mice for the purpose of providing a theoretical basis for the development and utilization of mulberry leaves. Methods: D-galactose was used to establish a mouse model of oxidative damage. Afterwards, the mice were intragastrically administered with low (50 mg/kg mb), medium (100 mg/kg mb) and high (200 mg/kg mb) doses of mulberry leaf alkaloids every day. After 45 days of administration, the concentrations of D-lactic acid (D-LA), lipopolysaccharide (LPS) and intestinal fatty acid binding protein (iFABP) and the activity of diamine oxidase (DAO) in serum were determined, histopathological characteristics of small intestinal tissue were observed by hematoxylin and eosin (HE) staining, and the mRNA expression of the genes encoding the tight junction proteins occludin, claudins, and ZO-1 in small intestinal tissue was also detected by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Results: The different doses of mulberry leaf alkaloids significantly improved the levels of all the above indexes compared to the model group, and the high dose had the best effect in this regard. Compared with the model group, the high dose of mulberry leaf alkaloids reduced the contents of D-LA, LPS, and iFABP and the activity of DAO in serum by 22.14%, 32.12%, 19.98%, 23.22%, respectively (P < 0.05), and up-regulated the mRNA expression levels of occludin, claudins, and ZO-1 by 272.78%, 81.16%, 154.67%, respectively (P < 0.05). In addition, histopathological observations showed that mulberry leaf alkaloids significantly improved the apoptosis and arrangement disorder of intestinal cells, and restored the tight junctions between cells. Conclusion: Mulberry leaf alkaloids can effectively ameliorate intestinal barrier damage. The mechanism may be related to their ability to significantly up-regulate the mRNA expression levels of occludin, claudins, and ZO-1, attenuate pathological damage of intestinal tissue and restore the tight junction structure between cells.

Key words: mulberry leaf alkaloids; intestinal barrier damage; oxidative stress; tight junction proteins