To evaluate whether a tea extract rich in polysaccharides and polyphenols (TEPP) can improve the intestinal response to oxidative stress induced by D-galactose in mice, and to explore its antioxidant mechanism.

Mice were injected intraperitoneally with 10% D-galactose for eight weeks to establish an oxidative stress model. After the model was successfully established, the normal and model groups were gavaged with distilled water, the positive group was gavaged with 200 mg/kg m_b of reduced glutathione, the low-, medium- and high-dose TEPP groups were respectively administered with 40, 100 and 250 mg/kg m_b of TEPP, and the tea polyphenol group was administered with 50 mg/kg m_b of tea polyphenols. Enzyme-linked immunosorbent assay kits were used to detect the total antioxidant capacity (T-AOC), reactive oxygen species (ROS) content, glutathione reductase (GR) activity, heme oxygenase (HO) activity in the intestinal tissues of the mice in each group, and the mRNA expression levels of toll-like receptors (TLR4), p38, nuclear factor-erythroid 2-related factor 2 (Nrf2), GR and HO were detected by fluorescent quantitative real-time polymerase chain reaction (qPCR).

Compared with the model group, the T-AOC of the high-dose TEPP group increased by 2.2 times, and the activities of GR and HO increased by 2.8 times and 1.7 times, respectively. The ROS content decreased by 72.8%, the mRNA expression of TLR4 and p38 declined by 39.1% and 82.4%, and the mRNA expression of Nrf2, GR and HO increased by 83.6%, 8.3 times and 96.3%, respectively. All of these changes were statistically significant (P < 0.05).

TEPP can improve the intestinal response of mice to oxidative stress induced by D-galactose through the TLR4/p38 mitogenactivated protein kinase (MAPK)/Nrf2 pathway.

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.

D-galactose was used to establish a mouse model of oxidative damage. Afterwards, the mice were intragastrically administered with low (50 mg/kg m_b), medium (100 mg/kg m_b) and high (200 mg/kg m_b) 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).

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.

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.

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.

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 m_b), medium (100 mg/kg m_b) and high (200 mg/kg m_b) 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.

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.