Mulberroside A from Cortex Mori Enhanced Gut Integrity in Diabetes

BACKGROUND: Diabetic endotoxemia has been recognized as one of the hallmarks of type 2 diabetes mellitus (T2DM). Recent findings suggest that gut leak plays a pivotal role in diabetic endotoxemia. Cortex Mori (CM) has been widely applied in China to ameliorate development of T2DM, but its effect on endotoxemia is unknown. METHODS: The study was constructed with two parts: (1) in vivo study of CM on diabetic endotoxemia in db/db mice. Eight C57BL/6 mice were set as normal control; (2) in vitro study of mulberroside A (MBA) from CM on diabetic endotoxemia. Potential mechanism of MBA on ameliorating diabetic endotoxemia was also explored. RESULTS: The present study found that CM water extract decreased levels of blood glucose, ameliorated liver and renal damage in db/db mice, and ameliorated diabetic endotoxemia (p < 0.01). We also found that the water extract enhanced gut integrity and decreased gut inflammatory protein ICAM-1 expression in db/db mice as detected by H&E staining and immunohistochemistry methods. In the in vitro study, MBA decreased levels of MDA and ROS induced by LPS (p < 0.01) and enhanced the integrity of gut epithelial barrier (p < 0.01). CONCLUSIONS: We found that Cortex Mori and its active component mulberroside A could ameliorate diabetic endotoxemia by preserving gut integrity.