Mulberroside A from Cortex Mori Enhanced Gut Integrity in Diabetes

Abstract

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.