王不留行苷通过抑制ERK/MLCK通路增强2型糖尿病小鼠肠道屏障功能

Abstract

: Aims Hyperglycemia and insulin resistance drive intestinal barrier dysfunction in type 2 diabetes (T2DM). Vaccarin, the main active component in the semen of traditional Chinese medicine Vaccaria has a definite effect on T2DM mice. The purpose of this study was to investigate whether vaccarin can enhance the intestinal barrier function in T2DM. Main methods The T2DM mice model was established by streptozocin and high-fat diet. Vaccarin at a dose of 1 mg/kg/day was administered. We evaluated the effects of vaccarin on gut microbiota and intestinal barrier function by 16S rRNA sequencing, Western blot , quantitative fluorescent PCR (qPCR), and morphological observation. Moreover, we constructed a single layer of the human intestinal epithelium model to determine the effect of vaccarin in vitro . Results The experimental results showed that vaccarin alleviated inflammatory mediators in serum and intestinal tissue of mice ( P  < 0.05), which may depend on the improvement of tight junctions and gut microbiota ( P  < 0.05). Activation of extracellular regulated protein kinases (Erk1/2) stimulated myosin light chain kinase (MLCK). By inhibiting ERK expression ( P  < 0.05), vaccarin had similar effects to ERK inhibitors. In addition, the regulation of tight junction barriers also involved the abovementioned pathways in vivo . Conclusion Vaccarin could protect the intestinal barrier by inhibiting the ERK/MLCK signaling pathway and modulate the composition of the microbiota. These results suggested that vaccarin may be an effective candidate for improving intestinal barrier changes in T2DM.