Post-treatment with yiqifumai injection and its main ingredients attenuates lipopolysaccharide-induced microvascular disturbance in mesentery and ileum.

Abstract

To investigate the effect of Yiqifumai injection (YQFM), a compound Chinese medicine, and its main active ingredients on lipopolysaccharide (LPS)-induced microvascular disturbance in mesentery and ileum. Rats were infused with LPS (5mg/kg/h) for 90min. Thirty minutes after initiation of LPS administration, YQFM (160mg/kg/h), Rb1 (5mg/kg/h), Sch (2.5mg/kg/h), or Rb1+Sch (5mg/kg/h+2.5mg/kg/h) was infused until 90min. Human umbilical vein endothelial cells (HUVECs) were incubated with LPS (100ng/ml) for 90min. YQFM (1mg/ml), Rb1 (100µM), Sch (100µM), or Rb1+Sch (200µM) was added 30min after initiation of LPS stimulation. Yiqifumai injection and Rb1+Sch inhibited mesenteric venule hyperpermeability, suppressed microvillar erosion and submucosal edema, and protected claudin-5 from downregulation and interleukin-1β from upregulation in ileal tissues after LPS. Study in HUVECs confirmed the effect of YQFM and Rb1+Sch on JAM-1 after LPS and revealed a similar effect on other junction proteins. Moreover, YQFM and Rb1+Sch attenuated the dysfunctional energy metabolism and the activation of TLR-4/Src/NF-κB signaling with Rb1 and Sch being partially effective. These results demonstrated the beneficial effect of post-treatment with YQFM, which is attributable to its main ingredient Rb1 and Sch, and likely mediated by targeting TLR-4/Src/NF-κB signaling pathway.