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

Microcirculation. 2021 May;28(4):e12680. doi: 10.1111/micc.12680. Epub 2021 Feb 5.

Abstract

Objective: 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.

Methods: Rats were infused with LPS (5 mg/kg/h) for 90 min. Thirty minutes after initiation of LPS administration, YQFM (160 mg/kg/h), Rb1 (5 mg/kg/h), Sch (2.5 mg/kg/h), or Rb1+Sch (5 mg/kg/h + 2.5 mg/kg/h) was infused until 90 min. Human umbilical vein endothelial cells (HUVECs) were incubated with LPS (100 ng/ml) for 90 min. YQFM (1 mg/ml), Rb1 (100 µM), Sch (100 µM), or Rb1+Sch (200 µM) was added 30 min after initiation of LPS stimulation.

Results: 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.

Conclusion: 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.

Keywords: LPS; Src tyrosine kinase; Yiqifumai injection; energy metabolism; microvascular hyperpermeability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiovascular Agents* / administration & dosage
  • Drugs, Chinese Herbal* / administration & dosage
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Ileum / blood supply*
  • Lipopolysaccharides / toxicity
  • Mesentery / blood supply*
  • Microvessels / drug effects*
  • NF-kappa B
  • Rats
  • Toll-Like Receptor 4
  • Vascular Diseases / drug therapy*
  • Vascular Diseases / etiology

Substances

  • Cardiovascular Agents
  • Drugs, Chinese Herbal
  • Lipopolysaccharides
  • NF-kappa B
  • Toll-Like Receptor 4
  • yi-qi-fu-mai