Suppressive effects of zingerone on TGFBIp-mediated septic responses.

Zingerone (ZGR), a phenolic alkanone isolated from ginger, has been reported to possess various pharmacological activities. Transforming growth factor β-induced protein (TGFBIp) is an extracellular matrix protein whose expression in several cell types is greatly increased by TGF-β. TGFBIp is released by human umbilical vein endothelial cells and functions as a mediator of experimental sepsis. We hypothesized that ZGR could reduce TGFBIp-mediated severe inflammatory responses in human endothelial cells and mice. Here, we investigated the anti-septic effects and underlying mechanisms of ZGR against TGFBIp-mediated septic responses. ZGR effectively inhibited lipopolysaccharide-induced release of TGFBIp and suppressed TGFBIp-mediated septic responses. In addition, ZGR suppressed TGFBIp-induced sepsis lethality and pulmonary injury. In conclusion, ZGR suppressed TGFBIp-mediated and CLP-induced septic responses. Therefore, ZGR could be a potential therapeutic agent for treatment of various severe vascular inflammatory diseases via inhibition of the TGFBIp signaling pathway.