13-Methylberberine reduces HMGB1 release in LPS-activated RAW264.7 cells and increases the survival of septic mice through AMPK/P38 MAPK activation.

摘要: High mobility group box 1 (HMGB1), a late phase cytokine of sepsis, is viewed as potential target for the treatment sepsis. The authors considered that 13-methylberberine (13-MB) might reduce circulating HMGB1 levels and increase survival in mouse model sepsis by activating AMP-activated protein kinase (AMPK). Western blot analysis vascular contraction testing were performed using RAW264.7 cells rat thoracic aorta, respectively. mechanisms responsible investigated various signal inhibitors small interfering RNA techniques. 13-MB significantly reduced release LPS-activated cells, this was prevented silencing AMPK or p38, pretreating with p38 MAPKinase inhibitor, suggesting activations observed reduction release. As expected, increased phosphorylations AMPK. Interestingly, inhibited AMPKsiRNA, indicating lies upstream p38. Furthermore, concentration-dependently IκB phosphorylation aortic rings, co-treatment LPS 8h, vitro, restored isometric induced phenylephrine. Importantly, rate LPS-induced endotoxemic mice. These results suggest may be useful treating diseases which target.