Luteolin improves vasoconstriction function and survival of septic mice via AMPK/NF-κB pathway.

Septic shock, the leading cause of death in sepsis, is related to vasoconstriction dysfunction. To investigate the effects of Luteolin (LTL), a flavonoid polyphenol compound, on vasoconstriction dysfunction in septic mice and the underlying mechanism, cecal ligation and puncture (CLP) surgery was performed on wild-type C57BL/6 mice to induce septic shock. Mice were intraperitoneally injected with 0.2 mg/kg LTL within 10 min after CLP surgery with or without 20 mg/kg Compound C (AMPK inhibitor) (CC) 1 h before CLP surgery, and re-administrated every 12 h. The survival rate, systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP) were explored. After the mice were sacrificed, the vasoconstriction function, inflammatory indicators, and possible regulatory signaling pathways were examined. Our data showed that CLP decreased the survival rate, SAP, DAP, MAP, vasoconstriction function, and expression of ADRA1A and p-AMPK/AMPK, as well as increased the mRNA expression of inflammatory cytokines and iNOS, the serum levels of inflammatory cytokines, and the levels of iNOS, p-p65/p65, and p-IκBα/IκBα in aortas (P < 0.05), which could be reversed by LTL treatment (P < 0.05). However, inhibition of AMPK could abolish the protective effects of LTL (P < 0.05). In conclusion, our study manifested that LTL could prevent vasoconstriction dysfunction and increase survival of septic mice via activating AMPK, which suggested that LTL could be a novel therapeutic option for patients with sepsis.