Conclusion
IQC attenuates LPS-induced cardiac dysfunction by inhibiting inflammatory responses and by enhancing fatty acid oxidation, partially by activating AMPKα. IQC might be a potential drug for sepsis-induced cardiac dysfunction.
Results
C57BL/6 mice or H9c2 cardiomyoblasts are subjected to LPS challenge for 12 h. Pretreatment with IQC attenuates LPS-induced cardiac dysfunction. IQC remarkably reduces LPS-mediated inflammatory responses by inhibiting the mRNA levels of TNF-α, IL6, and MCP1 as well as the protein levels of p-IKKβ, p-IκBα, and p-p65 in vivo and in vitro. Interestingly, IQC administration also improves energy deficiencies caused by LPS, manifesting as significant increases in cardiac and cellular ATP levels. Furthermore, ATP levels increase due to the upregulation of PGC1β and PPAR-α, which enhances fatty acid oxidation in vivo and in vitro. However, the protective roles of IQC against LPS-mediated increased inflammatory responses and decreased acid fatty oxidation are partially blunted by inhibiting AMPKα in vitro, and suppressing AMPKα partially blocks the increased cardiac function elicited by IQC in LPS-treated mice.