Isoquercitrin Attenuated Cardiac Dysfunction Via AMPKα-Dependent Pathways in LPS-Treated Mice.

SCOPE: Isoquercitrin (IQC) has been reported to play a protective role in many pathological conditions. Here, we investigated the effects of IQC on lipopolysaccharide (LPS)-induced cardiac dysfunction, exploring its potential molecular mechanisms.

METHODS AND RESULTS: C57BL/6 mice or H9c2 cardiomyoblasts were subjected to LPS challenge for 12 hours. Pretreatment with IQC attenuated LPS-induced cardiac dysfunction. IQC remarkably reduced LPS-mediated inflammatory responses by inhibiting the mRNA levels of TNFα, 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 improved energy deficiencies caused by LPS, manifesting as significant increases in cardiac and cellular ATP levels. Furthermore, ATP levels increased due to the upregulation of PGC1β and PPARα, which enhanced 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 were partially blunted by inhibiting AMPKα in vitro, and suppressing AMPKα partially blocked the increased cardiac function elicited by IQC in LPS-treated mice.

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. This article is protected by copyright. All rights reserved.