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Mol Nutr Food Res. 2018 Dec;62(24):e1800955. doi: 10.1002/mnfr.201800955. Epub 2018 Nov 4.

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

Huang SH1,2,3, Xu M1,2,3, Wu HM1,2,3, Wan CX1,2,3, Wang HB1,2,3, Wu QQ1,2,3, Liao HH1,2,3, Deng W1,2,3, Tang QZ1,2,3.

Author information

1
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, P.R. China.
2
Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, P.R. China.
3
Hubei Key Laboratory of Cardiology, Wuhan, 430060, P.R. China.

Abstract

SCOPE:

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

METHODS AND 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.

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.

KEYWORDS:

AMPKα; cardiac dysfunction; inflammation; isoquercitrin; metabolism

PMID:
30359483
DOI:
10.1002/mnfr.201800955
[Indexed for MEDLINE]

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