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

• Published in: Molecular nutrition & food research Vol. 62; no. 24; pp. e1800955 - n/a
• Main Authors: Huang, Si‐Hui, Xu, Man, Wu, Hai‐Ming, Wan, Chun‐Xia, Wang, Hui‐Bo, Wu, Qing‐Qing, Liao, Hai‐Han, Deng, Wei, Tang, Qi‐Zhu
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-12-2018
• Subjects: Adenosine Triphosphate - metabolism; AMP-Activated Protein Kinases - antagonists & inhibitors; AMP-Activated Protein Kinases - metabolism; AMPKα; Animals; ATP; Attenuation; cardiac dysfunction; Cardiotonic Agents - pharmacology; Cell Line; Fatty acids; Fatty Acids - metabolism; Heart Diseases - drug therapy; Heart Diseases - metabolism; Heart Diseases - physiopathology; Inflammation; Interleukin 6; isoquercitrin; Lipopolysaccharides; Lipopolysaccharides - toxicity; Male; metabolism; Mice; Mice, Inbred C57BL; Molecular modelling; mRNA; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Oxidation; Peroxisome proliferator-activated receptors; Pretreatment; Proteins; Quercetin - analogs & derivatives; Quercetin - pharmacology; Rats; Rodents; Sepsis; Tumor necrosis factor; AMPKα; cardiac dysfunction; metabolism; inflammation; isoquercitrin
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201800955

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.
Isoquercitrin (IQC) attenuates LPS‐induced cardiac dysfunction. IQC increases p‐AMPKα expression that is inactivated by lipopolysaccharide, consequently inhibiting the levels of p‐IKKβ, p‐IκBα, and p‐p65 and the gene expression of TNF‐α, MCP1, and IL6. Additionally, activating AMPKα enhances PGC1β and PPARα expression, thus improving ATP generation via the upregulation of genes involved in fatty acid oxidation.