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

Area of Science:

• Cardiology
• Pharmacology
• Biochemistry

Background:

• Isoquercitrin (IQC) exhibits protective effects in various pathological conditions.
• Sepsis-induced cardiac dysfunction is a critical complication with limited therapeutic options.

Purpose of the Study:

• To investigate the protective effects of Isoquercitrin (IQC) against lipopolysaccharide (LPS)-induced cardiac dysfunction.
• To elucidate the underlying molecular mechanisms of IQC's action.

Main Methods:

• Mice and H9c2 cardiomyoblasts were challenged with LPS.
• IQC pretreatment was administered.
• Inflammatory markers (TNF-α, IL6, MCP1, p-IKKβ, p-IκBα, p-p65) and energy metabolism markers (ATP, PGC1β, PPAR-α, fatty acid oxidation) were assessed.
• AMP-activated protein kinase alpha (AMPKα) inhibition was used to explore its role.

Main Results:

• IQC attenuated LPS-induced cardiac dysfunction and reduced inflammatory responses.
• IQC increased cardiac and cellular ATP levels by upregulating PGC1β and PPAR-α, enhancing fatty acid oxidation.
• AMPKα activation was identified as a partial mediator of IQC's protective effects.

Conclusions:

• Isoquercitrin mitigates LPS-induced cardiac dysfunction by inhibiting inflammation and enhancing fatty acid oxidation.
• AMPKα plays a partial role in mediating the cardioprotective effects of IQC.
• IQC shows potential as a therapeutic agent for sepsis-induced cardiac dysfunction.