Kaempferitrin Attenuates Lipopolysaccharide-Induced Cardiac Dysfunction Through Suppression of the NF-κB/NLRP3

Hongyu Kuang1, Qiang Li2, Min Chen3

  • 1Department of Cardiology, University-Town Hospital of Chongqing Medical University, Chongqing, China.

PubMed

Insights

Kaempferitrin (Kae) protects against sepsis-induced heart dysfunction by inhibiting the NF-κB/NLRP3 inflammatory pathway. This flavonoid compound reduces cardiomyocyte injury and apoptosis, offering a potential therapeutic strategy for septic cardiomyopathy.

Area of Science:

  • Cardiovascular Research
  • Molecular Biology
  • Pharmacology

Background:

  • Sepsis-induced cardiac dysfunction involves cardiomyocyte inflammation and metabolic disorders.
  • Kaempferitrin (Kae), a flavonoid, exhibits anti-inflammatory and anti-glycation properties.
  • Investigating Kae's protective effects against sepsis-induced cardiac dysfunction is crucial.

Purpose of the Study:

  • To evaluate the protective effects of Kaempferitrin (Kae) against lipopolysaccharide (LPS)-induced cardiac dysfunction in a mouse model.
  • To elucidate the underlying molecular mechanisms, focusing on the NF-κB/NLRP3 signaling pathway.

Main Methods:

  • In vivo studies involved treating C57BL/6J mice with Kae followed by LPS, with subsequent echocardiography, serum tests, and pathological analysis.
  • Transcriptomics, western blotting, and RT-PCR were employed to explore molecular mechanisms.
  • In vitro experiments utilized H9c2 and AC16 cardiomyocyte cell lines pretreated with Kae and stimulated with LPS.

Main Results:

  • Kae pretreatment mitigated LPS-induced cardiac dysfunction, reducing pro-inflammatory cytokines (IL-6, TNF-α, IL-1β, IL-18) and cardiomyocyte injury/apoptosis.
  • Transcriptomic analysis identified the NF-κB/NLRP3 signaling pathway as a key mechanism, showing Kae attenuated LPS-induced activation and pyroptosis.
  • In vitro and NLRP3-knockout mouse models confirmed Kae's inhibition of the NF-κB/NLRP3 pathway and its protective role in septic cardiomyopathy.

Conclusions:

  • Kaempferitrin (Kae) alleviates left ventricular remodeling and cardiac dysfunction in sepsis.
  • The protective mechanism involves the suppression of the NF-κB/NLRP3/pyroptosis pathway.
  • Kae demonstrates potential as a therapeutic agent for sepsis-related cardiac complications.
Abstract

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