Cardioprotective Effects of Phlorizin on Hyperlipidemia-induced Myocardial Injury: Involvement of Suppression in Pyroptosis via Regulating HK1/NLRP3/Caspase-1 Signaling Pathway.
Appl Biochem Biotechnol
; 2024 Sep 03.
Article
en En
| MEDLINE
| ID: mdl-39223343
ABSTRACT
Hyperlipidemia (HLP) is a prevalent and intricate condition that plays a pivotal role in impairing heart function. The primary objective of this study was to assess the lipid-lowering and cardioprotective properties of phlorizin (PHZ) and to investigate its potential molecular mechanisms in rats. In this investigation, Sprague-Dawley rats were subjected to a high-fat diet for a period of 28 days to induce an HLP model. Subsequently, the rats received oral doses of PHZ or metformin from day 14 to day 28. We assessed various parameters using commercially available kits, including serum lipid deposition, myocardial injury biomarkers, oxidative stress markers, and inflammatory cytokine levels. We also employed electron microscopy to examine myocardial ultrastructural changes and conducted Western blot analyses to assess apoptosis factors and pyroptosis markers. Comparing the PHZ group with the model group, we observed significant improvements in blood lipid deposition and heart injury biomarkers. Furthermore, PHZ demonstrated a clear reduction in myocardial tissue oxidative stress and inflammatory factors, as well as a suppression of cell apoptosis. Subsequent investigations indicated that PHZ treatment led to a decreased inflammatory response and lowered levels of hexokinase 1 (HK1), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and Caspase-1. In summary, PHZ proved to be an effective remedy for alleviating HLP-induced cardiac damage by reducing blood lipid levels, mitigating oxidative stress, curbing inflammation, and suppressing pyroptosis. The inhibition of pyroptosis by PHZ appears to be linked to the regulation of the HK1/NLRP3/Caspase-1 signaling pathway.
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1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Appl Biochem Biotechnol
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos