beta-elemene blocks lipid-induced inflammatory pathways via PPAR beta activation in heart failure

Abstract

This study aims to investigate the effects of beta-elemene on a mouse model of heart failure (HF) and to elucidate the underlying mechanisms in vitro approaches. In this study, left anterior descending (LAD)-induced HF mouse model and oxygen-glucose deprivation/recovery (OGD/R)-induced H9C2 model were leveraged to assess the therapeutic effects of beta-elemene. Histological examination, western blot and quantitative real-time PCR analysis (RT-qPCR) and immunofluorescence staining was utilized to elucidate mechanism of beta-elemene in lipid-induced inflammation. Results showed that beta-elemene improved heart function in HF mice evidenced by the increase of cardiac ejection fraction (EF) and fractional shortening (FS) values. Furthermore, beta-elemene administration rescued ventricular dilation, lipid accumulation, and inflammatory infiltration in arginal areas of mice myocardial infarction. At transcription level, beta-elemene augmented the mRNA expression of fatty acid oxidation-associated genes, such as peroxisome proliferator-activated receptor-beta (PPAR beta). In vitro, treatment of beta-elemene increased carnitine palmitoyltransferase 1A (CPT1A) and sirtuin 3 (SIRT3). Hallmarks of inflammation including the nuclear translocation of nuclear factor kappa B (NF-kappa B) and the degradation of inhibitory kappa B alpha (I kappa B alpha) were significantly suppressed. Consistently, we observed down-regulation of interleukin-6 (IL-6) and pro-inflammatory cytokines (such as TNF alpha) in beta-elemene treated H9C2 cells. Finally, molecular docking model predicted an interaction between beta-elemene and PPAR beta protein. Furthermore, beta-elemene increased the expression of PPAR beta, which was validated by antagonist of PPAR beta and siRNA for PPAR beta.