1. β-elemene blocks lipid-induced inflammatory pathways via PPARβ activation in heart failure.
- Author
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Shao M, Wang M, Ma L, Wang Q, Gao P, Tian X, Li C, Lu L, Li C, Wang W, and Wang Y
- Subjects
- Animals, Anti-Inflammatory Agents therapeutic use, Cardiotonic Agents therapeutic use, Cell Line, Cell Survival drug effects, Disease Models, Animal, Endoribonucleases metabolism, Heart Failure chemically induced, Heart Failure pathology, Inflammation chemically induced, Lipids toxicity, Male, Mice, Mitochondria drug effects, Molecular Docking Simulation, Multienzyme Complexes metabolism, NF-KappaB Inhibitor alpha metabolism, NF-kappa B metabolism, PPAR-beta chemistry, PPAR-beta genetics, PPAR-beta metabolism, Protein Serine-Threonine Kinases metabolism, Rats, Sesquiterpenes chemistry, Sesquiterpenes therapeutic use, Anti-Inflammatory Agents pharmacology, Cardiotonic Agents pharmacology, Heart Failure metabolism, Heart Failure prevention & control, Inflammation metabolism, PPAR-beta agonists, Sesquiterpenes pharmacology
- Abstract
This study aims to investigate the effects of β-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 β-elemene. Histological examination, western blot and quantitative real-time PCR analysis (RT-qPCR) and immunofluorescence staining was utilized to elucidate mechanism of β-elemene in lipid-induced inflammation. Results showed that β-elemene improved heart function in HF mice evidenced by the increase of cardiac ejection fraction (EF) and fractional shortening (FS) values. Furthermore, β-elemene administration rescued ventricular dilation, lipid accumulation, and inflammatory infiltration in arginal areas of mice myocardial infarction. At transcription level, β-elemene augmented the mRNA expression of fatty acid oxidation-associated genes, such as peroxisome proliferator-activated receptor-β (PPARβ). In vitro, treatment of β-elemene increased carnitine palmitoyltransferase 1A (CPT1A) and sirtuin 3 (SIRT3). Hallmarks of inflammation including the nuclear translocation of nuclear factor κB (NF-κB) and the degradation of inhibitory κBα (IκBα) were significantly suppressed. Consistently, we observed down-regulation of interleukin-6 (IL-6) and pro-inflammatory cytokines (such as TNFα) in β-elemene treated H9C2 cells. Finally, molecular docking model predicted an interaction between β-elemene and PPARβ protein. Furthermore, β-elemene increased the expression of PPARβ, which was validated by antagonist of PPARβ and siRNA for PPARβ., (Copyright © 2021. Published by Elsevier B.V.)
- Published
- 2021
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