β-elemene blocks lipid-induced inflammatory pathways via PPARβ activation in heart failure.

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.

• Authors: Mingyan Shao, Mingmin Wang, Lin Ma, Qian Wang, Pengrong Gao, Xue Tian, Changxiang Li, Linghui Lu, Chun Li, Wei Wang, Yong Wang
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 910 Pg. 174450 (Nov 05 2021) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 34454927 (Publication Type: Journal Article)
• Copyright: Copyright © 2021. Published by Elsevier B.V.

Chemical References

• Anti-Inflammatory Agents
• Cardiotonic Agents
• Ern1 protein, rat
• Lipids
• Multienzyme Complexes
• NF-kappa B
• PPAR-beta
• Sesquiterpenes
• beta-elemene
• NF-KappaB Inhibitor alpha
• Protein Serine-Threonine Kinases
• Endoribonucleases

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Cardiotonic Agents (pharmacology, therapeutic use)
• Cell Line
• Cell Survival (drug effects)
• Disease Models, Animal
• Endoribonucleases (metabolism)
• Heart Failure (chemically induced, metabolism, pathology, prevention & control)
• Inflammation (chemically induced, metabolism)
• Lipids (toxicity)
• Male
• Mice
• Mitochondria (drug effects)
• Molecular Docking Simulation
• Multienzyme Complexes (metabolism)
• NF-KappaB Inhibitor alpha (metabolism)
• NF-kappa B (metabolism)
• PPAR-beta (agonists, chemistry, genetics, metabolism)
• Protein Serine-Threonine Kinases (metabolism)
• Rats
• Sesquiterpenes (chemistry, pharmacology, therapeutic use)