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

• Published in: European journal of pharmacology 2021-11, Vol.910, p.174450-174450, Article 174450
• Main Authors: Shao, Mingyan, Wang, Mingmin, Ma, Lin, Wang, Qian, Gao, Pengrong, Tian, Xue, Li, Changxiang, Lu, Linghui, Li, Chun, Wang, Wei, Wang, Yong
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Cardiotonic Agents - pharmacology; Cardiotonic Agents - therapeutic use; Cell Line; Cell Survival - drug effects; Disease Models, Animal; Endoribonucleases - metabolism; Heart failure; Heart Failure - chemically induced; Heart Failure - metabolism; Heart Failure - pathology; Heart Failure - prevention & control; Inflammation; Inflammation - chemically induced; Inflammation - metabolism; Lipid accumulation; Lipids - toxicity; Male; Mice; Mitochondria - drug effects; Molecular Docking Simulation; Multienzyme Complexes - metabolism; NF-kappa B - metabolism; NF-KappaB Inhibitor alpha - metabolism; PPAR-beta - agonists; PPAR-beta - chemistry; PPAR-beta - genetics; PPAR-beta - metabolism; PPARβ; Protein Serine-Threonine Kinases - metabolism; Rats; Sesquiterpenes - chemistry; Sesquiterpenes - pharmacology; Sesquiterpenes - therapeutic use; β-elemene
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2021.174450

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.