PMID- 34454927
OWN - NLM
STAT- MEDLINE
DCOM- 20220127
LR  - 20220127
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 910
DP  - 2021 Nov 5
TI  - beta-elemene blocks lipid-induced inflammatory pathways via PPARbeta activation in 
      heart failure.
PG  - 174450
LID - S0014-2999(21)00604-X [pii]
LID - 10.1016/j.ejphar.2021.174450 [doi]
AB  - 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 (PPARbeta). 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 
      kappaB (NF-kappaB) and the degradation of inhibitory kappaBalpha (IkappaBalpha) were significantly 
      suppressed. Consistently, we observed down-regulation of interleukin-6 (IL-6) and 
      pro-inflammatory cytokines (such as TNFalpha) in beta-elemene treated H9C2 cells. 
      Finally, molecular docking model predicted an interaction between beta-elemene and 
      PPARbeta protein. Furthermore, beta-elemene increased the expression of PPARbeta, which 
      was validated by antagonist of PPARbeta and siRNA for PPARbeta.
CI  - Copyright (c) 2021. Published by Elsevier B.V.
FAU - Shao, Mingyan
AU  - Shao M
AD  - Beijing Key Laboratory of Traditional Chinese Medicine Syndrome and Formula, 
      School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, 
      China.
FAU - Wang, Mingmin
AU  - Wang M
AD  - Beijing Key Laboratory of Traditional Chinese Medicine Syndrome and Formula, 
      Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, 
      China.
FAU - Ma, Lin
AU  - Ma L
AD  - Beijing Key Laboratory of Traditional Chinese Medicine Syndrome and Formula, 
      School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, 
      China.
FAU - Wang, Qian
AU  - Wang Q
AD  - State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical 
      Sciences, Peking University, Beijing, 100191, China.
FAU - Gao, Pengrong
AU  - Gao P
AD  - Beijing Key Laboratory of Traditional Chinese Medicine Syndrome and Formula, 
      School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, 
      China.
FAU - Tian, Xue
AU  - Tian X
AD  - Beijing Key Laboratory of Traditional Chinese Medicine Syndrome and Formula, 
      School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, 
      China.
FAU - Li, Changxiang
AU  - Li C
AD  - Beijing Key Laboratory of Traditional Chinese Medicine Syndrome and Formula, 
      College of Traditional Chinese Medicine, University of Chinese Medicine, Beijing 
      100029, China.
FAU - Lu, Linghui
AU  - Lu L
AD  - Beijing Key Laboratory of Traditional Chinese Medicine Syndrome and Formula, 
      College of Traditional Chinese Medicine, University of Chinese Medicine, Beijing 
      100029, China.
FAU - Li, Chun
AU  - Li C
AD  - Beijing Key Laboratory of Traditional Chinese Medicine Syndrome and Formula, 
      Modern Research Center of Traditional Chinese Medicine, School of Traditional 
      Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100029, 
      China. Electronic address: lichun19850204@163.com.
FAU - Wang, Wei
AU  - Wang W
AD  - Beijing Key Laboratory of Traditional Chinese Medicine Syndrome and Formula, 
      College of Traditional Chinese Medicine, University of Chinese Medicine, Beijing 
      100029, China. Electronic address: wangwei26960@126.com.
FAU - Wang, Yong
AU  - Wang Y
AD  - Beijing Key Laboratory of Traditional Chinese Medicine Syndrome and Formula, 
      School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, 
      China; Beijing Key Laboratory of Traditional Chinese Medicine Syndrome and 
      Formula, College of Traditional Chinese Medicine, University of Chinese Medicine, 
      Beijing 100029, China. Electronic address: wangyong@bucm.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20210826
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cardiotonic Agents)
RN  - 0 (Ern1 protein, rat)
RN  - 0 (Lipids)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (NF-kappa B)
RN  - 0 (PPAR-beta)
RN  - 0 (Sesquiterpenes)
RN  - 0 (beta-elemene)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 3.1.- (Endoribonucleases)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology/therapeutic use
MH  - Cardiotonic Agents/*pharmacology/therapeutic use
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Disease Models, Animal
MH  - Endoribonucleases/metabolism
MH  - Heart Failure/chemically induced/*metabolism/pathology/*prevention & control
MH  - Inflammation/chemically induced/*metabolism
MH  - Lipids/toxicity
MH  - Male
MH  - Mice
MH  - Mitochondria/drug effects
MH  - Molecular Docking Simulation
MH  - Multienzyme Complexes/metabolism
MH  - NF-KappaB Inhibitor alpha/metabolism
MH  - NF-kappa B/metabolism
MH  - PPAR-beta/*agonists/chemistry/genetics/metabolism
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Rats
MH  - Sesquiterpenes/chemistry/*pharmacology/therapeutic use
OTO - NOTNLM
OT  - Heart failure
OT  - Inflammation
OT  - Lipid accumulation
OT  - PPARbeta
OT  - beta-elemene
EDAT- 2021/08/30 06:00
MHDA- 2022/01/28 06:00
CRDT- 2021/08/29 20:43
PHST- 2021/05/25 00:00 [received]
PHST- 2021/08/24 00:00 [revised]
PHST- 2021/08/25 00:00 [accepted]
PHST- 2021/08/30 06:00 [pubmed]
PHST- 2022/01/28 06:00 [medline]
PHST- 2021/08/29 20:43 [entrez]
AID - S0014-2999(21)00604-X [pii]
AID - 10.1016/j.ejphar.2021.174450 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2021 Nov 5;910:174450. doi: 10.1016/j.ejphar.2021.174450. Epub 
      2021 Aug 26.