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Am J Chin Med. 2015;43(5):879-92. doi: 10.1142/S0192415X15500512. Epub 2015 Jul 30.

Cinnamaldehyde Contributes to Insulin Sensitivity by Activating PPARδ, PPARγ, and RXR.

Author information

1
Department of Chinese Medicine, Shaanxi Provincial People's Hospital, Xi'an 710068, China.
2
Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China.
3
Department of Medicine and Clinical Science, School of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya 663-8179, Japan.
4
Department of Nephrology and Blood Purification, Institute of Biomedical Research and Innovation, Kobe Medical Frontier Center, Kobe 650-0047, Japan.
5
Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Kyoto 612-8555, Japan.

Abstract

Cinnamon is a traditional folk herb used in Asia and has been reported to have antidiabetic effects. Our previous study showed that cinnamaldehyde (CA), a major effective compound in cinnamon, exhibited hypoglycemic and hypolipidemic effects together in db/db mice. The aim of the present study was to elucidate the molecular mechanisms of the effects of CA on the transcriptional activities of three peroxisome proliferator-activated receptors, (PPAR) α, δ, and γ. We studied the effects of CA through a transient expression assay with TSA201 cells, derivatives of human embryonic kidney cell line (HEK293). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis was also performed to evaluate mRNA expression levels. We show here that CA induced PPARδ, PPARγ and retinoid X receptor (RXR) activation. CA may activate PPARγ in a different manner than pioglitazone, as CA selectively stimulated PPARγ S342A mutant while pioglitazone did not. In addition, CA and L-165041 had a synergistic effect on PPARδ activation. To gather the biological evidence that CA increases PPARs transcription, we further measured the expressions of PPARδ and PPARγ target genes in 3T3-L1 adipocytes. The data showed CA induced the expression of PPARδ and PPARγ target genes, namely aP2 and CD36, in differentiated adipocytes. As a result, PPARδ, PPARγ and their heterodimeric partner RXR appear to play a part in the CA action in the target tissues, thereby enhancing insulin sensitivity and fatty acid β-oxidation and energy uncoupling in skeletal muscle and adipose tissue.

KEYWORDS:

Cinnamaldehyde; PPARs; RXR

PMID:
26227398
DOI:
10.1142/S0192415X15500512
[Indexed for MEDLINE]

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