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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.

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


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.


Cinnamaldehyde; PPARs; RXR

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