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Int. J. Mol. Sci. 2016, 17(3), 323; doi:10.3390/ijms17030323

Dietary Apigenin Exerts Immune-Regulatory Activity in Vivo by Reducing NF-κB Activity, Halting Leukocyte Infiltration and Restoring Normal Metabolic Function

1
Department of Physiology and Cell Biology, the Heart and Lung Research Institute, the Ohio State University, Columbus, OH 43210, USA
2
Department of Molecular Genetics, the Ohio State University, Columbus, OH 43210, USA
3
Molecular Cellular and Developmental Biology Graduate Program, the Ohio State University, Columbus, OH 43210, USA
4
Nutrition Graduate Program, the Ohio State University, Columbus, OH 43210, USA
5
Comprehensive Cancer Center, the Ohio State University, Columbus, OH 43210, USA
6
Center for Applied Plant Sciences, the Ohio State University, Columbus, OH 43210, USA
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Gopinadhan Paliyath
Received: 20 January 2016 / Revised: 16 February 2016 / Accepted: 16 February 2016 / Published: 1 March 2016
(This article belongs to the Special Issue The Mechanism of Action of Food Components in Disease Prevention)
View Full-Text   |   Download PDF [11219 KB, uploaded 1 March 2016]   |  

Abstract

The increasing prevalence of inflammatory diseases and the adverse effects associated with the long-term use of current anti-inflammatory therapies prompt the identification of alternative approaches to reestablish immune balance. Apigenin, an abundant dietary flavonoid, is emerging as a potential regulator of inflammation. Here, we show that apigenin has immune-regulatory activity in vivo. Apigenin conferred survival to mice treated with a lethal dose of Lipopolysaccharide (LPS) restoring normal cardiac function and heart mitochondrial Complex I activity. Despite the adverse effects associated with high levels of splenocyte apoptosis in septic models, apigenin had no effect on reducing cell death. However, we found that apigenin decreased LPS-induced apoptosis in lungs, infiltration of inflammatory cells and chemotactic factors’ accumulation, re-establishing normal lung architecture. Using NF-κB luciferase transgenic mice, we found that apigenin effectively modulated NF-κB activity in the lungs, suggesting the ability of dietary compounds to exert immune-regulatory activity in an organ-specific manner. Collectively, these findings provide novel insights into the underlying immune-regulatory mechanisms of dietary nutraceuticals in vivo. View Full-Text
Keywords: apoptosis; flavonoids; apigenin; leukocytes; NF-κB; inflammation; sepsis; mitochondria; cardiac dysfunction apoptosis; flavonoids; apigenin; leukocytes; NF-κB; inflammation; sepsis; mitochondria; cardiac dysfunction
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Cardenas, H.; Arango, D.; Nicholas, C.; Duarte, S.; Nuovo, G.J.; He, W.; Voss, O.H.; Gonzalez-Mejia, M.E.; Guttridge, D.C.; Grotewold, E.; Doseff, A.I. Dietary Apigenin Exerts Immune-Regulatory Activity in Vivo by Reducing NF-κB Activity, Halting Leukocyte Infiltration and Restoring Normal Metabolic Function. Int. J. Mol. Sci. 2016, 17, 323.

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