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Int J Mol Sci. 2016 Mar 1;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.

Author information

1
Department of Physiology and Cell Biology, the Heart and Lung Research Institute, the Ohio State University, Columbus, OH 43210, USA. horacio.cardenas@northwestern.edu.
2
Department of Molecular Genetics, the Ohio State University, Columbus, OH 43210, USA. horacio.cardenas@northwestern.edu.
3
Department of Physiology and Cell Biology, the Heart and Lung Research Institute, the Ohio State University, Columbus, OH 43210, USA. dany33co@gmail.com.
4
Department of Molecular Genetics, the Ohio State University, Columbus, OH 43210, USA. dany33co@gmail.com.
5
Molecular Cellular and Developmental Biology Graduate Program, the Ohio State University, Columbus, OH 43210, USA. dany33co@gmail.com.
6
Department of Physiology and Cell Biology, the Heart and Lung Research Institute, the Ohio State University, Columbus, OH 43210, USA. nicholas.40@buckeyemail.osu.edu.
7
Department of Molecular Genetics, the Ohio State University, Columbus, OH 43210, USA. nicholas.40@buckeyemail.osu.edu.
8
Molecular Cellular and Developmental Biology Graduate Program, the Ohio State University, Columbus, OH 43210, USA. nicholas.40@buckeyemail.osu.edu.
9
Department of Physiology and Cell Biology, the Heart and Lung Research Institute, the Ohio State University, Columbus, OH 43210, USA. duartesanmiguel.1@osu.edu.
10
Department of Molecular Genetics, the Ohio State University, Columbus, OH 43210, USA. duartesanmiguel.1@osu.edu.
11
Nutrition Graduate Program, the Ohio State University, Columbus, OH 43210, USA. duartesanmiguel.1@osu.edu.
12
Comprehensive Cancer Center, the Ohio State University, Columbus, OH 43210, USA. gerard.nuovo@osumc.edu.
13
Molecular Cellular and Developmental Biology Graduate Program, the Ohio State University, Columbus, OH 43210, USA. he.115@osu.edu.
14
Comprehensive Cancer Center, the Ohio State University, Columbus, OH 43210, USA. he.115@osu.edu.
15
Department of Molecular Genetics, the Ohio State University, Columbus, OH 43210, USA. ollivoss39@gmail.com.
16
Department of Physiology and Cell Biology, the Heart and Lung Research Institute, the Ohio State University, Columbus, OH 43210, USA. elba.gonzalezmejia@gmail.com.
17
Department of Molecular Genetics, the Ohio State University, Columbus, OH 43210, USA. elba.gonzalezmejia@gmail.com.
18
Comprehensive Cancer Center, the Ohio State University, Columbus, OH 43210, USA. denis.guttridge@osumc.edu.
19
Department of Molecular Genetics, the Ohio State University, Columbus, OH 43210, USA. Grotewold.1@osu.edu.
20
Center for Applied Plant Sciences, the Ohio State University, Columbus, OH 43210, USA. Grotewold.1@osu.edu.
21
Department of Physiology and Cell Biology, the Heart and Lung Research Institute, the Ohio State University, Columbus, OH 43210, USA. doseff.1@osu.edu.
22
Department of Molecular Genetics, the Ohio State University, Columbus, OH 43210, USA. doseff.1@osu.edu.

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.

KEYWORDS:

NF-κB; apigenin; apoptosis; cardiac dysfunction; flavonoids; inflammation; leukocytes; mitochondria; sepsis

PMID:
26938530
PMCID:
PMC4813185
DOI:
10.3390/ijms17030323
[Indexed for MEDLINE]
Free PMC Article

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