title: Dietary Apigenin Exerts Immune-Regulatory Activity in Vivo by Reducing NF-κB Activity, Halting Leukocyte Infiltration and Restoring Normal Metabolic Function.
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.
authors.affiliation: Department of Physiology and Cell Biology, the Heart and Lung Research Institute, the Ohio State University, Columbus, OH 43210, USA. horacio.cardenas@northwestern.edu.|Department of Molecular Genetics, the Ohio State University, Columbus, OH 43210, USA. horacio.cardenas@northwestern.edu.
authors.forename: Horacio
authors.initials: H
authors.lastname: Cardenas
authors.affiliation: Department of Physiology and Cell Biology, the Heart and Lung Research Institute, the Ohio State University, Columbus, OH 43210, USA. dany33co@gmail.com.|Department of Molecular Genetics, the Ohio State University, Columbus, OH 43210, USA. dany33co@gmail.com.|Molecular Cellular and Developmental Biology Graduate Program, the Ohio State University, Columbus, OH 43210, USA. dany33co@gmail.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Arango
authors.affiliation: 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.|Department of Molecular Genetics, the Ohio State University, Columbus, OH 43210, USA. nicholas.40@buckeyemail.osu.edu.|Molecular Cellular and Developmental Biology Graduate Program, the Ohio State University, Columbus, OH 43210, USA. nicholas.40@buckeyemail.osu.edu.
authors.forename: Courtney
authors.initials: C
authors.lastname: Nicholas
authors.affiliation: Department of Physiology and Cell Biology, the Heart and Lung Research Institute, the Ohio State University, Columbus, OH 43210, USA. duartesanmiguel.1@osu.edu.|Department of Molecular Genetics, the Ohio State University, Columbus, OH 43210, USA. duartesanmiguel.1@osu.edu.|Nutrition Graduate Program, the Ohio State University, Columbus, OH 43210, USA. duartesanmiguel.1@osu.edu.
authors.forename: Silvia
authors.initials: S
authors.lastname: Duarte
authors.affiliation: Comprehensive Cancer Center, the Ohio State University, Columbus, OH 43210, USA. gerard.nuovo@osumc.edu.
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Nuovo
authors.affiliation: Molecular Cellular and Developmental Biology Graduate Program, the Ohio State University, Columbus, OH 43210, USA. he.115@osu.edu.|Comprehensive Cancer Center, the Ohio State University, Columbus, OH 43210, USA. he.115@osu.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: Department of Molecular Genetics, the Ohio State University, Columbus, OH 43210, USA. ollivoss39@gmail.com.
authors.forename: Oliver H
authors.initials: OH
authors.lastname: Voss
authors.affiliation: Department of Physiology and Cell Biology, the Heart and Lung Research Institute, the Ohio State University, Columbus, OH 43210, USA. elba.gonzalezmejia@gmail.com.|Department of Molecular Genetics, the Ohio State University, Columbus, OH 43210, USA. elba.gonzalezmejia@gmail.com.
authors.forename: M Elba
authors.initials: ME
authors.lastname: Gonzalez-Mejia
authors.affiliation: Comprehensive Cancer Center, the Ohio State University, Columbus, OH 43210, USA. denis.guttridge@osumc.edu.
authors.forename: Denis C
authors.initials: DC
authors.lastname: Guttridge
authors.affiliation: Department of Molecular Genetics, the Ohio State University, Columbus, OH 43210, USA. Grotewold.1@osu.edu.|Center for Applied Plant Sciences, the Ohio State University, Columbus, OH 43210, USA. Grotewold.1@osu.edu.
authors.forename: Erich
authors.initials: E
authors.lastname: Grotewold
authors.affiliation: Department of Physiology and Cell Biology, the Heart and Lung Research Institute, the Ohio State University, Columbus, OH 43210, USA. doseff.1@osu.edu.|Department of Molecular Genetics, the Ohio State University, Columbus, OH 43210, USA. doseff.1@osu.edu.
authors.forename: Andrea I
authors.initials: AI
authors.lastname: Doseff
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D047310:Apigenin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D019587:Dietary Supplements; D017254:Leukemic Infiltration / Q000188:drug therapy* / Q000276:immunology; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047310:Apigenin
keywords: NF-κB; apigenin; apoptosis; cardiac dysfunction; flavonoids; inflammation; leukocytes; mitochondria; sepsis