The Aryl Hydrocarbon Receptor (AhR) Mediates the Counter-Regulatory Effects of Pelargonidins in Models of Inflammation and Metabolic Dysfunctions

Nutrients
Michele BiagioliStefano Fiorucci

Abstract

Pelargonidins are anthocyanidins thought to be beneficial for the human health, although controversies exist over the doses needed and the unclear mechanism of action, along with poor systemic bioavailability. One putative target of pelargonidins is the aryl hydrocarbon receptor (AhR). A synthetic pelargonidin (Mt-P) was synthesized by the methylation of the pelargonidin (the natural compound indicated as P). Mt-P transactivated the AhR with an EC50 of 1.97 µM and was ~2-fold more potent than the natural compound. In vitro Mt-P attenuated pro-inflammatory activities of Raw264.7 macrophage cells in an AhR-dependent manner. In vivo, administration of the Mt-P in Balb/c mice resulted in a dose-dependent attenuation of signs and symptoms of colitis induced by TNBS. A dose of 5 mg/kg Mt-P, but not the natural compound P, reversed intestinal inflammation and increased expression of Tnf-α, Ifn-ƴ, and Il-6, while promoted the expansion of regulatory T cells and M2 macrophages. In C57BL/6J mice fed a high fat diet (HFD), Mt-P attenuated body weight gain, intestinal and liver inflammation, and ameliorated insulin sensitivity, while worsened liver steatosis by up-regulating the liver expression of Cd36 and Apo100b. These effects were abro...Continue Reading

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Citations

Mar 28, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michele BiagioliStefano Fiorucci
Dec 29, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Adriana CarinoStefano Fiorucci
Feb 20, 2021·Frontiers in Immunology·Abigail R BassonAlex Rodriguez-Palacios
Apr 20, 2021·Toxicological Research·Stephen SafeRupesh Shrestha

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Methods Mentioned

BETA
X-ray
Immunoprecipitation
sedation
Flow Cytometry
flow-cytometry
ChIP

Software Mentioned

PerARNT
Macromodel
Modeller
Protein Preparation Wizard
Maestro
Prism
Sim
GraphPad

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