The Aryl Hydrocarbon Receptor (AhR) Mediates the Counter-Regulatory Effects of Pelargonidins in Models of Inflammation and Metabolic Dysfunctions
| Autor: | Agostino Bruno, Adriana Carino, Martina Bordoni, Eleonora Distrutti, Monia Baldoni, Cristina Di Giorgio, Stefano Fiorucci, Silvia Marchianò, Gabriele Costantino, Federica Castiglione, Michele Biagioli, Patrizia Ricci, Giannamaria Annunziato, Rosalinda Roselli, Andrea Faccini, Chiara Fiorucci |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Agonist medicine.drug_class pelargonidins colitis CD36 Anti-Inflammatory Agents Inflammation lcsh:TX341-641 Pharmacology Methylation Pelargonidin Article Anthocyanins 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Aryl hydrocarbon receptor Colitis Hepatic steatosis Inflammation n receptor Pelargonidins In vivo medicine Animals Humans Mice Knockout Mice Inbred BALB C Nutrition and Dietetics biology Chemistry aryl hydrocarbon receptor hepatic steatosis Macrophages Hep G2 Cells medicine.disease Fatty Liver Mice Inbred C57BL 030104 developmental biology RAW 264.7 Cells Mechanism of action Receptors Aryl Hydrocarbon 030220 oncology & carcinogenesis biology.protein medicine.symptom Caco-2 Cells lcsh:Nutrition. Foods and food supply Food Science |
| Zdroj: | Nutrients Nutrients, Vol 11, Iss 8, p 1820 (2019) Volume 11 Issue 8 |
| ISSN: | 2072-6643 |
| Popis: | 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 µ M 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-&alpha 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 abrogated by AhR gene ablation. Mt-P is a synthetic pelargonidin endowed with robust AhR agonist activity that exerts beneficial effects in murine models of inflammation and metabolic dysfunction. |
| Databáze: | OpenAIRE |
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