The Aryl Hydrocarbon Receptor, Epigenetics and the Aging Process

Abudahab, Sara; Price, Elvin; Dozmorov, Mikhail G.; Deshpande, Laxmikant S.; McClay, Joseph L.

doi:10.1007/s12603-023-1908-1

Cited by 7 publications

(3 citation statements)

References 116 publications

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“…Curcumin, used as a spice, has been proven to be an excellent anti-inflammatory and antioxidant substance, as well as an antiaging element, especially in diseases that are more frequent in adults like cancer and cardiovascular and neurodegenerative diseases. The pathway responsible for its effects implicates the AhR receptor, which will act on CYP1A1 [ 110 ]. Securigera securidaca ’s alcohol extract was used in some studies.…”

Section: Plant Extracts and Phytochemical Compounds With A Positive E...mentioning

confidence: 99%

The Role of Polyphenols in Modulating PON1 Activity Regarding Endothelial Dysfunction and Atherosclerosis

Sirca,

Mureșan,

Pallag

et al. 2024

IJMS

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The incidence and prevalence of cardiovascular diseases are still rising. The principal mechanism that drives them is atherosclerosis, an affection given by dyslipidemia and a pro-inflammatory state. Paraoxonase enzymes have a protective role due to their ability to contribute to antioxidant and anti-inflammatory pathways, especially paraoxonase 1 (PON1). PON1 binds with HDL (high-density lipoprotein), and high serum levels lead to a protective state against dyslipidemia, cardiovascular diseases, diabetes, stroke, nonalcoholic fatty liver disease, and many others. Modulating PON1 expression might be a treatment objective with significant results in limiting the prevalence of atherosclerosis. Lifestyle including diet and exercise can raise its levels, and some beneficial plants have been found to influence PON1 levels; therefore, more studies on herbal components are needed. Our purpose is to highlight the principal roles of Praoxonase 1, its implications in dyslipidemia, cardiovascular diseases, stroke, and other diseases, and to emphasize plants that can modulate PON1 expression, targeting the potential of some flavonoids that could be introduced as supplements in our diet and to validate the hypothesis that flavonoids have any effects regarding PON1 function.

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Section: Plant Extracts and Phytochemical Compounds With A Positive E...mentioning

confidence: 99%

The Role of Polyphenols in Modulating PON1 Activity Regarding Endothelial Dysfunction and Atherosclerosis

Sirca,

Mureșan,

Pallag

et al. 2024

IJMS

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“…The positive effect of AHR agonists in colitis models has also been proved ( Benson and Shepherd, 2011 ; Furumatsu et al., 2011 ; Monteleone et al., 2011 ; Singh et al., 2011 ; Huang et al., 2013 ; Qiu and Zhou, 2013 ; Hanieh, 2014 ; Ji et al., 2015 ; Park et al., 2015 ; Aoki et al., 2018 ; Lv et al., 2018a ; Lv et al., 2018b ; Wang et al., 2018 ; Yu et al., 2018 ; Marafini et al., 2019 ; Singh et al., 2019 ; Chen et al., 2020 ; Liu et al., 2020 ; Lin et al., 2023 ). However, both the markable immunotoxic effects and even carcinogenesis properties of most recognized exogenous synthetic AHR ligands have been elucidated ( Murray et al., 2014 ; Stockinger et al., 2021 ; Abudahab et al., 2023 ; Chen et al., 2023 ), which limited clinical widespread application in IBD patients. Therefore, searching for non-toxic natural AHR ligands and exploring a series of potential mechanisms in the treatment of IBD has become a research hotspot in recent years.…”

Section: Ahr–gut Microbiota Axis In Ibdmentioning

confidence: 99%

“…Several studies have confirmed that colitis can be alleviated by AHR ligands through activating the AHR ( Hanieh, 2014 ; Lv et al., 2018a ; Lv et al., 2018b ; Yu et al., 2018 ; Marafini et al., 2019 ; Chen et al., 2020 ; Lin et al., 2023 ). However, most of the recognized exogenous synthetic AHR ligands have been associated with toxicity, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polycyclic aromatic hydrocarbon (PAH) ( Abudahab et al., 2023 ), which hamper the widespread application of AHR-ligand therapy and forces us to find non-toxic natural AHR ligands.…”

Section: Introductionmentioning

confidence: 99%

Activation of the aryl hydrocarbon receptor in inflammatory bowel disease: insights from gut microbiota

Hou,

Ma,

Qin

2023

Front. Cell. Infect. Microbiol.

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Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disease that affects more than 3.5 million people, with rising prevalence. It deeply affects patients’ daily life, increasing the burden on patients, families, and society. Presently, the etiology of IBD remains incompletely clarified, while emerging evidence has demonstrated that altered gut microbiota and decreased aryl hydrocarbon receptor (AHR) activity are closely associated with IBD. Furthermore, microbial metabolites are capable of AHR activation as AHR ligands, while the AHR, in turn, affects the microbiota through various pathways. In light of the complex connection among gut microbiota, the AHR, and IBD, it is urgent to review the latest research progress in this field. In this review, we describe the role of gut microbiota and AHR activation in IBD and discussed the crosstalk between gut microbiota and the AHR in the context of IBD. Taken as a whole, we propose new therapeutic strategies targeting the AHR–microbiota axis for IBD, even for other related diseases caused by AHR-microbiota dysbiosis.

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Punicalagin as a novel selective aryl hydrocarbon receptor (AhR) modulator upregulates AhR expression through the PDK1/p90RSK/AP-1 pathway to promote the anti-inflammatory response and bactericidal activity of macrophages

Dai,

Yin,

Wang

et al. 2024

Cell Commun Signal

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Aryl hydrocarbon receptor (AhR) plays an important role in inflammation and immunity as a new therapeutic target for infectious disease and sepsis. Punicalagin (PUN) is a Chinese herbal monomer extract of pomegranate peel that has beneficial anti-inflammatory, antioxidant and anti-infective effects. However, whether PUN is a ligand of AhR, its effect on AhR expression, and its signaling pathway remain poorly understood. In this study, we found that PUN was a unique polyphenolic compound that upregulated AhR expression at the transcriptional level, and regulated the AhR nongenomic pathway. AhR expression in lipopolysaccharide-induced macrophages was upregulated by PUN in vitro and in vivo in a time- and dose-dependent manner. Using specific inhibitors and siRNA, induction of AhR by PUN depended on sequential phosphorylation of 90-kDa ribosomal S6 kinase (p90RSK), which was activated by the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) and phosphoinositide-dependent protein kinase (PDK)1 pathways. PUN promoted p90RSK-mediated activator protein-1 (AP-1) activation. AhR knockout or inhibitors reversed suppression of interleukin (IL)-6 and IL-1β expression by PUN. PUN decreased Listeria load and increased macrophage survival via AhR upregulation. In conclusion, we identified PUN as a novel selective AhR modulator involved in AhR expression via the MEK/ERK and PDK1 pathways targeting p90RSK/AP-1 in inflammatory macrophages, which inhibited macrophage inflammation and promoted bactericidal activity. Supplementary Information The online version contains supplementary material available at 10.1186/s12964-024-01847-9.

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The Aryl Hydrocarbon Receptor, Epigenetics and the Aging Process

Cited by 7 publications

References 116 publications

The Role of Polyphenols in Modulating PON1 Activity Regarding Endothelial Dysfunction and Atherosclerosis

The Role of Polyphenols in Modulating PON1 Activity Regarding Endothelial Dysfunction and Atherosclerosis

Activation of the aryl hydrocarbon receptor in inflammatory bowel disease: insights from gut microbiota

Punicalagin as a novel selective aryl hydrocarbon receptor (AhR) modulator upregulates AhR expression through the PDK1/p90RSK/AP-1 pathway to promote the anti-inflammatory response and bactericidal activity of macrophages

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