Differential Protective Effect of Resveratrol and Its Microbial Metabolites on Intestinal Barrier Dysfunction is Mediated by the AMPK Pathway

Journal of Agricultural and Food Chemistry, Год журнала: 2022, Номер 70(36), С. 11301 - 11313

Опубликована: Сен. 6, 2022

The effectiveness of resveratrol (RES) on intestinal barrier dysfunction and colitis has been extensively studied. However, the specific effects its microbial metabolites gut function remain unclear. Hence, we compared protective RES dihydroresveratrol (DHR) 3-(4-hydroxyphenyl)-propionic acid (4HPP) against injury colitis. Only 4HPP significantly reduced paracellular permeability secretion proinflammatory cytokines in lipopolysaccharides (LPS)-treated Caco-2 cells, which was consistent with upregulation tight junction (TJ) proteins. Furthermore, ameliorated colonic inflammation mice, while DHR did not. In particular, expressions TJ proteins Muc2 were restored by 4HPP. molecular mechanism involved adenosine monophosphate-activated protein kinase (AMPK)-mediated activation CDX2 regulation SIRT1/NF-κB pathway. These findings provide new insights into understanding damage

Язык: Английский

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Sesamol alleviates manganese-induced neuroinflammation and cognitive impairment via regulating the microglial cGAS-STING/NF-κB pathway

Environmental Pollution, Год журнала: 2022, Номер 319, С. 120988 - 120988

Опубликована: Дек. 31, 2022

Toxic effects of excessive manganese (Mn) from occupational or environmental exposure cause harm to human health. Excessive Mn is intimately associated with neurodegeneration and cognitive dysfunction. Inflammatory responses mediated by microglia are essential contributors the pathogenesis Mn-induced neurotoxicity. Inhibition microglia-mediated inflammation has been shown alleviate Sesamol, derived sesame, neuroprotective properties in various disease models, including neurological diseases. Whether sesamol protects against injuries not determined. Here, both vivo vitro models were established address beneficial on We showed that administration mitigated learning memory deficits mice treated Mn. Furthermore, reduced microglial activation expression proinflammatory mediators (TNF-α, iNOS, Cxcl10), while exerting a marginal effect anti-inflammation phagocytosis. activated cGAS-STING pathway inhibited this reducing phosphorylation STING NF-κB, concomitantly decreasing IFN-α IFN-β synthesis. In summary, our novel results indicated exerted its protective neuroinflammation impairment via cGAS-STING/NF-κB pathway, providing evidence may serve as an effective therapeutic for preventing treating

Язык: Английский

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Mechanisms of manganese-induced neurotoxicity and the pursuit of neurotherapeutic strategies

Frontiers in Pharmacology, Год журнала: 2022, Номер 13

Опубликована: Дек. 20, 2022

Chronic exposure to elevated levels of manganese

Язык: Английский

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Multi-omics analysis reveals Mn exposure affects ferroptosis pathway in zebrafish brain

Ecotoxicology and Environmental Safety, Год журнала: 2023, Номер 253, С. 114616 - 114616

Опубликована: Фев. 15, 2023

Manganese (Mn) accumulates in the central nervous system and can cause neurotoxicity, but mechanisms of Mn-induced neurotoxicity remain unclear. We performed single-cell RNA sequencing (scRNA-seq) zebrafish brain after Mn exposure identified 10 cell types by marker genes: cholinergic neurons, dopaminergic (DA) glutaminergic GABAergic neuronal precursors, other microglia, oligodendrocyte, radial glia, undefined cells. Each type has its distinct transcriptome profile. Pseudotime analysis revealed that DA neurons had a critical role neurological damage. Combined with metabolomic data, chronic significantly impaired amino acid lipid metabolic processes brain. Furthermore, we found disrupted ferroptosis signaling pathway zebrafish. Overall, our study employed joint multi-omics is novel potential mechanism neurotoxicity.

Язык: Английский

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Ferroptosis at the crossroads of manganese-induced neurotoxicity: A retrospective study

Toxicology, Год журнала: 2024, Номер 502, С. 153727 - 153727

Опубликована: Янв. 10, 2024

Язык: Английский

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