ArticleInternational journal of molecular sciences2022
Urolithin A Inactivation of TLR3/TRIF Signaling to Block the NF-κB/STAT1 Axis Reduces Inflammation and Enhances Antioxidant Defense in Poly(I:C)-Induced RAW264.7 Cells.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 30 citations in OpenAlex.
- Review
- Urolithin A attenuates inflammation and enhances barrier integrity in an experimental NEC-in-a-Dish model.Pediatric research · 2026Article
- Functional Food-Derived Urolithins: Molecular Mechanisms, Health Effects, and Interactomics with Proteins and Extracellular Vesicles.Molecules (Basel, Switzerland) · 2026Review
- In Vitro Evaluation of Antioxidant and Cytokine-Modulating Activity of Tormentil Rhizome Extract and Its Microbial Metabolites in Human Immune Cells.International journal of molecular sciences · 2025Article
- Ellagic Acid and Gut Microbiota: Interactions, and Implications for Health.Food science & nutrition · 2025Review
- Liposomal Lactoferrin Reduces Brain Neuroinflammation in Rats and Alleviates Jetlag and Improves Sleep Quality After Long-Haul Travel.NeuroSci · 2025Article
- Urolithin A exerts a protective effect on lipopolysaccharide-induced acute lung injury by regulating HMGB1-mediated MAPK and NF-κB signaling pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Recognition of Mycobacterium tuberculosis by macrophage Toll-like receptor and its role in autophagy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Review
- The effect of chronic, non-pathogenic maternal immune activation on offspring postnatal muscle and immune outcomes.Journal of animal science · 2024Article
- Microbiota, natural products, and human health: exploring interactions for therapeutic insights.Frontiers in cellular and infection microbiology · 2024Review
- Pharmacological Effects of Urolithin A and Its Role in Muscle Health and Performance: Current Knowledge and Prospects.Nutrients · 2023Review
- Role of Plant-Derived Compounds in the Molecular Pathways Related to Inflammation.International journal of molecular sciences · 2023Review
- Photobiomodulation promotes spinal cord injury repair by inhibiting macrophage polarization through lncRNA TUG1-miR-1192/TLR3 axis.Cellular & molecular biology letters · 2023Article
- Potential roles of gut microbes in biotransformation of natural products: An overview.Frontiers in microbiology · 2022Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Urolithin A is an active compound of gut-microbiota-derived metabolites of polyphenol ellagic acid that has anti-aging, antioxidative, and anti-inflammatory effects. However, the effects of urolithin A on polyinosinic acid-polycytidylic acid (poly(I:C))-induced inflammation remain unclear. Poly(I:C) is a double-stranded RNA (dsRNA) similar to a virus and is recognized by Toll-like receptor-3 (TLR3), inducing an inflammatory response in immune cells, such as macrophages. Inflammation is a natural defense process of the innate immune system. Therefore, we used poly(I:C)-induced RAW264.7 cells and attenuated the inflammation induced by urolithin A. First, our data suggested that 1-30 μM urolithin A does not reduce RAW264.7 cell viability, whereas 1 μM urolithin A is sufficient for antioxidation and the decreased production of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and C-C chemokine ligand 5. The inflammation-related proteins cyclooxygenase-2 and inducible nitric oxide synthase were also downregulated by urolithin A. Next, 1 μM urolithin A inhibited the levels of interferon (INF)-α and INF-β. Urolithin A was applied to investigate the blockade of the TLR3 signaling pathway in poly(I:C)-induced RAW264.7 cells. Moreover, the TLR3 signaling pathway, subsequent inflammatory-related pathways, and antioxidation pathways showed changes in nuclear factor-κB (NF-κB) signaling and blocked ERK/mitogen-activated protein kinase (MAPK) signaling. Urolithin A enhanced catalase (CAT) and superoxide dismutase (SOD) activities, but decreased malondialdehyde (MDA) levels in poly(I:C)-induced RAW264.7 cells. Thus, our results suggest that urolithin A inhibits TLR3-activated inflammatory and oxidative-associated pathways in macrophages, and that this inhibition is induced by poly(I:C). Therefore, urolithin A may have antiviral effects and could be used to treat viral-infection-related diseases.
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