ArticleNutrients2018
Phloretin as a Potent Natural TLR2/1 Inhibitor Suppresses TLR2-Induced Inflammation.
Article in Nutrients, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Therapeutic benefits of flavonoids against neuroinflammation: a systematic review.Inflammopharmacology · 2022Pooled it
- Honey as a Natural Flavorful Product: A Comprehensive Review of Its Potential Biological Activities and Recent Studies.Food science & nutrition · 2026Review
- Identification and validation of microglia-associated genes in ischemic stroke using single-cell and bulk RNA-seq.Molecular brain · 2025Article
- Fucosylated Glycosaminoglycan Oligosaccharide HS14, Derived from Sea Cucumbers, Is a Novel Inhibitor of Platelet Toll-like Receptor 2.Marine drugs · 2025Article
- The Possible Mechanistic Basis of Individual Susceptibility to Spike Protein Injury.Advances in virology · 2025Review
- Phloretin attenuates inflammation induced by subarachnoid hemorrhage through regulation of the TLR2/MyD88/NF-kB pathway.Scientific reports · 2024Article
- Proteomic Analysis of Signaling Pathways Modulated by Fatty Acid Binding Protein 5 (FABP5) in Macrophages.The Journal of pharmacology and experimental therapeutics · 2024Article
- Inhibition of NAMPT by PAK4 Inhibitors.International journal of molecular sciences · 2024Article
- Antimicrobial Effect of Honey Phenolic Compounds againstPharmaceuticals (Basel, Switzerland) · 2024Article
- AgeAnnoMO: a knowledgebase of multi-omics annotation for animal aging.Nucleic acids research · 2024Article
- Characterization of the Antimicrobial Activities ofPharmaceutics · 2023Article
- Review
- Molecular mechanism underlying the TLR4 antagonistic and antiseptic activities of papiliocin, an insect innate immune response molecule.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Role of Toll-Like Receptors and Th Responses in Viral Myocarditis.Frontiers in immunology · 2022Review
- Dynamics of Phloridzin and Related Compounds in Four Cultivars of Apple Trees during the Vegetation Period.Molecules (Basel, Switzerland) · 2021Article
- Extracellular vesicles secreted by Giardia duodenalis regulate host cell innate immunity via TLR2 and NLRP3 inflammasome signaling pathways.PLoS neglected tropical diseases · 2021Article
- Dietary Grape Seed Meal Bioactive Compounds Alleviate Epithelial Dysfunctions and Attenuates Inflammation in Colon of DSS-Treated Piglets.Foods (Basel, Switzerland) · 2021Article
- Phloretin, an Apple Polyphenol, Inhibits Pathogen-Induced Mucin Overproduction.Molecular nutrition & food research · 2021Article
- Role of Toll-Like Receptors in Neuroimmune Diseases: Therapeutic Targets and Problems.Frontiers in immunology · 2021Review
- Phloretin Protects Macrophages fromJournal of microbiology and biotechnology · 2020Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toll-like receptor 2 (TLR2) responses are involved in various inflammatory immune disorders. Phloretin is a naturally occurring dietary flavonoid that is abundant in fruit. Here, we investigated whether the anti-inflammatory activity of phloretin is mediated through TLR2 pathways, and whether phloretin acts as an inhibitor of TLR2/1 heterodimerization using the TLR2/1 agonist Pam₃CSK₄. We tested the effects of phloretin on tumor necrosis factor (TNF)-α production induced by various TLRs using known TLR-specific agonists. Phloretin significantly inhibited Pam₃CSK₄-induced TRL2/1 signaling in Raw264.7 cells compared to TLR signaling induced by the other agonists tested. Therefore, we further tested the effects of phloretin in human embryonic kidney (HEK) 293-hTLR2 cells induced by Pam₃CSK₄, and confirmed that phloretin has comparable inhibition of TLR2/1 heterodimerization to that induced by the known TLR2 inhibitor CU-CPT22. Moreover, phloretin reduced the secretion of the inflammatory cytokines TNF-α and interleukin (IL)-8 in Pam₃CSK₄-induced HEK293-hTLR2 cells, whereas it did not significantly reduce these cytokines under Pam₂CSK₄-induced activation. Western blot results showed that phloretin significantly suppressed Pam₃CSK₄-induced TLR2 and NF-κB p65 expression. The molecular interactions between phloretin and TLR2 were investigated using bio-layer interferometry and in silico docking. Phloretin bound to TLR2 with micromolar binding affinity, and we proposed a binding model of phloretin at the TLR2⁻TLR1 interface. Overall, we confirmed that phloretin inhibits the heterodimerization of TLR2/1, highlighting TLR2 signaling as a therapeutic target for treating TLR2-mediated inflammatory immune diseases.
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