{"doi":"10.1016/j.jbc.2022.102651","title":"Dietary polyphenols link extracellular histones and nonhistone proteins","abstract":"Numerous studies have demonstrated antioxidant, anti-inflammatory, antimicrobial, anticancer, and cardio-protective activities of dietary polyphenols, but due to diverse structures and subclasses of polyphenols, little is known about their mechanisms of action. The study by Yamaguchi et al. published in JBC provides mechanistic insights into how dietary polyphenols confer histone-binding ability on certain proteins and motivates the research community to further explore health benefits of polyphenols. Numerous studies have demonstrated antioxidant, anti-inflammatory, antimicrobial, anticancer, and cardio-protective activities of dietary polyphenols, but due to diverse structures and subclasses of polyphenols, little is known about their mechanisms of action. The study by Yamaguchi et al. published in JBC provides mechanistic insights into how dietary polyphenols confer histone-binding ability on certain proteins and motivates the research community to further explore health benefits of polyphenols. Polyphenols constitute a large family of organic compounds containing one or more hydroxylated aromatic rings. Produced by plants as metabolites, polyphenols are abundantly present in fruit, vegetables, tea, herbs, and wine, essentially accounting for their flavor and color and often for their pharmacological properties. Polyphenols have been extensively studied as natural therapeutic tools beneficial in preventing various human diseases and ailments, but they have also been found to impact disease progression and even exhibit curative properties (1Wan M.L.Y. Co V.A. El-Nezami H. Dietary polyphenol impact on gut health and microbiota.Crit. Rev. Food Sci. Nutr. 2021; 61: 690-711Google Scholar, 2Brglez Mojzer E. Knez Hrncic M. Skerget M. Knez Z. Bren U. Polyphenols: extraction methods, antioxidative action, bioavailability and anticarcinogenic effects.Molecules. 2016; 21: 901Google Scholar). Despite recent interest in exploring the therapeutic potential of polyphenols, especially in combination with existing drugs and conventional therapies, our understanding of the molecular mechanisms underlying their anticancer and anti-inflammatory activities remains very limited. Generally, these mechanisms relate to the antioxidative properties of polyphenols, which alter the cell signaling cascades that trigger cell cycle arrest and apoptosis of cancer cells or attenuate their adhesiveness, reducing their metastatic potential (2Brglez Mojzer E. Knez Hrncic M. Skerget M. Knez Z. Bren U. Polyphenols: extraction methods, antioxidative action, bioavailability and anticarcinogenic effects.Molecules. 2016; 21: 901Google Scholar). Through other mechanisms, polyphenols interfere with cytokine production and immune responses, modulate gut microbiota, or amend gene expression and the pattern of epigenetic marks, such as DNA methylation and histone posttranslational modifications (2Brglez Mojzer E. Knez Hrncic M. Skerget M. Knez Z. Bren U. Polyphenols: extraction methods, antioxidative action, bioavailability and anticarcinogenic effects.Molecules. 2016; 21: 901Google Scholar). Consumed polyphenols are predominantly polyglycosylated and therefore are characterized by high molecular weight and complex structures, which markedly impede their absorption and penetration of the cell membrane, thus constraining their activity largely to the extracellular space. Although histones are well recognized as DNA-binding nuclear proteins and major components of chromatin, they are also found on the surface of human blood monocytes, activated lymphocytes, leukocytes, and apoptotic cells (3Das R. Plow E.F. Phosphatidylserine as an anchor for plasminogen and its plasminogen receptor, histone H2B, to the macrophage surface.J. Thromb. Haemost. 2011; 9: 339-349Google Scholar). In addition, neutrophils release the neutrophil extracellular trap, a web-like complex of chromatin and antimicrobial proteins, into the extracellular space to fight pathogens that are too large for ph","journal":"Journal of Biological Chemistry","year":2022,"id":293353,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.951,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":314067,"name":"Tatiana G. Kutateladze","orcid":"0000-0001-7375-6990","position":1,"is_corresponding":false},{"id":314066,"name":"Jiuyang Liu","orcid":"0000-0003-4178-1184","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-19T00:30:53.818562Z","pmid":"36377105","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}