{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T23:44:49Z","timestamp":1785368689945,"version":"3.55.0"},"reference-count":105,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures","award":["163\/7\/10.01.2023"],"award-info":[{"award-number":["163\/7\/10.01.2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Periodontitis is unanimously accepted to be the sixth complication of diabetes mellitus (DM), while the inverse relationship of causality is still to be deciphered. Among the proposed mechanisms is gut dysbiosis, which is responsible for the systemic release of proinflammatory mediators. In this process, Gram-negative bacteria from the oral cavity enter the general circulation, leading to the emergence of bi-hormonal beta-pancreatic cells that lack the ability to secrete insulin. Additionally, epigenetic and adaptive mechanisms in affected cells may play a role in reducing inflammation. The release of reactive oxygen species, proinflammatory cytokines, and adipokines, such as interleukins, tumor necrosis factor alpha, leptin, prostaglandin E2, C-reactive protein, or matrix metalloproteinases, determine epigenetic changes, such as the methylation of DNA nucleotides or changes in the activity of histone acetylases\/deacetylases. The management of periodontitis involves targeting inflammation, and its potential connection to epigenetic modulation observed in other chronic conditions may help to explain its role in preventing DM in affected patients. This review focuses on the key epigenetic changes in periodontitis that might contribute to DM development, and explores the mechanisms and novel multi-drug therapies that could help to prevent these effects.<\/jats:p>","DOI":"10.3390\/ijms26072853","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T10:10:08Z","timestamp":1742551808000},"page":"2853","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Targeting Epigenetic Plasticity to Reduce Periodontitis-Related Inflammation in Diabetes: CBD, Metformin, and Other Natural Products as Potential Synergistic Candidates for Regulation? A Narrative Review"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9704-869X","authenticated-orcid":false,"given":"Amelia","family":"Tero-Vescan","sequence":"first","affiliation":[{"name":"Department of Medical Chemistry and Biochemistry, Faculty of Medicine in English, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, 540139 T\u00e2rgu Mure\u015f, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3767-4861","authenticated-orcid":false,"given":"Mark","family":"Slevin","sequence":"additional","affiliation":[{"name":"Centre for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, 540139 T\u00e2rgu Mure\u015f, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia","family":"Pu\u0219ca\u0219","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Chemistry of the Environmental Factors, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, 540139 T\u00e2rgu Mure\u015f, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Drago\u0219","family":"Sita","sequence":"additional","affiliation":[{"name":"Department of Odontology and Oral Pathology, Faculty of Dental Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, 540139 T\u00e2rgu Mure\u015f, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3346-3867","authenticated-orcid":false,"given":"Ruxandra","family":"\u0218tef\u0103nescu","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy and Phytotherapy, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, 540139 T\u00e2rgu Mure\u015f, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Dong, Z., Wu, L., and Hong, H. 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