{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T20:48:55Z","timestamp":1793047735048,"version":"4.5.0"},"reference-count":40,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004564","name":"Ministry of Education, Science, and Technological Development of the Republic of Serbia","doi-asserted-by":"crossref","award":["451-03-137\/2025-03\/200113"],"award-info":[{"award-number":["451-03-137\/2025-03\/200113"]}],"id":[{"id":"10.13039\/501100004564","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Numerous plant-derived products have shown notable potential in preclinical studies and traditional use for the management of periodontitis, although clinical studies validating their efficacy remain scarce. The present study investigated the efficacy of a polyherbal phytopreparation as an adjunctive therapy to scaling and root planing (SRP) in patients with periodontitis, and further examined its underlying mechanisms of action, pharmacokinetic behavior, and toxicological profile using in silico approaches. Methods: Eighty patients with moderate periodontitis (stage II, grade A) were randomly assigned to two groups: a control group (n = 40) treated with SRP alone, and an experimental group (n = 40) receiving SRP followed by topical phytotherapeutic treatment with the polyherbal Tinctura paradentoica\u00ae. Efficacy was evaluated using the gingival index, periodontal pocket depth, and cytomorphometric analysis of gingival cells before treatment and one month after. The in silico analysis, guided by HPLC profiling, included MolDock-based docking to assess interactions of bioactive compounds with cyclooxygenase isoforms COX-1 and COX-2 as anti-inflammatory targets, and evaluation of their pharmacokinetic and toxicity properties (ADME\/Tox) using SwissADME, ProTox-3.0, and pkCSM. Results: Compared with SRP treatment, the experimental treatment significantly reduced the gingival index and periodontal pocket depth (p &lt; 0.05), as well as the assessed cytomorphometric parameters (nuclear area, perimeter, and Feret\u2019s diameter values) (p &lt; 0.001). Rerank analysis revealed van der Waals-driven isoform selectivity: compact phenolic acids and aglycones favored COX-1, whereas bulky glycosides (e.g., rutin, narcissoside) were optimized for COX-2, with luteolin-7-O-glucoside showing near-balanced engagement. The ADME\/Tox analysis indicated generally favorable pharmacokinetic and safety characteristics of phenolic compounds from the phytopreparation, including low systemic absorption and no predicted mutagenicity or skin sensitization potential. Conclusions: The topical application of the polyherbal phytopreparation demonstrated significant potential to enhance the efficacy of conventional SRP therapy by promoting the regression of gingival inflammation in patients with moderate periodontitis, further supported by in silico findings.<\/jats:p>","DOI":"10.3390\/ph19030398","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T16:06:59Z","timestamp":1772467619000},"page":"398","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Topical Polyherbal Phytopreparation Reduces Gingival Inflammation: Evidence from a Randomized Controlled Clinical Study Supported by In Silico Analysis"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6564-5131","authenticated-orcid":false,"given":"Milica","family":"Petrovi\u0107","sequence":"first","affiliation":[{"name":"Department of Oral Medicine and Periodontology, Dental Clinic, Faculty of Medicine, University of Ni\u0161, 18108 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ljiljana","family":"Kesi\u0107","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine and Periodontology, Dental Clinic, Faculty of Medicine, University of Ni\u0161, 18108 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jovana","family":"Veselinovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Novi Sad, University of Business Academy, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Popovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Restorative Dentistry and Endodontics, Dental Clinic, Faculty of Medicine, University of Ni\u0161, 18108 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikola","family":"\u017divkovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pathology, Institute of Pathology, Clinical Center, Faculty of Medicine, University of Ni\u0161, 18108 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2880-6519","authenticated-orcid":false,"given":"Bojana","family":"Miladinovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine, University of Ni\u0161, 18108 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0039-0929","authenticated-orcid":false,"given":"Milo\u0161 S.","family":"Jovanovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine, University of Ni\u0161, 18108 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4375-7519","authenticated-orcid":false,"given":"Branislava","family":"Stojkovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Preventive and Pediatric Dentistry, Dental Clinic, Faculty of Medicine, University of Ni\u0161, 18108 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Stojanovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery, Dental Clinic, Faculty of Medicine, University of Ni\u0161, 18108 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8551-274X","authenticated-orcid":false,"given":"Du\u0161anka","family":"Kiti\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine, University of Ni\u0161, 18108 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/prd.12104","article-title":"Molecular aspects of the pathogenesis of periodontitis","volume":"69","author":"Meyle","year":"2015","journal-title":"Periodontology 2000"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S68","DOI":"10.1002\/JPER.20-0262","article-title":"Maintaining barrier function of infected gingival epithelial cells by inhibition of DNA methylation","volume":"91","author":"Barros","year":"2020","journal-title":"J. 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