{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:47:35Z","timestamp":1792806455840,"version":"4.5.0"},"reference-count":41,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T00:00:00Z","timestamp":1745625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Silesia, Katowice","award":["BNW-1-011\/K\/4\/O"],"award-info":[{"award-number":["BNW-1-011\/K\/4\/O"]}],"id":[{"id":"https:\/\/ror.org\/005k7hp45","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Medical University of Silesia, Katowice","award":["PCN-1-173\/N\/2\/F"],"award-info":[{"award-number":["PCN-1-173\/N\/2\/F"]}],"id":[{"id":"https:\/\/ror.org\/005k7hp45","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: The link between periodontal pathogens, inflammation, and neurodegenerative processes, including Alzheimer\u2019s disease (AD), is evident. Porphyromonas gingivalis and Treponema denticola release lipopolysaccharide (LPS), constituting a virulence factor that takes part in the brain inflammatory process. Human gingival fibroblasts (HGF-1) are a source of pro-inflammatory cytokines released during periodontal diseases. Propolis is a rich source of quercetin and apigenin, which exhibit anti-inflammatory and immunomodulatory activities, influencing the concentration of pro-inflammatory cytokines. Considering this aspect, models with stimulated HGF-1, followed by LPS and\/or interferon-\u03b1 (IFN-\u03b1), were used. Aim: This study was designed to evaluate the concentrations of selected cytokines produced by HGF-1, which may influence brain inflammation. The immunomodulatory effects of apigenin and quercetin were investigated by measuring the concentration of interleukin-1\u03b2 (IL-1\u03b2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-15 (IL-15), and tumour necrosis factor (TNF-\u03b1). This study\u2019s novelty is based on insights into the immunomodulatory effects of selected flavonoids by correlating the secretion of pro-inflammatory cytokines by gingival fibroblasts during periodontal disease with inflammatory processes in the brain. The cytotoxicity of apigenin and quercetin was estimated using the MTT assay. Fibroblasts were stimulated with LPS at 200 ng\/mL and\/or IFN-\u03b1 at 100 U\/mL concentration, followed by incubation with apigenin (25\u201350 \u00b5g\/mL) and quercetin (25\u201350 \u00b5g\/mL). Cytokine concentrations were measured using the xMAP technology. Results: The most pronounced and statistically significant reduction in cytokine levels, particularly IL-6 and IL-15, was observed for quercetin in both concentrations (25 \u00b5g\/mL and 50 \u00b5g\/mL), especially following LPS stimulation. Apigenin in both analysed concentrations also significantly decreased the level of IL-6. These results suggest that quercetin and apigenin may indirectly act as potential immunomodulators in preventing brain inflammation by inhibiting the inflammatory process in periodontitis; however, this should be confirmed in further studies.<\/jats:p>","DOI":"10.3390\/ph18050628","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T08:28:11Z","timestamp":1746174491000},"page":"628","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Immunomodulatory Effects of Apigenin and Quercetin on Cytokine Secretion by the Human Gingival Fibroblast Cell Line and Their Potential Link to Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2006-6715","authenticated-orcid":false,"given":"Anna","family":"Kurek-G\u00f3recka","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9266-2292","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"K\u0142\u00f3sek","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6173-2702","authenticated-orcid":false,"given":"Rados\u0142aw","family":"Balwierz","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, University of Opole, Oleska 48, 45-052 Opole, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gra\u017cyna","family":"Pietsz","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8216-4495","authenticated-orcid":false,"given":"Zenon P.","family":"Czuba","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"162750","DOI":"10.1155\/2013\/162750","article-title":"Chemistry and Biological Activities of Flavonoids: An Overview","volume":"2013","author":"Kumar","year":"2013","journal-title":"Sci. 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