The Immunomodulatory Effects of Apigenin and Quercetin on Cytokine Secretion by the Human Gingival Fibroblast Cell Line and Their Potential Link to Alzheimer’s Disease
<b>Background:</b> The link between periodontal pathogens, inflammation, and neurodegenerative processes, including Alzheimer’s disease (AD), is evident. <i>Porphyromonas gingivalis</i> and <i>Treponema denticola</i> release lipopolysaccharide (LPS), constituting...
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2025-04-01
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| author | Anna Kurek-Górecka Małgorzata Kłósek Radosław Balwierz Grażyna Pietsz Zenon P. Czuba |
| author_facet | Anna Kurek-Górecka Małgorzata Kłósek Radosław Balwierz Grażyna Pietsz Zenon P. Czuba |
| author_sort | Anna Kurek-Górecka |
| collection | DOAJ |
| description | <b>Background:</b> The link between periodontal pathogens, inflammation, and neurodegenerative processes, including Alzheimer’s disease (AD), is evident. <i>Porphyromonas gingivalis</i> and <i>Treponema denticola</i> 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-α (IFN-α), were used. <b>Aim:</b> 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-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-15 (IL-15), and tumour necrosis factor (TNF-α). This study’s 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-α at 100 U/mL concentration, followed by incubation with apigenin (25–50 µg/mL) and quercetin (25–50 µg/mL). Cytokine concentrations were measured using the xMAP technology. <b>Results:</b> The most pronounced and statistically significant reduction in cytokine levels, particularly IL-6 and IL-15, was observed for quercetin in both concentrations (25 µg/mL and 50 µg/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. |
| format | Article |
| id | doaj-art-fa944f7af0bb44b4a54775db4d82de58 |
| institution | Kabale University |
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| spelling | doaj-art-fa944f7af0bb44b4a54775db4d82de582025-08-20T03:47:58ZengMDPI AGPharmaceuticals1424-82472025-04-0118562810.3390/ph18050628The Immunomodulatory Effects of Apigenin and Quercetin on Cytokine Secretion by the Human Gingival Fibroblast Cell Line and Their Potential Link to Alzheimer’s DiseaseAnna Kurek-Górecka0Małgorzata Kłósek1Radosław Balwierz2Grażyna Pietsz3Zenon P. Czuba4Department of Microbiology and Immunology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, PolandDepartment of Microbiology and Immunology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, PolandInstitute of Chemistry, University of Opole, Oleska 48, 45-052 Opole, PolandDepartment of Microbiology and Immunology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, PolandDepartment of Microbiology and Immunology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, Poland<b>Background:</b> The link between periodontal pathogens, inflammation, and neurodegenerative processes, including Alzheimer’s disease (AD), is evident. <i>Porphyromonas gingivalis</i> and <i>Treponema denticola</i> 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-α (IFN-α), were used. <b>Aim:</b> 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-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-15 (IL-15), and tumour necrosis factor (TNF-α). This study’s 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-α at 100 U/mL concentration, followed by incubation with apigenin (25–50 µg/mL) and quercetin (25–50 µg/mL). Cytokine concentrations were measured using the xMAP technology. <b>Results:</b> The most pronounced and statistically significant reduction in cytokine levels, particularly IL-6 and IL-15, was observed for quercetin in both concentrations (25 µg/mL and 50 µg/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.https://www.mdpi.com/1424-8247/18/5/628neurodegenerative diseasecytokinesapigeninquercetinperiodontitis |
| spellingShingle | Anna Kurek-Górecka Małgorzata Kłósek Radosław Balwierz Grażyna Pietsz Zenon P. Czuba The Immunomodulatory Effects of Apigenin and Quercetin on Cytokine Secretion by the Human Gingival Fibroblast Cell Line and Their Potential Link to Alzheimer’s Disease Pharmaceuticals neurodegenerative disease cytokines apigenin quercetin periodontitis |
| title | The Immunomodulatory Effects of Apigenin and Quercetin on Cytokine Secretion by the Human Gingival Fibroblast Cell Line and Their Potential Link to Alzheimer’s Disease |
| title_full | The Immunomodulatory Effects of Apigenin and Quercetin on Cytokine Secretion by the Human Gingival Fibroblast Cell Line and Their Potential Link to Alzheimer’s Disease |
| title_fullStr | The Immunomodulatory Effects of Apigenin and Quercetin on Cytokine Secretion by the Human Gingival Fibroblast Cell Line and Their Potential Link to Alzheimer’s Disease |
| title_full_unstemmed | The Immunomodulatory Effects of Apigenin and Quercetin on Cytokine Secretion by the Human Gingival Fibroblast Cell Line and Their Potential Link to Alzheimer’s Disease |
| title_short | The Immunomodulatory Effects of Apigenin and Quercetin on Cytokine Secretion by the Human Gingival Fibroblast Cell Line and Their Potential Link to Alzheimer’s Disease |
| title_sort | immunomodulatory effects of apigenin and quercetin on cytokine secretion by the human gingival fibroblast cell line and their potential link to alzheimer s disease |
| topic | neurodegenerative disease cytokines apigenin quercetin periodontitis |
| url | https://www.mdpi.com/1424-8247/18/5/628 |
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