Kurek-Górecka Anna, Kłósek Małgorzata, Balwierz Radosław, Pietsz Grażyna, Czuba Zenon P
Department of Microbiology and Immunology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, Poland.
Institute of Chemistry, University of Opole, Oleska 48, 45-052 Opole, Poland.
Pharmaceuticals (Basel). 2025 Apr 26;18(5):628. doi: 10.3390/ph18050628.
The link between periodontal pathogens, inflammation, and neurodegenerative processes, including Alzheimer's disease (AD), is evident. and 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. 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. 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.
牙周病原体、炎症与神经退行性过程（包括阿尔茨海默病（AD））之间的联系是明显的。 并释放脂多糖（LPS），构成参与脑部炎症过程的毒力因子。人牙龈成纤维细胞（HGF-1）是牙周疾病期间释放的促炎细胞因子的来源。蜂胶富含槲皮素和芹菜素，它们具有抗炎和免疫调节活性，影响促炎细胞因子的浓度。考虑到这一方面，使用了用LPS和/或干扰素-α（IFN-α）刺激后的HGF-1模型。 本研究旨在评估HGF-1产生的可能影响脑部炎症的特定细胞因子的浓度。通过测量白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、白细胞介素-15（IL-15）和肿瘤坏死因子（TNF-α）的浓度，研究了芹菜素和槲皮素的免疫调节作用。本研究的新颖之处在于，通过将牙周疾病期间牙龈成纤维细胞促炎细胞因子的分泌与脑部炎症过程相关联，深入了解选定黄酮类化合物的免疫调节作用。使用MTT法评估芹菜素和槲皮素的细胞毒性。用浓度为200 ng/mL的LPS和/或浓度为100 U/mL的IFN-α刺激成纤维细胞，然后与芹菜素（25 - 50 µg/mL）和槲皮素（25 - 50 µg/mL）孵育。使用xMAP技术测量细胞因子浓度。 在两种浓度（25 µg/mL和50 µg/mL）下，槲皮素均观察到细胞因子水平最显著且具有统计学意义的降低，尤其是IL-6和IL-15，特别是在LPS刺激后。两种分析浓度的芹菜素也显著降低了IL-6的水平。这些结果表明，槲皮素和芹菜素可能通过抑制牙周炎中的炎症过程，间接作为预防脑部炎症的潜在免疫调节剂；然而，这一点应在进一步研究中得到证实。
