银杏内酯B通过抑制p-IκBα/NF-κB信号通路减轻脂多糖诱导的人牙周膜干细胞成骨分化抑制
Ginkgolide B Alleviates LPS-Induced Inhibition of Osteogenic Differentiation in Human Periodontal Ligament Stem Cells by Suppressing the p-IκBα/NF-κB Pathway.
作者信息
Du Simeng, Yang Daiwei, Liu Qing, Yang Peng, Wu Zhaoyan, Zhang Yvxing, Chen Siyu, Zhang Jun
机构信息
Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, People's Republic of China.
Department of Orthodontics, Taian Maternal and Child Health Hospital, Taian, Shandong, People's Republic of China.
出版信息
Drug Des Devel Ther. 2025 Sep 15;19:8309-8326. doi: 10.2147/DDDT.S541290. eCollection 2025.
BACKGROUND
Ginkgolide B (GB) is a widely utilized natural anti-inflammatory drug in clinical practice. This study investigates GB's effects on human periodontal stem cells (HPDLSCs) osteogenic differentiation under inflammation and its underlying mechanism, while evaluating its protective role against periodontal destruction in a rat periodontitis model.
METHODS
HPDLSCs were isolated and identified in vitro. Lipopolysaccharide (LPS) was used to establish an inflammatory environment. Proliferation and osteogenic differentiation of HPDLSCs were assessed using the Cell-counting Kit-8 (CCK-8), Alizarin Red Staining (ARS), quantitative calcium assay, alkaline phosphatase (ALP) staining and activity assay, and immunofluorescence assay. In addition, the expression of osteogenesis-related genes and proteins was detected by qRT-PCR and Western blot analysis. To verify the role of the NF-κB (nuclear factor kappa-B) pathway in this mechanism, the expression level of NF-κB pathway-related protein was detected by Western blot analysis after using BAY-11-7082 (a NF-κB signaling pathway inhibitor). The rat periodontitis model was established in vivo experiments. Micro-computed tomography (micro-CT) quantified alveolar bone loss, while immunohistochemical staining (IHC) assessed tissue remodeling. Tests were analyzed using GraphPad Prism 8 software. Differences between more than two groups were analyzed by one-way or two-way analysis of variance (ANOVA) followed by Tukey's test. Values of p < 0.05 were considered statistically significant.
RESULTS
LPS treatment triggered inflammation and suppressed osteogenesis in HPDLSCs in vitro, while GB (25, 100 μM) reversed these effects. The results of the Western blot assay showed that both GB and BAY11-7082 exhibited similar inhibitory effects on the NF-κB pathway. In vivo, GB mitigated alveolar bone loss and inflammatory tissue destruction in periodontitis rats.
CONCLUSION
GB can mitigate periodontitis by blocking the NF-κB pathway, offering dual anti-inflammatory and bone-protective effects.
背景
银杏内酯B（GB）是临床实践中广泛应用的天然抗炎药物。本研究探讨GB在炎症条件下对人牙周膜干细胞（HPDLSCs）成骨分化的影响及其潜在机制，同时评估其在大鼠牙周炎模型中对牙周组织破坏的保护作用。
方法
体外分离并鉴定HPDLSCs。使用脂多糖（LPS）建立炎症环境。采用细胞计数试剂盒-8（CCK-8）、茜素红染色（ARS）、定量钙测定、碱性磷酸酶（ALP）染色及活性测定和免疫荧光测定评估HPDLSCs的增殖和成骨分化。此外，通过qRT-PCR和蛋白质免疫印迹分析检测成骨相关基因和蛋白质的表达。为验证核因子κB（NF-κB）通路在该机制中的作用，使用BAY-11-7082（一种NF-κB信号通路抑制剂）后，通过蛋白质免疫印迹分析检测NF-κB通路相关蛋白的表达水平。体内实验建立大鼠牙周炎模型。微计算机断层扫描（micro-CT）定量牙槽骨吸收，而免疫组织化学染色（IHC）评估组织重塑。使用GraphPad Prism 8软件进行测试分析。多组间差异采用单因素或双因素方差分析（ANOVA），随后进行Tukey检验。p<0.05的值被认为具有统计学意义。
结果
LPS处理在体外引发炎症并抑制HPDLSCs的成骨作用，而GB（25、100μM）可逆转这些作用。蛋白质免疫印迹分析结果显示，GB和BAY11-7082对NF-κB通路均表现出相似的抑制作用。在体内，GB减轻了牙周炎大鼠的牙槽骨吸收和炎症组织破坏。
结论
GB可通过阻断NF-κB通路减轻牙周炎，具有抗炎和保护骨组织的双重作用。
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