Ginkgolide B Alleviates LPS-Induced Inhibition of Osteogenic Differentiation in Human Periodontal Ligament Stem Cells by Suppressing the p-IκBα/NF-κB Pathway.

IF 5.1 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2025-09-15 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S541290

Simeng Du, Daiwei Yang, Qing Liu, Peng Yang, Zhaoyan Wu, Yvxing Zhang, Siyu Chen, Jun Zhang

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引用次数: 0

Abstract

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.

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银杏内酯B通过抑制p -κB α/NF-κB通路减轻lps诱导的人牙周韧带干细胞成骨分化的抑制作用

背景：银杏内酯B （Ginkgolide B， GB）是临床广泛应用的天然抗炎药物。本研究在大鼠牙周炎模型中探讨了GB对人牙周干细胞成骨分化的影响及其机制，并评价了其对牙周破坏的保护作用。方法：体外分离鉴定HPDLSCs。采用脂多糖（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）、定量钙法、碱性磷酸酶（ALP）染色和活性法、免疫荧光法评估HPDLSCs的增殖和成骨分化。采用qRT-PCR和Western blot检测成骨相关基因和蛋白的表达。为了验证NF-κB （nuclear factor kappa-B）通路在该机制中的作用，我们使用NF-κB信号通路抑制剂BAY-11-7082后，采用Western blot分析检测NF-κB通路相关蛋白的表达水平。采用体内实验建立大鼠牙周炎模型。显微计算机断层扫描（micro-CT）量化了牙槽骨丢失，而免疫组织化学染色（IHC）评估了组织重塑。使用GraphPad Prism 8软件对测试结果进行分析。两组以上的差异分析采用单向或双向方差分析（ANOVA），然后进行Tukey检验。p < 0.05为差异有统计学意义。结果：LPS刺激HPDLSCs产生炎症，抑制其成骨，而GB（25、100 μM）可逆转这一作用。Western blot检测结果显示，GB和BAY11-7082对NF-κB通路具有相似的抑制作用。在体内，GB减轻了牙周炎大鼠的牙槽骨丢失和炎症组织破坏。结论：GB可通过阻断NF-κB通路减轻牙周炎，具有抗炎和保护骨的双重作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.