Simeng Du, Daiwei Yang, Qing Liu, Peng Yang, Zhaoyan Wu, Yvxing Zhang, Siyu Chen, Jun Zhang
{"title":"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","authors":"Simeng Du, Daiwei Yang, Qing Liu, Peng Yang, Zhaoyan Wu, Yvxing Zhang, Siyu Chen, Jun Zhang","doi":"10.2147/DDDT.S541290","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>GB can mitigate periodontitis by blocking the NF-κB pathway, offering dual anti-inflammatory and bone-protective effects.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8309-8326"},"PeriodicalIF":5.1000,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447967/pdf/","citationCount":"0","resultStr":"{\"title\":\"Ginkgolide B Alleviates LPS-Induced Inhibition of Osteogenic Differentiation in Human Periodontal Ligament Stem Cells by Suppressing the p-IκBα/NF-κB Pathway.\",\"authors\":\"Simeng Du, Daiwei Yang, Qing Liu, Peng Yang, Zhaoyan Wu, Yvxing Zhang, Siyu Chen, Jun Zhang\",\"doi\":\"10.2147/DDDT.S541290\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>GB can mitigate periodontitis by blocking the NF-κB pathway, offering dual anti-inflammatory and bone-protective effects.</p>\",\"PeriodicalId\":11290,\"journal\":{\"name\":\"Drug Design, Development and Therapy\",\"volume\":\"19 \",\"pages\":\"8309-8326\"},\"PeriodicalIF\":5.1000,\"publicationDate\":\"2025-09-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447967/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug Design, Development and Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/DDDT.S541290\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Design, Development and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/DDDT.S541290","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Ginkgolide B Alleviates LPS-Induced Inhibition of Osteogenic Differentiation in Human Periodontal Ligament Stem Cells by Suppressing the p-IκBα/NF-κB Pathway.
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.
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
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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.
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