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Updated: Oct 26, 2025
Robust Ligature-Induced Model of Murine Periodontitis for the Evaluation of Oral Neutrophils
Published on: January 21, 2020
Nobiletin Decreases Inflammatory Mediator Expression in Tumor Necrosis Factor-Stimulated Human Periodontal Ligament
Yoshitaka Hosokawa1, Ikuko Hosokawa1, Kazumi Ozaki2
1Department of Conservative Dentistry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Tokushima, Japan.
Abstract:
Nobiletin, a biologically active substance in the skin of citrus fruits, has been reported to be an effective anti-inflammatory, anticancer, and antimicrobial agent. In this study, we aimed to examine the anti-inflammatory effects of nobiletin on tumor necrosis factor- (TNF-) stimulated human periodontal ligament cells (HPDLCs). Our results demonstrated that nobiletin treatment could decrease the expressions of inflammatory cytokines (C-X-C motif chemokine ligand (CXCL)10, C-C motif chemokine ligand (CCL)2, and interleukin- (IL-) 8), matrix metalloproteinases (MMPs) (MMP1 and MMP3), and prostaglandin-endoperoxide synthase 2 (PTGS2) in TNF-stimulated HPDLCs. Moreover, we revealed that nobiletin could inhibit the activation of nuclear factor- (NF-) κB and protein kinase B (AKT1) pathways in TNF-stimulated HPDLCs. Furthermore, nobiletin treatment enhanced nuclear factor, erythroid 2 like 2 (NFE2L2) and heme oxygenase 1 (HMOX1) expressions in TNF-stimulated HPDLCs. In conclusion, these findings suggest that nobiletin can inhibit inflammatory responses in TNF-stimulated HPDLCs by inhibiting NF-κB and AKT1 activations and upregulating the NFE2L2 and HMOX1 expression.
Insights
Nobiletin, a citrus fruit compound, reduces inflammation in human periodontal ligament cells by blocking key inflammatory pathways and boosting protective responses. This suggests potential therapeutic applications for nobiletin in managing inflammatory conditions.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Nobiletin, a natural flavonoid from citrus fruit peels, exhibits known anti-inflammatory, anticancer, and antimicrobial properties.
- Periodontal diseases involve chronic inflammation of the tissues supporting the teeth, often exacerbated by inflammatory cytokines.
Purpose of the Study:
- To investigate the anti-inflammatory effects of nobiletin on human periodontal ligament cells (HPDLCs) stimulated with tumor necrosis factor-alpha (TNF-α).
Main Methods:
- HPDLCs were treated with nobiletin and stimulated with TNF-α.
- Gene and protein expression levels of inflammatory markers, matrix metalloproteinases (MMPs), and key signaling pathway components were analyzed.
Main Results:
- Nobiletin significantly reduced the expression of inflammatory cytokines (CXCL10, CCL2, IL-8), MMPs (MMP1, MMP3), and PTGS2 in TNF-α-stimulated HPDLCs.
- Nobiletin inhibited the activation of nuclear factor-kappa B (NF-κB) and protein kinase B (AKT1) pathways.
- Nobiletin treatment increased the expression of NFE2L2 and HMOX1, indicating activation of the antioxidant response.
Conclusions:
- Nobiletin demonstrates potent anti-inflammatory effects in HPDLCs by suppressing NF-κB and AKT1 signaling.
- Upregulation of NFE2L2 and HMOX1 by nobiletin contributes to its protective effects against TNF-α-induced inflammation.
- These findings highlight nobiletin's potential as a therapeutic agent for inflammatory periodontal conditions.
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