Nobiletin Decreases Inflammatory Mediator Expression in Tumor Necrosis Factor-Stimulated Human Periodontal Ligament Cells

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 period...

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Main Authors: Yoshitaka Hosokawa, Ikuko Hosokawa, Kazumi Ozaki
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2021/5535844
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author Yoshitaka Hosokawa
Ikuko Hosokawa
Kazumi Ozaki
author_facet Yoshitaka Hosokawa
Ikuko Hosokawa
Kazumi Ozaki
author_sort Yoshitaka Hosokawa
collection DOAJ
description 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.
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institution Kabale University
issn 0962-9351
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language English
publishDate 2021-01-01
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series Mediators of Inflammation
spelling doaj-art-dc7c894046624dee852445f5020ab6f12025-02-03T07:23:31ZengWileyMediators of Inflammation0962-93511466-18612021-01-01202110.1155/2021/55358445535844Nobiletin Decreases Inflammatory Mediator Expression in Tumor Necrosis Factor-Stimulated Human Periodontal Ligament CellsYoshitaka Hosokawa0Ikuko Hosokawa1Kazumi Ozaki2Department of Conservative Dentistry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Tokushima, JapanDepartment of Conservative Dentistry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Tokushima, JapanDepartment of Oral Health Care Promotion, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Tokushima, JapanNobiletin, 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.http://dx.doi.org/10.1155/2021/5535844
spellingShingle Yoshitaka Hosokawa
Ikuko Hosokawa
Kazumi Ozaki
Nobiletin Decreases Inflammatory Mediator Expression in Tumor Necrosis Factor-Stimulated Human Periodontal Ligament Cells
Mediators of Inflammation
title Nobiletin Decreases Inflammatory Mediator Expression in Tumor Necrosis Factor-Stimulated Human Periodontal Ligament Cells
title_full Nobiletin Decreases Inflammatory Mediator Expression in Tumor Necrosis Factor-Stimulated Human Periodontal Ligament Cells
title_fullStr Nobiletin Decreases Inflammatory Mediator Expression in Tumor Necrosis Factor-Stimulated Human Periodontal Ligament Cells
title_full_unstemmed Nobiletin Decreases Inflammatory Mediator Expression in Tumor Necrosis Factor-Stimulated Human Periodontal Ligament Cells
title_short Nobiletin Decreases Inflammatory Mediator Expression in Tumor Necrosis Factor-Stimulated Human Periodontal Ligament Cells
title_sort nobiletin decreases inflammatory mediator expression in tumor necrosis factor stimulated human periodontal ligament cells
url http://dx.doi.org/10.1155/2021/5535844
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AT ikukohosokawa nobiletindecreasesinflammatorymediatorexpressionintumornecrosisfactorstimulatedhumanperiodontalligamentcells
AT kazumiozaki nobiletindecreasesinflammatorymediatorexpressionintumornecrosisfactorstimulatedhumanperiodontalligamentcells