scholarly journals The Marine-Derived Natural Product Epiloliolide Isolated from Sargassum horneri Regulates NLRP3 via PKA/CREB, Promoting Proliferation and Anti-Inflammatory Effects of Human Periodontal Ligament Cells

Marine Drugs ◽  
2021 ◽  
Vol 19 (7) ◽  
pp. 388
Author(s):  
Eun-Nam Kim ◽  
Woguti Yvonne Nabende ◽  
Hyeyoon Jeong ◽  
Dongyup Hahn ◽  
Gil-Saeng Jeong
Keyword(s):  
Periodontal Ligament ◽  
Treatment Strategies ◽  
Sargassum Horneri ◽  
Periodontal Ligament Cells ◽  
Differentiation Potential ◽  
Proinflammatory Mediators ◽  
Human Periodontal Ligament Cells ◽  
Anti Inflammatory ◽  
The Impact ◽  
Inflammatory Effect

Currently, periodontitis treatment relies on surgical operations, anti-inflammatory agents, or antibiotics. However, these treatments cause pain and side effects, resulting in a poor prognosis. Therefore, in this study, we evaluated the impact of the compound epiloliolide isolated from Sargassum horneri on the recovery of inflammatory inhibitors and loss of periodontal ligaments, which are essential treatment strategies for periodontitis. Here, human periodontal ligament cells stimulated with PG-LPS were treated with the compound epiloliolide, isolated from S. horneri. In the results of this study, epiloliolide proved the anti-inflammatory effect, cell proliferation capacity, and differentiation potential of periodontal ligament cells into osteoblasts, through the regulation of the PKA/CREB signaling pathway. Epiloliolide effectively increased the proliferation and migration of human periodontal ligament cells without cytotoxicity and suppressed the protein expression of proinflammatory mediators and cytokines, such as iNOS, COX-2, TNF-α, IL-6, and IL-1β, by downregulating NLRP3 activated by PG-LPS. Epiloliolide also upregulated the phosphorylation of PKA/CREB proteins, which play an important role in cell growth and proliferation. It was confirmed that the anti-inflammatory effect in PG-LPS-stimulated large cells was due to the regulation of PKA/CREB signaling. We suggest that epiloliolide could serve as a potential novel therapeutic agent for periodontitis by inhibiting inflammation and restoring the loss of periodontal tissue.

scholarly journals Anti-inflammatory activity of psoralen in human periodontal ligament cells via estrogen receptor signaling pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Huxiao Li ◽  
Jianrong Xu ◽  
Xiaotian Li ◽  
Yi Hu ◽  
Yue Liao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Periodontal Ligament ◽  
Target Genes ◽  
Chinese Herb ◽  
Periodontal Ligament Cells ◽  
Human Periodontal Ligament Cells ◽  
Estrogen Receptor Signaling ◽  
Receptor Signaling Pathway ◽  
Anti Inflammatory ◽  
Molecule Docking

AbstractPsoralen is one of the most effective ingredients extracted from the Chinese herb, Psoralea corylifolia L. Studies have found that psoralen has anti-inflammatory and estrogen-like effects; however, little research has been conducted to elucidate the mechanisms underlying these effects. Through the molecule docking assay, psoralen was found to have a better combination with ERα than ERβ. In human periodontal ligament cells, psoralen was found to upregulate the estrogen target genes (e.g., CTSD, PGR, TFF1) and down-regulate the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-8) stimulated by P. gingivalis LPS, as well as TLR4-IRAK4-NF-κb signaling pathway proteins. These effects were reversed by the ER antagonist ICI 182780. These results indicated that psoralen may exert anti-inflammatory effects as an agonist to ER, which could provide a theoretical basis for the use of psoralen for adjuvant therapy and prevention of periodontitis.

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

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Yoshitaka Hosokawa ◽  
Ikuko Hosokawa ◽  
Kazumi Ozaki
Keyword(s):  
Tumor Necrosis Factor ◽  
Periodontal Ligament ◽  
Tumor Necrosis ◽  
Periodontal Ligament Cells ◽  
Heme Oxygenase 1 ◽  
Nuclear Factor ◽  
Human Periodontal Ligament Cells ◽  
Chemokine Ligand ◽  
Anti Inflammatory ◽  
Necrosis Factor

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.

scholarly journals Panax ginseng Fruit Has Anti-Inflammatory Effect and Induces Osteogenic Differentiation by Regulating Nrf2/HO-1 Signaling Pathway in In Vitro and In Vivo Models of Periodontitis

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1221
Author(s):  
Eun-Nam Kim ◽  
Tae-Young Kim ◽  
Eui Kyun Park ◽  
Jae-Young Kim ◽  
Gil-Saeng Jeong
Keyword(s):  
Panax Ginseng ◽  
Periodontal Ligament ◽  
Therapeutic Agent ◽  
Alveolar Bone ◽  
Periodontal Ligament Cells ◽  
In Vivo Models ◽  
Human Periodontal Ligament Cells ◽  
Anti Inflammatory

Periodontitis is an infectious inflammatory disease of tissues around teeth that destroys connective tissues and is characterized by the loss of periodontal ligaments and alveolar bone. A new treatment strategy is needed owing to the limitations of the current surgical treatment method and the side effects of anti-inflammatory drugs. Therefore, here, we assessed whether Panax ginseng fruit extract (PGFE) is a new therapeutic agent for periodontitis in vitro and in vivo. According to the results, PGFE suppressed pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1β, and IL-6, and pro-inflammatory mediators such as inducible nitric oxide synthase and cyclooxygenase-2 through heme oxygenase-1 expression in human periodontal ligament cells stimulated with Porphyromonas gingivalis lipopolysaccharide (PG-LPS). In addition, the osteogenic induction of human periodontal ligament cells was inhibited by PG-LPS, and protein and mRNA levels of osteogenic markers such as alkaline phosphatase, collagen type 1 (COL1), osteopontin (OPN), and runt-related transcription factor 2 (RUNX2) were increased. The efficacy of PGFE for inhibiting periodontitis in vitro was demonstrated in a representative in vitro model of periodontitis induced by ligature and PG-LPS. Subsequently, hematoxylin and eosin staining and micro-computed tomography of the euthanized experimental animal model confirmed suppressed periodontal inflammation, which is an important strategy for treating periodontitis and for recovering the resulting alveolar bone loss. Therefore, PGFE is a potential, novel therapeutic agent for periodontal diseases.

Globular C1q receptor (p33) binds and stabilizes pro-inflammatory MCP-1: a novel mechanism for regulation of MCP-1 production and function

2018 ◽  
Vol 475 (4) ◽  
pp. 775-786 ◽  
Author(s):  
Emma Anders ◽  
Daniel Nebel ◽  
Johannes Westman ◽  
Heiko Herwald ◽  
Bengt-Olof Nilsson ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Periodontal Ligament ◽  
Molecular Mechanisms ◽  
Periodontal Ligament Cells ◽  
Physical Interaction ◽  
Functional Importance ◽  
Vitro Assay ◽  
Human Periodontal Ligament Cells ◽  
And Function ◽  
The Impact

The protein gC1qR (globular C1q receptor), also named p33, was originally identified as a binding partner of the globular heads of C1q in the complement system. gC1qR/p33 is abundantly expressed in many cell types, but the functional importance of this protein is not completely understood. Here, we investigate the impact of gC1qR/p33 on the production and function of the pathophysiologically important chemokine monocyte chemoattractant protein-1 (MCP-1) and the underlying molecular mechanisms. Knockdown of gC1qR/p33 negatively regulated the production of MCP-1, but had no effect on the expression of transcript for MCP-1 in human periodontal ligament cells, suggesting a translational/post-translational mechanism of action. Laser scanning confocal microscopy showed considerable cytosolic co-localization of gC1qR/p33 and MCP-1, and co-immunoprecipitation disclosed direct physical interaction between gC1qR/p33 and MCP-1. Surface plasmon resonance analysis revealed a high-affinity binding (KD = 10.9 nM) between gC1qR/p33 and MCP-1. Using a transwell migration assay, we found that recombinant gC1qR/p33 enhances MCP-1-induced migration of human THP-1 monocytes, pointing to a functional importance of the interaction between gC1qR/p33 and MCP-1. An in vitro assay revealed a rapid turnover of the MCP-1 protein and that gC1qR/p33 stabilizes MCP-1, hence preventing its degradation. We propose that endogenous gC1qR/p33 physically interacts with MCP-1 causing stabilization of the MCP-1 protein and stimulation of its activity in human periodontal ligament cells, suggesting a novel gC1qR/p33-mediated pro-inflammatory mechanism of action.

scholarly journals Osteoinductive and anti-inflammatory effect of royal jelly on periodontal ligament cells

2011 ◽  
Vol 32 (4) ◽  
pp. 285-291 ◽  
Author(s):  
Manabu Yanagita ◽  
Yuko Kojima ◽  
Kenta Mori ◽  
Satoru Yamada ◽  
Shinya Murakami
Keyword(s):  
Periodontal Ligament ◽  
Royal Jelly ◽  
Periodontal Ligament Cells ◽  
Anti Inflammatory ◽  
Inflammatory Effect
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