Simultaneous Quantitative Analysis of Ginsenosides Isolated from the Fruit of Panax ginseng C.A. Meyer and Regulation of HO-1 Expression through EGFR Signaling Has Anti-Inflammatory and Osteogenic Induction Effects in HPDL Cells

Periodontitis is a set of chronic inflammatory diseases caused by the accumulation of Gram-negative bacteria on teeth, resulting in gingivitis, pocket formation, alveolar bone loss, tissue destruction, and tooth loss. In this study, the contents of ginsenosides isolated from Panax ginseng fruit extract were quantitatively analyzed, and the anti-inflammatory effects were evaluated in human periodontal ligament cells. The major ginsenosides, Re, Ra8, and Rf, present in ginseng fruit were simultaneously analyzed by a validated method using high-performance liquid chromatography with a diode-array detector; Re, Ra8, and Rf content per 1 g of P. ginseng fruit extract was 1.01 ± 0.03, 0.33 ± 0.01, and 0.55 ± 0.04 mg, respectively. Ginsenosides-Re, -Ra8, and -Rf inhibited the production of pro-inflammatory factors and the expression of important cytokines in periodontitis by inducing the expression of heme oxygenase 1 (HO-1), promoting osteoblast differentiation of periodontal ligament cells, suppressing alveolar bone loss, and promoting the expression of osteoblast-specific genes, such as alp, opn, and runx2. An inhibitory effect of these ginsenosides on periodontitis and alveolar bone loss was observed via the regulation of HO-1 and subsequent epidermal growth factor receptor (EGFR) signaling. Silencing EGFR with EGFR siRNA confirmed that the effect of ginsenosides on HO-1 is mediated by EGFR. In conclusion, this study evaluated the contents of ginsenosides-Re, -Ra8, and -Rf isolated from P. ginseng fruit extract. Therefore, these results provide important basic data for future P. ginseng fruit component studies and suggest that ginsenosides Re, Ra8, and Rf have potential as future treatment options for periodontitis.

Download Full-text

Quercetin Prevents Oxidative Stress-Induced Injury of Periodontal Ligament Cells and Alveolar Bone Loss in Periodontitis

Drug Design Development and Therapy ◽

10.2147/dddt.s315249 ◽

2021 ◽

Vol Volume 15 ◽

pp. 3509-3522

Author(s):

Yu Wei ◽

Jiayao Fu ◽

Wenjing Wu ◽

Pengfei Ma ◽

Le Ren ◽

...

Keyword(s):

Oxidative Stress ◽

Bone Loss ◽

Periodontal Ligament ◽

Alveolar Bone ◽

Alveolar Bone Loss ◽

Periodontal Ligament Cells

Download Full-text

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 ◽

10.3390/antiox9121221 ◽

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.

Download Full-text

3,4,5-Trihydroxybenzoic acid attenuates ligature-induced periodontal disease in Wistar rats.

Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry ◽

10.2174/1871523019666200206094335 ◽

2020 ◽

Vol 19 ◽

Author(s):

Ozkan Karatas ◽

Fikret Gevrek

Keyword(s):

Bone Loss ◽

Gallic Acid ◽

Wistar Rats ◽

Alveolar Bone ◽

Alveolar Bone Loss ◽

Collagenase Activity ◽

Osteoblastic Activity ◽

Cell Counts ◽

Experimental Periodontitis ◽

Anti Inflammatory

Background: 3,4,5-Trihydroxybenzoic acid, which is also known as gallic acid, is an anti-inflammatory agent who could provide beneficial effects in preventing periodontal inflammation. The present study aimed to evaluate the anti-inflammatory effects of gallic acid on experimental periodontitis in Wistar rats. Alveolar bone loss, osteoclastic activity, osteoblastic activity, and collagenase activity were also determined. Methods: 32 Wistar rats were used in the present study. Study groups were created as following: Healthy control (C,n=8) group; periodontitis (P,n=8) group; periodontitis and 30 mg/kg gallic acid administered group (G30,n=8); periodontitis and 60 mg/kg gallic acid administered group (G60,n=8). Experimental periodontitis was created by placing 4-0 silk sutures around the mandibular right first molar tooth. Morphological changes in alveolar bone were determined by stereomicroscopic evaluation. Mandibles were undergone histological evaluation. Matrix metalloproteinase (MMP)-8, tissue inhibitor of MMPs (TIMP)-1, bone morphogenetic protein (BMP)-2 expressions, tartrate-resistant acid phosphatase (TRAP) positive osteoclast cells, osteoblast, and inflammatory cell counts were determined. Results: Highest alveolar bone loss was observed in the periodontitis group. Both doses of gallic acid decreased alveolar bone loss compared to the P group. TRAP-positive osteoclast cell counts were higher in the P group, and gallic acid successfully lowered these counts. Osteoblast cells also increased in gallic acid administered groups. Inflammation in the P group was also higher than those of C, G30, and G60 groups supporting the role of gallic acid in preventing inflammation. 30 and 60 mg/kg doses of gallic acid decreased MMP-8 levels and increased TIMP-1 levels. BMP levels increased in gallic acid administered groups, similar to several osteoblasts. Conclusion: Present results revealed an anti-inflammatory effect of gallic acid, which was indicated by decreased alveolar bone loss and collagenase activity and increased osteoblastic activity.

Download Full-text

Anti-inflammatory, anti-osteoclastic, and antioxidant activities of genistein protect against alveolar bone loss and periodontal tissue degradation in a mouse model of periodontitis

Journal of Biomedical Materials Research Part A ◽

10.1002/jbm.a.36109 ◽

2017 ◽

Vol 105 (9) ◽

pp. 2510-2521 ◽

Cited By ~ 25

Author(s):

Govinda Bhattarai ◽

Sher Bahadur Poudel ◽

Sung-Ho Kook ◽

Jeong-Chae Lee

Keyword(s):

Bone Loss ◽

Mouse Model ◽

Alveolar Bone ◽

Antioxidant Activities ◽

Alveolar Bone Loss ◽

Periodontal Tissue ◽

Tissue Degradation ◽

Anti Inflammatory

Download Full-text

Resolution phase agonists &bone remodeling

10.12681/eadd/44255 ◽

2016 ◽

Author(s):

Ευάγγελος Παπαθανασίου

Keyword(s):

Bone Loss ◽

Alveolar Bone ◽

Peritoneal Macrophages ◽

Alveolar Bone Loss ◽

Cytokine Signaling ◽

Periodontal Inflammation ◽

Oral Inoculation ◽

Tnf Α ◽

Socs Proteins ◽

Anti Inflammatory

Periodontitis is the 6th most prevalent disease in the world and the primary cause for tooth loss in adults. The host immune response plays a key role in bacteria-induced alveolar bone resorption. Endogenous control of the magnitude and duration of inflammatory signaling is considered an important determinant of the extent of periodontal pathology. Suppressor of cytokine signaling (SOCS) proteins are inhibitors of cytokine signaling pathways and may play a role in controlling periodontal inflammation. SOCS proteins are also considered crucial intracellular mediators of the anti-inflammatory actions of lipid mediator agonists including resolvins such as RvE1. We hypothesized that SOCS-3 regulates inflammatory cytokine signaling and alveolar bone loss in experimental periodontitis and that the anti-inflammatory actions of RvE1 are SOCS-3 dependent. Periodontal bone loss was induced in myeloid-specific SOCS-3-knockout (KO) and SOCS-3-wild-type (WT) C57Bl6-B.129 mice by oral inoculation with 1×109 colony-forming units (CFU) P. gingivalis A7436 using an oral gavage model for periodontitis. Sham controls for both types of mice received vehicle without bacteria. The mice were euthanized 6 weeks after the last oral inoculation. Morphometric, histomorphometric, and µCT analyses were performed to assess alveolar bone loss. Peritoneal macrophages were elicited with 4% thioglycolate broth and isolated from myeloid SOCS-3-KO and SOCS-3-WT mice by differential centrifugation. Macrophages were cultured at a concentration of 1.5×106 cells/ml in 6-well plates. After 2 hours, non-adherent cells were discarded and the remaining adherent cells were treated with either culture medium alone (control) or with 100 ng/ml P. gingivalis A7436 LPS or with culture medium and 100nM RvE1 or with 100 ng/ml P. gingivalis A7436 LPS and RvE1 100nM (n≥3 wells per group). Supernatants and cells were collected after 12 hours. Cytokine levels were assessed using Luminex multiplex bead immunoassay and RNA was extracted by Trizol and processed for qRT-PCR. Increased bone loss was demonstrated in P. gingivalis-infected SOCS-3- KO mice compared to P. gingivalis-infected WT mice by direct morphological measurements, µCT analyses and quantitative histology. Loss of SOCS-3 function resulted in increased number of alveolar bone osteoclasts and increased RANKL expression after P. gingivalis infection. SOCS-3 deficiency in myeloid cells also promoted a higher P. gingivalis LPS-induced inflammatory response by inducing a higher secretion of IL-1β, IL-6, TNF-α and KC (IL-8) by peritoneal macrophages from SOCS-3-KO mice. 100nM RvE1 resulted in a significant decrease in P. gingivalis LPS-induced secretion of IL-6, TNF-α and IL-8 by increasing mRNA expression of SOCS-3 and ERV1 in macrophages from SOCS-3-WT mice compared to macrophages from myeloid SOCS-3-KO ones. Our data implicate SOCS-3 as a critical negative regulator of alveolar bone loss in experimental periodontitis and P. gingivalis LPS-induced inflammatory response. SOCS-3 regulates the anti-inflammatory actions of RvE1 on P. gingivalis LPS-induced inflammatory cytokines in macrophages. Understanding further the role of SOCS proteins in regulating periodontal inflammation may provide novel pathways of host susceptibility to periodontitis and new therapeutic targets for modulating the immune response to achieve successful resolution of periodontal inflammation.

Download Full-text