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      Inhibitory Effect of Asplenium incisum on Bacterial Growth, Inflammation, and Osteoclastogenesis

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          Abstract

          Background and Objectives: Asplenium incisum, a natural plant, is known to possess numerous pharmacological and biochemical properties. However, the inhibitory effect of A. incisum against Porphyromonas gingivalis and other factors related to periodontal disease have not yet been demonstrated. This study aimed to investigate the potential of A. incisum extract as a phytotherapeutic candidate for improving periodontal diseases by assessing its antibacterial, anti-inflammatory, and anti-osteoclastogenic activities. Materials and Methods: The inhibition of proliferation of P. gingivalis by A. incisum and the sustainability of its antibacterial activity were evaluated in this study. The production of inflammatory cytokines (tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)) and nitric oxide (NO) from lipopolysaccharide-stimulated RAW 264.7 cells was assessed using an enzyme-linked immunosorbent assay. To identify the anti-osteoclastogenic activity, tartrate-resistant acid phosphatase (TRAP) staining and TRAP activity analyses were performed on bone marrow macrophages. Results: The proliferation of P. gingivalis was significantly inhibited by A. incisum ( p < 0.001), and the antibacterial activity was sustained for up to 3 days. A. incisum showed anti-inflammatory activities by significantly decreasing the release of TNF-α, IL-6 ( p < 0.05), and NO ( p < 0.01). In addition, A. incisum significantly suppressed TRAP-positive cells and TRAP activity (at 30 μg/mL, p < 0.01) without causing any cytotoxicity ( p > 0.05). Conclusions: A. incisum showed antibacterial, anti-inflammatory, and anti-osteoclastogenic activities, suggesting it has strong therapeutic potential against periodontal diseases.

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          Inflammatory responses and inflammation-associated diseases in organs

          Inflammation is a biological response of the immune system that can be triggered by a variety of factors, including pathogens, damaged cells and toxic compounds. These factors may induce acute and/or chronic inflammatory responses in the heart, pancreas, liver, kidney, lung, brain, intestinal tract and reproductive system, potentially leading to tissue damage or disease. Both infectious and non-infectious agents and cell damage activate inflammatory cells and trigger inflammatory signaling pathways, most commonly the NF-κB, MAPK, and JAK-STAT pathways. Here, we review inflammatory responses within organs, focusing on the etiology of inflammation, inflammatory response mechanisms, resolution of inflammation, and organ-specific inflammatory responses.
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            Porphyromonas gingivalis: An Overview of Periodontopathic Pathogen below the Gum Line

            Periodontal disease represents a group of oral inflammatory infections initiated by oral pathogens which exist as a complex biofilms on the tooth surface and cause destruction to tooth supporting tissues. The severity of this disease ranges from mild and reversible inflammation of the gingiva (gingivitis) to chronic destruction of connective tissues, the formation of periodontal pocket and ultimately result in loss of teeth. While human subgingival plaque harbors more than 500 bacterial species, considerable research has shown that Porphyromonas gingivalis, a Gram-negative anaerobic bacterium, is the major etiologic agent which contributes to chronic periodontitis. This black-pigmented bacterium produces a myriad of virulence factors that cause destruction to periodontal tissues either directly or indirectly by modulating the host inflammatory response. Here, this review provides an overview of P. gingivalis and how its virulence factors contribute to the pathogenesis with other microbiome consortium in oral cavity.
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              Mechanisms of Bone Resorption in Periodontitis

              Alveolar bone loss is a hallmark of periodontitis progression and its prevention is a key clinical challenge in periodontal disease treatment. Bone destruction is mediated by the host immune and inflammatory response to the microbial challenge. However, the mechanisms by which the local immune response against periodontopathic bacteria disturbs the homeostatic balance of bone formation and resorption in favour of bone loss remain to be established. The osteoclast, the principal bone resorptive cell, differentiates from monocyte/macrophage precursors under the regulation of the critical cytokines macrophage colony-stimulating factor, RANK ligand, and osteoprotegerin. TNF-α, IL-1, and PGE2 also promote osteoclast activity, particularly in states of inflammatory osteolysis such as those found in periodontitis. The pathogenic processes of destructive inflammatory periodontal diseases are instigated by subgingival plaque microflora and factors such as lipopolysaccharides derived from specific pathogens. These are propagated by host inflammatory and immune cell influences, and the activation of T and B cells initiates the adaptive immune response via regulation of the Th1-Th2-Th17 regulatory axis. In summary, Th1-type T lymphocytes, B cell macrophages, and neutrophils promote bone loss through upregulated production of proinflammatory mediators and activation of the RANK-L expression pathways.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Medicina (Kaunas)
                Medicina (Kaunas)
                medicina
                Medicina
                MDPI
                1010-660X
                1648-9144
                22 June 2021
                July 2021
                : 57
                : 7
                : 641
                Affiliations
                [1 ]Department of Dental Biomaterials, Institute of Biomaterials & Implant, College of Dentistry, Wonkwang University, 460 Iksan-daero, Iksan 54538, Korea; shmoon06@ 123456gmail.com (S.-H.M.); shoh@ 123456wku.ac.kr (S.-H.O.)
                [2 ]Department of Dental Hygiene, Wonkwang Health Science University, 514 Iksan-daero, Iksan 54538, Korea; julee890716@ 123456naver.com
                [3 ]Department of Dental Biomaterials, College of Dentistry, Wonkwang University, 460 Iksan-daero, Iksan 54538, Korea; ko2742@ 123456naver.com
                [4 ]Innovative Target Research Center, Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, Korea; hwan@ 123456krict.re.kr
                Author notes
                [* ]Correspondence: baejimy@ 123456wku.ac.kr ; Tel.: +82-63-850-6859
                Author information
                https://orcid.org/0000-0002-7250-721X
                https://orcid.org/0000-0002-8607-8604
                Article
                medicina-57-00641
                10.3390/medicina57070641
                8307819
                34206271
                96b24d83-9c4d-4ec2-badd-f3d0cde77930
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 04 May 2021
                : 15 June 2021
                Categories
                Article

                antibacterial,asplenium incisum,inflammation,periodontitis,osteoclast differentiation

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