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      KCI등재 SCIE SCOPUS

      Madecassic acid protects human periodontal ligament fibroblasts against hydrogen peroxide-induced cell damage by maintaining mitochondrial membrane potential

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      https://www.riss.kr/link?id=A107986560

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      다국어 초록 (Multilingual Abstract)

      Background Oxidative stress is involved in the pathogenesis of various inflammatory diseases, such as periodontitis. When periodontitis occurs, reactive oxygen species (ROS) are overproduced and cannot be balanced by the antioxidant defense system, re...

      Background Oxidative stress is involved in the pathogenesis of various inflammatory diseases, such as periodontitis. When periodontitis occurs, reactive oxygen species (ROS) are overproduced and cannot be balanced by the antioxidant defense system, resulting in tissue damage. Madecassic acid (MA), an abundant triterpenoid in Centella asiatica (L.) Urban, has been used as a wound healing, antiinflammatory, and anticancer agent. Moreover, recent studies have shown that MA has an antioxidative effect, but the underlying mechanism remains unclear.
      Objective Here, we established an effective oxidative stress model induced by hydrogen peroxide (H 2 O 2 ) in human periodontal ligament fi broblasts (hPDLFs) to investigate the antioxidant and protective effects of MA against cell damage and its underlying mechanism of action.
      Results Pretreatment with MA inhibited cell apoptosis and promoted cell invasion and migration against oxidative injury induced by H 2 O 2 . In addition, MA was able to maintain mitochondrial membrane potential (ΔΨm) under oxidative stress.
      Notably, we found that MA restored redox balance by reducing intracellular ROS production. Furthermore, we investigated apoptosis-related proteins and found that the levels of anti-apoptosis markers Bcl-xL and Bcl-2 were remarkably upregulated, whereas that of the pro-apoptotic marker Bax was strikingly downregulated.
      Conclusions Collectively, these findings suggest that MA inhibits H 2 O 2 -induced oxidative stress and apoptosis of hPDLFs by reducing intracellular ROS production to maintain ΔΨm stability.

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      참고문헌 (Reference)

      1 Yuqin Jin, "rhPDGF-BB Via ERK Pathway Osteogenesis and Adipogenesis Balancing in ADSCs for Critical-Sized Calvarial Defect Repair" Mary Ann Liebert Inc 20 (20): 3303-3313, 2014

      2 Ah-Reum Han, "Triterpenoids from the Leaves of Centella asiatica Inhibit Ionizing Radiation-Induced Migration and Invasion of Human Lung Cancer Cells" Hindawi Limited 2020 : 1-7, 2020

      3 Yuqin Jin, "Tensile force-induced PDGF-BB/PDGFRβ signals in periodontal ligament fibroblasts activate JAK2/STAT3 for orthodontic tooth movement" Springer Science and Business Media LLC 10 (10): 2020

      4 Smit Jayant Dangaria, "Successful Periodontal Ligament Regeneration by Periodontal Progenitor Preseeding on Natural Tooth Root Surfaces" Mary Ann Liebert Inc 20 (20): 1659-1668, 2011

      5 Saowanee Wannasarit, "Strategies for Improving Healing of the Gastric Epithelium Using Oral Solid Dispersions Loaded with Pentacyclic Triterpene–Rich Centella Extract" Springer Science and Business Media LLC 20 (20): 277-, 2019

      6 Katja Diercke, "Strain-dependent Up-regulation of Ephrin-B2 Protein in Periodontal Ligament Fibroblasts Contributes to Osteogenesis during Tooth Movement" Elsevier BV 286 (286): 37651-37664, 2011

      7 Ali Alqahtani, "Seasonal variation of triterpenes and phenolic compounds in Australian Centella asiatica (L.) Urb" Wiley 26 (26): 436-443, 2015

      8 Aki Takimoto, "Scleraxis and osterix antagonistically regulate tensile force-responsive remodeling of the periodontal ligament and alveolar bone" The Company of Biologists 142 (142): 787-796, 2015

      9 Daniela Miricescu, "Salivary biomarkers: Relationship between oxidative stress and alveolar bone loss in chronic periodontitis" Informa UK Limited 72 (72): 42-47, 2013

      10 Ei Hsu Hlaing E, "Role of intracellular Ca(2+)-based mechanotransduction of human periodontal ligament fibroblasts" 33 : 10409-10424, 2019

      1 Yuqin Jin, "rhPDGF-BB Via ERK Pathway Osteogenesis and Adipogenesis Balancing in ADSCs for Critical-Sized Calvarial Defect Repair" Mary Ann Liebert Inc 20 (20): 3303-3313, 2014

      2 Ah-Reum Han, "Triterpenoids from the Leaves of Centella asiatica Inhibit Ionizing Radiation-Induced Migration and Invasion of Human Lung Cancer Cells" Hindawi Limited 2020 : 1-7, 2020

      3 Yuqin Jin, "Tensile force-induced PDGF-BB/PDGFRβ signals in periodontal ligament fibroblasts activate JAK2/STAT3 for orthodontic tooth movement" Springer Science and Business Media LLC 10 (10): 2020

      4 Smit Jayant Dangaria, "Successful Periodontal Ligament Regeneration by Periodontal Progenitor Preseeding on Natural Tooth Root Surfaces" Mary Ann Liebert Inc 20 (20): 1659-1668, 2011

      5 Saowanee Wannasarit, "Strategies for Improving Healing of the Gastric Epithelium Using Oral Solid Dispersions Loaded with Pentacyclic Triterpene–Rich Centella Extract" Springer Science and Business Media LLC 20 (20): 277-, 2019

      6 Katja Diercke, "Strain-dependent Up-regulation of Ephrin-B2 Protein in Periodontal Ligament Fibroblasts Contributes to Osteogenesis during Tooth Movement" Elsevier BV 286 (286): 37651-37664, 2011

      7 Ali Alqahtani, "Seasonal variation of triterpenes and phenolic compounds in Australian Centella asiatica (L.) Urb" Wiley 26 (26): 436-443, 2015

      8 Aki Takimoto, "Scleraxis and osterix antagonistically regulate tensile force-responsive remodeling of the periodontal ligament and alveolar bone" The Company of Biologists 142 (142): 787-796, 2015

      9 Daniela Miricescu, "Salivary biomarkers: Relationship between oxidative stress and alveolar bone loss in chronic periodontitis" Informa UK Limited 72 (72): 42-47, 2013

      10 Ei Hsu Hlaing E, "Role of intracellular Ca(2+)-based mechanotransduction of human periodontal ligament fibroblasts" 33 : 10409-10424, 2019

      11 Derek Richards, "Review finds that severe periodontitis affects 11% of the world population" Springer Science and Business Media LLC 15 (15): 70-71, 2014

      12 Huan Chen, "Recombinant Klotho Protects Human Periodontal Ligament Stem Cells by Regulating Mitochondrial Function and the Antioxidant System during H2O2-Induced Oxidative Stress" Hindawi Limited 2019 : 1-14, 2019

      13 Gary Tse, "Reactive Oxygen Species, Endoplasmic Reticulum Stress and Mitochondrial Dysfunction: The Link with Cardiac Arrhythmogenesis" Frontiers Media SA 7 : 2016

      14 Yu Zhang, "Puerarin attenuates neurological deficits via Bcl-2/Bax/cleaved caspase-3 and Sirt3/SOD2 apoptotic pathways in subarachnoid hemorrhage mice" Elsevier BV 109 : 726-733, 2019

      15 Jungwoon Lee, "Pharmacological Regulation of Oxidative Stress in Stem Cells" Hindawi Limited 2018 : 1-13, 2018

      16 Yunhe Zhao, "Periodontitis-level butyrate-induced ferroptosis in periodontal ligament fibroblasts by activation of ferritinophagy" Springer Science and Business Media LLC 6 (6): 2020

      17 Gerard J. Linden, "Periodontal systemic associations: review of the evidence" Wiley 84 (84): S8-S19, 2013

      18 Tomoko Kurita-Ochiai, "Periodontal Disease-Induced Atherosclerosis and Oxidative Stress" MDPI AG 4 (4): 577-590, 2015

      19 Mengmeng Chen, "Oxidative stress‐related biomarkers in saliva and gingival crevicular fluid associated with chronic periodontitis: A systematic review and meta‐analysis" Wiley 46 (46): 608-622, 2019

      20 H Sies, "Oxidative stress: oxidants and antioxidants" Wiley 82 (82): 291-295, 1997

      21 Nelli Giribabu, "Oral administration of Centella asiatica (L.) Urb leave aqueous extract ameliorates cerebral oxidative stress, inflammation, and apoptosis in male rats with type-2 diabetes" Springer Science and Business Media LLC 28 (28): 1599-1622, 2020

      22 Hong Wang, "Ochratoxin A-Induced Apoptosis of IPEC-J2 Cells through ROS-Mediated Mitochondrial Permeability Transition Pore Opening Pathway" American Chemical Society (ACS) 65 (65): 10630-10637, 2017

      23 Yanli Liu, "Nrf2 Inhibits Periodontal Ligament Stem Cell Apoptosis under Excessive Oxidative Stress" MDPI AG 18 (18): 1076-, 2017

      24 Carmen M. Díaz, "Molecular inflammation and oxidative stress are shared mechanisms involved in both myocardial infarction and periodontitis" Wiley 55 (55): 519-528, 2020

      25 Paola Venditti, "Mitochondrial metabolism of reactive oxygen species" Elsevier BV 13 (13): 71-82, 2013

      26 Xiaoyu Sun, "Mitochondrial dysfunction is involved in the aggravation of periodontitis by diabetes" Wiley 44 (44): 463-471, 2017

      27 Chuck Blajszczak, "Mitochondria targeting by environmental stressors: Implications for redox cellular signaling" Elsevier BV 391 : 84-89, 2017

      28 Xiaotian Xu, "Madecassic acid, the contributor to the anti-colitis effect of madecassoside, enhances the shift of Th17 toward Treg cells via the PPARγ/AMPK/ACC1 pathway" Springer Science and Business Media LLC 8 (8): e2723-e2723, 2017

      29 Boyu Yang, "Madecassic Acid protects against hypoxia-induced oxidative stress in retinal microvascular endothelial cells via ROS-mediated endoplasmic reticulum stress" Elsevier BV 84 : 845-852, 2016

      30 Ana S. C. Valdeira, "Madecassic Acid Derivatives as Potential Anticancer Agents: Synthesis and Cytotoxic Evaluation" American Chemical Society (ACS) 82 (82): 2094-2105, 2019

      31 Jiajia Hua, "MITF acts as an anti-oxidant transcription factor to regulate mitochondrial biogenesis and redox signaling in retinal pigment epithelial cells" Elsevier BV 170 : 138-147, 2018

      32 A Perelman, "JC-1: alternative excitation wavelengths facilitate mitochondrial membrane potential cytometry" Springer Science and Business Media LLC 3 (3): e430-e430, 2012

      33 Byoung-Moo Seo, "Investigation of multipotent postnatal stem cells from human periodontal ligament" Elsevier BV 364 (364): 149-155, 2004

      34 Juliane Cruz Campos, "Increased Clearance of Reactive Aldehydes and Damaged Proteins in Hypertension-Induced Compensated Cardiac Hypertrophy: Impact of Exercise Training" Hindawi Limited 2015 : 1-11, 2015

      35 Can Ni, "Gold nanoparticles modulate the crosstalk between macrophages and periodontal ligament cells for periodontitis treatment" Elsevier BV 206 : 115-132, 2019

      36 Valko M, "Free radicals and antioxidants in normal physiological functions and human disease" 39 : 44-84, 2007

      37 Aurigena Antunes de Araújo, "Effects of metformin on inflammation, oxidative stress, and bone loss in a rat model of periodontitis" Public Library of Science (PLoS) 12 (12): e0183506-, 2017

      38 Yu-qin Jin, "Dalbergioidin (DAL) protects MC3T3-E1 osteoblastic cells against H2O2-induced cell damage through activation of the PI3K/AKT/SMAD1 pathway" Springer Science and Business Media LLC 390 (390): 711-720, 2017

      39 Dikalov S, "Cross talk between mitochondria and NADPH oxidases" 51 : 1289-1301, 2011

      40 KS Rao, "Comparative study on anti-oxidant and anti-inflammatory activities of Caesalpinia crista and Centella asiatica leaf extracts" Medknow 6 (6): 86-, 2014

      41 Erinna F. Lee, "BCL-XL and MCL-1 are the key BCL-2 family proteins in melanoma cell survival" Springer Science and Business Media LLC 10 (10): 2019

      42 Shudan Wang, "Anti-liver cancer effect and the mechanism of arsenic sulfide in vitro and in vivo" Springer Science and Business Media LLC 83 (83): 519-530, 2018

      43 Carlotta Giorgi, "Alterations in Mitochondrial and Endoplasmic Reticulum Signaling by p53 Mutants" Frontiers Media SA 6 : 42-, 2016

      44 Fu X, "Activation of the ERK/Creb/Bcl-2 pathway protects periodontal ligament stem cells against hydrogen peroxide-induced oxidative stress" 19 : 3649-3657, 2019

      45 Xiangting Gao, "Aconitine induces apoptosis in H9c2 cardiac cells via mitochondria‑mediated pathway" Spandidos Publications 2017

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