본문 바로가기
KERD
논문KCI 등재

Ecklonia cava Extract Containing Dieckol Suppresses RANKL-Induced Osteoclastogenesis via MAP Kinase/NF-κB Pathway Inhibition and Heme Oxygenase-1 Induction

1

조회

0

다운로드

4

인용

0

참고문헌

키워드

주제분류생물학

초록

Ecklonia cava, an edible marine brown alga (Laminariaceae), is a rich source of bioactive compounds such as fucoidan and phlorotannins. Ecklonia cava extract (ECE) was prepared using 70% ethanol extraction and ECE contained 67% and 10.6% of total phlorotannins and dieckol, respectively. ECE treatment significantly inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation of RAW 264.7 cells and pit formation in bone resorption assay (p <0.05). Moreover, it suppressed RANKL-induced NF-κB and mitogen-activated protein kinase signaling in a dose dependent manner. Downregulated osteoclast-specific gene (tartrate-resistant acid phosphatase, cathepsin K, and matrix metalloproteinase-9) expression and osteoclast proliferative transcriptional factors (nuclear factor of activated T cells-1 and c-fos) confirmed ECE-mediated suppression of osteoclastogenesis. ECE treatment (100 μg/ml) increased heme oxygenase-1 expression by 2.5-fold and decreased intercellular reactive oxygen species production during osteoclastogenesis. The effective inhibition of RANKL-stimulated osteoclast differentiation and oxidative stress by ECE suggest that ECE has therapeutic potential in alleviating osteoclast-associated disorders.

Abstract

Ecklonia cava, an edible marine brown alga (Laminariaceae), is a rich source of bioactive compounds such as fucoidan and phlorotannins. Ecklonia cava extract (ECE) was prepared using 70% ethanol extraction and ECE contained 67% and 10.6% of total phlorotannins and dieckol, respectively. ECE treatment significantly inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation of RAW 264.7 cells and pit formation in bone resorption assay (p <0.05). Moreover, it suppressed RANKL-induced NF-κB and mitogen-activated protein kinase signaling in a dose dependent manner. Downregulated osteoclast-specific gene (tartrate-resistant acid phosphatase, cathepsin K, and matrix metalloproteinase-9) expression and osteoclast proliferative transcriptional factors (nuclear factor of activated T cells-1 and c-fos) confirmed ECE-mediated suppression of osteoclastogenesis. ECE treatment (100 μg/ml) increased heme oxygenase-1 expression by 2.5-fold and decreased intercellular reactive oxygen species production during osteoclastogenesis. The effective inhibition of RANKL-stimulated osteoclast differentiation and oxidative stress by ECE suggest that ECE has therapeutic potential in alleviating osteoclast-associated disorders.

참고문헌 (39)

  1. Asagiri M, "The molecular understanding of osteoclast differentiation", Bone, 40, pp.251~264 (2007)
  2. Vaananen HK, "Osteoclast lineage and function", Arch. Biochem. Biophys, 473, pp.132~138 (2008)
  3. Wagner EF, "Fos", AP-1 proteins in bone and the immune system, 2005, pp.208, 126~140
  4. Logar DB, "Expression of bone resorption genes in osteoarthritis and in osteoporosis", J. Bone Miner Metab, 25, pp.219~225 (2007)
  5. Wijesekara I, "Phlorotannins from Ecklonia cava(Phaeophyceae) : biological activities and potential health benefits", Biofactors, 36, pp.408~414 (2010)
  6. Shibata T, "Local and chemical distribution of phlorotannins in brown algae", J. Appl. Phycol, 16, pp.291~296 (2004)
  7. Li Y, "Chemical components and its antioxidant properties in vitro : an edible marine brown alga, Ecklonia cava", Bioorg. Med. Chem, 17, pp.1963~1973 (2009)
  8. Kang MC, "Dieckol isolated from brown seaweed Ecklonia cava attenuates type II diabetes in db", db mouse model, 2014, pp.158, 433~437
  9. Kang KA, "Eckol isolated from Ecklonia cava attenuates oxidative stress induced cell damage in lung fibroblast cells", FEBS Lett, 579, pp.6295~6304 (2005)
  10. Yang YI, "6, 6’-Bieckol, isolated from marine alga Ecklonia cava, suppressed LPS-induced nitric oxide and PGE2 production and inflammatory cytokine expression in macrophages : The inhibition of NFκB", Int. Immunopharmacol, 12, pp.510~517 (2012)
  11. Jung WK, "Inhibitory effects and molecular mechanism of dieckol isolated from marine brown alga on COX-2 and iNOS in microglial cells", J. Agric. Food Chem, 57, pp.4439~4446 (2009)
  12. Kim MM, "Phlorotannins in Ecklonia cava extract inhibit matrix metalloproteinase activity", Life Sci, 79, pp.1436~1443 (2006)
  13. Lee D, "AMP kinase activation and inhibition of nuclear factor-kappa B(NF-κB)translocation contribute to the anti-inflammatory effect of tricin", J. Food Biochem, 41, pp.e12293~ (2017)
  14. 신현철, "An Antioxidative and Antiinflammatory Agent for Potential Treatment of Osteoarthritis from Ecklonia cava", Archives of Pharmacal Research, 29(2), pp.165~171 (2006), 대한약학회
  15. Lee JH, "Preparative isolation and purification of phlorotannins from Ecklonia cava using centrifugal partition chromatography by one-step", Food Chem, 158, pp.433~437 (2014)
  16. Hayman AR, "Tartrate-resistant acid phosphatase(TRAP)and osteoclast", immune cell dichotomy, 2008, pp.41, 218~223
  17. Rahim AH, "Regulation by phloroglucinol of Nrf2", Maf-mediated expression of antioxidant enzymes and inhibition of osteoclastogenesis via the RANKL, Acta Infom. Med, pp.2015, 23[DOI]
  18. Boyce BF, "Functions of RANKL", RANK, Arch. Biochem. Biophys, pp.2008, 473[DOI]
  19. Ihn HJ, "Diphlorethohydroxycarmalol from Ishige okamurae suppresses osteoclast differentiation by downregulating the NF-κB signaling pathway", Int. J. Mol. Sci, 18, pp.12~ (2017)
  20. Takayanagi H, "Induction and activation of the transcription factor NFATc1(NFAT2)integrate RANKL signaling in terminal differentiation of osteoclasts", Dev. Cell, 3, pp.899~901 (2002)
  21. Zhao Q, "NFATc1 : Functions in osteoclasts", Int. J. Biochem. Cell Biol, 42, pp.576~579 (2010)
  22. Matsuo K, "Nuclear factor of activated T-cells(NFAT)rescues osteoclastogenesis in precursors lacking c-Fos", J. Biol. Chem, 272, pp.26475~26480 (2004)
  23. Wada T, "RANKL RANK signaling in osteoclastogenesis and bone disease", Trends Mol. Med, 12, pp.17~25 (2006)
  24. Ikeda F, "Critical roles of c-Jun signaling in regulation of NFAT family and RANKL-regulated osteoclast differentiation", J. Clin. Invest, 114, pp.475~484 (2004)
  25. Yamashita T, "NF-κB p50 and p52 regulate receptor activator of NF-κB Ligand(RANKL)and tumor necrosis factor-induced osteoclast precursor differentiation by activating c-Fos and NFATc1", J. Biol. Chem, 282, pp.18245~18253 (2007)
  26. Kim MM, "Effect of phloroglucinol on oxidative stress and inflammation", Food Chem. Toxicol, 48, pp.2925~2933 (2010)
  27. Kim AR, "Phlorofucofuroeckol A inhibits the LPS-stimulated iNOS and COX-2 expressions in macrophages via inhibition of NF-κB, Akt, and p38 MAPK", Toxicol. In Vitro, 25, pp.1789~1795 (2011)
  28. Jung WK, "Ecklonia cava ethanolic extracts inhibit lipopolysaccharideinduced cyclooxygenase-2 and inducible nitric oxide synthase expression in BV2 microglia via the MAP kinase and NF-κB pathways", Food Chem. Toxicol, 47, pp.410~417 (2009)
  29. Keller A, "Analysis of dichlorodihydrofluorescein and dihydrocalcein as probes for the detection of intracellular reactive oxygen species", Free Radic. Res, 38, pp.1257~1267 (2004)
  30. Wauquier F, "Oxidative stress in bone remodeling and disease", Trend Mol. Med, 15, pp.468~477 (2009)
  31. Sasaki H, "NADPH oxidase-derived reactive species are essential for differentiation of a mouse macrophage cell line (RAW264,7) into osteoclast", J. Med. Invest, 56, pp.33~41 (2009)
  32. Srinivasan S, "Role of mitochondrial reactive oxygen species in osteoclast differentiation", Ann. NY Acad. Sci, 1192, pp.245~252 (2010)
  33. Kwon YB, "Anti-osteoclastic effect of caffeic acid phenethyl ester in murine macrophages depends upon the suppression of superoxide anion production through the prevention of an active-Nox1 complex formation", J. Nutr. Biochem, 58, pp.158~168 (2018)
  34. 박선주, "Dieckol from Ecklonia cava Suppresses the Migration and Invasion of HT1080 Cells by Inhibiting the Focal Adhesion Kinase Pathway Downstream of Rac1-ROS Signaling", Molecules and Cells, 33(2), pp.141~149 (2012), 한국분자세포생물학회
  35. Bai XC, "Reactive oxygen species stimulates receptor activator of NF-κB ligand expression in osteoblast", J. Biol. Chem, 280, pp.17497~17506 (2005)
  36. Sakai E, "Fisetin inhibits osteoclastogenesis through prevention of RANKL induced ROS production by Nrf2-mediated up-regulation of phase II antioxidant enzymes", J. Pharmacol. Sci, 121, pp.288~298 (2013)
  37. Kim KC, "Up-regulation of Nrf2-mediated heme oxygenase-1expression by eckol, a phlorotannin compound, through activation of Erk and PI3K", Akt, 2010, pp.42, 297~305
  38. Ke K, "Hemeoxygenase-1 maintains bone mass via attenuating a redox imbalance in osteoclast", Mol. Cell. Endocrinol, 409, pp.11~20 (2015)
  39. Pi SH, "Heme oxygenase-1 mediates nicotine-and lipopolysaccharide-induced expression of cyclooxygenase-2and inducible nitric oxide synthase in human periodontal ligament cells", J. Periodontal Res, 45, pp.177~183 (2010)

관련 논문AI추천

Inhibitory Effect of Biotransformed- Fucoidan on the Differentiation of Osteoclasts Induced by Receptor for Activation of Nuclear Factor-κB Ligand김광연, 안순철, Chang Jeong Hyun, Choi Sung Jong, Kim Sang-Hun, Lee Junwon, Park Bobae, Yang Eun Ju, Yu Sun Nyoung한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2022 · 제32권 제8호Extracts of Flavoparmelia sp. Inhibit Receptor Activator of Nuclear Factor-κB Ligand-Mediated Osteoclast Differentiation김광진, 손영진, 이용진, 정민혜, 허재선대한골대사학회 · 대한골대사학회지2019 · 제26권 제2호Bavachin counteracts receptor activator of nuclear factor-κB-induced osteoclastogenesis though the suppression of nuclear factor-κB signaling pathway in RAW264.7 cells강경록, 김수관, 김재성, 이숙영, 정서윤, 조인아, Bok Hee Kim치의학연구원 · Oral Biology Research2018 · 제42권 제3호Inhibitory effect of Chaenomelis Fructus ethanol extract on receptor activator of nuclear factor-kappa B ligand-mediated osteoclastogenesis구동련, 박근하, 이승훈대한구강생물학회 · International Journal of Oral Biology2020 · 제45권 제1호Methanol Extract of Croton Pycnanthus Benth. Inhibits Osteoclast Differentiation by Suppressing the MAPK and NF-κB Signaling Pathways김홍희, 이지연대한골대사학회 · 대한골대사학회지2014 · 제21권 제4호Inhibitory effects of Oxya chinensis sinuosa ethanol extract on RANKL-induced osteoclast differentiation김봉선, 김인우, 박소현, 서민철, 이준하, Hae Yong Kweon, Ra-Yeong Choi한국잠사학회 · International Journal of Industrial Entomology and Biomaterials2024 · 제48권 제1호

이 간행물의 다른 논문 (11건)