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      KCI등재 SCIE SCOPUS

      Upregulation of heme oxygenase-1 by ginsenoside Ro attenuates lipopolysaccharide-induced inflammation in macrophage cells

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      https://www.riss.kr/link?id=A103810111

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      다국어 초록 (Multilingual Abstract)

      Background: The beneficial effects of ginsenoside species have been well demonstrated in a number of studies. However, the function of ginsenoside Ro (GRo), an oleanane-type saponin, has not been suffi- ciently investigated. Thus, the aim of the present study was to investigate the anti-inflammatory effects of GRo in vitro using the Raw 264.7 mouse macrophage cell line treated with lipopolysaccharide (LPS), and to clarify the possible mechanism of GRo involving heme oxygenase-1 (HO-1), which itself plays a critical role in self-defense in the presence of inflammatory stress.
      Methods: Raw 264.7 cells were pretreated with GRo (up to 200mM) for 1 h before treatment with 1 mg/ mL LPS, and both cell viability and inflammatory markers involving HO-1 were evaluated.
      Results: GRo significantly increased cell viability in a dose dependent manner following treatment with LPS, and decreased levels of reactive oxygen species and nitric oxide. GRo decreased inflammatory cytokines such as nitric oxide synthase and cyclooxygenase-2 induced by LPS. Moreover, GRo increased the expression of HO-1 in a dose dependent manner. Cotreatment of GRo with tin protoporphyrin IX, a selective inhibitor of HO-1, not only inhibited upregulation of HO-1 induced by GRo, but also reversed the anti-inflammatory effect of GRo in LPS treated Raw 264.7 cells.
      Conclusion: GRo induces anti-inflammatory effects following treatment with LPS via upregulation of HO-1.
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      Background: The beneficial effects of ginsenoside species have been well demonstrated in a number of studies. However, the function of ginsenoside Ro (GRo), an oleanane-type saponin, has not been suffi- ciently investigated. Thus, the aim of the prese...

      Background: The beneficial effects of ginsenoside species have been well demonstrated in a number of studies. However, the function of ginsenoside Ro (GRo), an oleanane-type saponin, has not been suffi- ciently investigated. Thus, the aim of the present study was to investigate the anti-inflammatory effects of GRo in vitro using the Raw 264.7 mouse macrophage cell line treated with lipopolysaccharide (LPS), and to clarify the possible mechanism of GRo involving heme oxygenase-1 (HO-1), which itself plays a critical role in self-defense in the presence of inflammatory stress.
      Methods: Raw 264.7 cells were pretreated with GRo (up to 200mM) for 1 h before treatment with 1 mg/ mL LPS, and both cell viability and inflammatory markers involving HO-1 were evaluated.
      Results: GRo significantly increased cell viability in a dose dependent manner following treatment with LPS, and decreased levels of reactive oxygen species and nitric oxide. GRo decreased inflammatory cytokines such as nitric oxide synthase and cyclooxygenase-2 induced by LPS. Moreover, GRo increased the expression of HO-1 in a dose dependent manner. Cotreatment of GRo with tin protoporphyrin IX, a selective inhibitor of HO-1, not only inhibited upregulation of HO-1 induced by GRo, but also reversed the anti-inflammatory effect of GRo in LPS treated Raw 264.7 cells.
      Conclusion: GRo induces anti-inflammatory effects following treatment with LPS via upregulation of HO-1.

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      참고문헌 (Reference)

      1 Tsatsanis C, "Signalling networks regulating cyclooxygenase-2" 38 : 1654-1661, 2006

      2 Lee SH, "Selective expression of mitogen-inducible cyclooxygenase in macrophages stimulated with lipopolysaccharide" 267 : 25934-25938, 1992

      3 Fujii H, "Protective role of heme oxygenase-1 in the intestinal tissue injury in an experimental model of sepsis" 31 : 893-902, 2003

      4 Gillis CN, "Panax ginseng pharmacology: a nitric oxide link?" 54 : 1-8, 1997

      5 Nathan C, "Nitric oxide synthases: roles, tolls, and controls" 78 : 915-918, 1994

      6 Pacher P, "Nitric oxide and peroxynitrite in health and disease" 87 : 315-424, 2007

      7 Ran S, "Macrophage-mediated lymphangiogenesis: the emerging role of macrophages as lymphatic endothelial progenitors" 4 : 618-657, 2012

      8 ssol, "LPS-induced cytokine production in human monocytes and macrophages" 31 : 379-446, 2011

      9 McCoubrey Jr WK, "Isolation and characterization of a cDNA from the rat brain that encodes hemoprotein heme oxygenase-3" 247 : 725-732, 1997

      10 Zuo Z, "Inhalational anesthetics upregulate constitutive and lipopolysaccharide-induced inducible nitric oxide synthase expression and activity" 52 : 606-612, 1997

      1 Tsatsanis C, "Signalling networks regulating cyclooxygenase-2" 38 : 1654-1661, 2006

      2 Lee SH, "Selective expression of mitogen-inducible cyclooxygenase in macrophages stimulated with lipopolysaccharide" 267 : 25934-25938, 1992

      3 Fujii H, "Protective role of heme oxygenase-1 in the intestinal tissue injury in an experimental model of sepsis" 31 : 893-902, 2003

      4 Gillis CN, "Panax ginseng pharmacology: a nitric oxide link?" 54 : 1-8, 1997

      5 Nathan C, "Nitric oxide synthases: roles, tolls, and controls" 78 : 915-918, 1994

      6 Pacher P, "Nitric oxide and peroxynitrite in health and disease" 87 : 315-424, 2007

      7 Ran S, "Macrophage-mediated lymphangiogenesis: the emerging role of macrophages as lymphatic endothelial progenitors" 4 : 618-657, 2012

      8 ssol, "LPS-induced cytokine production in human monocytes and macrophages" 31 : 379-446, 2011

      9 McCoubrey Jr WK, "Isolation and characterization of a cDNA from the rat brain that encodes hemoprotein heme oxygenase-3" 247 : 725-732, 1997

      10 Zuo Z, "Inhalational anesthetics upregulate constitutive and lipopolysaccharide-induced inducible nitric oxide synthase expression and activity" 52 : 606-612, 1997

      11 Idriss NK, "Hemoxygenase-1 in cardiovascular disease" 52 : 971-978, 2008

      12 Maines MD, "Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications" 2 : 2557-2568, 1988

      13 Otterbein LE, "Heme oxygenase-1:unleashing the protective properties of heme" 24 : 449-455, 2003

      14 Li QF, "Heme oxygenase-1 mediates the antiinflammatory effect of isoflurane preconditioning in LPS-stimulated macrophages" 30 : 228-234, 2009

      15 Tsoyi K, "HO-1 and JAK-2/STAT-1 signals are involved in preferential inhibition of iNOS over COX-2 gene expression by newly synthesized tetrahydroisoquinoline alkaloid, CKD712, in cells activated with lipopolysacchride" 20 : 1839-1847, 2008

      16 Murthy HN, "Ginsenosides:prospective for sustainable biotechnological production" 98 : 6243-6254, 2014

      17 Yu JL, "Ginsenoside-Ro enhances cell proliferation and modulates Th1/Th2 cytokines production in murine splenocytes" 40 : 332-336, 2005

      18 Murata K, "Effects of ginseng rhizome and ginsenoside Ro on testosterone 5alpha-reductase and hair regrowth in testosterone-treated mice" 26 : 48-53, 2012

      19 Wang A, "Determination of major ginsenosides in Panax quinquefolius (American ginseng) using high-performance liquid chromatography" 16 : 272-277, 2005

      20 Jia L, "Current evaluation of the millennium phytomedicineginseng (II): collected chemical entities, modern pharmacology, and clinical applications emanated from traditional Chinese medicine" 16 : 2924-2942, 2009

      21 Motterlini R, "Curcumin, an antioxidant and antiinflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress" 28 : 1303-1312, 2000

      22 Maines MD, "Characterization of two constitutive forms of rat liver microsomal heme oxygenase. Only one molecular species of the enzyme is inducible" 261 : 411-419, 1986

      23 Sato K, "Carbon monoxide generated by heme oxygenase-1 suppresses the rejection of mouse-to-rat cardiac transplants" 166 : 4185-4194, 2001

      24 Matsuda H, "Antihepatitic activity of ginesenoside ro1" 57 : 523-526, 1991

      25 Matsuda H, "Anti-inflammatory activity of ginsenoside Ro" 56 : 19-23, 1990

      26 Jun MS, "Anti-inflammatory action of methanol extract of Carthamus tinctorius involves in heme oxygenase-1 induction" 133 : 524-530, 2011

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