DOI QR코드

DOI QR Code

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

  • Kim, Sokho (Department of Laboratory Animal Medicine, Chonbuk National University) ;
  • Oh, Myung-Hoon (Department of Laboratory Animal Medicine, Chonbuk National University) ;
  • Kim, Bum-Seok (Bio-safety Institute, College of Veterinary Medicine, Chonbuk National University) ;
  • Kim, Won-Il (Bio-safety Institute, College of Veterinary Medicine, Chonbuk National University) ;
  • Cho, Ho-Seong (Bio-safety Institute, College of Veterinary Medicine, Chonbuk National University) ;
  • Park, Byoung-Yong (Bio-safety Institute, College of Veterinary Medicine, Chonbuk National University) ;
  • Park, Chul (Bio-safety Institute, College of Veterinary Medicine, Chonbuk National University) ;
  • Shin, Gee-Wook (Bio-safety Institute, College of Veterinary Medicine, Chonbuk National University) ;
  • Kwon, Jungkee (Department of Laboratory Animal Medicine, Chonbuk National University)
  • Received : 2015.01.29
  • Accepted : 2015.03.27
  • Published : 2015.10.15

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 sufficiently 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 $200{\mu}M$) 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.

Keywords

References

  1. Ran S, Montgomery KE. Macrophage-mediated lymphangiogenesis: the emerging role of macrophages as lymphatic endothelial progenitors. Cancers (Basel) 2012;4:618-57. https://doi.org/10.3390/cancers4030618
  2. Rossol M, Heine H, Meusch U, Quandt D, Klein C, Sweet MJ, Hauschildt S. LPS-induced cytokine production in human monocytes and macrophages. Crit Rev Immunol 2011;31:379-446. https://doi.org/10.1615/CritRevImmunol.v31.i5.20
  3. Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev 2007;87:315-424. https://doi.org/10.1152/physrev.00029.2006
  4. Nathan C, Xie QW. Nitric oxide synthases: roles, tolls, and controls. Cell 1994;78:915-8. https://doi.org/10.1016/0092-8674(94)90266-6
  5. Lee SH, Soyoola E, Chanmugam P, Hart S, Sun W, Zhong H, Liou S, Simmons D, Hwang D. Selective expression of mitogen-inducible cyclooxygenase in macrophages stimulated with lipopolysaccharide. J Biol Chem 1992;267:25934-8.
  6. Tsatsanis C, Androulidaki A, Venihaki M, Margioris AN. Signalling networks regulating cyclooxygenase-2. Int J Biochem Cell Biol 2006;38:1654-61. https://doi.org/10.1016/j.biocel.2006.03.021
  7. Maines MD, Trakshel GM, Kutty RK. Characterization of two constitutive forms of rat liver microsomal heme oxygenase. Only one molecular species of the enzyme is inducible. J Biol Chem 1986;261:411-9.
  8. McCoubrey Jr WK, Huang TJ, Maines MD. Isolation and characterization of a cDNA from the rat brain that encodes hemoprotein heme oxygenase-3. Eur J Biochem 1997;247:725-32. https://doi.org/10.1111/j.1432-1033.1997.00725.x
  9. Idriss NK, Blann AD, Lip GY. Hemoxygenase-1 in cardiovascular disease. J Am Coll Cardiol 2008;52:971-8. https://doi.org/10.1016/j.jacc.2008.06.019
  10. Tsoyi K, Kim HJ, Shin JS, Kim DH, Cho HJ, Lee SS, Ahn SK, Yun-Choi HS, Lee JH, Seo HG, et al. 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. Cell Signal 2008;20:1839-47. https://doi.org/10.1016/j.cellsig.2008.06.012
  11. Maines MD. Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. FASEB J 1988;2:2557-68. https://doi.org/10.1096/fasebj.2.10.3290025
  12. Jia L, Zhao Y, Liang XJ. Current evaluation of the millennium phytomedicineginseng (II): collected chemical entities, modern pharmacology, and clinical applications emanated from traditional Chinese medicine. Curr Med Chem 2009;16:2924-42. https://doi.org/10.2174/092986709788803204
  13. Wang A, Wang CZ, Wu JA, Osinski J, Yuan CS. Determination of major ginsenosides in Panax quinquefolius (American ginseng) using high-performance liquid chromatography. Phytochem Anal 2005;16:272-7. https://doi.org/10.1002/pca.838
  14. Gillis CN. Panax ginseng pharmacology: a nitric oxide link? Biochem Pharmacol 1997;54:1-8. https://doi.org/10.1016/S0006-2952(97)00193-7
  15. Murata K, Takeshita F, Samukawa K, Tani T, Matsuda H. Effects of ginseng rhizome and ginsenoside Ro on testosterone 5alpha-reductase and hair regrowth in testosterone-treated mice. Phytother Res 2012;26:48-53. https://doi.org/10.1002/ptr.3511
  16. Matsuda H, Samukawa K, Kubo M. Anti-inflammatory activity of ginsenoside Ro. Planta Med 1990;56:19-23. https://doi.org/10.1055/s-2006-960875
  17. Sato K, Balla J, Otterbein L, Smith RN, Brouard S, Lin Y, Csizmadia E, Seviqny J, Robson SC, Vercellotti G, et al. Carbon monoxide generated by heme oxygenase-1 suppresses the rejection of mouse-to-rat cardiac transplants. J Immunol 2001;166:4185-94. https://doi.org/10.4049/jimmunol.166.6.4185
  18. Matsuda H, Samukawa K, Kubo M. Antihepatitic activity of ginesenoside ro1. Planta Med 1991;57:523-6. https://doi.org/10.1055/s-2006-960198
  19. Yu JL, Dou DQ, Chen XH, Yang HZ, Hu XY, Cheng GF. Ginsenoside-Ro enhances cell proliferation and modulates Th1/Th2 cytokines production in murine splenocytes. Yao Xue Xue Bao 2005;40:332-6.
  20. Murthy HN, Georgiev MI, Kim YS, Jeong CS, Kim SJ, Park SY, et al. Ginsenosides: prospective for sustainable biotechnological production. Appl Microbiol Biotechnol 2014;98:6243-54. https://doi.org/10.1007/s00253-014-5801-9
  21. Zuo Z, Johns RA. Inhalational anesthetics upregulate constitutive and lipopolysaccharide-induced inducible nitric oxide synthase expression and activity. Mol Pharmacol 1997;52:606-12. https://doi.org/10.1124/mol.52.4.606
  22. Fujii H, Takahashi T, Nakahira K, Uehara K, Shimizu H, Matsumi M, Morita K, Hirakawa M, Akaqi R, Sassa S. Protective role of heme oxygenase-1 in the intestinal tissue injury in an experimental model of sepsis. Crit Care Med 2003;31:893-902. https://doi.org/10.1097/01.CCM.0000050442.54044.06
  23. Jun MS, Ha YM, Kim HS, Jang HJ, Kim YM, Lee YS, Kim HJ, Seo HG, Lee JH, Lee SH, et al. Anti-inflammatory action of methanol extract of Carthamus tinctorius involves in heme oxygenase-1 induction. J Ethnopharmacol 2011;133:524-30. https://doi.org/10.1016/j.jep.2010.10.029
  24. Motterlini R, Foresti R, Bassi R, Green CJ. Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress. Free Radic Biol Med 2000;28:1303-12. https://doi.org/10.1016/S0891-5849(00)00294-X
  25. Otterbein LE, Soares MP, Yamashita K, Bach FH. Heme oxygenase-1: unleashing the protective properties of heme. Trends Immunol 2003;24:449-55. https://doi.org/10.1016/S1471-4906(03)00181-9
  26. Li QF, Zhu YS, Jiang H, Xu H, Sun Y. Heme oxygenase-1 mediates the anti-inflammatory effect of isoflurane preconditioning in LPS-stimulated macrophages. Acta Pharmacol Sin 2009;30:228-34. https://doi.org/10.1038/aps.2008.19

Cited by

  1. Inhibitory Effects of Cytosolic Ca 2+ Concentration by Ginsenoside Ro Are Dependent on Phosphorylation of IP 3 RI and Dephosphorylation of ERK in Human Platelets vol.2015, pp.None, 2015, https://doi.org/10.1155/2015/764906
  2. A new rearranged eudesmane sesquiterpene and bioactive sesquiterpenes from the twigs of Lindera glauca (Sieb. et Zucc.) Blume vol.39, pp.12, 2016, https://doi.org/10.1007/s12272-016-0838-1
  3. Molecular association of CD98, CD29, and CD147 critically mediates monocytic U937 cell adhesion vol.20, pp.5, 2015, https://doi.org/10.4196/kjpp.2016.20.5.515
  4. Flavonoids and a Limonoid from the Fruits of Citrus unshiu and Their Biological Activity vol.64, pp.38, 2016, https://doi.org/10.1021/acs.jafc.6b03465
  5. Bioconversion, health benefits, and application of ginseng and red ginseng in dairy products vol.26, pp.5, 2015, https://doi.org/10.1007/s10068-017-0159-2
  6. The Anti-inflammatory Activities of Two Major Withanolides from Physalis minima Via Acting on NF-κB, STAT3, and HO-1 in LPS-Stimulated RAW264.7 Cells vol.40, pp.2, 2015, https://doi.org/10.1007/s10753-016-0485-1
  7. Thymus vulgaris L. and thymol assist murine macrophages (RAW 264.7) in the control of in vitro infections by Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans vol.65, pp.4, 2015, https://doi.org/10.1007/s12026-017-8933-z
  8. Beauvericin, a cyclic peptide, inhibits inflammatory responses in macrophages by inhibiting the NF-κB pathway vol.21, pp.4, 2017, https://doi.org/10.4196/kjpp.2017.21.4.449
  9. Hydroquinone suppresses IFN-β expression by targeting AKT/IRF3 pathway vol.21, pp.5, 2015, https://doi.org/10.4196/kjpp.2017.21.5.547
  10. The traditional Chinese medicine Achyranthes bidentata and our de novo conception of its metastatic chemoprevention: from phytochemistry to pharmacology vol.7, pp.None, 2015, https://doi.org/10.1038/s41598-017-02054-y
  11. New Acetophenone Derivatives from Acronychia oligophlebia and Their Anti‐inflammatory and Antioxidant Activities vol.15, pp.5, 2015, https://doi.org/10.1002/cbdv.201800080
  12. Target Molecular-Based Neuroactivity Screening and Analysis of Panax ginseng by Affinity Ultrafiltration, UPLC-QTOF-MS and Molecular Docking vol.47, pp.6, 2019, https://doi.org/10.1142/s0192415x19500691
  13. Inhibitory Effects of Ginsenoside Ro on Clot Retraction through Suppressing PI3K/Akt Signaling Pathway in Human Platelets vol.24, pp.1, 2015, https://doi.org/10.3746/pnf.2019.24.1.56
  14. Supramolecular host-guest interactions of pseudoginsenoside F11 with β- and γ-cyclodextrin: Spectroscopic/spectrometric and computational studies vol.1195, pp.None, 2015, https://doi.org/10.1016/j.molstruc.2019.05.134
  15. Pro-Resolving Effect of Ginsenosides as an Anti-Inflammatory Mechanism of Panax ginseng vol.10, pp.3, 2020, https://doi.org/10.3390/biom10030444
  16. Four new compounds from Neoboletus magnificus vol.34, pp.8, 2015, https://doi.org/10.1080/14786419.2018.1553878
  17. Fermented ginseng attenuates lipopolysaccharide-induced inflammatory responses by activating the TLR4/MAPK signaling pathway and remediating gut barrier vol.12, pp.2, 2015, https://doi.org/10.1039/d0fo02404j
  18. Ginsenoside Ro Ameliorates High-Fat Diet-Induced Obesity and Insulin Resistance in Mice via Activation of the G Protein-Coupled Bile Acid Receptor 5 Pathway vol.377, pp.3, 2015, https://doi.org/10.1124/jpet.120.000435
  19. Modulation of Hair Growth Promoting Effect by Natural Products vol.13, pp.12, 2015, https://doi.org/10.3390/pharmaceutics13122163