DOI QR코드

DOI QR Code

Protopine reduces the inflammatory activity of lipopolysaccharide-stimulated murine macrophages

  • Received : 2011.09.29
  • Accepted : 2011.10.13
  • Published : 2012.02.29

Abstract

Protopine is an isoquinoline alkaloid contained in plants in northeast Asia. In this study, we investigated whether protopine derived from Hypecoum erectum L could suppress lipopolysaccharide (LPS)-induced inflammatory responses in murine macrophages (Raw 264.7 cells). Protopine was found to reduce nitric oxide (NO), cyclooxygenase-2 (COX-2), and prostaglandin $E_2$ ($PGE_2$) production by LPS-stimulated Raw 264.7 cells, without a cytotoxic effect. Pre-treatment of Raw 264.7 cells with protopine reduced the production of pro-inflammatory cytokines. These inhibitory effects were caused by blocking phosphorylation of mitogen-activated protein kinases (MAP kinases) and also blocking activation of a nuclear factor kappa-light-chain-enhancer of activated B cells (NF-${\kappa}B$).

Keywords

Cyclooxygenase-2;Cytokine;Inflammation;Macrophage;Nitric oxide;Protopine

References

  1. Shen, Z. Q., Chen, Z. H. and Duan, L. (1999) Effect of protopine on cytosolic Ca2+ in rabbit platelets. Zhongguo Yao Li Xue Bao 20, 338-340.
  2. Saeed, S. A., Gilani, A. H., Majoo, R. U. and Shah, B. H. (1997) Anti-thrombotic and anti-inflammatory activities of protopine. Pharmacol Res. 36, 1-7. https://doi.org/10.1006/phrs.1997.0195
  3. Cosar, G., Bilgehan, H. and Gozler, T. (1981) The antibacterial effects of some alkaloids isolated from Glaucium flavum Crantz. Mikrobiyol. Bul. 15, 105-109.
  4. Ustunes, L., Laekeman, G. M., Gozler, B., Vlietinck, A. J., Ozer, A. and Herman, A. G. (1988) In vitro study of the anticholinergic and antihistaminic activities of protopine and some derivatives. J. Nat. Prod. 51, 1021-1022. https://doi.org/10.1021/np50059a043
  5. Duval, D. L., Miller, D. R., Collier, J. and Billings, R. E. (1996) Characterization of hepatic nitric oxide synthase: identification as the cytokine-inducible form primarily regulated by oxidants. Mol. Pharmacol. 50, 277-284.
  6. Lowenstein, C. J., Hill, S. L., Lafond-Walker, A., Wu, J., Allen, G., Landavere, M., Rose, N. R. and Herskowitz, A. (1996) Nitric oxide inhibits viral replication in murine myocarditis. J. Clin. Invest. 97, 1837-1843. https://doi.org/10.1172/JCI118613
  7. Stichtenoth, D. O. and Frolich, J. C. (1998) Nitric oxide and inflammatory joint diseases. Br. J. Rheumatol. 37, 246-257. https://doi.org/10.1093/rheumatology/37.3.246
  8. Kim, S. H., Kim, J. and Sharma, R. P. (2004) Inhibition of p38 and ERK MAP kinases blocks endotoxin-induced nitric oxide production and differentially modulates cytokine expression. Pharmacol. Res. 49, 433-439. https://doi.org/10.1016/j.phrs.2003.11.004
  9. Inoue, H., Yokoyama, C., Hara, S., Tone, Y. and Tanabe, T. (1995) Transcriptional regulation of human prostaglandinendoperoxide synthase-2 gene by lipopolysaccharide and phorbol ester in vascular endothelial cells. Involvement of both nuclear factor for interleukin-6 expression site and cAMP response element. J. Biol. Chem. 270, 24965-24971. https://doi.org/10.1074/jbc.270.42.24965
  10. Crofford, L. J., Wilder, R. L., Ristimaki, A. P., Sano, H., Remmers, E. F., Epps, H. R. and Hla, T. (1994) Cyclooxygenase-1 and-2 expression in rheumatoid synovial tissues. Effects of interleukin-1 beta, phorbol ester, and corticosteroids. J. Clin. Invest. 93, 1095-1101. https://doi.org/10.1172/JCI117060
  11. Beutler, B. and Cerami, A. (1989) The biology of cachectin/ TNF-a primary mediator of the host response. Annu. Rev. Immunol. 7, 625-655. https://doi.org/10.1146/annurev.iy.07.040189.003205
  12. Arend, W. P. and Dayer, J. M. (1995) Inhibition of the production and effects of interleukin-1 and tumor necrosis factor alpha in rheumatoid arthritis. Arthritis. Rheum. 38, 151-160. https://doi.org/10.1002/art.1780380202
  13. Feldmann, M., Brennan, F. M. and Maini, R. N. (1996) Role of cytokines in rheumatoid arthritis. Annu. Rev. Immunol. 14, 397-440. https://doi.org/10.1146/annurev.immunol.14.1.397
  14. Brennan, F. M., Maini, R. N. and Feldmann, M. (1998) Role of pro-inflammatory cytokines in rheumatoid arthritis. Springer Semin. Immunopathol. 20, 133-147. https://doi.org/10.1007/BF00832003
  15. Lawrence, T., Gilroy, D. W., Colville-Nash, P. R. and Willoughby, D. A. (2001) Possible new role for NF-kappaB in the resolution of inflammation. Nat. Med. 7, 1291-1297. https://doi.org/10.1038/nm1201-1291
  16. Johnson, G. L. and Lapadat, R. (2002) Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298, 1911-1912. https://doi.org/10.1126/science.1072682
  17. Bian, Z. M., Elner, S. G., Yoshida, A. and Elner, V. M. (2003) Human RPE-monocyte co-culture induces chemokine gene expression through activation of MAPK and NIK cascade. Exp. Eye Res. 76, 573-583. https://doi.org/10.1016/S0014-4835(03)00029-0
  18. Narumi, S., Finke, J. H. and Hamilton, T. A. (1990) Interferon gamma and interleukin 2 synergize to induce selective monokine expression in murine peritoneal macrophages. J. Biol. Chem. 265, 7036-7041.
  19. Stuehr, D. J. and Marletta, M. A. (1987) Induction of nitrite/nitrate synthesis in murine macrophages by BCG infection, lymphokines, or interferon-gamma. J. Immunol. 139, 518-525.
  20. Huk, I., Brovkovych, V., Nanobash Vili, J., Weigel, G., Neumayer, C., Partyka, L., Patton, S. and Malinski, T. (1998) Bioflavonoid quercetin scavenges superoxide and increases nitric oxide concentration in ischaemia-reperfusion injury: an experimental study. Br. J. Surg. 85, 1080-1085. https://doi.org/10.1046/j.1365-2168.1998.00787.x
  21. Giuliani, C., Napolitano, G., Bucci, I., Montani, V. and Monaco, F. (2001) Nf-kB transcription factor: role in the pathogenesis of inflammatory, autoimmune, and neoplastic diseases and therapy implications. Clin. Ter. 152, 249-253.
  22. Zhang, Y., Mills, G. L. and Nair, M. G. (2003) Cyclooxygenase inhibitory and antioxidant compounds from the fruiting body of an edible mushroom, Agrocybe aegerita. Phytomedicine 10, 386-390. https://doi.org/10.1078/0944-7113-00272
  23. O'Leary, K. A., de Pascual-Tereasa, S., Needs, P. W., Bao, Y. P., O'Brien, N. M. and Williamson, G. (2004) Effect of flavonoids and vitamin E on cyclooxygenase-2 (COX-2) transcription. Mutat. Res. 551, 245-254. https://doi.org/10.1016/j.mrfmmm.2004.01.015
  24. Butler, D. M., Malfait, A. M., Mason, L. J., Warden, P. J., Kollias, G., Maini, R. N., Feldmann, M. and Brennan, F. M. (1997) DBA/1 mice expressing the human TNF-alpha transgene develop a severe, erosive arthritis: characterization of the cytokine cascade and cellular composition. J. Immunol. 159, 2867-2876.
  25. Dinarello, C. A. (1996) Biologic basis for interleukin-1 in disease. Blood 87, 2095-2147.
  26. Kishimoto, T., Akira, S., Narazaki, M. and Taga, T. (1995) Interleukin-6 family of cytokines and gp130. Blood 86, 1243-1254.
  27. Barnes, P. J. and Karin, M. (1997) Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N. Engl. J. Med. 336, 1066-1071. https://doi.org/10.1056/NEJM199704103361506
  28. Pan, C. H., Kim, E. S., Jung, S. H., Nho, C. W. and Lee, J. K. (2008) Tectorigenin inhibits IFN-gamma/LPS-induced inflammatory responses in murine macrophage RAW 264.7 cells. Arch. Pharm. Res. 31, 1447-1456. https://doi.org/10.1007/s12272-001-2129-7

Cited by

  1. Ginsenoside Metabolite Compound K Promotes Recovery of Dextran Sulfate Sodium-Induced Colitis and Inhibits Inflammatory Responses by Suppressing NF-κB Activation vol.9, pp.2, 2014, https://doi.org/10.1371/journal.pone.0087810
  2. Anti-inflammatory effects of Salviae Miltiorrhizae Radix extract on RAW264.7 cell. via anti-oxidative activities vol.30, pp.4, 2015, https://doi.org/10.6116/kjh.2015.30.4.89.
  3. Salicortin suppresses lipopolysaccharide-stimulated inflammatory responses via blockade of NF-κB and JNK activation in RAW 264.7 macrophages vol.47, pp.6, 2014, https://doi.org/10.5483/BMBRep.2014.47.6.200
  4. Ethanol extract of Cnidium officinale exhibits anti-inflammatory effects in BV2 microglial cells by suppressing NF-κB nuclear translocation and the activation of the PI3K/Akt signaling pathway vol.32, pp.4, 2013, https://doi.org/10.3892/ijmm.2013.1447
  5. Floridoside suppresses pro-inflammatory responses by blocking MAPK signaling in activated microglia vol.46, pp.8, 2013, https://doi.org/10.5483/BMBRep.2013.46.8.237
  6. Ganoderma lucidum ethanol extract inhibits the inflammatory response by suppressing the NF-κB and toll-like receptor pathways in lipopolysaccharide-stimulated BV2 microglial cells vol.5, pp.3, 2013, https://doi.org/10.3892/etm.2013.895
  7. Anti-inflammatory effects of saponins derived from the roots of Platycodon grandiflorus in lipopolysaccharide-stimulated BV2 microglial cells vol.31, pp.6, 2013, https://doi.org/10.3892/ijmm.2013.1330
  8. Sanguinaria canadensis: Traditional Medicine, Phytochemical Composition, Biological Activities and Current Uses vol.17, pp.9, 2016, https://doi.org/10.3390/ijms17091414
  9. Intestinal anti-inflammatory effects of total alkaloid extract from Fumaria capreolata in the DNBS model of mice colitis and intestinal epithelial CMT93 cells vol.23, pp.9, 2016, https://doi.org/10.1016/j.phymed.2016.05.003
  10. Flavonoids Isolated from Flowers ofLonicera japonicaThunb. Inhibit Inflammatory Responses in BV2 Microglial Cells by Suppressing TNF-α and IL-β Through PI3K/Akt/NF-kb Signaling Pathways vol.30, pp.11, 2016, https://doi.org/10.1002/ptr.5688
  11. Modulation by Central MAPKs/PI3K/sGc of the TNF-α/iNOS-dependent Hypotension and Compromised Cardiac Autonomic Control in Endotoxic Rats vol.68, pp.2, 2016, https://doi.org/10.1097/FJC.0000000000000400
  12. Determination of Protopine in Rat Brain Tissues by RRLC-ESI/Q-TOF-MS Method vol.6, pp.2, 2014, https://doi.org/10.1016/S1674-6384(14)60019-8
  13. Antioxidant and Anti-Inflammatory Effects of Chaenomeles sinensis Leaf Extracts on LPS-Stimulated RAW 264.7 Cells vol.21, pp.4, 2016, https://doi.org/10.3390/molecules21040422
  14. Anti-inflammatory effects of 5-hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone via NF-κB inactivation in lipopolysaccharide-stimulated RAW 264.7 macrophage vol.9, pp.4, 2014, https://doi.org/10.3892/mmr.2014.1922
  15. Anti-inflammatory effect of austroinulin and 6-O-acetyl-austroinulin from Stevia rebaudiana in lipopolysaccharide-stimulated RAW264.7 macrophages vol.62, 2013, https://doi.org/10.1016/j.fct.2013.09.011
  16. Immunomodulatory effect of Wedelia chinensis and demethylwedelolactone by interfering with various inflammatory mediators vol.15, pp.1, 2015, https://doi.org/10.1007/s13596-014-0178-y
  17. Anthocyanins Downregulate Lipopolysaccharide-Induced Inflammatory Responses in BV2 Microglial Cells by Suppressing the NF-κB and Akt/MAPKs Signaling Pathways vol.14, pp.1, 2013, https://doi.org/10.3390/ijms14011502
  18. Apigenin isolated from Daphne genkwa Siebold et Zucc. inhibits 3T3-L1 preadipocyte differentiation through a modulation of mitotic clonal expansion vol.101, pp.1-2, 2014, https://doi.org/10.1016/j.lfs.2014.02.012
  19. Holistic Psychopharmacology of <i>Fumaria indica</i> (Fumitory) vol.03, pp.04, 2012, https://doi.org/10.4236/cm.2012.34028
  20. Efficient copper(I)-catalyzed, microwave-assisted, one-pot synthesis of 3,4-diaryl isoquinolines vol.41, pp.6, 2015, https://doi.org/10.1007/s11164-013-1462-z
  21. Evaluation of direct antiviral activity of the Deva-5 herb formulation and extracts of five Asian plants against influenza A virus H3N8 vol.14, pp.1, 2014, https://doi.org/10.1186/1472-6882-14-235
  22. Sesamin increases heme oxygenase-1 protein in RAW 264.7 macrophages through inhibiting its ubiquitination process vol.741, 2014, https://doi.org/10.1016/j.ejphar.2014.08.015
  23. Isoquinoline alkaloids supplementation on performance and carcass traits of feedlot bulls vol.31, pp.9, 2018, https://doi.org/10.5713/ajas.17.0868