Skip to main content
Log in

Evaluation of inhibitory activities of plant extracts on production of LPS-stimulated pro-inflammatory mediators in J774 murine macrophages

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Whole plant methanolic extracts of 14 traditionally used medicinal herbs were evaluated for their anti-inflammatory activity. Extracts of Grindelia robusta, Salix nigra, Arnica montana, and Quassia amara showed up to 4.5-fold inhibition of nitric oxide (NO) production in the J774 murine macrophage cells challenged with LPS without cytotoxicity. These four selected extracts significantly reduced the protein levels of inducible NO synthase (iNOS) and the cyclooxygenase-2 (COX-2) as observed by Western blot analysis. Culture supernatants from cells treated with these extracts indicated 3–5-fold reduction of tumor necrosis factor-α (TNF-α). However, only G. robusta and Q. amara extracts significantly inhibited (by 50%) IL-1β and IL-12 secretions. Furthermore, all these plant extracts were shown to prevent the LPS-mediated nuclear translocation of nuclear factor-κB (NF-κB). All the above observations indicate the anti-inflammatory potential of these plant extracts.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Harvey AL (2008) Natural products in drug discovery. Drug Discov Today. doi:10.1016/j.drudis.2008.07.004

  2. Chang J (2000) Medicinal herbs: drugs or dietary supplements? Biochem Pharmacol 59:211–219

    Article  CAS  PubMed  Google Scholar 

  3. Raghav SK, Gupta B, Shrivastava A, Das HR (2007) Inhibition of lipopolysaccharide-inducible nitric oxide synthase and IL-1β through suppression of NF-κB activation by 3-(1′-1′-dimethyl-allyl)-6-hydroxy-7-methoxy-coumarin isolated from Ruta graveolens L. Eur J Pharmacol 560:69–80

    Article  CAS  PubMed  Google Scholar 

  4. Newman DJ, Cragg GM, Snader KM (2000) The influence of natural products upon drug discovery. Nat Prod Rep 17:215–234

    Article  CAS  PubMed  Google Scholar 

  5. Raskin I, Ripoll C (2004) Can an apple a day keep the doctor away? Curr Pharm Des 10:3419–3429

    Article  CAS  PubMed  Google Scholar 

  6. Mendelson R, Balick MJ (1995) The value of undiscovered pharmaceuticals in tropical forests. Econ Bot 49:223–228

    Google Scholar 

  7. Raskin I, Ribnicky DM, Komarnytsky S et al (2002) Plants and human health in the 21st century. Trends Biotechnol 20:522–531

    Article  CAS  PubMed  Google Scholar 

  8. Ohshima H, Bartsch H (1994) Chronic infections and inflammatory processes as cancer risk factors, possible role of nitric oxide in carcinogenesis. Mutat Res 305:253–264

    CAS  PubMed  Google Scholar 

  9. Esposito K, Giugliano D (1994) The metabolic syndrome and inflammation, association or causation? Nutr Metab Cardiovasc Dis 14:228–232

    Article  Google Scholar 

  10. Krakauer T (2004) Molecular therapeutic targets in inflammation, cyclooxygenase and NFκβ. Curr Drug Targets 3:317–324

    Article  CAS  Google Scholar 

  11. Bonizzi G, Karin M (2004) The two NF-κB activation pathwaysand their role in innate and adaptive immunity. Trends Immunol 25:280–288

    Article  CAS  PubMed  Google Scholar 

  12. Duffield JS (2003) The inflammatory macrophage: a story of Jekyll and Hyde. Clin Sci 104:27–38

    Article  CAS  PubMed  Google Scholar 

  13. Nagatoshi F, Kazuo K (2005) Macrophages in inflammation. Curr Drug Targets 4:281–286

    Article  Google Scholar 

  14. Juni P, Reichenbach S, Egger M (2005) COX2 inhibitors, traditional NSAIDs and the heart. Br Med J 330:1342–1343

    Article  Google Scholar 

  15. Pathak SK, Sharma RA, Steward WP et al (2005) Oxidative stress and cyclooxygenase activity in prostate carcinogenesis: targets for chemopreventive strategies. Eur J Cancer 41:61–70

    Article  CAS  PubMed  Google Scholar 

  16. Nathan C, Xie QW (1994) Nitric oxide synthases: roles, tolls, and controls. Cell 78:915–918

    Article  CAS  PubMed  Google Scholar 

  17. Li Q, Verma IM (2002) NF-κB regulation in the immune system. Nat Rev Immunol 2:725–734

    Article  CAS  PubMed  Google Scholar 

  18. Li Q, Withoff S, Verma IM (2005) Inflammation-associated cancer, NF-kappaB is the lynchpin. Trends Immunol 26:318–325

    Article  PubMed  Google Scholar 

  19. Lee DU, Kang YJ, Park MK et al (2003) Effects of 13-alkyl-substituted berberine alkaloids on the expression of COX-II, TNF-α, iNOS and IL-12 production in LPS stimulated macrophages. Life Sci 73:1401–1412

    Article  CAS  PubMed  Google Scholar 

  20. Schreiber E, Harshman K, Kemler I et al (1990) Astrocytes and glioblastoma cells express novel octamer-DNA binding proteins distinct from the ubiquitous Oct-1 and B cell type Oct-2 proteins. Nucleic Acids Res 18:5495–5503

    Article  CAS  PubMed  Google Scholar 

  21. Kilbourn RG, Belloni P (1990) Endothelial cell production of nitric oxide in response to interferon-γ in combination with tumor necrosis factor, interleukin-1, or endotoxin. J Natl Cancer Inst 82:772–776

    Article  CAS  PubMed  Google Scholar 

  22. Nathan C (1992) Nitric oxide as a secretory product of mammalian cells. FASEB J 6:3051–3064

    CAS  PubMed  Google Scholar 

  23. Murakami A, Takahashi D, Hagihara K et al (2003) Combinatorial effects of nonsteroidal anti-inflammatory drugs and food constituents on production of prostaglandin E2 and tumor necrosis factor alpha in RAW264.7 murine macrophages. Biosci Biotechnol Biochem 67:1056–1062

    Article  CAS  PubMed  Google Scholar 

  24. Zhang G, Ghosh S (2000) Molecular mechanisms of NF-κB activation induced by bacterial lipopolysaccharide through Toll-like receptors. J Endotoxin Res 6:453–457

    Article  CAS  PubMed  Google Scholar 

  25. Albina JL, Reichner JS (1998) Role of nitric oxide mediation of macrophage cytotoxicity and apoptosis. Cancer Metastasis Rev 17:39–53

    Article  CAS  PubMed  Google Scholar 

  26. Boucher JL, Moali C, Tenu JP (1999) Nitric oxide biosynthesis, nitric oxide synthase inhibitors and arginase competition for l-arginine utilization. Cell Mol Life Sci 55:1015–1028

    Article  CAS  PubMed  Google Scholar 

  27. Reddy ST, Herschman HR (1994) Ligand-induced prostaglandin synthase requires expression of the TIS10/PGS-2 prostaglandin synthase gene in murine fibroblast and macrophages. J Biol Chem 269:473–480

    Google Scholar 

  28. Lee SH, Soyoola E, Chanmugam P et al (1992) Selective expression of mitogen-inducible cyclooxygenase in macrophages stimulated with lipopolysaccharide. J Biol Chem 267:934–938

    Google Scholar 

  29. Hughes FJ, Buttery LD, Hukkanen MV, O’Donnell A, Maclouf J, Polak JM (1999) Cytokine induced prostaglandin E2 synthesis and cyclooxygenase-2 activity are regulated both by a nitric oxide dependent and independent mechanism in rat osteoblasts in vitro. J Biol Chem 274:1776–1782

    Article  CAS  PubMed  Google Scholar 

  30. Jachak SM (2006) Cyclooxygenase inhibitory natural products: current status. Curr Top Med Chem 13:659–678

    CAS  Google Scholar 

  31. Kim SJ, Jeong HJ, Moon PD (2005) Anti-inflammatory activity of gumiganghwaltang through the inhibition of nuclear factor-kappa B activation in peritoneal macrophages. Biol Pharm Bull 28:233–237

    Article  CAS  PubMed  Google Scholar 

  32. Anderson KV (2000) Toll signaling pathways in the innate immune response. Curr Opin Immunol 12:13–19

    Article  CAS  PubMed  Google Scholar 

  33. Ghosh S, May MJ, Kopp EB (1998) NF-κB and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol 16:225–260

    Article  CAS  PubMed  Google Scholar 

  34. Baldwin AS (1996) The NF-κB and IκB proteins: new discoveries and insights. Ann Rev Immunol 14:649–683

    Article  CAS  Google Scholar 

  35. Guha M, Mackman N (2001) LPS induction of gene expression in human monocytes. Cell Signal 13:85–94

    Article  CAS  PubMed  Google Scholar 

  36. Beutler B (2000) Tlr4: central component of the sole mammalian LPS sensor. Curr Opin Immunol 12:20–26

    Article  CAS  PubMed  Google Scholar 

  37. Yang H, Young DW, Gusovsky F, Chow JC (2000) Cellular events mediated by lipopolysaccharide-stimulated toll-like receptor 4. MD-2 is required for activation of mitogen-activated protein kinases and Elk-1. J Biol Chem 275:20861–20866

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Authors wish to thank the Council of Scientific and Industrial Research, India for the financial assistance.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rakha H. Das.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 63 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Verma, N., Tripathi, S.K., Sahu, D. et al. Evaluation of inhibitory activities of plant extracts on production of LPS-stimulated pro-inflammatory mediators in J774 murine macrophages. Mol Cell Biochem 336, 127–135 (2010). https://doi.org/10.1007/s11010-009-0263-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-009-0263-6

Keywords

Navigation