Anti-inflammatory Effect of MeOH Extracts of the Stem of Polygonum multiflorum in LPS-stimulated Mouse Peritoneal Macrophages

  • Published : 2009.06.30

Abstract

Polygoni multiflori Ramulus (PM), the stem of Polygonum multiflorum Thunb. has been widely used as a traditional medicine for the treatment of lots of diseases. In macrophages, nitric oxide is released as an inflammatory mediator and has been proposed to be an important modulator of many pathophysiological conditions in inflammation. In the present study, it was investigated that the inhibitory effects on NO and proinflammatory cytokines such as tumor necrosis factor alpha (TNF-${\alpha}$), interleukin-6 (IL-6) and the mechanism of down-regulation of immune response by 85% methanol extracts of PM in mouse (C57BL/6) peritoneal macrophages. Extracts of PM (0.1, 1 mg/ml) suppressed NO production and showed inhibition of proinflammatory cytokines like TNF-${\alpha}$, IL-6 and it attenuated iNOS and COX-2 expression via down-regulation of NF-${\kappa}$B activation. The present results indicate that the 85% methanol extracts of PM has an inhibitory effect on the production of NO through down-regulation of iNOS expression in LPS stimulated mouse peritoneal macrophages and therefore may be beneficial in diseases which related to macrophage-mediated inflammatory disorders.

Keywords

References

  1. Ambs, S., Merriam, W.G., Bennett, W.P., Felley-Bosco, E., Ogunfusika, M.O., Oser, S.M., Klein, S., Shields, P.G., Billiar, T.R., and Harris, C.C., Frequent nitric oxide synthase-2 expression in human colon adenomas: implication for tumor angiogenesis and colon cancer progression. Cancer Res. 58, 334-341 (1998)
  2. Baek, W.K., Park, J.W., Lim, J.H., Suh, S.I., Suh, M.H., Gabrielson, E., and Kwon, T.K., Molecular cloning and characterization of the human budding uninhibited by benomyl (BUB3) promoter. Gene 295, 117- 123 (2002) https://doi.org/10.1016/S0378-1119(02)00827-2
  3. Baeuerle, P.A. and Baltimore, D., NF-kappa B: ten years after. Cell 87, 13-20 (1996) https://doi.org/10.1016/S0092-8674(00)81318-5
  4. Bertolini, A., Ottani, A., and Sandrini, M., Dual acting anti-inflammatory drugs: a reappraisal. Pharmacol. Res. 44, 437-450 (2001) https://doi.org/10.1006/phrs.2001.0872
  5. Cao, X.Y., Dong, M., Shen, J.Z., Wu, B.B., Wu, P.M., Du, X.D., Wang, Z., Qi, Y.T., and Li, B.Y., Tilmicosin and tylosin have antiinflammatory properties via modulation of COX-2 and iNOS gene expression and production of cytokines in LPS-induced macrophages and monocytes. Int. J. Antimicrob. Agents 27, 431-438 (2006) https://doi.org/10.1016/j.ijantimicag.2005.12.010
  6. Chan, Y.C., Wang, M.F., and Chang, H.C., Polygonum multiflorum extracts improve cognitive performance in senescence accelerated mice. Am. J. Chin. Med. 31, 171-179 (2003) https://doi.org/10.1142/S0192415X03000862
  7. Chen, F., Sun, S.C., Kuh, D.C., Gaydos, L.J., and Demers, L.M., Essential role of NF-kappa B activation in silica-induced inflammatory mediator production in macrophages. Biochem. Biophys. Res. Commun. 214, 985-992 (1995) https://doi.org/10.1006/bbrc.1995.2383
  8. Chen, Y.J., Hsu, K.W., Tssai, J.N., Hung, C.H., Kuo, T.C., and Chen, Y.L., Involvement of protein kinase C in the inhibition of lipopolysaccharide- induced nitiric oxide production by thapsigargin in RAW 264.7 macrophages. Int. J. Biochem. Cell. Biol. 37, 2574-2585 (2005) https://doi.org/10.1016/j.biocel.2005.07.002
  9. Chiu, P.Y., Mak, D.H., Poon, M.K., and Ko, K.M., In vivo antioxidant action of a lignan-enriched extract of Schisandra fruit and an anthraquinone-containing extract of Polygonum root in comparison with schisandrin B and emodin. Planta. Med. 68, 951-956 (2002) https://doi.org/10.1055/s-2002-35661
  10. Erridge, C., Bennett-Guerrero, E., and Poxton, I.R., Structure and function of lipopolysaccharides. Microbes. Infect. 4, 837-851 (2002) https://doi.org/10.1016/S1286-4579(02)01604-0
  11. Evans, C.H., Nitric oxide: what role does it play in inflammation and tissue destruction? Agents Actions Supplement 47, 107-116 (1995)
  12. Goldstein, S.R., Yang, G.Y., Chen, X., Curtis, S.K., and Yang, C.S., Studies of iron deposits, inducible nitric oxide synthase and nitrotyrosine in a rat model for esophageal adenocarcinoma. Carcinogenesis 19, 1445-1449 (1998) https://doi.org/10.1093/carcin/19.8.1445
  13. Gorman, J.D., Sack, K.E., and Davis, J.C., Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor alpha. New Engl. J. Med. 346, 1349-1356 (2002) https://doi.org/10.1056/NEJMoa012664
  14. Haslberger, A., Romanin, C., and Koerber, R., Membrane potential modulates release of tumor necrosis factor in lipopolysaccharidestimulated mouse macrophages. Mol. Biol. Cell. 3, 451-460 (1992)
  15. Hewett, J.A., and Roth, R.A., Hepatic and extrahepatic pathobiology of bacterial lipopolysaccharides. Pharmacol. Rev. 45, 382-411 (1993)
  16. Jeon, Y.J., Li, M.H., Lee, K.Y., Kim, J.S., You, J.H., Lee, S.K., Sohn, H.M., Choi, S.J., Koh, J.W., and Chang, I.Y., KIOM-79 inhibits LPSinduced iNOS gene expression by blocking NF-κB/Rel and p38 kinase activation in murine macrophages. J. Ethnopharmacol. 108, 38-45 (2006) https://doi.org/10.1016/j.jep.2006.04.007
  17. Kang, S.C., Lee, C.M., Choi, H., Lee, J.H., Oh, J.S., Kwak, J.H., and Zee, O.P., Evaluation of oriental medicinal herbs for estrogenic and antiproliferative activities. Phytother. Res. 20, 1017-1019 (2006) https://doi.org/10.1002/ptr.1987
  18. Karin, M. and Ben-Neriah, Y., Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. Annu. Rev. Immunol. 18, 621-663 (2000) https://doi.org/10.1146/annurev.immunol.18.1.621
  19. Kim, K.S., Cho, H.S., Lee, S.D., Kim, K.H., Cho, J.Y., Chung, K.H., Lee, Y.C., Moon, S.K., and Kim, C.H., Inhibitory effect of Buthus martensi Karsch extracts on interleukin-1 beta-induced expression of nitric oxide (NO) synthase and production of NO in human chondrocytes and LPS-induced NO and prostaglandin E2 production in mouse peritoneal macrophages. Toxicol. In Vitro 19, 757-769 (2005) https://doi.org/10.1016/j.tiv.2005.04.008
  20. Kim, Y.H., Woo, K.J., Lim, J.H., Kim, S., Lee, T.J., Jung, E.M., Lee, J.M., Park, J.W., and Kwon, T.K., 8-Hydroxyquinoline inhibits iNOS expression and nitric oxide production by down-regulating LPSinduced activity of NF-κB and C/EBP$\beta$ in Raw 264.7 cells. Biochem. Biophys. Res. Commun. 329, 591-597 (2005) https://doi.org/10.1016/j.bbrc.2005.01.159
  21. Lee, Y.S., Han, O.K., Park, C.W., Yang, C.H., Jeon, T.W., Yoo, W.K., Kim, S.H., and Kim, H.J., Pro-inflammatory cytokine gene expression and nitric oxide regulation of aqueous extracted Astragali radix in RAW 264.7 macrophage cells. J. Ethnopharmacol. 100, 289-294 (2005) https://doi.org/10.1016/j.jep.2005.03.009
  22. Li, R.W., David, L.G., Myers, S.P., and Leach, D.N., Anti-inflammatory activity of Chinese medicinal vine plants. J. Ethnopharmacol. 85, 61- 67 (2003) https://doi.org/10.1016/S0378-8741(02)00339-2
  23. Li, X., Matsumoto, K., Murakami, Y., Tezuka, Y., Wu, Y., and Kadota, S., Neuroprotective effects of Polygonum multiflorum on nigrostriatal dopaminergic degeneration induced by paraquat and maneb in mice. Pharmacol. Biochem. Behav. 82, 345-352 (2005) https://doi.org/10.1016/j.pbb.2005.09.004
  24. Ohshima, H. and Bartsch, H., Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis. Mutat. Res. 305, 253-264 (1994) https://doi.org/10.1016/0027-5107(94)90245-3
  25. O'Shea, J.J. and Ma A, Lipsky., Cytokines and autoimmunity. Nature Reviews Immunology 2, 37-45 (2002) https://doi.org/10.1038/nri702
  26. MacMicking, J., Xie, Q.W., and Nathan, C., Nitric oxide and macrophage function. Annu. Rev. Immunol. 15, 323-350 (1997) https://doi.org/10.1146/annurev.immunol.15.1.323
  27. Marcinkiewicz, J., Grabowska, A., and Chain, B., Nitric oxide upregulates the release of inflammatory mediators by mouse macrophages. Eur. J. Immunol. 25, 947-951 (1995) https://doi.org/10.1002/eji.1830250414
  28. Minghetti, L. and Levi, G., Microglia as effector cells in brain damage and repair: focus on prostanoids and nitric oxide. Prog. Neurobiol. 54, 99-125 (1998) https://doi.org/10.1016/S0301-0082(97)00052-X
  29. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65: 55-63 https://doi.org/10.1016/0022-1759(83)90303-4
  30. Muller, J.M., Ziegler-Heitbrock, H.W., and Baeuerle, P.A., Nuclear factor kappa B, a mediator of lipopolysaccharide effects. Immunobiology 187, 233-256 (1993)
  31. Park, J.E., Kang, Y.J., Park, M.K., Lee, Y.S., Kim, H.J., Seo, H.G., Lee, J.H., Shin, J.S., Lee, H.W., Ahn, S.K., and Chang, K.C., Enantiomers of higenamine inhibit LPS-induced iNOS in a macrophage cell line and improve the survival of mice with experimental endotoxemia. Int. Immunopharmacol. 6, 226-233 (2006) https://doi.org/10.1016/j.intimp.2005.08.007
  32. Park, S.J., Lee, S.C., Hong, S.H., and Kim, H.M., Degradation of IkappaBalpha in activated RAW264.7 cells is blocked by the phosphatidylinositol 3-kinase inhibitor LY294002. Cell. Biol. Toxicol. 18, 121-130 (2002) https://doi.org/10.1023/A:1015384201785
  33. Park, S.J., Jung, J.A., Lee, J.S., and Kim, H.M., The phosphatidylinositol 3-kinase inhibitor, LY294002, blocks TNF-α and IL-6 production in activated RAW-264.7 cells. Bulletin of Life Science and Biotechnology 6, 3-17 (1999)
  34. Park, Y.M., Won, J.H., Yun, K.J., Ryu, J.H., Han, Y.N., Choi, S.K., and Lee, K.T., Preventive effect of Ginkgo biloba extract (GBB) on the lipopolysaccharide-induced expressions of inducible nitric oxide synthase and cyclooxygenase-2 via suppression of nuclear factorkappaB in RAW 264.7 cells. Biol. Pharm. Bull. 29, 985-990 (2006) https://doi.org/10.1248/bpb.29.985
  35. Rakel, D.P. and Rindfleisch, A., Inflammation: nutritional, botanical, and mind-body influences. South Med. J. 98, 303-310 (2005) https://doi.org/10.1097/01.SMJ.0000154775.16761.A9
  36. Sanchez-Perez, I., Benitah, S.A., Martinez-Gomariz, M., Lacal, J.C., and Perona, R., Cell stress and MEKK1-mediated c-Jun activation modulate NF-kappaB activity and cell viability. Mol. Biol. Cell 13, 2933-2945 (2002) https://doi.org/10.1091/mbc.E02-01-0022
  37. Seitz, M., Loetscher, P., Dewald, B., Towbin, H., Rordorf, C., Gallati, H., and Gerber, N.J., Interleukin 1 (IL-1) receptor antagonist, soluble tumor necrosis factor receptors, IL-1 beta, and IL-8 markers of remission in rheumatoid arthritis during treatment with methotrexate. J. Rheumatol. 23, 1512-1516 (1996)
  38. Seo, W.G., Pae, H.O., Oh, G.S., Chai, K.Y., Kwon, T.O., Yun, Y.G., Kim, N.Y., and Chung, H.T., Inhibitory effects of methanol extract of Cyperus rotundus rhizomes on nitric oxide and superoxide productions by murine macrophage cell line, RAW 264.7 cells. J. Ethnopharmacol 76, 59-64 (2001) https://doi.org/10.1016/S0378-8741(01)00221-5
  39. Shacter, E., arzadon, G.K., and Williams, J.A., Stimulation of interleukin- 6 and prostaglandin E2 secretion from peritoneal macrophages by polymers of albumin. Blood 82, 2853-2864 (1993)
  40. Sradnyk, A.W., Gillan, T.L., and Anderson, R., Respiratory syncytial virus triggers synthesis of IL-6 in BALB/c mouse alveolar macrophages in the absence of virus replication. Cell Immunol. 176, 122-126 (1997) https://doi.org/10.1006/cimm.1996.1075
  41. Szabo, C., Alterations in nitric oxide production in various forms of circulatory shock. New Horiz. 3, 2-32 (1995)
  42. Thiemermann, C. and Vane, J., Inhibition of nitric oxide synthesis reduces the hypotension induced by bacterial lipopolysaccharides in the rat in vivo. Eur. J. Pharmacol. 182, 591-595 (1990) https://doi.org/10.1016/0014-2999(90)90062-B
  43. Um, M.Y., Choi, W.H, Aan, J.Y., Kim, S.R., and Ha, T.Y., Protective effect of Polygonum multiflorum Thunb on amyloid beta-peptide 25- 35 induced cognitive deficits in mice. J. Ethnopharmacol 104, 144- 148 (2006) https://doi.org/10.1016/j.jep.2005.08.054
  44. Verma, I.M., Stevenson, J.K., Schwarz, E.M., Van Antwerp, D., and Miyamoto, S., Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation. Genes Dev. 9, 2723-2735 (1995) https://doi.org/10.1101/gad.9.22.2723
  45. Wallace, J.L., Distribution and expression of cyclooxygenase (COX) isoenzymes, their physiological roles, and the categorization of nonsteroidal anti-inflammatory drugs (NSAIDs). Am. J. Med. 13, 107,11S-16S; discussion 16S-17S (1999) https://doi.org/10.1016/S0002-9343(99)00363-0
  46. Wang, W., Cao, C.Y., Wang, D.Q., and Zhao, D.Z., Effect of prepared Polygonum multiflorum on striatum extracellular acetylcholine and choline in rats of intracerebral perfusion with sodium azide. Zhongguo Zhong Yao Za Zhi 31, 751-753 (2006)
  47. Wang, X., Zhao, L., Han, T., Chen, S., and Wang, J., Protective effects of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside, an active component of Polygonum multiflorum Thunb, on experimental colitis in mice. Eur. J. Pharmacol. 578, 339-348 (2008) https://doi.org/10.1016/j.ejphar.2007.09.013
  48. Wilson, K.T., Fu, S., Ramanujam, K.S., and Meltzer, S.J., Increased expression of inducible nitric oxide synthase and cyclooxygenase-2 in Barrett's esophagus and associated adenocarcinomas. Cancer Res. 58, 2929-2934 (1998)
  49. Xiao, P.G., Xing, S.T., and Wang, L.W., Immunological aspects of Chinese medicinal plants as antiageing drugs. J. Ethnopharmacol. 38, 167-175 (1993) https://doi.org/10.1016/0378-8741(93)90013-U
  50. Yim, T.K., Wu, W.K., Mak, D.H., and Ko, K.M., Myocardial protective effect of an anthraquinone-containing extract of Polygonum multiflorum ex vivo. Planta. Med. 64, 607-611 (1998) https://doi.org/10.1055/s-2006-957531
  51. Zhang, C.Z., Wang, S.X., Zhang, Y., Chen, J.P., and Liang, X.M., In vitro estrogenic activities of Chinese medicinal plants traditionally used for the management of menopausal symptoms. J. Ethnopharmacol. 98, 295-300 (2005) https://doi.org/10.1016/j.jep.2005.01.033
  52. Zhang, H., Jeong, B.S, and Ma, T.H., Antimutagenic property of an herbal medicine, Polygonum multiftorum Thunb. detected by the Tradescantia micronucleus assay. J. Environ. Pathol. Toxicol. Oncol. 18, 127-130 (1999)
  53. Zhang, Y.Z., Shen, J.F., Xu, J.Y., Xiao, J.H., and Wang, J.L., Inhibitory effects of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside on experimental inflammation and cyclooxygenase 2 activity. J. Asian Nat. Prod. Res. 9, 355-363 (2007) https://doi.org/10.1080/10286020600727772