Food Science and Biotechnology

Korean Society of Food Science and Technology (한국식품과학회)
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Antioxidant and Suppressive Effects of Ethanolic Extract Fractions from Safflower (Carthamus tinctorius L.) Flower on the Biosynthesis of Inflammatory Mediators from LPS-stimulated RAW 264.7 Cells

  • Lee, Je-Hyuk (Plant Resources Research Institute, Duksung Women's University) ;
  • Jeon, Choon-Sik (College of Pharmacy, Duksung Women's University) ;
  • Kim, Gun-Hee (Plant Resources Research Institute, Duksung Women's University)
  • Published : 2009.02.28
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Abstract

The aim of this study was to elucidate the anti-inflammatory activity of safflower (Carthamus tinctorius L.) ethanolic extract fractions (CFEFs). Butanol fraction had the strongest antioxidant activity, and all CFEFs, except for chloroform fraction, partly inhibited lipopolysaccharide (LPS)-induced nitrite production in RAW 264.7 cells. In the cell-free system, hexane and butanol fractions chemically quenched nitric oxide (NO). In addition, the iNOS mRNA transcription was suppressed by ethanol extract and hexane fraction in LPS-stimulated RAW 264.7 cells. Taken together, the inhibitory effect of CFEFs on NO production from LPS-stimulated RAW 264.7 cells, might be due to both the chemical NO quenching activity and the suppression of iNOS mRNA transcription partially. The synthesis of prostaglandin $E_2$ ($PGE_2$) was potently inhibited by ethanol extract to below basal label, and the transcription of cyclooxygenase-2 (COX-2), an enzyme involving in $PGE_2$ synthesis, was partially suppressed by ethanol extract and hexane fraction. Based on these results, CFEFs may be useful as an alternative medicine for the relief and retardation of immunological inflammatory responses through the reduction of inflammatory mediators, including NO and $PGE_2$ production.

Keywords

References

  1. Kim HJ, Bae YC, Park RW, Choi SW, Cho SH, Choi YS, Lee WJ. Bone protecting effect of safflower seeds in ovariectomized rats. Calcified. Tissue Int. 71: 88-94 (2002) https://doi.org/10.1007/s00223-001-1080-4
  2. Roh JS, Han JY, Kim JH, Hwang JK. Inhibitory effects of active compounds isolated from safflower (Carthamus tinctorius L.) seeds for melanogenesis. BioI. Pharm. Bull. 27: 1976-1978 (2004) https://doi.org/10.1248/bpb.27.1976
  3. Park YH, Park HK, Lee HJ, Park SM, Choi SW, Lee WJ. Phytoestrogen-induced phosphorylation of MAP kinase in osteoblasts in mediated by membrane estrogen receptor. Korean J. Physiol. Pharmacol. 6: 165-169 (2002)
  4. Roh JS, Sun WS, Oh SU, Lee JI, Oh WT, Kim JH. In vitro antioxidant activity of safflower (Carthamus tinctorius L.) seeds. Food Sci. Biotechnol. 8: 88-92 (1999)
  5. Kim DH, Lee JH, Ahn EM, Lee YH. Baek NI, Kim IH. Phenolic glycosides isolated from safflower seeds increase the alkaline phosphatase (ALP) activity of human osteoblast-like cells. Food Sci. Biotechnol. 15: 781-785 (2006)
  6. Kim EO, Oh JH, Lee SK, Lee JY, Choi SW. Antioxidant properties and quantification of phenolic compounds from safflower (Carthamus tinctorius L.) seeds. Food Sci. Biotechnol. 16: 71-77 (2007)
  7. Cho SH, Choi SW, Choi YS, Kim HJ, Park YH, Bae YC, Lee WJ. Effect of ethanol extract of safflower seed on bond loss in ovariectomized rat. Food Sci. Biotechnol. 16: 392-397 (2007)
  8. Kim JH, Kim JK, Kang WW, Ha YS, Choi SW, Moon KD. Chemical compositions and DPPH radical scavenger activity in different sections of safflower. J. Food Sci. Nutr. 32: 733-738 (2003) https://doi.org/10.3746/jkfn.2003.32.5.733
  9. Luss H, Nussler NC, Beger HG, Nussler AK. Expression and detection of inducible nitric oxide synthase in experimental models of inflammation. Methods 10: 51-60 (1996) https://doi.org/10.1006/meth.1996.0078
  10. Korhonen R, Lathi A, Kankaanranta H, Moilanen E. Nitric oxide production and signaling in inflammation. Curr. Drug TargetsInflamm. Allergy 4: 471-479 (2005) https://doi.org/10.2174/1568010054526359
  11. Lu Y, Wahl LM. Metalloproteinase-1, cyclooxygenase-2, and prostaglandin E2 through enhancement of NF-$\kappa$B activity in lipopolysaccharideactivated human primary monocytes oxidative stress augments the production of mactrix. J. Immunol. 175: 5423-5429 (2005) https://doi.org/10.4049/jimmunol.175.8.5423
  12. Meade EA, Smith WL, DeWitt DL. Differential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isozymes by aspirin and other non-steroidal anti-inflammatory drugs. J. BioI. Chem. 268: 6610-6614 (1993)
  13. Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB, Lipsky PE. Cyclooxygenase in biology and disease. FASEB J. 12: 1063-1073 (1998) https://doi.org/10.1096/fasebj.12.12.1063
  14. Lai WC, Zhou M, Shankavaram U, Peng G, Wahl LM. Differential regulation of lopopolysaccharide-induced monocyte matrix metalloproteinase (MMP)-1 and MMP-9 by p38 and extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase. J. Immunol. 170: 6244-6249 (2003) https://doi.org/10.4049/jimmunol.170.12.6244
  15. Davies P, Bailey PJ, Goldenberg MM, Ford-Hutchinson AW. The role of arachidonic acid oxygenation products in pain and inflammation. Annu. Rev. Immunol. 2: 335-357 (1984) https://doi.org/10.1146/annurev.iy.02.040184.002003
  16. Park GY, Christman Jw. Involvement of cyclooxigenase-2 and prostaglandins in the molecular pathogenesis of inflammatory lung diseases. Am. J. Physiol.-Lung C. 290: L 797-L805 (2006) https://doi.org/10.1152/ajplung.00513.2005
  17. Lee EJ, Kim KS, Jung HY, Kim DH, Jang HD. Antioxidant activities of garlic (Allium sativum L.) with growing districts. Food Sci. Biotechnol. 14: 123-130 (2005)
  18. Oyaizu M. Studies on product of browning reaction: Antioxidative activities of products of browning reaction prepared from glucosamine. Jpn. J. Nutr. 44: 307-315 (1986) https://doi.org/10.5264/eiyogakuzashi.44.307
  19. Chattopadhyay S, Bhaumik S, Purkayastha M, Basu S, Chaudhuri AN, Gupta SD. Apoptosis and necrosis in developing brain cells due to arsenic toxicity and protection with antioxidants. Toxicol. Lett. 136: 65-76 (2002) https://doi.org/10.1016/S0378-4274(02)00282-5
  20. Sutherland H, Khundkar R, Zolle O, McArdle A, Simpson AW, Jarvis JC, Salmons S. A fluorescence-based method for measuring nitric oxide in extracts of skeletal muscle. Nitric Oxide 5: 475-481 (2001) https://doi.org/10.1006/niox.2001.0374
  21. Babu BH, Shylesh BS, Padikkala J. Antioxidant and hepatoprotective effect of Acanthus ilicifolius. Fitoterapia 72: 272-277 (2001) https://doi.org/10.1016/S0367-326X(00)00300-2
  22. Wei T, Chen C, Hau J, Zhao B, Xin W, Mori A. The antioxidant EPC-K1 attenuates NO-induced mitochondrial dysfunction, lipid peroxidation, and apoptosis in cerebellar granule cells. Toxicology 134: 117-126 (1999) https://doi.org/10.1016/S0300-483X(99)00030-X
  23. Ahn KS, Noh EJ, Zhao HL, Jung SH, Kang SS, Kim YS. Inhibition of inducible nitric oxide synthase and cylooxygenase II by platycodon grandiflorum saponins via suppression of nuclear factor-$\kappa$B activation in RAW 264.7 cells. Life Sci. 76: 2321-2328 (2005)
  24. Leirisalo-Repo M, Paimela L, Koskimies S, Repo H. Functions of polymorphonuclear leukocytes in early rheumatoid arthritis. Inflammation 17: 427-442 (1993) https://doi.org/10.1007/BF00916583
  25. Babior BM. The respiratory burst oxidase. Adv. Enzymol. RAMB 65: 49-95 (1992)
  26. Valentine JS, Wertz DL, Lyons TJ, Liou LI, Goto JJ, Gralla EB. The dark side of dioxygen biochemistry. Curr. Opin. Chem. BioI. 2: 253-262 (1998) https://doi.org/10.1016/S1367-5931(98)80067-7
  27. Gordon MH. The mechanism of antioxidant action in vitro. pp. 1-18. In: Food Antioxidants. Hudson BJF (ed). Elsevier, London, UK (1990)
  28. Padayatty SJ, Levine M. New insights into the physiology and pharmacology of vitamin C. Can. Med. Assoc. J. 164: 353-355 (2001)
  29. Perez-Sala D, Lamas S. Regulation of cyclooxygenase-2 expression by nitric oxide in cells. Antioxid. Redox Sign. 3: 231-248 (2001) https://doi.org/10.1089/152308601300185197
  30. Salvemini D. Regulation of cyclooxygenase enzymes by nitric oxide. Cell Mol. Life Sci. 53: 576-582 (1997) https://doi.org/10.1007/s000180050074
  31. Prabhu KS, Zamamiri-Davis F, Stewart JB, Thomson JT, Sordillo LM, Reddy CC. Selenium deficiency increases the expression of inducible nitric oxide synthase in RAW 264.7 macrophage: Role of nuclear factor-KS in up-regulation. Biochem. J. 366: 203-209 (2002)
  32. Bowie AG, Moynagh PN, O Neill LA. Lipid peroxidation is involved in the activation of NF-$\kappa$B by tumor necrosis factor but interleukin-I in the human endothelial cell line ECV304. J. BioI. Chem. 272: 25941-25950 (1997) https://doi.org/10.1074/jbc.272.41.25941
  33. Schreck R, Meier B, Mannel DN, Droge W, Baeuerle PA. Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells. J. Exp. Med. 175: 1181-1194 (1992) https://doi.org/10.1084/jem.175.5.1181
  34. Bonizzi G, Piette J, Schoonbroodt S, Greimers R, Havard L, Merville MP, Bours V. Reactive oxygen intermediate-dependent NF-$\kappa$B activation by interleukin-1$\beta$ requires 5-lipoxygenase or NADPH oxidase activity. Mol. Cell. BioI. 19: 1950-1960 (1999)
  35. Pan MH, Lai CS, Wang YJ. Acacetin suppressed LPS-induced upexpression of iNOS and COX-2 in murine macrophages and TPA-induced tumor promotion in mice. Biochem. Pharmacol. 72: 1293-1303 (2006) https://doi.org/10.1016/j.bcp.2006.07.039
  36. Gorgoni B, Caivano M, Arizmendi C, Poli V. The transcription factor C/EBP$\beta$ is essential for inducible expression of the COX-2 gene in macrophages but not in fibroblasts. J. BioI. Chem. 276: 40769-40777 (2001) https://doi.org/10.1074/jbc.M106865200
  37. Van Dross RT, Hong X, Pelling JC. Inhibition of TPA-induced cyclooxygenase-2 (COX-2) expression by apigenin through downregulation of Akt signal transduction in human keratinocytes. Mol. Carcinogen. 44: 83-91 (2005) https://doi.org/10.1002/mc.20123
  38. Franzotti EM, Santos CV, Rodrigues HM, Mourao RH, Andrade MR, Antoniolla AR. Anti-inflammatory, analgesic activity and acute toxicity of Sida cordifolia L. (Malva-branca). J. Ethnopharmacol. 72: 273-277 (2000) https://doi.org/10.1016/S0378-8741(00)00205-1
  39. Ojewole JAO. Antinociceptive, anti-inflammatory, and antidiabetic properties of Hypoxis hemerocallidea Fisch. & C.A. Mey. (Hypoxidaceae) corm ['African potato'] aqueous extract in mice and rats. J. Ethnophannacol. 103: 126-134 (2006) https://doi.org/10.1016/j.jep.2005.07.012
  40. Spector WG, Willoughb DA. The inflammatory response. Bacteriol. Rev. 27: 117-154 (1963)
  41. Nantel F, Denis D, Gordon R, Northey A, Cirino M, Metters KM, Chan CC. Distribution and regulation of cyclooxygenase-2 in carrageenaninduced inflammation. Brit. J. Pharmacol. 128: 853-859 (1999) https://doi.org/10.1038/sj.bjp.0702866