Planta Med 2006; 72(1): 65-68
DOI: 10.1055/s-2005-873145
Letter
© Georg Thieme Verlag KG Stuttgart · New York

Luteolin Inhibits LPS-Stimulated Inducible Nitric Oxide Synthase Expression in BV-2 Microglial Cells

Ji Sun Kim1 , Hwa Jin Lee1 , Ming Hong Lee1 , Jaeyeon Kim1 , Changbae Jin2 , Jae-Ha Ryu1
  • 1College of Pharmacy, Sookmyung Women’s University, Seoul, Korea
  • 2Division of Life Sciences, Korea Institute of Science & Technology, Seoul, Korea
Further Information

Publication History

Received: December 23, 2004

Accepted: June 10, 2005

Publication Date:
14 October 2005 (online)

Abstract

Overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) acts as a neurotoxic effector in the central nervous system, resulting in neurodegenerative diseases. From the alcoholic extracts of Perilla frutescens, we have purified an inhibitor of NO production in lipopolysaccharide (LPS)-activated microglia by activity-guided purification. The active compound was identified as luteolin by spectral analysis. Luteolin inhibited the NO production in LPS-activated microglia in a dose-dependent manner (IC50 = 6.9 μM). Luteolin also suppressed the degradation of I-κB-α, the expression of protein and mRNA of iNOS in LPS-activated microglia as observed in Western blot analysis and RT-PCR experiments. Luteolin may have beneficial effects in the treatment of neuro-inflammatory diseases through the inhibition of iNOS expression.

References

  • 1 McGeer P L, McGeer E G. The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases.  Brain Res Brain Res Rev. 1995;  21 195-218
  • 2 Bredt D S, Snyder S H. Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme.  Proc Natl Acad Sci USA. 1990;  87 682-5
  • 3 Lowenstein C J, Glatt C S, Bredt D S, Snyder S H. Cloned and expressed macrophage nitric oxide synthase contrasts with the brain enzyme.  Proc Natl Acad Sci USA. 1992;  89 6711-5
  • 4 Chabrier P E, Demerle-Pallardy C, Auguet M. Nitric oxide synthases: targets for therapeutic strategies in neurological diseases.  Cell Mol Life Sci. 1999;  55 1029-35
  • 5 Beckman J S, Beckman T W, Chen J, Marshall P A, Freeman B A. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide.  Proc Natl Acad Sci USA. 1990;  87 1620-4
  • 6 Green L C, Wagner D A, Glogowski J, Skipper P L, Wishnok J S, Tannenbaum S R. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids.  Anal Biochem. 1982;  126 131-8
  • 7 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.  J Immunol Methods. 1983;  65 55-63
  • 8 Hu C, Kitts D D. Luteolin and luteolin-7-O-glucoside from dandelion flower suppress iNOS and COX-2 in RAW264.7 cells.  Mol Cell Biochem. 2004;  265 107-13
  • 9 van Meeteren M E, Hendriks J J, Dijkstra C D, van Tol E A. Dietary compounds prevent oxidative damage and nitric oxide production by cells involved in demyelinating disease.  Biochem Pharmacol. 2004;  67 967-75
  • 10 Li H, Xia N, Brausch I, Yao Y, Forstermann U. Flavonoids from artichoke (Cynara scolymus L.) up-regulate endothelial-type nitric-oxide synthase gene expression in human endothelial cells.  J Pharmacol Exp Ther. 2004;  310 926-32
  • 11 Xagorari A, Papapetropoulos A, Mauromatis A, Economou M, Fotsis T, Roussos C. Luteolin inhibits an endotoxin-stimulated phosphorylation cascade and proinflammatory cytokine production in macrophages.  J Pharmacol Exp Ther. 2001;  296 181-7
  • 12 Perry V H, Gordon S. Macrophages and microglia in the nervous system.  Trends Neurosci. 1988;  11 273-7
  • 13 Gonzalez-Scarano F, Baltuch G. Microglia as mediators of inflammatory and degenerative diseases.  Annu Rev Neurosci. 1999;  22 219-40
  • 14 Makino T, Ono T, Ito M, Muso E, Honda G. Effect of Perilla frutescens extract on nitric oxide production by cultured murine mesangial cells.  Biol Pharm Bull. 1999;  22 476-80
  • 15 Ueda H, Yamazaki M. Inhibition of tumor necrosis factor-alpha production by orally administering a perilla leaf extract.  Biosci Biotechnol Biochem. 1997;  61 1292-5
  • 16 Ryu J H, Son H J, Lee S H, Sohn D H. Two neolignans from Perilla frutescens and their inhibition of nitric oxide synthase and tumor necrosis factor-alpha expression in murine macrophage cell line RAW 264.7  Bioorg Med Chem Lett. 2002;  12 649-51
  • 17 Ueda H, Yamazaki C, Yamazaki M. Luteolin as an anti-inflammatory and anti-allergic constituent of Perilla frutescens .  Biol Pharm Bull. 2002;  25 1197-202
  • 18 Hougee S, Sanders A, Faber J, Graus Y M, van den Berg W B, Garssen J, Smit H F, Hoijer M A. Decreased pro-inflammatory cytokine production by LPS-stimulated PBMC upon in vitro incubation with the flavonoids apigenin, luteolin or chrysin, due to selective elimination of monocytes/macrophages.  Biochem Pharmacol. 2005;  69 241-8
  • 19 Sasaki N, Toda T, Kaneko T, Baba N, Matsuo M. Protective effects of flavonoids on the cytotoxicity of linoleic acid hydroperoxide toward rat pheochromocytoma PC12 cells.  Chem Biol Interact. 2003;  145 101-16
  • 20 Kang S S, Lee Y J, Choi Y K, Kim S G, Han B H. Neuroprotective effects of flavones on hydrogen peroxide-induced apoptosis in SH-SY5Y neuroblostoma cells.  Bioorg Med Chem Lett. 2004;  14 2261-4

Jae-Ha Ryu

College of Pharmacy

Sookmyung Women’s University

53-12 Chungpa-Dong

Yongsan-Gu

Seoul 140-742

Korea

Phone: +82-2-710-9568

Fax: +82-2-714-0745

Email: ryuha@sookmyung. ac.kr