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DOI: 10.1055/s-2004-832616
© Georg Thieme Verlag KG Stuttgart · New York
Phenylpropanoid NF-κB inhibitors from Bupleurum fruticosum
Publication History
Received: April 26, 2004
Accepted: July 15, 2004
Publication Date:
18 October 2004 (online)
![](https://www.thieme-connect.de/media/plantamedica/200410/lookinside/thumbnails/10.1055-s-2004-832616-1.jpg)
Abstract
Two phenylpropanoids from Bupleurum fruticosum (Apiaceae/Umbelliferae) were shown to inhibit the transcriptional activity induced by PMA or TNFα of an NF-κB-controlled reporter gene. Western blot experiments indicated that the phenylpropanoids did not prevent IκBα degradation, suggesting that their molecular target is at a post-IKB degradation level. Both compounds prevented cytokine (IL-1, IL-6, TNF, IL-8) release and prostaglandin E2 synthesis.
Abbreviations
AINP:anti-inflammatory natural products (EU-FP5-QLK3-2000-00463)
IκB:inhibitor of NF-κB
IL:interleukin
NF-κB:nuclear factor kappa B
Key words
NF-κB - Bupleurum fruticosum - Apiaceae - phenylpropanoids - anti-inflammatory natural products (AINP) - cytokine
References
- 1 Palladino M A, Bahjat F R, Theodorakis E A, Modawer L L. Anti-TNF-alpha therapies the next generation. Nat Rev Drug Discov. 2003; 2 717-26
- 2 Bremner P, Heinrich M. Natural products as modulators of the NF-κB-pathway. J Pharm Pharmacol. 2002; 54 453-72
- 3 Calixto J B, Otuki M F, Santos A RS. Anti-inflammatory compounds of plant origin. Part 1. Planta Med. 2003; 69 973-83
- 4 Ghosh S, Karin M. Missing pieces in the NF-κB puzzle. Cell. 2002; 109 81-S96
- 5 Karin M, Cao Y X, Greten F R, Li Z W. NF-κ B in cancer: from innocent bystander to major culprit. Nat Rev Cancer. 2002; 2 301-10
- 6 Gunther R T. The Greek Herbal of Dioscorides. Hafner Publishing Company London; 1968: p 297
- 7 Ballero M, Fresu I. Piante officinali impiegate in fitoterapia nel territoriao de Margonoai. Fitoterapia. 1991; 62 524-7
- 8 Massanet G M, Guerra F M, Jorge Z D, Casalvázquez L G. Phenylpropanoids from Bupleurum fruticosum . Phytochemistry. 1997; 44 173-7
- 9 Pistelli L, Bilia A R, Bertoli A, Moerelli I, Marsili A. Phenylpropanoids from Bupleurum fruticosum . J Nat Prod. 1995; 58 112-6
- 10 Guinea M C, Parellada J, Lacaille-Dubois M A, Wagner H. Biologically active triterpene saponins from Bupleurum fruticosum . Planta Med. 1994; 60 163-7
- 11 Bork P M, Schmitz M L, Kuhnt M, Escher C, Heinrich M. Sesquiterpene lactone containing Mexican Indian medicinal plants and pure sesquiterpene lactones as potent inhibitors of transcription factor NF-κB. FEBS Lett. 1997; 402 85-90
- 12 Fiebich B L, Chrubasik S. Effects of an ethanolic salix extract on the release of selected inflammatory mediators in vitro . Phytomedicine.. 2004; 11 135-8
- 13 Schmitz M L, Bacher S, Kracht M. IκB-independent control of NF-κB activity by modulatory phosphorylations. Trends Biochem Sci. 2001; 26 186-90
- 14 Madrid L V, Mayo M W, Reuther J Y, Baldwin Jr A S. Akt stimulates the transactivation potential of the RelA/p65 subunit of NF-κB through utilization of the IκB kinase and activation of the mitogen-activated protein kinase p38. J Biol Chem. 2001; 276 18 934-40
- 15 Vermeulen J L, Wilde G d e, Damme P v an, Berghe W V anden, Haegeman G. Transcriptional activation of the NF-κB p65 subunit by mitogen- and stress-activated protein kinase-1 (MSK1). EMBO J. 2003; 22 1313-24
- 16 Anrather V, Csizmadia M, Soares P, Winkler H. Regulation of NF-κB RelA phosphorylation and transcriptional activity by p21(ras) and protein kinase Cζ in primary endothelial cells. J Biol Chem. 1999; 274 13 594-603
- 17 Wang D, Westerheide S D, Hanson J L, Baldwin Jr A S. Tumor necrosis factor α-induced phosphorylation of RelA/p65 on Ser529 is controlled by casein kinase II. J Biol Chem. 2000; 275 32 592-7
- 18 Sakurai H, Chiba H, Miyoshi H, Sugita T, Toriumi W. IκB kinases phosphorylate NF-κB p65 subunit on serine 536 in the transactivation domain. J Biol Chem. 1999; 274 30 353-6
- 19 Jang M K, Goo Y H, Sohn Y C, Kim Y S, Lee S K, Kang H, Cheong J, Lee J W. Ca2+/calmodulin-dependent protein kinase IV stimulates nuclear factor-kappa B transactivation via phosphorylation of the p65 subunit. J Biol Chem. 2001; 276 20 005-10
- 20 Sing S, Aggarwal B B. Activation of transcription factor NF-κB is suppressed by curcumin (diferuloylmethane). J Biol Chem. 1995; 270 4995-5000
- 21 Márquez N, Sancho R, Macho A, Calzado M A, Fiebich B L, Muñoz E. Caffeic acid phenethyl ester inhibits T-cell activation by targeting both nuclear factor of activated T-cells and NF-κB transcription factors. J Pharmacol Exp Ther. 2004; 308 993-1001
- 22 Cho M K, Park J W, Jang Y P, Kim Y C, Kim S G. Potent inhibition of lipopolysaccharide-induced nitric oxide synthase expression by dibenzylbutyrolactone lignans through inhibition of I-κBα phorphorylation and of p65 nuclear translocation in macrophages. Int Immunopharmacol. 2002; 2 05-16
Professor Michael Heinrich
Centre for Pharmacognosy and Phytotherapy
The School of Pharmacy
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