Phenylpropanoid NF-κB inhibitors from Bupleurum fruticosum

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