Tetrahydrofuran Lignans from Illicium floridanum and Their Activity in a Luminol Enhanced Chemiluminescence Assay

Abstract

Two lignans of the tetrahydrofuran type, di-O-methyltetrahydrofuroguaiacin B (1) and (+)-veraguensin (2) were isolated from fruits and leaves of Illicium floridanum Ellis (Illiciaceae). These compounds are the first genuine lignans isolated from the genus Illicium. We investigated their radical scavenging potency towards 1,1-diphenyl-2-picrylhydrazyl radical reagent and their influence on luminol enhanced chemiluminescence (CHL) induced by different stimuli in human polymorphonuclear neutrophils (PMN). Both compounds were inactive in the TLC assay for chemical radical scavenge. In the PMN assay, the symmetric lignan 1 at concentrations below 1.0 μM displayed a strong inhibition of CHL induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP). At concentrations above 5 μM, 1 led to a pronounced increase of fMLP induced CHL. When CHL was stimulated with opsonized zymosan, both compounds were completely inactive. Thus, 1 must interfere selectively with a step in the signal cascade evoked by fMLP. In addition to their known PAF-receptor antagonism tetrahydrofuran lignans may thus also interfere with inflammatory reponses by inhibition of free radical formation.

References

• 1 Schmidt  T J,, Peters  W,, Fronczek  F R,, Fischer  N H.. Revision of the structure of dunnianin and related sesquiterpene lactones from Illicium species.  Journal of Natural Products. 1997;;  60 783-7
• 2 Schmidt  T J,, Schmidt  H M,, Müller  E,, Peters  W,, Fronczek  F R,, Truesdale  A,, Fischer  N H.. New sesquiterpene lactones from Illicium floridanum. .  Journal of Natural Products. 1998;;  61 230-6
• 3 Schmidt  T J.. Novel seco-prezizaane sesquiterpenes from North American Illicium species.  Journal of Natural Products. 1999;;  62 684-7
• 4 King  F E,, Wilson  J G.. The chemistry of extractives from hardwoods. Part XXXVI. The lignans of Guaiacum officinale L.  Journal of the Chemical Society. 1964;;  4011-24
• 5 Crossley  N S,, Djerassi  C.. Naturally occurring oxygen heterocyclics. Part XI. Veraguensin.  Journal of the Chemical Society. 1962;;  1459-62
• 6 Fonseca  S F,, Barata  L E,, Ruveda  E A,, Baker  P M.. ¹³C Nuclear magnetic resonance spectral and conformational analysis of naturally occurring tetrahydrofuran lignans.  Canadian Journal of Chemistry. 1979;;  57 441-3
• 7 Sy  L K,, Saunders  R MK,, Brown  G D.. Phytochemistry of Illicium dunnianum and the systematic position of the Illiciaceae.  Phytochemistry. 1997;;  44 1099-108
• 8 Ayres  D C,, Loike  J D.. Lignans - Chemical, Biological and Clinical Properties. Cambridge University Press, Cambridge; 1990
• 9 Vincent  M A.. Illicium Linnaeus. Flora of North America,. Online Version: http://www.fna.org
• 10 Heilmann  J,, Merfort  I,, Weiss  M.. Radical scavenger activity of different 3′,4′-dihydroxyflavonols and 1,5-dicaffeoylquinic acid studied by inhibition of chemiluminescence.  Planta Medica. 1995;;  61 435-8
• 11 Lobitz  G O,, Heilmann  J,, Zschocke  S,, Tamayo-Castillo  G,, Bauer  R,, Merfort  I.. Bornyl cinnamate derivatives with anti-inflammatory activity from Verbesina turbacensis.  Pharmaceutical and Pharmacological Letters. 1998;;  8 115-8
• 12 Biftu  T,, Gamble  N F,, Doebber  T,, Hwang  S B,, Shen  T Y,, Snyder  J,, Springer  J P,, Stevenson  R.. Conformation and activity of tetrahydrofuran lignans and analogues as specific platelet activating factor antagonists.  Journal of Medicinal Chemistry. 1986;;  29 1917-21
• 13 Hattori  M,, Hada  S,, Kawata  Y,, Tezuka  Y,, Kikuchi  T,, Namba  T.. New 2,5-bis-aryl-3,4-dimethyltetrahydrofuran lignans from the aril of Myristica fragrans. .  Chemical & Pharmaceutical Bulletin. 1987;;  35 3315-22