Sesquiterpene lactone from Tanacetum parthenium

Stimulation of macrophages by lipopolysaccharide (LPS) results in activation of members of MAPKs, ERKl and ERK2. The main sesquiterpene lactone from Tanacetum parthenium (Asteraceae), parthenolide (28), suppressed LPS-stimulated tyrosine phosphorylation of various proteins in RAW 264.7 cells. Of these proteins the MAPKs exhibited the most dramatic inhibition in response to parthenolide. 

In 1959-61, a Czech group [8,9] reported the isolation of a new sesquiterpene lactone from Chrysanthemum (Tanacetum) parthenium as part of a study of the sesquiterpene lactones of the Compositae family. They named it parthenolide. The initial structure for parthenolide was later revised [10,11] and the accepted structure for parthenolide today is represented by structure (1). Parthenolide is a germacranolide-type sesquiterpene lactone. The crystal structure for parthenolide has also been reported [12]. Extractions of C. (T.) parthenium grown in Mexico, known locally as santamaria, did not yield parthenolide [13], but a closely related compound was isolated and named santamarine (3). This suggests that regional variations in the chemical constituents may occur. 

Parthenolide, isolated from Tanacetum parthenium and other species, is a sesquiterpene lactone widely investigated for its anti-inflammatory activity [168,169,170]. Recent in vitro studies have shown that this compound inhibits the NF-kB pathway. A study on the effect of parthenolide in endotoxic shock in rodents showed that treatment with this compound stopped nitrotyrosine formation, PARP synthetase expression, and apoptosis. It also reduced iNOS mRNA content in the tissues studied. All these effects are brought about by the compound s inhibition of NF-kB [171]. In addition, parthenolide mimicked the effects of IkBoc in that it inhibited both NF-kB DNA binding activity as well as Mn-SOD expression, while simultaneously increasing paclitaxel-induced apoptosis of breast cancer cells [90]. 

Bohlmann F, Zdero C 1982 Naturally occurring terpene derivatives. Part 454. Sesquiterpene lactones and other constituents from Tanacetum parthenium. Phytochemistry 21 2543-2549... 

More than 11,000 Sesquiterpenes have been isolated from natural sources [3]. Feverfew (Tanacetum parthenium (L.) Sch. Bip.,. Compositae) is a common herb utilized for fever, arthritis and migraine. The leaves of feverfew contain large amounts of sesquiterpene lactones. The chloroform extracts of fresh leaves and a commercial leaf product show dose-dependent inhibiting the production of throboxane B2 (TXB2) and leukotriene B4 (LTB4) in rat and human leukocytes. Sesquiterpene lactones isolated from the leaves of feverfew, such as parthenolide and tanaparthin-a-peroxide, demonstrate potent dual inhibitions of COX and LOX pathways with IC50 for COX at 6 17 pg/ml, and for LOX at 12 17 pg/ml, respectively [135],... 

Many sesquiterpenes contain a pentacyclic lactone group and are therefore referred to as sesquiterpene lactones. These compounds occur abundantly in the family Asteraceae. Because of their bitter taste sesquiterpene lactones presumably serve as feeding deterrents of herbivores (Heinrich et al., 1998). Pharmacologically active sesquiterpene lactones often show anti-inflammatory effects due to inhibition of the transcription factor NF-kB that mediates immunological responses and inflammation (LyB et al., 1998). Sesquiterpenes with such activities occur, for example, in chamomile Matricaria recutita), one ofthe most popular medicinal plants. Antimigraine action of some sesquiterpene lactones, e.g., par-thenolide from feverfew (Tanacetum parthenium), is mediated by inhibition of platelet aggregation... 

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