Sesquiterpene lactones factors

Arnica montana L. (Arnica) has been used for treating bruises and swelling in Western medicine on account of its ability to elaborate sesquiterpene lactones, such as hele-nalin and dihydrohelenalin, which are thought to inhibit the activation of transcription factor nuclear factor (NF)-kB, which is responsible for the transcription of genes involved in encoding mediators for the inflammatory process. 

Kim EJ, Hye KJ, Yong KK, et al. Suppression by a sesquiterpene lactone from Carpe-sium divaricatum of inducible nitric oxide synthase by inhibiting nuclear factor-KB activation. Biochem Pharmacol 2001 61 903-910. 

The capsules contained a mean of 82 mg feverfew and thus the level of activity calculated as parthenolide can be estimated as 0.67%. Other studies quote 0.87% sesquiterpene lactones calculated as parthenolide [27] and 0.25-0.30% of active (antimicrobial) material [33]. Bohlmann s extraction of individual components from the dried plant yielded 116 mg sesquiterpene lactones/kg dried feverfew which amounts to less than 0.01 % [17]. Another extraction yielded 330 mg endoperoxides/kg and 56 mg canin/kg alone [19] which would amount to a level of sesquiterpene lactones of at least 0.04%. Thus, the level of sesquiterpene lactones appears to vary with different sources of the plant and this could have been due to a number of factors including the conditions in which feverfew was grown, the season in which it was picked and the way in which it was stored. Another important determinant of the parthenolide content of feverfew appears to be the geographical location. A recent survey of commercial preparations found that all the North American commercial products tested contained less that 0.1% parthenolide, wheras much higher values were obtained for British products. A minimum level of 0.2% parthenolide in commercial products has been proposed by the Health Protection Branch of Health and Welfare Canada [71]. 

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-kappaB., FEBS Lett., 1997,402,85-90. 

Tanacetum parthenium (Asteraceae), commonly known as feverfew, is a popular herbal remedy used a prophylactic in the treatment of migraine [88]. Studies have revealed that the action of feverfew is probably mediated by the sesquiterpene lactone parthenolide. Indeed, feverfew and parthenolide produce anti-inflammatory and antinociceptive effects in experimental animals [89]. Parthenolide is a potent inhibitor of the transcription factor NF-kB activation, a key regulator of pro-inflammatory protein production, such as cytokines, COX-2 and inducible nitric oxide synthase [90]. However, a clinical study revealed that feverfew did not provide any benefit in the treatment of rheumatoid arthritis [91]. Additional clinical studies must be carried out to explore the feverfew efficacy as an analgesic. 

Paulsen, E., A. Otkjaer, and K.E. Andersen. 2008. Sesquiterpene lactone dermatitis in the young Is atopy a risk factor Contact Dermat. 59(l) l-6. 

In 1999, Irmgard Merfort and her group published a thorough smdy of sesquiterpene lactones and their NF-kB inhibitory activity [53, 54]. The term nuclear transcription factor (NF) applies to a family of highly homologous protein occurring ubiquitously in mammalian cells. NF-kB consists of two subunits of 50 and... 

Siedle B, Garcfa-Pineres AJ, Murillo R, Schulte-Monting J, Castro V, Riingeler P, Klaas CA, Da Costa FB, Kisiel W, Merfort I (2004) Quantitative structure-activity relationship of sesquiterpene lactones as inhibitors of the transcription factor NF-kB. J Med Chem 47(24) 6042-6054... 

Riingeler P, Castro V, Mora G, Goren N, Vichnewski W, Pahl HL, Merfort I, Schmidt TJ (1999) Inhibition of transcription factor NF-kappa B by sesquiterpene lactones a proposed molecular mechanism of action. Bioorg Med Chem 7(ll) 2343-2352... 

Danaei G, Vander HS, Lopez AD, Murray CJ, Ezzati M (2005) Causes of cancer in the world comparative risk assessment of nine behavioural and environmental risk factors. Lancet 366 1784 Boik J (2001) Natural compounds in cancer therapy, printed in USA, p 1 Hansel R, Kartarahardja M, Huang JT, Bohlmann E (1980) Sesquiterpen lacton-d-glucopyranoside sowie ein neues Eudesmanolid aus Taraxacum officinale. Phytochemistry 19 857... 

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... 

LyB G, Knorr A, Schmidt TJ, Pahl HL, Merfort I (1998) The anti-inflammatory sesquiterpene lactone helenalin inhibits the transcription factor NF-kB by directly targeting p65. J Biol Chem... 

The factor responsible for cytotoxicity of the sesquiterpene lactones is the 0=C-( i=CH2 moiety. 38 Total synthesis of the tumor-inhibitory apor-phine alkaloids, thalicarpine (24) and hernandallne was accomplished. 

Control of pH is especially important in plant enzyme isolation. As a generalization, low pH is desirable. Phenolic compounds, which are ubiquitous in plants, ionize at high pH, and this makes them subject to spontaneous air-oxidation (and subsequent covalent-addition reactions). Ionized phenolics will not form H-bonded complexes either with proteins or with adsorbent polymers. The former might be desirable, but the latter is not. A principal target of covalent addition reactions with proteins is the un-ionized -NH2 group. This applies to 1, 4-addition by quinones md sesquiterpene lactones and to the isothiocyanate addition reaction. Low pH converts amino groups to the unreactive ionized form. Obviously the general factors of protein chemistry also apply, such as possible denaturation or isoelectric precipitation. 

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