Sesquiterpene lactones inhibition

There is an expanding body of evidence to suggest that sesquiterpene lactones inhibit the synthesis NO synthetase. One such compound is an ambrosanolides-type sesquiterpene known as cumanin characterized from Ambrosia psilostachya. This sesquiterpene inhibit the enzymatic activity of NO synthetase with an IC50 value of 9.38 xM (49). Another example is the well-known artemisinin, a sesquiterpene used as an alternative drug in the treatment of severe and multidrug-resistant malaria, which inhibits NO synthesis in cytokine-stimulated human astrocytoma T67 cells (50). 

WONG, H.R., MENENDEZ, I.Y., Sesquiterpene lactones inhibit inducible nitric oxide synthase gene expression in cultured rat aortic smooth muscle cells., Biochem. Biophys. Res. Comm., 1999,262,375-380. 

The dlterpene lactone 17-acetoxyacanthoaustralide (25) has minor effects, showing promotion of clover (112%), cucumber (109%) and Palmer amaranth (111%) and inhibition of carrot germination (91%). The flavonoid artemetin (26) at 0.05 mM concentrations slightly affects onion (93%), oat (91%) and promotes seed germinations In carrot (116%) and Palmer amaranth (113%). In closing, it is noteworthy to point out that lettuce and cress are not significantly affected by all ten sesquiterpene lactones as well as the dlterpene (25) and artemetin (26). 

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. 

Classical examples of anti-inflammatory Asteraceae are Arnica montana and Calendula officinalis, both used in European medicine to treat bruises and contusions. There is an expanding body of evidences to suggest that Asteraceae could be a useful source of anti-inflammatories, such as sesquiterpene lactones and/or triterpene alcohols, the latter being known to inhibit 12-O-tetra-decanoylphorbol-13-acetate (TPA)-induced inflammation in mice as efficiently as commercial indomethacine by possible inhibition of phospholipase A2 (10). 

The family Asteraceae is a prolific source of sesquiterpene lactones, among which, melampolides have been shown to inhibit the enzymatic activity of elastases. Melampolides are a common member of the Melampodi-inae subtribe. Examples of medicinal Asteraceae known to elaborate melampolides are Sigesbeckia orientalis L. and Mikania cordata (Burm.f.) B.L. Robinson. 

Mikania cordata is known to elaborate a series of sesquiterpene lactones, among which deoxymikanolide significantly inhibits acetic acid-induced writhing in mice (44,45). The plant also contains a series of melampolides that inhibit the enzymatic activity of elastase (46). 

In Malaysia, a paste of the roots is applied to fingers to treat eruptions. The plant is known contain some sesquiterpene lactones including neolinderane, zeylanine, zey-lanicine and zeylanidine (59-61), the potential of which as an inhibitor of NOS would be worth investigation because pseudoneolinderane and linderalactone inhibited the production of superoxide anion generation by human neutrophils in response to fMLP/CB. The IC50 values for pseudoneolinderane and linderalactonewere 3.21 and 8.48 (xg/mL, respectively (62). 

Sumner H, Umit S, Knight DW, Hoult JRS. Chrysanthemum parthenium (L.) Bernh. Inhibition of 5-lipoxygenase and cyclooxygenase in leukocytes by feverfew Involvement of sesquiterpene lactones and other components. Biochem Pharmacol 1992 43 2313-2320. 

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. 

Pollen allelopathy is phenomenon when pollen chemicals (e.g., phenols, terpenoids, sesquiterpene lactones, etc.) inhibit sexual reproduction in heterospecific individuals due to influencing of fertilization (Murphy 1992). The phenomenon includes excretion of signaling compounds from the donor cell (pollens, pistil stigma), recognition of a specific signal, transmission of information (pollen), and the development of a characteristic response in the acceptor cell. The possible mechanism of the effect was described in Roshchina (2001). 

The primary active chemical constituent in feverfew is parthenolide, a sesquiterpenoid lactone (figure 8.8) (Robbers et al. 1996). Levels of sesquiterpene lactones vary across different types of extracts ethanol extracts contain about 0.5%, whereas aqueous ones contain 0.3% (Gromek et al. 1991). The sesquiterpene lactones in feverfew inhibit the... 

Hwang D, Fischer NH, Jang BC, Tak H, Kim JK, Lee W. (1996). Inhibition of the expression of inducible cyclooxygenase and proinflammatory cytokines by sesquiterpene lactones in macrophages correlates with the inhibition of MAP kinases. Biochem Biophys Res Common. 226(3) 810-18. 

The ability of feverfew extract to inhibit 5HT-secretion in platelets was used to identify compounds responsible for the inhibitory effects on platelets [44], A crude feverfew extract was separated by chromatography and fractions were screened for antisecretory activity induced by adrenaline. In five active fractions compounds were identified as the sesquiterpene lactones parthenolide (1), canin (19), artecanin (20), secotanapartholide A (24) and 3 8-hydroxyparthenolide (2). The ability of parthenolide to affect platelet activity induced by other agents was confirmed in a study of direct comparison of crude feverfew extract with parthenolide [43], Parthenolide in the micromolar concentration range inhibited platelet 5HT-secretion. 

Investigations of medicinal plants used traditionally in Greek folk medicine to treat gastric ailments, and peptic ulcer disease have been tested against HP in vitro Konstantinopoulou and coworkers demonstrated that a lipophilic extract of Anthemis altissima L. (Asteraceae) inhibited the growth of several HP strains. Several sesquiterpene lactones (Fig. 1),... 

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