Inhibition of the T cell receptor (TCR) pathway represents an effective strategy for the treatment of T cell-mediated inflammatory and autoimmune diseases. To identify natural compounds that could inhibit inflammatory T cell responses, we screened 13 sesquiterpene lactones, including achillin, arglabin, argolide, argracin, 3β-hydroxyarhalin, artesin, artemisinin, estafiatin, grosheimin, grossmisin, leucomisine, parthenolide, and taurine, for their ability to modulate activation-induced Ca mobilization in Jurkat T cells. Five of the compounds (arglabin, grosheimin, argracin, parthenolide, and estafiatin) inhibited anti-CD3-induced mobilization of intercellular Ca ([Ca⁺]) in Jurkat cells, with the most potent being parthenolide and argacin (IC = 5.6 and 6.1 μM, respectively). Likewise, phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 in activated Jurkat cells was inhibited by these five compounds, with the most potent being parthenolide and estafiatin (IC = 13.8 and 15.4 μM, respectively). These compounds also inhibited ERK1/2 phosphorylation in primary human T cells and depleted intracellular glutathione. In contrast, none of the sesquiterpene lactones inhibited ERK1/2 phosphorylation in HL60 cells transfected with N-formyl peptide receptor 2 (FPR2) and stimulated with the FPR2 peptide agonist WKYMVM, indicating specificity for T cell activation. Estafiatin, a representative sesquiterpene lactone, was also profiled in a cell-based phosphokinase array for 43 kinase phosphorylation sites, as well as in a cell-free competition binding assay for its ability to compete with an active-site directed ligand for 95 different protein kinases. Besides inhibition of ERK1/2 phosphorylation, estafiatin also inhibited phosphorylation of p53, AMPKα1, CREB, and p27 elicited by TCR activation in Jurkat cells, but it did not bind to any of 95 kinases evaluated. These results suggest that arglabin, grosheimin, agracin, parthenolide, and estafiatin can selectively inhibit initial phases of TCR activation and may be natural compounds with previously undescribed immunotherapeutic properties.

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Chemical components from the aerial part of the Kazakhstan population of Artemisia pontica, from which the rarely encountered flavonoids 7-O-methyl-and 4′,7-di-O-methyl-esters of apigenin were isolated for the first time, were identified. The complete chemical composition of the essential oil was established using GC-MS.

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The aim of the study was to investigate volatile compounds from the aerial parts of Viola canina L. of the family Violaceae grown wild in Northern Kazakhstan for the first time. Viola canina is a common and widespread species of the temperate northern hemisphere. The oil from the aerial parts of V. canina, was obtained by hydrodistillation and investigated by gas chromatography combined with mass spectrometry. The main component of V. canina essential oil was phytol (55.2%). The obtained results showed differences in the composition of already studied Viola essential oils, such as essential oil of V. odorata L., V. etrusca Erben, V. tricolor L., V. arvensis Murr., V. tianshanica Maxim., V. serpens Wall. and V. hamiltoniana D. Don. There is a certain similarity with the composition of the essential oil of V. arvensis where phytol was also found as one of the main component (11.4%).

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