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STAT3 is a transcription factor that regulates various cellular processes with oncogenic potential, thereby promoting tumorigenesis when activated uncontrolled. STAT3 activation is mediated by its tyrosine phosphorylation, triggering dimerization and nuclear translocation. STAT3 also contains a serine phosphorylation site, with a postulated regulatory role in STAT3 activation and G2/M transition. Interleukin-6, a major activator of STAT3, is present in elevated concentrations in uveal melanomas, suggesting contribution of dysregulated STAT3 activation to their pathogenesis. Here, we studied the impact of chelidonine on STAT3 signaling in human uveal melanoma cells. Chelidonine, an alkaloid isolated from Chelidonium majus, disrupts microtubules, causes mitotic arrest and provokes cell death in numerous tumor cells. According to our flow cytometry and confocal microscopy data, chelidonine abrogated IL-6-induced activation and nuclear translocation, but amplified constitutive serine phosphorylation of STAT3. Both effects were restricted to a fraction of cells only, in an all-or-none fashion. A partial overlap could be observed between the affected subpopulations; however, no direct connection could be proven. This study is the first proof on a cell-by-cell basis for the opposing effects of a microtubule-targeting agent on the two types of STAT3 phosphorylation.

Due to certain differences in terms of molecular structure, isoquinoline alkaloids from Chelidonium majus engage in various biological activities. Apart from their well-documented antimicrobial potential, some phenanthridine and protoberberine derivatives as well as C. majus extract present with anti-inflammatory and cytotoxic effects. In this study, the LC&ndash, MS/MS method was used to determine alkaloids, phenolic acids, carboxylic acids, and hydroxybenzoic acids. We investigated five individually tested alkaloids (coptisine, berberine, chelidonine, chelerythrine, and sanguinarine) as well as C. majus root extract for their effect on the secretion of IL-1&beta, IL-8, and TNF-&alpha, in human polymorphonuclear leukocytes (neutrophils). Berberine, chelidonine, and chelerythrine significantly decreased the secretion of TNF-&alpha, in a concentration-dependent manner. Sanguinarine was found to be the most potent inhibitor of IL-1&beta, secretion. However, the overproduction of IL-8 and TNF-&alpha, and a high cytotoxicity for these compounds were observed. Coptisine was highly cytotoxic and slightly decreased the secretion of the studied cytokines. The extract (1.25&ndash, 12.5 &mu, g/mL) increased cytokine secretion in a concentration-dependent manner, but an increase in cytotoxicity was also noted. The alkaloids were active at very low concentrations (0.625&ndash, 2.5 &mu, M), but their potential cytotoxic effects, except for chelidonine and chelerythrine, should not be ignored.

The effect of cultivation practises on both the phytochemical profile and biological activity of aqueous ethanol extracts of Chelidonium majus L. was studied. Extracts were prepared from aerial parts of the same plant population collected in the wild and grown under organic farming conditions. Both qualitative and quantitative analyses of alkaloids and flavonoid derivatives were performed by LC/MS methods, and the cytotoxicity of lyophilised extracts was studied in B16-F10, HepG2, and CaCo-2 cells. Coptisine was the dominant alkaloid of extracts prepared from wild-grown plants, whereas after cultivation, chelidonine was the most abundant alkaloid. The total alkaloid content was significantly increased by cultivation. Ten flavonol glycoconjugates were identified in C. majus extracts, and quantitative analysis did not reveal significant differences between extracts prepared from wild-grown and cultivated specimens. Treatment with C. majus extracts resulted in a dose-dependent increase in cytotoxicity in all three cell lines. The extracts prepared from cultivated specimens showed higher cytotoxicity than the extracts prepared from wild-grown plants. The strongest cytotoxic effect of cultivated C. majus was observed in B16-F10 cells (IC50 = 174.98 ± 1.12 µg/mL). Cultivation-induced differences in the phytochemical composition of C. majus extracts resulted in significant increases in the cytotoxic activities of the preparations.

The antimicrobial properties of herbs from Papaveraceae have been used in medicine for centuries. Nevertheless, mutual relationships between the individual bioactive substances contained in these plants remain poorly elucidated. In this work, phytochemical composition of extracts from the aerial and underground parts of five Papaveraceae species (Chelidonium majus L., Corydalis cava (L.) Schweigg. and Körte, C. cheilanthifolia Hemsl., C. pumila (Host) Rchb., and Fumaria vaillantii Loisel.) were examined using LC-ESI-MS/MS with a triple quadrupole analyzer. Large differences in the quality and quantity of all analyzed compounds were observed between species of different genera and also within one genus. Two groups of metabolites predominated in the phytochemical profiles. These were isoquinoline alkaloids and, in smaller amounts, non-phenolic carboxylic acids and phenolic compounds. In aerial and underground parts, 22 and 20 compounds were detected, respectively. These included: seven isoquinoline alkaloids: protopine, allocryptopine, coptisine, berberine, chelidonine, sanguinarine, and chelerythrine, five of their derivatives as well as non-alkaloids: malic acid, trans-aconitic acid, quinic acid, salicylic acid, trans-caffeic acid, p-coumaric acid, chlorogenic acid, quercetin, and kaempferol, and vanillin. The aerial parts were much richer in phenolic compounds regardless of the plant species. Characterized extracts were studied for their antimicrobial potential against planktonic and biofilm-producing cells of S. aureus, P. aeruginosa, and C. albicans. The impact of the extracts on cellular metabolic activity and biofilm biomass production was evaluated. Moreover, the antimicrobial activity of the extracts introduced to the polymeric carrier made of bacterial cellulose was assessed. Extracts of C. cheilanthifolia were found to be the most effective against all tested human pathogens. Multiple regression tests indicated a high antimicrobial impact of quercetin in extracts of aerial parts against planktonic cells of S. aureus, P. aeruginosa, and C. albicans, and no direct correlation between the composition of other bioactive substances and the results of antimicrobial activity were found. Conclusively, further investigations are required to identify the relations between recognized and unrecognized compounds within extracts and their biological properties.

Chelidonium majus (Papaveraceae) extracts exhibit antimicrobial activity due to the complex alkaloid composition. The aim of the research was to evaluate the antimicrobial potential of extracts from wild plants and in vitro cultures, as well as seven major individual alkaloids. Plant material derived from different natural habitats and in vitro cultures was used for the phytochemical analysis and antimicrobial tests. The composition of alkaloids was analyzed using chromatographic techniques (HPLC with DAD detection). The results have shown that roots contained higher number and amounts of alkaloids in comparison to aerial parts. All tested plant extracts manifested antimicrobial activity, related to different chemical structures of the alkaloids. Root extract used at 31.25&ndash, 62.5 mg/L strongly reduced bacterial biomass. From the seven individually tested alkaloids, chelerythrine was the most effective against P. aeruginosa (MIC at 1.9 mg/L), while sanguinarine against S. aureus (MIC at 1.9 mg/L). Strong antifungal activity was observed against C. albicans when chelerythrine, chelidonine, and aerial parts extract were used. The experiments with plant extracts, individually tested alkaloids, and variable combinations of the latter allowed for a deeper insight into the potential mechanisms affecting the activity of this group of compounds.

A novel strategy was developed to identify hepatotoxic compounds in traditional Chinese medicines (TCMs). It is based on the exposure of HL-7702 cells to a TCM extract, followed by the identification and further determination of potential hepatotoxic compounds accumulated in the cells by liquid chromatography&ndash, tandem mass spectrometry (LC&ndash, MS/MS). As a case study, potential hepatotoxic components in Chelidonium majus L. were screened out. Five alkaloids (sanguinarine, coptisine, chelerythrine, protopine, and chelidonine) were identified by LC&ndash, MS/MS within 10 min, and their intracellular concentrations were first simultaneously measured by LC&ndash, MS/MS with a run time of 4 min. A cell viability assay was performed to assess the cytotoxicity of each alkaloid. With their higher intracellular concentrations, sanguinarine, coptisine, and chelerythrine were identified as the main hepatotoxic constituents in Ch. majus. The study provides a powerful tool for the fast prediction of cytotoxic components in complex natural mixtures on a high-throughput basis.