The chemical composition of Succisa pratensis is not well known. The existing data indicate a substantial content of flavonoids, which include luteolin and apigenin 7-glucosides. The aim of this study was to elaborate the isolation protocol of these flavonoids from flowers and leaves of S. pratensis, to carry out their characterization, as well as evaluate the effect of S. pratensis extracts on activation of transcription factor NF-κB and α-amylase activity. The extraction protocol applied in this study allowed isolation and characterization of flavonoid fraction of S. pratensis. Their identity was confirmed by NMR spectra analysis, UV spectroscopy and electrospray ionization-tandem MS evaluation. Treatment of pancreatic α-amylase with S. pratensis extract inhibited this enzyme’s activity to an extent comparable to that of isolated luteolin and apigenin 7-glucosides. Incubation of HepG2 cells for 24 h with S. pratensis extracts or isolated flavonoids resulted in moderate reduction in NF-κB transcription factor activation evaluated in terms of translocation of its active subunits from cytosol into nucleus and subsequently diminished expression of the COX-2 gene. Expression of NF-κB was also reduced. The most significantly diminished NF-κB activation and expression, as well as COX-2 expression, was found to result from treatment with isolated flavonoids and ethyl acetate extract of S. pratensis leaves. These results indicate that S. pratensis flavonoids may modulate the metabolic and signaling pathways whose deregulation is related to pathogenesis of liver cancer. Further studies are required to confirm these observations and assess the chemopreventive and/or therapeutic potential of the S. pratensis herb.

The study aimed to evaluate the possible modulation of Nrf2, NF-ĸB and STAT3 signaling pathways in the colorectal cancer (CRC) cells line DLD-1 and HCT116 by secondary metabolites of lichens. An attempt was made to indicate the most promising targets in these signaling pathways. Attention was also paid to the effects of the compounds tested on CRC cells using anakoinosis—that is, simultaneous analysis of several signaling pathways. The effects of the tested natural compounds on the activity of selected transcriptional factors related to CRC were analyzed by Western blot and RT-PCR assays. The highest activity against CRC cells was shown by physodic and salazinic acids from the studied secondary metabolites of lichens. As a result, an increase in the activation of transcription factor Nrf2 and the expression of its selected target genes was observed. Physodic and salazinic acids induced the opposite effect in relation to the NF-κB and STAT3 pathways. These results confirmed our earlier observations that lichen-derived compounds have the ability to modulate signaling pathway networks. While caperatic acid affected Wnt/β-catenin to the most extent, salazinic acid was the most potent modulator of Nrf2, NF-κB and STAT3 pathways. Physodic acid seemed to affect all the investigated pathways.

Our previous study showed that the new synthetic methoxy-stilbenes, 3,4,2′-trimethoxy-trans-stilbene (3MS), 3,4,2′,4′-tetramethoxy-trans-stilbene (4MS), and 3,4,2′,4′,6′-pentamethoxy-trans-stilbene (5MS), modulate the constitutive expression of enzymes and receptors involved in estrogen metabolism in breast immortalized epithelial MCF10 cells. In this study, we evaluated the effect of 3MS, 4MS, and 5MS in comparison to resveratrol activity in MCF7 estrogen-dependent and MDA-MB-231 estrogen-independent breast cancer cell lines. 3MS similarly to resveratrol reduced the expression of estrogen receptor α in MCF7 cells. However, in these cells, 5MS reduced the most CYP19, the gene encoding aromatase, at mRNA transcript level. In contrast, in the MDA-MB-231 cells, the most efficient inhibitor of CYP19 expression was 3MS, reducing the level of its protein by ~ 25%. This stilbene also inhibited the aromatase activity in a recombinant protein system with IC50 value ~ 85 µM. Treatment with the methoxy-stilbenes reduced the level of estradiol in culture medium. The most significant reduction was exerted by 3MS. None of the tested stilbenes including resveratrol changed significantly the expression of AhR, although CYP1A1 protein level was slightly reduced in MDA-MB-231 cells, while CYP1B1 expression was increased in these cells as a result of treatment with 3MS, but only at the transcript level. Overall, these results show weak or moderate effect of the new methoxy-stilbenes on the expression of key proteins involved in estrogens metabolism in cancer breast cells. However, the reduced CYP19 expression and activity upon 3MS treatment in metastatic MDA-MB-231 cells require the further studies.

This study aimed to synthesize new thioderivative chalcones and analyze their impact on the NF-κB, STAT3, EGFR and Nrf2 signaling pathways in colorectal cancer cells. Among the studied compounds, derivatives 4 and 5 decreased the activation of NF-κB and the expression of the target gene COX-2. In the case of STAT3, we observed the inhibition of activation of this signaling pathway after influencing derivative 4. Increased activation of the Nrf2 signaling pathway was demonstrated for derivatives 5 and 7 in DLD-1 and HCT116 cells. The results of this study indicated that new chalcone derivatives, especially compounds 4, 5, and—to some degree—7, possess potential applications in the prevention of colorectal cancer.

Kale (Brassica oleracea L. var. acephala DC) is a leafy green vegetable which belongs to the Brassicaceae family, one of the most commonly cultivated and consumed edible plants. The aim of this study was to investigate the potential adverse effects and antioxidant properties of freeze-dried kale leaves in 90-day dietary experiment on Wistar rats. The kale leaf powder was added to a diet at levels: 10, 30, and 60 g/kg feed. The standard blood biochemical and hematological markers, antioxidant enzyme activities, level of lipid peroxidation, reduced glutathione content, and damage to DNA in the liver were measured. Antioxidant potential in serum was measured and expressed as Trolox equivalents antioxidant capacity (TEAC). The kale leaf phytochemicals, i.e., glucosinolates, phenolic acids and flavonols, were quantified. Major glucosinolates were glucoiberin (164.6 mg/100 g d.w.) and glucobrassicin (130.6 mg/100 g d.w.), whereas kaempferol (159.1 mg/100 g d.w.), quercetin (119.6 mg/100 g d.w.), and sinapic acid (73.8 mg/100 g d.w.) dominated among phenolics. The lowest dose of kale leaves augmented the activity of catalase by 34% in males and by 44% in females. The highest applied dose increased activities of glutathione reductase by 31%, superoxide dismutase by 27%, and glutathione S-transferase by 24% in males only. Kale administration did not affect the activities of glutathione peroxidase and paraoxonase 1, glutathione concentration, lipid peroxidation level, and the level of DNA damage in the liver and the whole blood leukocytes. TEAC increased upon all doses of kale leaves by 30-90% in males and by 40-90% in females. The diet with kale did not affect blood biochemical and hematological markers. Results confirm no adverse effects of dried kale leaves used in model rat's diet up to 60 g/kg for 90 days. The changes in hepatic antioxidant enzymes and plasma TEAC suggest beneficial effect of kale leaves on the antioxidant status in rats. Interestingly, these changes were more pronounced in male versus female animals.