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The aim of the present work was to investigate and compare the content of phenolic compounds in four taxa of Erigeron acris L. s. l.: E. acris (EAA), E. acris subsp. droebachiensis (O.F. Müll.) Arcang. (EAD), E. acris subsp. serotinus (Weihe) Greuter (EAS) and E. ×huelsenii Vatke (EH), a hybrid between E. acris and E. canadensis L. The total flavonoid content was determined by Christ-Müller method and the total phenolic acid content was determined by the method utilizing Arnov’s reagent. The method using ultra high performance liquid chromatography with photodiode array detection (UHPLC-PDA) was applied for the separation, identification and quantification of nine phenolic compounds (protocatechuic acid, chlorogenic acid, caffeic acid, 6′-O-caffeoylerigeroside, scutellarein-7-O-β-D-glucuronide, quercetin 3-O-glucoside, 4,5-dicaffeoylquinic acid, quercetin and luteolin) in the aerial parts of E. acris s. l. The chromatographic separation was carried out using a BEH C18 column packed with 1.7-μm particles and gradient elution with a mobile phase of water and methanol, both containing 0.02% (v/v) trifluoroacetic acid. The four investigated taxa of E. acris s. l. differed in the composition and the content of phenolic compounds. The main substances determined in the methanolic herbal extracts were: scutellarein-7-O-β-D-glucuronide (EAA, EAS, EAD and EH), 6′-O-caffeoylerigeroside (EAA, EAD and EH) and chlorogenic acid (EAS and EH). Moreover, the results indicated that five of the nine tested compounds were found in all investigated extracts from herbs of E. acris s. l. Two of them (6′-O-caffeoylerigeroside and scutellarein-7-O-β-D-glucuronide) could be selected as potential chemotaxonomic markers of the genus Erigeron L.

Rosmarinic acid (RA) is a natural phenylpropanoid with numerous pharmacological activities. Because of limited studies of the effects of RA action in gastric cancer cells we examined how 100 and 200 μM acid influences MMPs, TIMPs, collagen, MUC1 and specific sugar antigens in gastric adenocarcinoma CRL-1739 cells. We revealed inhibitory effect of RA on MMP-9 activity what was correlated with increased collagen type I expression, main ECM substrate degraded by MMPs. Tissue inhibitor of MMPs, TIMP-1 but not TIMP-2 was significantly decreased on the protein level and increased on mRNA level by RA action what can suggest TIMP-1 independent inhibitory action of an acid on MMP-9 activity. Glycosylation of gastric cancer proteins was also effected by RA. ELISA tests revealed inhibitory effect of an acid on Tn antigen in cell lysates and culture supernatant and on T antigen in cell lysates. RA inhibited also sialylated Tn antigen in protein of culture supernatant and sialyl T in cell lysates. Extracellular domain of MUC1 mucin, main carrier of Tn and T antigens was significantly inhibited by higher dose of RA. The data suggest potential usefulness of RA as a complementary agent supporting chemotherapy in cancer treatment.

CK2 is a pleiotropic, constitutively active protein kinase responsible for the phosphorylation of more than 300 physiological substrates. Typically, this enzyme is found in tetrameric form consisting of two regulatory subunits CK2β and two catalytic subunits CK2α or CK2α′. Several natural occurring flavonoids were tested for their ability to inhibit both CK2 holoenzymes, CK2α2β2 and CK2α′2β2. We identified few substances selectively inhibiting only the α′ subunit. Other compounds showed similar effect towards all four isoforms. In some cases, like chrysoeriol, pedalitin, apigenin, and luteolin, the α2β2 holoenzyme was at least six times better inhibited than the free α subunit. Otherwise, we have found a luteolin derivative decreased the kinase activity of CK2α′ with an IC50 value of 0.8 μM, but the holoenzyme only with 9.5 µM.

The present study investigated the magnitude and mechanism of the cytotoxic effect on selected cancer cell lines of 3,4-seco-urs-4(23),20(30)-dien-3-oic acid (1), 3,4-seco-olean-4(24)-en-19-oxo-3-oic acid (2), and 3,4-seco-urs-4(23),20(30)-dien-19-ol-3-oic acid (3) isolated from downy birch (Betula pubescens) buds by carbon dioxide supercritical fluid extraction and gradient column chromatography. Cell viability in six human cancer lines exposed to these compounds was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was quantified by annexin V/propidium iodide staining of gastric cancer AGS and colorectal cancer DLD-1 cells. To evaluate the mechanism of apoptosis, the expression of apoptosis-related proteins was analyzed by Western blot. Compound 1 exhibited non-specific toxicity, while compounds 2 and 3 were specifically toxic to colon and stomach cancer cells. The toxicity of compounds 2 and 3 against these two cell lines was greater than for compound 1. Cleavage of caspase-8, -9, and -3 was found in AGS and DLD-1 cells treated with all three seco-acids, indicating the induction of apoptosis via extrinsic and intrinsic pathways. Therefore, triterpene seco-acids (1&ndash, 3) decreased cell viability by apoptosis induction. AGS and DLD-1 cells were more susceptible to seco-acids with an oxidized C19 than normal fibroblasts. Hence, it made them a new group of triterpenes with potential anticancer activity.

The present study investigated the magnitude and mechanism of the cytotoxic effect on selected cancer cell lines of 3,4-seco-urs-4(23),20(30)-dien-3-oic acid (1), 3,4-seco-olean-4(24)-en-19-oxo-3-oic acid (2), and 3,4-seco-urs-4(23),20(30)-dien-19-ol-3-oic acid (3) isolated from downy birch (Betula pubescens) buds by carbon dioxide supercritical fluid extraction and gradient column chromatography. Cell viability in six human cancer lines exposed to these compounds was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was quantified by annexin V/propidium iodide staining of gastric cancer AGS and colorectal cancer DLD-1 cells. To evaluate the mechanism of apoptosis, the expression of apoptosis-related proteins was analyzed by Western blot. Compound 1 exhibited non-specific toxicity, while compounds 2 and 3 were specifically toxic to colon and stomach cancer cells. The toxicity of compounds 2 and 3 against these two cell lines was greater than for compound 1. Cleavage of caspase-8, -9, and -3 was found in AGS and DLD-1 cells treated with all three seco-acids, indicating the induction of apoptosis via extrinsic and intrinsic pathways. Therefore, triterpene seco-acids (1–3) decreased cell viability by apoptosis induction. AGS and DLD-1 cells were more susceptible to seco-acids with an oxidized C19 than normal fibroblasts. Hence, it made them a new group of triterpenes with potential anticancer activity.

The mixture of three phytosterols (campesterol, stigmasterol and β-sitosterol), β-sitosterol 3-O-glucoside and syringin were isolated from hexane and methanol extract of Cirsium rivulare roots after chromatographic separation. The main component of the source was syringin which was obtained with the yield 0.08% of the dry source. In hexane extract, the qualitative and quantitative composition of fatty acids was determined. The predominant component was linoleic acid (23.31 mg/g of extract). The extracts showed antioxidant activity. The ability to scavenge DPPH• free radical was in correlation with appointed total phenol content. The not-defatted methanolic extract was the most active. Hexane and defatted methanol extracts showed moderate antibacterial activity against G(+) and G(−) strains with MIC and MBC ranged from 25 to 200 μg/mL.

Birch buds (Gemmae Betulae) are widely used in Russian and Chinese traditional medicine mainly as a diuretic and diaphoretic agent but also as an antiseptic, anti-inflammatory and analgesic. Despite the long history of therapeutic use of birch buds in folk medicine, the existing information on their chemical composition and pharmacological effects is insufficient. This circumstance warrants further study of the chemistry and pharmacology of birch buds. The present study was designed to investigate (a) the chemical composition of buds from two species of white birch and (b) the in vitro cytotoxic effect of extracts from these sources on selected tumour cells. Extracts from Betula pubescens Ehrh. and Betula pendula Roth. buds were obtained using three different methods: carbon dioxide supercritical fluid extraction (SFE), washing of exudate covering whole buds, and extraction of milled buds with diethyl ether. The chemical composition of extracts was investigated by GC-MS. Cytotoxicity was determined by MTT assay, and cell proliferation was determined by [3H]thymidine uptake in cancer cells and normal skin fibroblasts. The GC-MS investigation identified a total of 150 substances of different classes. The chemical composition of B. pubescens and B. pendula buds differed, with bud extracts from the former containing a relatively high quantity of sesquiterpenoids and flavonoids, while the main components of extracts from the latter were triterpenoids. The results of the biological assay indicated that birch bud extracts demonstrated time- and concentration-dependent and differential cytotoxicity. The highest cytotoxic activity demonstrated bud exudates and SFE extracts obtained from both Betula species. The rich chemical composition of birch buds suggests the possibility of a wider spectrum of biological activity than previously thought. Birch bud extracts could be a promising source of compounds with cytotoxic activity against various cancers.

Many studies have shown that naturally occurring compounds may support prevention and treatment of various diseases, including cancer. Pharmacological investigations revealed a wide spectrum of Nigella sativa biological activities. Combining natural compounds together with synthetic drugs may increase the anticancer activity and limit severe side effects of such a treatment and may be an alternative to monotherapy. The aim of the study was to evaluate the cytotoxic and proapoptotic effects of a novel octahydropyrazino[2,1-a:5,4-a′]diisoquinoline derivative and its effect in combination with Nigella sativa seed oil or extract in human gastric cancer cells (AGS). Etoposide was used as a reference. Our studies proved that combination strategy based on novel octahydropyrazino[2,1-a:5,4-a′]diisoquinoline derivative (OM-90) with Nigella sativa seed oil or extract represents the strongest efficacy in AGS cancer cells as compared to monotherapy and combined treatment with Nigella sativa seed oil or extract together with etoposide. Such a combination also leads to the activation of mitochondrial pathway, which plays a significant role in molecular mechanism of induction of apoptosis by these compounds.

Matricaria is a widespread genus of flowering plants of the family Asteraceae that grow in temperate regions of Europe, Asia, America and Africa. Some of the species are also naturalized in Australia. Some species of this genus such as Chamomiles are recognized medicinal plants and cultivated in several countries for commercial purposes: to obtain its blue essence, as herbal tea, and for pharmaceutical or cosmeceutical uses. The phytochemical composition of Matricaria spp. includes volatile terpenoids (e.g., α-bisabolol, bisabolol oxide A and B, β-trans-farnesene and chamazulene), sesquiterpene lactones such as matricin, and phenolic compounds (flavonoids, coumarins and phenolic acids). Their essential oil is obtained from the fresh or dried inflorescences by steam distillation, and additionally cohobation of the remaining water. The volatile composition of the essential oil, especially the content of the valuable components α-bisabolol and chamazulene, depends on the plant part, origin and quality of the source, genetic, and environmental factors. Moreover, other parameters, such as season of harvest and methods of extraction, can affect the extraction yield of the essential oils/extracts, their composition and, therefore, their bioactivity. Due to the importance of this genus and particularly M. recutita (M. chamomilla), this review focus on its cultivation, factor affecting essential oils’ composition and their role in traditional medicine, as antibacterial agents and finally as food preservatives.

The composition of the essential oils of Cirsium palustre and C. rivulare and their antiproliferative activity against breast adenocarcinoma cells (MCF-7 and MDA-MBA-231) were investigated. The essential oils obtained by hydro-distillation from the roots (yield 0.2 and 0.1% v/w, respectively), leaves and inflorescences (yield below 0.01%), were analyzed by gas chromatography coupled with mass spectrometry (GC-MS). The composition of the essential oils in the respective organs of each plant differed considerably. On the other hand, similarities were observed in the composition of root and leaf oils. In C. palustre and C. rivulare root oil, 50 and 39 constituents were identified, accounting for 95.3% and 92.4% of the total content. The main components were aplotaxene and its derivatives, representing 78.6% and 46.6% of the total content. In leaf oils of both species, 59 and 49 compounds, respectively, were identified, representing 67.4% and 78.3% of the total content. The major constituents were beta-damascenone (4.1% and 13.4%, respectively) and beta-ionone (6.7% and 5.3%, respectively). Short-chain saturated and unsaturated aliphatic alcohols and aldehydes constituted another important group of compounds (17.7% and 9.0%, respectively). The essential oils of the roots have moderate anti-proliferative activity, with IC50 values ranging from 110 to 140 microg/mL. These concentrations were below the level able to inhibit the proliferation of healthy cells.

We recently reported that, in osteogenesis imperfecta (OI) type I with diminished type I collagen biosynthesis, flavonoids such as apigenin 7-O-glucuronide, apigenin 7-O-methylglucuronide and pectolinarin normalized the level of collagen type I without affecting total protein synthesis. In addition to collagen, glycosaminoglycans (GAGs) play an important role in the formation of a functional supramolecular complex in the extracellular matrix, and any changes in their content and/or composition may be involved in the OI phenotype. We previously detected a marked increase in sulphated GAG content in the OI fibroblasts of more severely affected patients (OI types II and III). These alterations were more pronounced in medium than in cells. Although, in OI type I cells, the increase observed in medium was much smaller (approximately 1.5-fold), it resulted in an increase of approximately 3-fold of the GAG to collagen type I ratio. Therefore, in the potential pharmacotherapy of OI type I with flavonoids, their effect on GAG level may be of importance. In the OI cells, some of the tested flavonoids applied at a concentration of 30 µM affected GAG content in quite the opposite way than type I collagen. Aglicones inhibiting collagen synthesis caused a marked increase in GAG concentration in medium, in contrast to the flavonoid glycosides, which exerted a stimulatory effect on type I collagen synthesis, but had a different effect on GAG content and distribution. Among these, apigenin 7-O-methylglucuronide did not affect GAG level or secretion, and thus may potentially be used in OI type I pharmacotherapy in patients with normal GAG content. However, in patients with increased concentrations of GAG, pectolinarin, which decreases GAG content by approximately 40%, may be more beneficial.

The aim of the present study was to identify bioactive compounds stimulating collagen biosynthesis with potential for osteogenesis imperfecta (OI) type I pharmacological therapy. Of the compounds tested, apigenin glycosides 7-O-glucuronide, 7-O-methylglucuronide and pectolinarin at 30 microM were found to significantly induce collagen type I synthesis in OI fibroblasts without an effect on the overall protein synthesis. None of the compounds displayed any toxicity at that concentration. Secretion of collagen into media was not affected by apigenin 7-O-glucuronide and was slightly increased in cells treated with apigenin 7-O-methylglucuronide and pectolinarin. Furthermore, procollagen secreted by treated cells underwent a more rapid processing into collagen as compared with control untreated cells. In addition, we elucidated the possible mechanism involved in their action. Stimulation of collagen biosynthesis was not due to an increase in cell proliferation, because no differences in DNA content between the compound-treated and untreated cells were observed. Since flavonoids are known as strong inhibitors of metalloproteinases degrading matrix proteins, the increased level of collagen could result from the inhibition of their activity. However, the compounds with a stimulatory effect on collagen synthesis did not influence the activities of collagenase type I, gelatinases A and B, and stromelysin. On the contrary, all compounds stimulated the activity of prolidase which catalyzes the final step of collagen degradation and plays an important role in collagen biosynthesis. Stimulation of collagen synthesis and prolidase activity by apigenin 7-O-glucuronide was accompanied by an increase in IGF-I receptor expression. In contrast, the compounds apigenin 7-O-methylglucuronide and pectolinarin which normalized collagen synthesis in OI cells may exert their effects through beta1-integrin-mediated signaling.

Four flavonoid aglycones (apigenin, kaempferol, luteolin, quercetin) were isolated from methanolic extract from the herb of Erigemn acris L. (Asteraceae). In this extract five phytosterols (campesterol, chondrillasterol, stigmast-7-en-3-ol(5alpha,3alpha), stigmasterol and spinasterone) were also identified.

Seven flavonoid compounds: tricin, apigenin, luteolin, hispidulin, acacetin 7-O-beta-D-rutinoside (linarin), apigenin 7-O-beta-D-glucuronide and apigenin 7-O-beta-D-glucoside were isolated from the flowers of Cirsium rivulare (Jacq.) All. Their structure were determined by chemical and spectroscopic methods (UV, 1H NMR, 13C NMR) and comparison data of the literature. Six of them were isolated for the first time from this plant.

The composition of the essential oils of Cirsium palustre and C. rivulare and their antiproliferative activity against breast adenocarcinoma cells (MCF-7 and MDA-MBA-231) were investigated. The essential oils obtained by hydro-distillation from the roots (yield 0.2 and 0.1% v/w, respectively), leaves and inflorescences (yield below 0.01%), were analyzed by gas chromatography coupled with mass spectrometry (GC-MS). The composition of the essential oils in the respective organs of each plant differed considerably. On the other hand, similarities were observed in the composition of root and leaf oils. In C. palustre and C. rivulare root oil, 50 and 39 constituents were identified, accounting for 95.3% and 92.4% of the total content. The main components were aplotaxene and its derivatives, representing 78.6% and 46.6% of the total content. In leaf oils of both species, 59 and 49 compounds, respectively, were identified, representing 67.4% and 78.3% of the total content. The major constituents were β-damascenone (4.1% and 13.4%, respectively) and β-ionone (6.7% and 5.3%, respectively). Short-chain saturated and unsaturated aliphatic alcohols and aldehydes constituted another important group of compounds (17.7% and 9.0%, respectively). The essential oils of the roots have moderate anti-proliferative activity, with IC50 values ranging from 110 to 140 μg/mL. These concentrations were below the level able to inhibit the proliferation of healthy cells.

The collagen metabolism alterations triggered by reactive oxygen species are involved in the development of various connective tissue diseases and skin aging. This study was designed to examine whether (E)-anethole possesses a protective effect on H2O2-induced alterations in collagen metabolism as well as whether it can prevent apoptosis in human skin fibroblasts. In cells treated with 300 µM H2O2, a decrease in collagen biosynthesis of 54 % was observed. Pretreatment of cells with 0.5 µM anethole for 1 h completely prevented this alteration. Changes at the protein level positively correlated with alterations of type I collagen mRNA expression. We have shown that H2O2 caused increase in the activity of MMP-2 and MMP-9 as well as that an increase in MMP-2 activity can contribute to the 8 % decrease in the amount of collagen secreted into the medium. The most efficient suppression of these changes was observed in the presence of 0.5 µM of anethole. At 10 µM, in addition to suppression, an inhibitory effect of anethole on MMP-9 activity was documented. Additionally, the 60 % H2O2-induced decrease in cell viability was suppressed by 1 µM of anethole and a 4-fold increase in cell apoptosis was suppressed by 0.5 µM of anethole. Our results suggest that anethole, which is a small lipophilic and non-toxic molecule with the ability to prevent H2O2-induced collagen metabolism alterations and apoptosis in human skin fibroblasts, would prove useful in the development of effective agents in pharmacotherapy of oxidative stress-related skin diseases.

The chemical composition of Cirsium vulgare flower heads was examined. Petrol and chloroform extracts of this plant material were analyzed by GC-MS for the presence of fatty acids, phytosterols, and triterpenes. Diethyl ether, ethyl acetate, and butanol fractions of the methanolic extract were subjected to multistep chromatographic separations, and as a result, fourteen flavonoids were obtained (1–14). All compounds were isolated from this morphological part for the first time and eleven from the plant. Among the identified components were four aglycones, eight glycosides, and two glycoside esters, derivatives of apigenin, luteolin, kaemferol, and quercetin. One of them was a rarely occurring compound apigenin 7- O-β-(6″-butyl)-glucuronide) (14). Total flavonoid content and antioxidant activity were determined in the various fractions of methanolic extract.

Antiproliferative and antifungal activities of essential oils from Erigeron acris root and herb and from Erigeron annuus herb were investigated. The cell viability assay was performed in cultured fi broblasts, cancer cell lines (MCF-7 and MDA-MBA-231), and endometrial adenocarcinoma (Ishikawa) cells as well as colon adenocarcinoma (DLD-1) cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The essential oil from E. acris root showed the highest antiproliferative activity in the MCF-7 cell line with an IC50 value of 14.5 μg/mL. No effect of the essential oil on normal cells at that concentration was found. Antifungal activity against various strains of five Candida species, i.e. C. albicans, C. glabrata, C. tropicalis, C. krusei, and C. parapsilosis, was tested by the microdilution method. It was found that all examined oils can be useful as antifungal agents against the abovementioned species, but the essential oil of E. acris herb was the most active. Their minimum inhibitory concentrations (MIC) ranged from 30 to 0.4 μL/mL. The data presented suggest that essential oils from E. acris and E. annuus possess antifungal activity against Candida spp. and antiproliferative activity against breast cancer MCF-7 cells