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1.
Melanoma is an enormous global health burden, and should be effectively addressed with better therapeutic strategies. Therefore, new therapeutic agents are needed for the management of this disease. The aim of this study was the investigation of cytotoxic activity of some isoquinoline alkaloid standards and extracts obtained from Sanguinaria canadensis—collected before, during, and after flowering—against three different human melanoma cells (A375, G361, SK-MEL-3). The cytotoxicity of these extracts was not previously tested on these melanoma cell lines. Determination of alkaloid contents was performed by HPLC-DAD using Polar RP column and mobile phase containing acetonitrile, water, and 1-butyl-3-methylimidazolium tetrafluoroborate. The cytotoxicity of alkaloid standards was investigated by determination of cell viability and calculation of IC50 values. Significant differences were observed in the alkaloids content and cytotoxic activity of the extracts, depending on the season of collection of the plant material. In the Sanguinaria canadensis extracts high contents of sanguinarine (from 4.8543 to 9.5899 mg/g of dry plant material) and chelerythrine (from 42.7224 to 6.8722 mg/g of dry plant material) were found. For both of these alkaloids, very high cytotoxic activity against the tested cell lines were observed. The IC50 values were in the range of 0.11–0.54 µg/mL for sanguinarine and 0.14 to 0.46 µg/mL for chelerythrine. IC50 values obtained for Sanguinaria canadensis extracts against all tested cell lines were also very low (from 0.88 to 10.96 µg/mL). Cytotoxic activity of alkaloid standards and Sanguinaria canadensis extracts were compared with the cytotoxicity of anticancer drugs—etoposide, cisplatin, and hydroxyurea. In all cases except the one obtained for cisplatin against A375, which was similar to that obtained for Sanguinaria canadensis after flowering against the same cell line, IC50 values obtained for anticancer drugs were higher than the IC50 values obtained for sanguinarine, chelerythrine, and Sanguinaria canadensis extracts. Our results showed that Sanguinaria canadensis extracts and isoquinoline alkaloids, especially sanguinarine and chelerythrine, could be recommended for further in vivo experiments in order to confirm the possibility of their application in the treatment of human melanomas.  相似文献   

2.
Mahonia aquifolium and its secondary metabolites have been shown to have anticancer potential. We performed MTT, scratch, and colony formation assays; analyzed cell cycle phase distribution and doxorubicin uptake and retention with flow cytometry; and detected alterations in the expression of genes involved in the formation of cell–cell interactions and migration using quantitative real-time PCR following treatment of lung adenocarcinoma cells with doxorubicin, M. aquifolium extracts, or their combination. MTT assay results suggested strong synergistic effects of the combined treatments, and their application led to an increase in cell numbers in the subG1 phase of the cell cycle. Both extracts were shown to prolong doxorubicin retention time in cancer cells, while the application of doxorubicin/extract combination led to a decrease in MMP9 expression. Furthermore, cells treated with doxorubicin/extract combinations were shown to have lower migratory and colony formation potentials than untreated cells or cells treated with doxorubicin alone. The obtained results suggest that nontoxic M. aquifolium extracts can enhance the activity of doxorubicin, thus potentially allowing the application of lower doxorubicin doses in vivo, which may decrease its toxic effects in normal tissues.  相似文献   

3.
In this study, the synergistic biological action of five celandine alkaloids in normal and cancer cells was investigated by capillary electrophoresis with light-emitting diode-induced native fluorescence detection. The specific capacity of each alkaloid to penetrate into the cells was estimated by monitoring alkaloid concentration decreases in the cell medium during incubation with murine fibroblast NIH/3T3, mouse melanoma B16F10, and human breast cancer MCF7 cell lines. Mixtures of isoquinoline alkaloids containing protopine, chelidonine, sanguinarine, allocryptopine, and stylopine were applied to cell cultures for 20 and 40 min, and the content of alkaloids in the cell media was measured by capillary electrophoresis (CE). CE separation of isoquinoline alkaloids was performed in 30 mM phosphate buffer (pH 2.5). As these alkaloids have native fluorescence, they were directly detected using the commercially available UV light-emitting diode without troublesome fluorescent derivatization. The results showed a differential ability of celandine alkaloids to penetrate into the normal and cancer cell interior, which was inversely proportional to their cytotoxic activity. While the most effective transport of celandine alkaloids from the cell medium to the cell interior was observed for normal murine fibroblast NIH/3T3 cells (about 55% of total content), cytotoxicity tests demonstrated selective and profound apoptotic effects of a five-alkaloid combination in the mouse melanoma B16F10 cell line.  相似文献   

4.
Plants belonging to the Rosa genus are known for their high content of bioactive molecules and broad spectrum of healing and cosmetic activities. Rosa platyacantha Schrenk is a wild-type species abundant in the mountainous regions of Kazakhstan. The phytochemical composition as well as the bioactivity of R. platyacantha extracts have not been fully investigated to date. In this study, various parts of R. platyacantha plant, collected in Almaty region, Kazakhstan, were used to prepare five hydroalcoholic extracts (R1–R5). The extracts were compared for the content of phytochemicals and selected biological activities, which are important for the potential cosmetic application of R. platyacantha. Extract R3, prepared from flower buds, showed the most significant antioxidant and tyrosinase inhibitory potential, decreasing the monophenolase and diphenolase activities of tyrosinase. Extract R3 showed also collagenase inhibitory activity and cytotoxicity against human melanoma cells A375, being less cytotoxic for noncancerous skin keratinocytes HaCaT. Analysis of fractions E and F, obtained from R3 extracts, revealed that quercetin, kaempferol, rutin, and their derivatives are more likely responsible for the tyrosinase inhibitory properties of R. platyacantha extracts.  相似文献   

5.
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.  相似文献   

6.
Stylophorum lasiocarpum (Oliv.) Fedde (Papaveraceae) belongs to traditional Chinese medicine herbs but there was minimal information on the content of alkaloids in this plant. Extracts from the aerial part and roots were examined by liquid chromatography with UV and mass spectrometric detection, with nineteen alkaloids identified. Changes in alkaloid content over the entire vegetation period of a one- and two-year old plant were studied. The protoberberine alkaloids, coptisine and stylopine, were found to be the main substances in extracts of the aerial part irrespective of the plant’s age and time of harvest. Variable amounts of protopine, sanguinarine, chelerythrine, chelirubine, macarpine, chelilutine and berberine were also recorded in the aerial part. The roots contained significantly larger quantities of all alkaloids than the aerial part with the levels of most alkaloids varying from May to October, peaking in the middle of the vegetation period. Coptisine was the dominant alkaloid in all samples. The antiproliferative activities of the root extract and of seven individual alkaloids were tested on A375 human malignant melanoma cells. The significant dose-dependent toxicity of the root extract was attributed largely to the quaternary benzo[c]phenanthridine alkaloids, macarpine and sanguinarine.  相似文献   

7.
Calotropis procera (family: Asclepiadaceae) contains cardiac glycosides which are cytotoxic to cancer cells. The extracts of C. procera have been reported to be cytotoxic to many cancer cell lines and this is the first report against the human skin melanoma cells (SK-MEL-2). The SK-MEL-2 cells treated with C. procera methanolic extract (CPME) were analysed for growth inhibition and apoptosis. The exposure of phosphatidylserine in apoptotic SK-MEL-2 was analysed by using the Annexin-V FITC flow cytometry method. In CPME-treated SK-MEL-2 cells, 19.6% of apoptotic and 58.3% dead cells were observed. The 15.97% and 15.85% of early apoptotic cells were found at 20 μg/mL of the ouabain and paclitaxel, respectively. Active caspases, nuclear degradation confirmed apoptotic SK-MEL-2 cells in time- and dose-dependent manner. The cell cycle analysis shows that CPME treated cells halt at G2/M phase. Significant cytotoxic activity of CPME against SK-MEL-2 may be attributed to its high cardenolide content.  相似文献   

8.
In this study, extracts of the root, branch and leaf parts of Cistus laurifolius L. were prepared using hexane, methylene chloride and ethanol solvents. DNA cleavage, cytotoxic and antioxidant properties of the prepared extracts were then investigated. The cytotoxic properties of the extracts were investigated in A549, DU-145, PNT-1A, MDA-MB231, CRL-4010 and HCT-116 cell lines. Among all prepared extracts, T4 (seed–methylene chloride) extract showed cytotoxic effects on more cancer cell lines compared to other extracts. Antioxidant tests were performed by DPPH (2,2-diphenyl-1-picrylhydrazil) radical scavenging and Folin-Ciocalteu methods. In both tests, it was determined that T7 (seed–ethanol) extract has a very strong antioxidant effect (IC50 = 0,000015 μg/ml for the DPPH method). In DNA cleavage studies, the results obtained confirm the protection of DNA from hydroxyl radical damage in the presence of methanolic plant extracts. Consequently, we determined that some of the Cistus laurifolius L. extracts have significant biological properties on the studied cell lines.  相似文献   

9.
ABSTRACT

Selected alkaloids were chromatographed on cyanopropyl-silica thin layers using nonaqueous and aqueous eluents containing various free silanol blocker agents. Because of the strong retention of these basic compounds, nonaqueous eluents containing medium polar diluents, strongly polar modifiers, or aqueous eluents containing organic modifier, water, and silanol blockers (ammonia, diethylamine, and ionic liquid) were required for analysis. Mobile phases containing addition of acids were also tested for separation of investigated alkaloids. The most selective and efficient systems were used in two-dimensional separations of isoquinoline alkaloids’ mixture and plant extracts.  相似文献   

10.
In this study, we introduced a simple and sensitive method of capillary electrophoresis with ultraviolet light-emitting diode-induced native fluorescence (UV-LEDIF) detection for the determination of isoquinoline alkaloids in extracts of Chelidonium majus L. Samples were extracted with acidic methanol and the extracts were directly analysed by CE. Simultaneous determination of protopine, chelidonine, coptisine, sanguinarine, allocryptopine, chelerythrine and stylopine was performed in 20mM phosphate buffer (pH 3.1). The baseline separation of these alkaloids was finished within 20 min. As these alkaloids have native fluorescence, they were directly detected using the commercially available UV light emitting diode without troublesome fluorescent derivatisation. Satisfactory LOD values were obtained for the studied compounds considering their appearance in natural extracts. Lower limits of detection were 0.05 μg/mL for protopine, 0.06 μg/mL for stylopine and allocryptopine, 0.07 μg/mL for chelidonine, 0.22 μg/mL for sanguinarine, 1.7 μg/mL for chelerythrine and 5.5 μg/mL for coptisine. The developed method was successfully applied to determine the contents of seven alkaloids in the aerial parts of Chelidonium majus L, which varied from 0.025 to 0.763% (w/w). Also, to demonstrate the potential of the proposed CE method, an estimation of the cytotoxic properties of selected Celandine alkaloids in a natural extract was carried out.  相似文献   

11.
An ion-pair HPLC-ESI-MS-MS method has been developed for the direct and rapid characterization of isoquinoline alkaloids in a crudely purified extract of the aerial parts of Eschscholtzia californica (Papaveraceae). This plant was chosen because of its increasing use in pharmaceutical industries and because its well known alkaloid composition allows the optimization of the experimental procedure through an on-line analytical sequence. Thus, 14 isoquinoline alkaloids of different types were detected and characterized. The identities of these compounds were confirmed unambigously by their fragmentation and UV spectra obtained by LC-diode-array detection. Various experiments including tandem mass spectrometry and in-orifice collision induced dissociation were performed and prove that MS-MS is a very efficient technique to identify these compounds. An explanation for each isoquinoline alkaloid type MS-MS fragmentation pattern is proposed and indicates similar neutral and/or radical losses. The order of the fragmentation depended on the type of compound but the lost fragments were similar.  相似文献   

12.
The dynamics of the accumulation of alkaloids in the epigeal part ofAconitum leucostromum Worosch. from various growth sites according to the vegetation periods have been studied. It has been shown that in all cases in the early period of development of the plant diterpene bases predominate in the total material, and in the fruit-bearing period isoquinoline bases.  相似文献   

13.
Carpesium divaricatum Sieb. & Zucc., a traditional medicinal plant used as an inflammation-relieving remedy, is a rich source of terpenoids. At least 40 germacrane-type sesquiterpene lactones, representatives of four different structural groups, were isolated from the plant. Cytotoxicity against cancer cells in vitro is the most frequently described biological activity of the compounds. However, little is known about the selectivity of the cytotoxic effect. The anti-inflammatory activity of the germacranolides is also poorly documented. The objective of the present study was to assess the cytotoxic activity of selected C. divaricatum germacranolides-derivatives of 4,5,8,9-tetrahydroxy-3-oxo-germacran-6,12-olide towards cancer and normal cell lines (including cells of different p53 status). Moreover, to assess the anti-inflammatory effect of the compounds, the release of four proinflammatory cytokines/chemokines (IL-1β, IL-8, TNF-α and CCL2) by lipopolysaccharide-stimulated human neutrophils was measured by ELISA. The investigated sesquiterpene lactones demonstrated nonselective activity towards prostate cancer (Du145 and PC3) and normal prostate epithelial cells (PNT2) as well as against melanoma cells (A375 and HTB140) and keratinocytes (HaCaT). Cytotoxic activity against osteosarcoma cells was independent of their p53 status. In sub-cytotoxic concentrations (0.5–2.5 µM) the studied compounds significantly decreased cytokine/chemokine release by lipopolysaccharide-stimulated human leukocytes.  相似文献   

14.
The antimicrobial effects of the Mexican medicinal plants Guazuma ulmifolia, Justicia spicigera, Opuntia joconostle, O. leucotricha, Parkinsonia aculeata, Phoradendron longifolium, P. serotinum, Psittacanthus calyculatus, Tecoma stans and Teucrium cubense were tested against several human multi-drug resistant pathogens, including three Gram (+) and five Gram (-) bacterial species and three fungal species using the disk-diffusion assay. The cytotoxicity of plant extracts on human cancer cell lines and human normal non-cancerous cells was also evaluated using the MTT assay. Phoradendron longifolium, Teucrium cubense, Opuntia joconostle, Tecoma stans and Guazuma ulmifolia showed potent antimicrobial effects against at least one multidrug-resistant microorganism (inhibition zone > 15 mm). Only Justicia spicigera and Phoradendron serotinum extracts exerted active cytotoxic effects on human breast cancer cells (IC50 < or = 30 microg/mL). The results showed that Guazuma ulmifolia produced potent antimicrobial effects against Candida albicans and Acinetobacter lwoffii, whereas Justicia spicigera and Phoradendron serotinum exerted the highest toxic effects on MCF-7 and HeLa, respectively, which are human cancer cell lines. These three plant species may be important sources of antimicrobial and cytotoxic agents.  相似文献   

15.
16.
The edible parts of the plants Camellia sinensis, Vitis vinifera and Withania somnifera were extensively used in ancient practices such as Ayurveda, owing to their potent biomedical significance. They are very rich in secondary metabolites such as polyphenols, which are very good antioxidants and exhibit anti-carcinogenic properties. This study aims to evaluate the anti-cancerous properties of these plant crude extracts on human liver cancer HepG2 cells. The leaves of Camellia sinensis, Withania somnifera and the seeds of Vitis vinifera were collected and methanolic extracts were prepared. Then, these extracts were subjected to DPPH, α- amylase assays to determine the antioxidant properties. A MTT assay was performed to investigate the viability of the extracts of HepG2 cells, and the mode of cell death was detected by Ao/EtBr staining and flow cytometry with PI Annexin- V FITC dual staining. Then, the protein expression of BAX and BCl2 was studied using fluorescent dye to determine the regulation of the BAX and BCl2 genes. We observed that all the three extracts showed the presence of bioactive compounds such as polyphenols or phytochemicals. The W. somnifera bioactive compounds were found to have the highest anti-proliferative activity on human liver cancer cells.  相似文献   

17.
In view of the abundant evidence that Lycopodiaceae alkaloids, including the well-known huperzine A (HupA), are among the potent acetylcholinesterase (AChE) inhibitors, an attempt was made to search for new compounds responsible for this property. For this purpose, three plant species belonging to the Lycopodiaceae family, commonly found in the Euro-Asia region, were subjected to the isolation of bioactive compounds, their identification and subsequent evaluation of their anticholinesterase and cytotoxic activities. Methanolic extracts of two Lycopodium and one Hupezia species were obtained via optimized pressurized liquid extraction (PLE) and then pre-purified using innovative gradient vacuum liquid chromatography (gVLC). For the first time, three sorbents of different porosity packed in polypropylene cartridges and mobile phase systems of different polarity were used to elute the target compounds. This technique proved to be a rapid tool for the obtainment of alkaloid fractions and allowed one to select the appropriate process conditions to yield potent AChE inhibitors in each of the species studied. More than 100 collected fractions were analyzed via HPLC/ESI-QTOF-MS, which enabled one to detect more than 50 compounds, including several new ones previously unreported. Some of them were present in high purity fractions (60–90% of the established purity). TLC bioautography assays proved that the analyzed species are rich sources of AChE inhibitors, but H. selago showed the highest anti-AChE activity. Additionally, the modified silanized silica gel sorbent used allowed one to isolate L. clavatum alkaloids more efficiently using an aqueous reversed-phase solvent system. Furthermore, the tested extracts from the three plant extracts were found to be safe, as they did not exhibit cytotoxicity to skin fibroblasts.  相似文献   

18.
The current study was aimed to evaluate the phenolic composition parameters of two hydro-alcoholic extracts of Ocimum basilicum L. (OB) obtained from the aerial part (without leaves) and leaves, in order to determine their contribution to the antioxidant activity (AOA). Both hydro-alcoholic extracts have proven to be rich in polyphenolic compounds, flavonoids, flavonols and tannins. Therefore, the leaves’ extracts reveal an inhibition percentage of 89%, almost comparable with the standard reference (95%). To complete the toxicological profile, the study also assessed the potential cytotoxicity of basil hydro-alcoholic extracts on immortalized human keratinocytes (HaCaT), skin human fibroblasts (1BR3), mice epidermis (JB6Cl41-5a) and primary human melanocytes (HEMa) cells, correlated to A375 antitumor in vitro activity. The extracts did not induce significant cytotoxic effect on any of the selected normal cell lines but showed relevant activity on A375 cells. Considering the low values obtained regarding the irritative effects in the chorionallantoic membrane of the egg on blood vessels, we can emphasize that both extracts can be considered as biocompatible ingredients. Regarding the potential activity of hydro-alcoholic extracts on human skin, the decrease of erythema values after the application of extracts was a relevant observation which indicates the anti-inflammatory potential of Ocimum basilicum L.  相似文献   

19.
Objectives: The toxicity of chemotherapeutic anticancer drugs is a serious issue in clinics. Drug discovery from edible and medicinal plants represents a promising approach towards finding safer anticancer therapeutics. Justicia insularis T. Anderson (Acanthaceae) is an edible and medicinal plant in Nigeria. This study aims to discover cytotoxic compounds from this rarely explored J. insularis and investigate their underlying mechanism of action. Methods: The cytotoxicity of the plant extract was evaluated in human ovarian cancer cell lines and normal human ovarian surface epithelia (HOE) cells using a sulforhodamine B assay. Bioassay-guided isolation was carried out using column chromatography including HPLC, and the isolated natural products were characterized using GC-MS, LC-HRMS, and 1D/2D NMR techniques. Induction of apoptosis was evaluated using Caspase 3/7, 8, and 9, and Annexin V and PI based flow cytometry assays. SwissADME and SwissTargetPrediction web tools were used to predict the molecular properties and possible protein targets of identified active compounds. Key finding: The two cytotoxic compounds were identified as clerodane diterpenoids: 16(α/β)-hydroxy-cleroda-3,13(14)Z-dien-15,16-olide (1) and 16-oxo-cleroda-3,13(14)E-dien-15-oic acid (2) from the Acanthaceous plant for the first time. Compound 1 was a very abundant compound (0.7% per dry weight of plant material) and was shown to be more potent than compound 2 with IC50 values in the micromolar range against OVCAR-4 and OVCAR-8 cancer cells. Compounds 1 and 2 were less cytotoxic to HOE cell line. Both compounds induced apoptosis by increasing caspase 3/7 activities in a concentration dependent manner. Compound 1 further increased caspase 8 and 9 activities and apoptosis cell populations. Compounds 1 and 2 are both drug like, and compound 1 may target various proteins including a kinase. Conclusions: Clerodane diterpenoids (1 and 2) in J. insularis were identified as cytotoxic to ovarian cancer cells via the induction of apoptosis, providing an abundant and valuable source of hit compounds for the treatment of ovarian cancer.  相似文献   

20.
UV radiations are principal causes of skin cancer and aging. Suntan creams were developed to protect epidermis and derma layers against photodegradation and photooxidation. The addition of antioxidant plant extracts (i.e. essential oil) to sunscreens is habitually performed, to increase their UV protective effects and to contrast pro‐radical and cytotoxic compounds present in these solutions. According to these observations, in the present work, the alteration of chemical composition and bioactive properties of Lavandula angustifolia Miller essential oil, exposed to UV light, was investigated. UV induced a significant deterioration of lavender oil biochemical profile. Moreover, the antioxidant activity of this solution, in in vitro tests and directly on B16‐F10 melanoma cells, greatly decreased after UV treatment. Our results also showed that essential oil was shielded from UV stress by propolis addition. Even after UV treatment, bee glue highly protected lavender oil secondary metabolites from degradation and also preserved their antiradical properties, both in in vitro antioxidant assays and in cell oxidative damage evaluations. This research proposed propolis as highly efficient UV protective and antiradical additive for sunscreens, cosmetics and alimentary or pharmaceutical products containing plant extracts.  相似文献   

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