RESUMO
Common ragweed (Ambrosia artemisiifolia L.) is an invasive plant in Europe with spreading use in the contemporary folk medicine. The chemical composition of the above-ground parts is extensively studied, however, the metabolites of the roots are less discovered. By multiple chromatographic purification of the root extracts, we isolated thiophene A (1), n-dodecene (2), taraxerol-3-O-acetate (3), α-linoleic acid (4), (+)-pinoresinol (5), and thiophene E (7,10-epithio-7,9-tridecadiene-3,5,11-triyne-1,2-diol) (6). The 1H NMR data published earlier for 1 were supplemented together with the assignment of 13C NMR data. Thiophene E (6), which is reported for the first time from this species, exerted cytotoxic and antiproliferative effects on A-431 epidermoid skin cancer cells, whereas taraxerol-3-O-acetate (3) and α-linoleic acid (4) had slight antiproliferative effect on gynecological cancer cell lines. Thiophene E (6) and taraxerol-3-O-acetate (3) displayed antiproliferative and cytotoxic effects on MRC-5 fibroblast cells. Thiophene E (6) exerted weak antibacterial activity (MIC 25 µg/mL) on MRSA ATCC 43300, on Staphylococcus aureus ATCC 25923, Escherichia coli AG100 and E. coli ATCC 25922 both thiophenes were inactive. Although the isolated compounds exerted no remarkable cytotoxic or antiproliferative activities, the effects on MRC-5 fibroblast cells highlight the necessity of further studies to support the safety of ragweed root.
Assuntos
Ambrosia , Neoplasias , Humanos , Escherichia coli , Ácido Linoleico/farmacologia , Linhagem Celular , Tiofenos/farmacologia , Acetatos/farmacologiaRESUMO
BACKGROUND: This study was designed as a continuation of a complex investigation about the phytochemical composition and biological activity of chamomile, parsley, and celery extracts against A375 human melanoma and dendritic cells. OBJECTIVE: The main aim was the evaluation of the antimicrobial potential of selected extracts as well as the in vitro anticancer activity against MCF7 human breast cancer cells. METHODS: In order to complete the picture regarding the phytochemical composition, molecular fingerprint was sketched out by the help of FTIR spectroscopy. The activity of two enzymes (acetylcholinesterase and butyrylcholinesterase) after incubation with the three extracts was spectrophotometrically assessed. The antimicrobial potential was evaluated by disk diffusion method. The in vitro anticancer potential against MCF7 human breast cancer cells was appraised by MTT, LDH, wound healing, cell cycle, DAPI, Annexin-V-PI assays. RESULTS: The results showed variations between the investigated extracts in terms of inhibitory activity against enzymes, such as acetyl- and butyrilcholinesterase. Chamomile and parsley extracts were active only against tested Gram-positive cocci, while all tested extracts displayed antifungal effects. Among the screened samples at the highest tested concentration, namely 60µg/mL, parsley was the most active extract in terms of reducing the viability of MCF7 - human breast adenocarcinoma cell line and inducing the release of lactate dehydrogenase. On the other hand, chamomile and celery extracts manifested potent anti-migratory effects. Furthermore, celery extract was the most active in terms of total apoptotic events, while chamomile extract induced the highest necrosis rate. CONCLUSION: The screened samples containing phytochemicals belonging in majority to the class of flavonoids and polyphenols can represent candidates for antimicrobial and anticancer agents.
Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Extratos Vegetais/farmacologia , Antibacterianos/química , Antifúngicos/química , Antineoplásicos Fitogênicos/química , Apium/química , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Camomila/química , Feminino , Fungos/efeitos dos fármacos , Humanos , Células MCF-7 , Micoses/tratamento farmacológico , Petroselinum/química , Extratos Vegetais/químicaRESUMO
Current plant-derived anticancer therapeutics aim to reach higher effectiveness, to potentiate chemosensitivity and minimize the toxic side effects compared to conventional chemotherapy. Cotinus coggygria Scop. is a herb with high pharmacological potential, widely applied in traditional phytotherapy. Our previous study revealed that leaf aqueous ethanolic extract from C. coggygria exerts in vitro anticancer activity on human breast, ovarian and cervical cancer cell lines. The objective of the present research was to investigate possible molecular mechanisms and targets of the antitumor activity of the extract in breast cancer MCF7 cells through analysis of cell cycle and apoptosis, clonogenic ability assessment, evaluation of the extract genotoxic capacity, characterization of cells thermodynamic properties, and analysis on the expression of genes involved in cellular epigenetic processes. The obtained results indicated that in MCF7 cells C. coggygria extract causes S phase cell cycle arrest and triggers apoptosis, reduces colony formation, induces DNA damage, affects cellular thermodynamic parameters, and tends to inhibit the relative expression of DNMT1, DNMT3a, MBD3, and p300. Further studies on the targeted molecules and the extract anti-breast cancer potential on animal experimental model system, need to be performed in the future.
Assuntos
Anacardiaceae/química , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Extratos Vegetais/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , DNA (Citosina-5-)-Metiltransferase 1/genética , DNA (Citosina-5-)-Metiltransferases/genética , Dano ao DNA/efeitos dos fármacos , DNA Metiltransferase 3A , Proteínas de Ligação a DNA/genética , Epigênese Genética/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , Extratos Vegetais/química , Folhas de Planta/químicaRESUMO
Phytochemical investigation of the whole plant of Filago vulgaris Lam. (Asteraceae) resulted in the isolation and characterization of seven compounds, including a rare methoxylated flavonol (araneol), tetrahydrofurofuranolignans (pinoresinol and syringaresinol), p-hydroxybenzaldehyde, vanillin, vanillic acid and scopoletin. The structures of the compounds were determined by NMR and mass spectroscopy. All compounds were first obtained from this species and reported for the genus Filago. Our results demonstrate that highly methoxylated flavonols lacking substituents on ring B and lignans can be regarded as taxonomic markers for the tribe Inuleae. The lipophilic extract of F. vulgaris was found to have antiproliferative activity against HeLa cells (62.1±0.9% inhibition at 30 µ/ml), and araneol was highly effective against this tumour cell line (IC50 8.36 µ M).
Assuntos
Asteraceae/química , Proliferação de Células/efeitos dos fármacos , Flavonoides/química , Flavonoides/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Linhagem Celular Tumoral , Flavonóis/química , Flavonóis/farmacologia , Furanos/química , Furanos/farmacologia , Células HeLa , Humanos , Lignanas/química , Lignanas/farmacologia , Células MCF-7RESUMO
BACKGROUND: The investigation of food-drug and plant-drug interactions has become increasingly important. In case of antibiotics, it is essential to achieve and maintain a plasma concentration sufficient for the antimicrobial action. Although, on theoretical basis, the interaction of polyphenols and antibiotics may be hypothesized, experimental data are lacking to assess its clinical relevance. The aim of our study was to assess the interaction between one of the most widely used antibiotics, amoxicillin, and green tea, the most frequently consumed drink with high polyphenol content. METHODS: The effects of green tea on the plasma level of amoxicillin was studied in an in vivo experiment in rats. The plasma level of amoxicillin was monitored by LC-MS/MS for 240 min after oral administration. The polyphenol content of green tea was determined by the Folin-Ciocalteu method. RESULTS: The peak plasma concentration of amoxicillin significantly decreased upon its co-administration with green tea, although the AUC0-240 of the antibiotic did not decrease significantly in the group treated with amoxicillin suspended in green tea. CONCLUSIONS: Our results suggest a potentially relevant interaction between green tea and amoxicillin, worth being further studied in humans.
Assuntos
Amoxicilina/farmacocinética , Antibacterianos/farmacocinética , Absorção Intestinal , Chá , Amoxicilina/sangue , Animais , Antibacterianos/sangue , Cromatografia Líquida , Masculino , Polifenóis/análise , Ratos , Ratos Wistar , Espectrometria de Massas em Tandem , Chá/químicaRESUMO
Apigenin (4',5,7-trihydroxyflavone) (Api) is an important component of the human diet, being distributed in a wide number of fruits, vegetables and herbs with the most important sources being represented by chamomile, celery, celeriac and parsley. This study was designed for a comprehensive evaluation of Api as an antiproliferative, proapoptotic, antiangiogenic and immunomodulatory phytocompound. In the set experimental conditions, Api presents antiproliferative activity against the A375 human melanoma cell line, a G2/M arrest of the cell cycle and cytotoxic events as revealed by the lactate dehydrogenase release. Caspase 3 activity was inversely proportional to the Api tested doses, namely 30 µM and 60 µM. Phenomena of early apoptosis, late apoptosis and necrosis following incubation with Api were detected by Annexin V-PI double staining. The flavone interfered with the mitochondrial respiration by modulating both glycolytic and mitochondrial pathways for ATP production. The metabolic activity of human dendritic cells (DCs) under LPS-activation was clearly attenuated by stimulation with high concentrations of Api. Il-6 and IL-10 secretion was almost completely blocked while TNF alpha secretion was reduced by about 60%. Api elicited antiangiogenic properties in a dose-dependent manner. Both concentrations of Api influenced tumour cell growth and migration, inducing a limited tumour area inside the application ring, associated with a low number of capillaries.
Assuntos
Inibidores da Angiogênese/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Apigenina/farmacologia , Dieta , Fatores Imunológicos/farmacologia , Inflamação/metabolismo , Melanoma , Trifosfato de Adenosina/metabolismo , Inibidores da Angiogênese/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Apigenina/uso terapêutico , Apoptose , Caspase 3/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Citocinas/metabolismo , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Humanos , Fatores Imunológicos/uso terapêutico , Inflamação/prevenção & controle , L-Lactato Desidrogenase/metabolismo , Lipopolissacarídeos , Magnoliopsida/química , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Melanoma/patologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
BACKGROUND: Phenanthrenes isolated from Juncus species possess different biological activities, including antiproliferative and antimigratory effects. PURPOSE: In this study, nine phenanthrenes isolated from the roots of Juncus inflexus were investigated for their antiproliferative activity on several gynecological cancer cell lines, using non-cancerous cells as controls. METHODS: Antiproliferative activities of the compounds were determined by means of MTT assay. Flow cytometry was used for cell cycle analysis and determination of mitotic cells. Activities of caspase-3, -8, and -9 were detected by colorimetric kits. Tubulin polymerization was followed by kinetic absorbance determination. Action on tumor cell migration was described using wound healing assay. Western blot assays were used to determine apoptosis-related factors at protein level. RESULTS: Among the compounds tested, juncusol exhibited the most substantial antiproliferative effect against cervical cancer HeLa cells. It was also revealed that juncusol has a distinct growth inhibitory effect in cervical cancer cell lines of various HPV status: it was highly active in HPV type 18-positive HeLa cells, while it was inactive in HPV type 16-positive SiHa and CaSki cells. Cell cycle analysis showed an increase in G2/M and subG1 cell populations after juncusol treatment. Caspase-3, -8, and -9 were detected to be activated by juncusol in HeLa cells, indicating that juncusol induces apoptotic cell death. Moreover, juncusol inhibited tubulin polymerization, as well as EGFR activation, suggesting two possible additional mechanisms that may account for juncusol's inducing a G2/M-phase cell cycle arrest and inhibiting cell migration. CONCLUSION: These results suggest that juncusol is a potent antiproliferative agent against HPV-18 related cervical cancer and may be considered as a lead compound for the development of innovative anticancer agents.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Magnoliopsida/química , Fenantrenos/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Antineoplásicos/química , Caspase 3/metabolismo , Caspase 8/metabolismo , Caspase 9/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Feminino , Humanos , Fenantrenos/química , Multimerização Proteica/efeitos dos fármacos , Tubulina (Proteína)/metabolismoRESUMO
Ephedra alata Decne. belongs to the Ephedraceae family. It is a species of Ephedra that grows mostly in the desert. Today, the main importance of Ephedra species in the medical field is due to the presence of the alkaloids derived from phenyl-alanine, which act on the sympathetic nervous system as a sympathomimetic. The aim of this study was to conduct a phytochemical characterization of the hydroalcoholic extract of the aerial part of Ephedra alata Decne., which is indigenous to Tunis, that involves the total phenolic content, individual phenolic content, and antioxidant activity as well as a biological screening for the evaluation of the antimicrobial, antifungal, antiproliferative, pro-apoptotic, and cytotoxic potential against the MCF-7 breast cancer cell line. The results show that the hydroalcoholic extract contains polyphenolic phytocompounds (156.226 ± 0.5 mgGAE/g extract) and elicits antioxidant activity (7453.18 ± 2.5 µmol Trolox/g extract). The extract acted as a bacteriostatic agent against all tested bacterial strains, but was bactericidal only against the Gram-positive cocci and Candida spp. In the set experimental parameters, the extract presents antiproliferative, pro-apoptotic, and cytotoxic potential against the MCF-7 human breast cancer cell line.
Assuntos
Antibacterianos/química , Anti-Infecciosos/química , Antioxidantes/química , Ephedra/química , Extratos Vegetais/química , Antibacterianos/farmacologia , Humanos , Células MCF-7 , Extratos Vegetais/farmacologia , Polifenóis/química , Polifenóis/farmacologiaRESUMO
Chamomile, parsley, and celery represent major botanical sources of apigenin, a well-known flavone with chemopreventive properties. The aim of this study was to assess the phytochemical composition, antioxidant, and anti-inflammatory potential of methanol extracts obtained from chamomile, parsley, and celery collected from Romania, as well as the biological activity against A375 human melanoma and human dendritic cells. Results have shown that all three extracts are rich in polyphenolic compounds and flavonoids, and they generate a radical scavenger capacity, iron chelation potential, as well as lipoxygenase inhibition capacity. Chamomile and celery extracts present weak antiproliferative and pro-apoptotic properties in the set experimental conditions, while parsley extract draws out significant pro-apoptotic potential against A375 human melanoma cells. Parsley and chamomile extracts affected the fibroblast-like morphology of the screened tumor cell line. On the other hand, chamomile and celery extracts abrogated the expansion of LPS-activated dendritic cells, while the metabolic activity was attenuated by stimulation with celery extract; chamomile and parsley extracts had no effect upon this parameter. Chamomile and parsley extracts incubation with naive dendritic cells did not trigger cytokine secretion (TNF-alpha, IL-6, IL-10), but celery extract stimulation significantly reduced the anti-inflammatory, cytokine IL-10.
Assuntos
Apium/química , Camomila/química , Células Dendríticas/efeitos dos fármacos , Melanoma/patologia , Petroselinum/química , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Flavonoides/análise , Flavonoides/farmacologia , Sequestradores de Radicais Livres/farmacologia , Humanos , Inibidores de Lipoxigenase/farmacologia , Extratos Vegetais/análise , Polifenóis/análise , Polifenóis/farmacologia , Proteína Supressora de Tumor p53/metabolismoRESUMO
Four new iridoids (1-4), together with three known iridoids (5-7), one known flavonoid glycoside, three phenolic acids and one phytosterol were isolated from the roots of Valeriana dioscoridis. Their structures were elucidated by means of NMR spectroscopy and mass spectrometry. This is the first report on the phytochemical composition of the non-volatile constituents of V. dioscoridis and the occurrence of a bis-iridoid glycoside in the genus Valeriana. The antiproliferative effects of the iridoids (1-7) were evaluated against three human cancer cell lines of gynacological origin (HeLa, A2780 and T47D) at 10, 30 and 60⯵M concentrations, using the MTT assay and they elicited modest antiproliferative activity when compared to the reference agent, cisplatin.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Iridoides/isolamento & purificação , Valeriana/química , Antineoplásicos Fitogênicos/farmacologia , Células HeLa , Humanos , Iridoides/farmacologia , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química , Plantas Medicinais/química , TurquiaRESUMO
Juncaceae species are rich sources of phenanthrenes. The present study has focused on the isolation and structure determination of biologically active components from Juncus compressus. Eleven compounds (nine phenanthrenes and two flavonoids) have been isolated from the plant by the combination of different chromatographic methods. Two compounds (compressins A (Compound 1) and B (Compound 2)) are novel natural products, while seven phenanthrenes (effusol (Compound 3), effususol (Compound 4), juncusol (Compound 5), 2-hydroxy-1-methyl-4-oxymethylene-5-vinyl-9,10-dihydrophenanthrene (Compound 6), 7-hydroxy-1-methyl-2-methoxy-5-vinyl-9,10-dihydrophenanthrene (Compound 7), effususin A (Compound 8), and dehydroeffusol (Compound 9)), and two flavonoids (apigenin (Compound 10) and luteolin (Compound 11) were isolated for the first time from the plant. Compressin B (Compound 2) is a dimeric phenanthrene, in which two juncusol monomers (Compound 5) are connecting through their C-3 atoms. The structure elucidation of the isolated compounds was carried out using 1D, 2D NMR spectroscopic methods and HR-MS measurements. In vitro investigation of the antiproliferative effect of the phenanthrenes on two cervical (HeLa and SiHa) and an ovarian human tumor cell line (A2780) revealed that compounds have remarkable antiproliferative activity, mainly on the HeLa cell line. Moreover, juncusol (Compound 5) proved to possess significant antiviral activity against the herpes simplex 2 virus (HSV-2).
Assuntos
Antineoplásicos Fitogênicos/química , Antivirais/química , Proliferação de Células/efeitos dos fármacos , Magnoliopsida/química , Fenantrenos/química , Extratos Vegetais/química , Simplexvirus/efeitos dos fármacos , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antivirais/isolamento & purificação , Antivirais/farmacologia , Linhagem Celular Tumoral , Dimerização , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Humanos , Fenantrenos/isolamento & purificação , Fenantrenos/farmacologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Relação Estrutura-AtividadeRESUMO
Mycochemical examination of a methanol extract of Scleroderma bovista Fr. (Agaricomycetes) led to the isolation of 7 compounds, which were, to our knowledge, identified for the first time in this species. The chemical structures of these compounds were determined through extensive spectroscopic methods (nuclear magnetic resonance and mass spectrometry). The fungal metabolites were identified as steroids based on ergostane (compounds 1-4) and lanostane (compounds 6 and 7) skeletons, whereas compound 5 was a ceramide derivative. We evaluated the antiproliferative activity of compounds 4-7 against human cancer cell lines (HeLa, A2780, MDA-MB-231, and MCF-7) using the MTT assay. The lanostane-type derivatives (compounds 6 and 7) and ergosterol peroxide 3-glucoside (compound 4) exerted significant antiproliferative property on 1 or more human cancer cell lines.
Assuntos
Basidiomycota/química , Proliferação de Células/efeitos dos fármacos , Estrutura Molecular , Metabolismo Secundário , Esteroides/química , Esteroides/farmacologia , Basidiomycota/metabolismo , Linhagem Celular Tumoral , Ceramidas/química , Ensaios de Seleção de Medicamentos Antitumorais , Ergosterol/análogos & derivados , Ergosterol/química , Carpóforos/química , Células HeLa , Humanos , Esteroides/isolamento & purificaçãoRESUMO
One-hundred and sixty-eight aqueous and organic extracts of 42 selected bryophyte species were screened in vitro for antiproliferative activity on a panel of human gynecological cancer cell lines containing HeLa (cervix epithelial adenocarcinoma), A2780 (ovarian carcinoma), and T47D (invasive ductal breast carcinoma) cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and for antibacterial activity on 11 strains using the disc-diffusion method. A total of 99 extracts derived from 41 species exerted ≥25% inhibition of proliferation of at least one of the cancer cell lines at 10 µg/mL. In the cases of Brachythecium rutabulum, Encalypta streptocarpa, Climacium dendroides, Neckera besseri, Pleurozium schreberi, and Pseudoleskeella nervosa, more than one extract was active in the antiproliferative assay, whereas the highest activity was observed in the case of Paraleucobryum longifolium. From the tested families, Brachytheciaceae and Amblystegiaceae provided the highest number of antiproliferative extracts. Only 19 samples of 15 taxa showed moderate antibacterial activity, including the most active Plagiomnium cuspidatum, being active on 8 tested strains. Methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus were the most susceptible to the assayed species. This is the first report on the bioactivities of these 14 species.
Assuntos
Anti-Infecciosos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Briófitas/química , Extratos Vegetais/farmacologia , Anti-Infecciosos/química , Antineoplásicos Fitogênicos/química , Bacillus subtilis/efeitos dos fármacos , Bacillus subtilis/crescimento & desenvolvimento , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Feminino , Humanos , Concentração Inibidora 50 , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Moraxella catarrhalis/efeitos dos fármacos , Moraxella catarrhalis/crescimento & desenvolvimento , Extratos Vegetais/químicaRESUMO
According to modern ethnobotanical records, the fruit of Hippophae rhamnoides is effective in the treatment of different allergic symptoms. In order to obtain pharmacological evidence for this observation, the fruit was investigated for anti-inflammatory activity using in vivo animal models. Aqueous and 70% MeOH extracts were tested in 48/80-induced rat paw edema assay after oral administration, and it was found that the 70% MeOH extract (500 mg/kg) reduced significantly edema volume (0.660 ± 0.082 mL vs. control 0.935 ± 0.041 mL). Extracts of different parts of the fruit (pulp, peel, seed) were investigated in the same assay, and the peel extract was shown to exhibit maximum edema-reducing effect (0.470 ± 0.124 mL vs. control 0.920 ± 0.111 mL). This extract was used to elucidate the mode of action. Different inflammation inducers (serotonin, histamine, dextran, bradykinin, and carrageenan) were applied in the rat paw model, but the extract inhibited only the compound 48/80 elicited inflammation. The active extract was then fractionated by solvent-solvent partitioning and chromatographic methods with the guidance of the 48/80-induced anti-inflammatory assay, and the main compounds responsible for the activity were identified as ursolic acid and oleanolic acid. Our data suggest that the activity is most probably based on a membrane stabilizing effect caused by the inhibition of degranulation of mast cells. Moreover, previously unknown 2,5-bis-aryl-3,4-dimethyltetrahydrofuran lignans, nectandrin B, fragransin A2, and saucernetindiol were isolated and identified from H. rhamnoides for the first time.
Assuntos
Anti-Inflamatórios/farmacologia , Frutas/química , Hippophae/química , Extratos Vegetais/farmacologia , Animais , Edema/tratamento farmacológico , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Masculino , Ratos , Ratos Sprague-Dawley , p-Metoxi-N-metilfenetilamina/farmacologiaRESUMO
The present study aimed at the phytochemical and pharmacological investigation of Sideritis montana L. (Lamiaceae). Two new abietane diterpenes [sideritins A (1) and B (2)] were isolated from the methanol extract of the plant. Six known compounds [pomiferin E (3), 9α,13α-epi-dioxyabiet-8(14)-en-18-ol (4), paulownin (5), 6-methoxysakuranetin (6), 3-oxo-α-ionol (7) and 4-allyl-2,6-dimethoxyphenol glucoside (8)] were also obtained from the plant. The structures were determined by means of HREIMS and NMR experiments. The antiproliferative effect of the isolated compounds was investigated on human cancer cell lines (HeLa, SiHa and C33A) at 10 and 30µM concentrations, using the MTT assay. The results demonstrated that pomiferin E (3) and 6-methoxysakuranetin (6) displayed considerable activity [inhibition (%)±SEM: 46.93±2.35 on HeLa (pomiferin E), and 51.52±2.45 on C33A (6-methoxysakuranetin)] at 30µM concentration.
Assuntos
Abietanos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Sideritis/química , Abietanos/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura MolecularRESUMO
Physalin D was isolated from the methanol extract of Physalis alkekengi L. fruits by combination of different chromatographic methods (CPC, TLC, HPLC). The structure was elucidated based on 1H and 13C NMR spectral analysis with the aid of 2D-correlation spectroscopy (1H, 1H-COSY, HSQC and HMBC) and comparison with literature data. The quantity of physalin D in mature and immature fruits and calyces was determined by RP-HPLC-UV method. Among the studied samples, immature calyx showed the highest content of physalin D (0.7880 ± 0.0612%), while mature calyx contained 4 times less amount (0.2028 ± 0.016%). The physalin D content of the fruit was much lower; immature fruits contained 0.0992 ± 0.0083% physalin D and mature fruits 0.0259 ± 0.0021%. The antiproliferative activity of the CHCl3 extract and its fractions was tested on three cancer cell lines (HeLa, MCF-7 and A431). The antiproliferative activity of physalin D is discussed with regard the published data.
Assuntos
Flores/química , Frutas/química , Neoplasias Experimentais/tratamento farmacológico , Physalis/química , Secoesteroides/administração & dosagem , Secoesteroides/química , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células HeLa , Humanos , Células MCF-7 , Neoplasias Experimentais/patologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/químicaRESUMO
BACKGROUND/AIM: Thanks to its biologically active constituents, Ruta graveolens L. (Rutaceae) is a widely used medicinal plant. In our study, six furanoacridone alkaloids isolated from Ruta graveolens were investigated for their antiproliferative and pro-apoptotic effects on human breast cancer cell lines (MCF-7, MDA-MB-361, MDA-MB-231 and T47D). MATERIALS AND METHODS: The cell lines were pretreated with alkaloid components (rutacridone, isogravacridone chlorine (IGC), gravacridonediol monomethyl ether, gravacridonediol, gravacridonetriol, a 1:1 mixture of gravacridonetriol and - diol monoglucosides) and their antiproliferative effects were determined by the MTT assay. RESULTS: IGC had the most marked effect on cell proliferation of MDA-MB-231 (half maximal inhibitory concentration (IC50)=2.27 µM). Cell-cycle analysis was applied to quantify the effect of IGC on subpopulations of MDA-MB-231 and MCF-7 cells. It caused a cell-cycle disturbance by decreasing the G2/M and G0/G1 and increasing the S phase and the appearance of the subdiploid (sub-G1) population. Hoechst 33258-propidium iodide staining was used to evaluate the morphological changes in IGC-pretreated MDA-MB-231 and MCF-7 cells, revealing the appearance of apoptotic features. IGC was found to cause a modest activation of caspase-3 and -9, but not caspase-8, indicating the activation of an intrinsic apoptotic pathway in MDA-MB-231 cells. CONCLUSIONS: These in vitro findings indicate that furanoacridones are suitable candidates for anticancer drug development.
Assuntos
Acridonas/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Ruta/química , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Ciclo Celular/efeitos dos fármacos , Feminino , Humanos , Células MCF-7RESUMO
Plants and plant extracts play a crucial role in the research into novel antineoplastic agents. Four sesquiterpene lactones, artecanin (1), 3ß-chloro-4α,10α-dihydroxy-1α,2α-epoxy-5α,7αH-guaia-11(13)-en-12,6α-olide (2), iso-seco-tanapartholide 3-O-methyl ether (3) and 4ß,15-dihydro-3-dehydrozaluzanin C (4), were isolated from two traditionally used Asteraceae species (Onopordum acanthium and Artemisia asiatica). When tested for antiproliferative action on HL-60 leukemia cells, these compounds exhibited reasonable IC50 values in the range 3.6-13.5 µM. Treatment with the tested compounds resulted in a cell cycle disturbance characterized by increases in the G1 and G2/M populations, while there was a decrease in the S phase. Additionally, 1-3 elicited increases in the hypodiploid (subG1) population. The compounds elicited concentration-dependent chromatin condensation and disruption of the membrane integrity, as revealed by Hoechst 33258-propidium staining. Treatment for 24 h resulted in significant increases in activity of caspases-3 and -9, indicating that the tested sesquiterpenes induced the mitochondrial pathway of apoptosis. The proapoptotic properties of the sesquiterpene lactones were additionally demonstrated withannexin V staining. Compounds 1 and 2 increased the Bax/Bcl-2 expression and decreased the expressions of CDK1 and cyclin B2, as determined at the mRNA level by means of RT-PCR. These experimental results indicate that sesquiterpene lactones may be regarded as potential starting structures for the development of novel anticancer agents.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Artemisia/química , Citostáticos/farmacologia , Onopordum/química , Sesquiterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Apoptose , Caspase 3/metabolismo , Caspase 9/metabolismo , Ciclo Celular/efeitos dos fármacos , Citostáticos/química , Ensaios de Seleção de Medicamentos Antitumorais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HL-60 , Humanos , Extratos Vegetais/química , Sesquiterpenos/químicaRESUMO
In recent years, nutraceuticals attracted a great amount of attention in the biomedical research due to their significant contribution as natural agents for prevention of various health issues. Ethanolic extracts from the ungerminated and germinated seeds of Lupinus albus L. and Lupinus angustifolius L. were analyzed for the content in isoflavones (genistein) and cinnamic acid derivatives. Additionally, the extracts were evaluated for antimicrobial, antiproliferative, and anti-inflammatory properties, using in vitro and in vivo tests. Germination proved to be a method of choice in increasing the amount of genistein and cinnamic acid derivatives in both Lupinus albus L. and Lupinus angustifolius L. seeds. Biological evaluation of all vegetal extracts revealed a weak therapeutic potential for both ungerminated and germinated seeds.
RESUMO
The aim of the present study was the evaluation of the antimicrobial and antiproliferative activities of selected Saharan species, which are applied in the traditional medicine but not studied thoroughly from chemical and pharmacological point of view. The studied plants, namely Anthyllis henoniana, Centropodia forskalii, Cornulaca monacantha, Ephedra alata var. alenda, Euphorbia guyoniana, Helianthemum confertum, Henophyton deserti, Moltkiopsis ciliata and Spartidium saharae were collected from remote areas of North Africa, especially from the Tunisian region of Sahara. After drying and applying the appropriate extraction methods, the plant extracts were tested in antimicrobial screening assay, performed on 19 Gram-positive and -negative strains of microbes. The inhibition zones produced by plant extracts were determined by disc-diffusion method. Remarkable antibacterial activities were exhibited by extracts of Ephedra alata var. alenda and Helianthemum confertum against B. subtilis, M. catarrhalis and methicillin-resistant and non-resistant S. aureus. Minimum inhibitory concentrations of these two species were also determined. Antiproliferative effects of the extracts were evaluated against 4 human adherent cell lines (HeLa, A431, A2780 and MCF7). Notable cell growth inhibition was found for extract of Helianthemum confertum and Euphorbia guyoniana. Our results provided data for selection of some plant species for further detailed pharmacological and phytochemical examinations.