RESUMO
Glycyrrhizic acid, glycyrrhetinic acid, and their oxo, ester, lactone, and other derivatives, are known for their anti-inflammatory, anti-oxidant, and hypoglycemic pharmacological activities. In this study, chryseno[2,1-c]oxepin-12-carboxylic acid (MG) was first biosynthesized from glycyrrhizic acid through sequential hydrolysis, oxidation, and esterification using Aspergillus terreus TMZ05-2, providing a novel in vitro biosynthetic pathway for glycyrrhizic acid derivatives. Assessing the influence of fermentation conditions and variation of strains during culture under stress-induction strategies enhanced the final molar yield to 88.3% (5 g/L glycyrrhizic acid). CCK8 assays showed no cytotoxicity and good cell proliferation, and anti-inflammatory experiments demonstrated strong inhibition of NO release (36.3%, low-dose MG vs. model), transcriptional downregulation of classical effective cellular factors tumor necrosis factor-α (TNF-α; 72.2%, low-dose MG vs. model), interleukin-6 (IL-6; 58.3%, low-dose MG vs. model) and interleukin-1ß (IL-1ß; 76.4%, low-dose MG vs. model), and decreased abundance of P-IKK-α, P-IKB-α, and P-P65 proteins, thereby alleviating inflammatory responses through the NF-κB pathway in LPS-induced RAW264.7 cells. The findings provide a reference for the biosynthesis of lactone compounds from medicinal plants.
Assuntos
Aspergillus , Ácido Glicirrízico , Oxepinas , Ácido Glicirrízico/farmacologia , Oxepinas/farmacologia , Transdução de Sinais , Ácidos Carboxílicos/farmacologia , Anti-Inflamatórios/farmacologia , NF-kappa B/metabolismo , Lactonas/farmacologia , Lipopolissacarídeos/farmacologia , Fator de Necrose Tumoral alfaRESUMO
BACKGROUND: Physciosporin (PHY) is one of the potent anticancer lichen compound. Recently, PHY was shown to suppress colorectal cancer cell proliferation, motility, and tumorigenesis through novel mechanisms of action. PURPOSE: We investigated the effects of PHY on energy metabolism and tumorigenicity of the human breast cancer (BC) cells MCF-7 (estrogen and progesterone positive BC) and MDA-MB-231 (triple negative BC). METHODS: The anticancer effect of PHY on cell viability, motility, cancer metabolism and tumorigenicity was evaluated by MTT assay, migration assay, clonogenic assay, anchorage-independent colony formation assay, glycolytic and mitochondrial metabolism analysis, qRT-PCR, flow cytometric analysis, Western blotting, immunohistochemistry in vitro; and by tumorigenicity study with orthotopic breast cancer xenograft model in vivo. RESULTS: PHY markedly inhibited BC cell viability. Cell-cycle profiling and Annexin V-FITC/PI double staining showed that a toxic dosage of PHY triggered apoptosis in BC cell lines by regulating the B-cell lymphoma-2 (Bcl-2) family proteins and the activity of caspase pathway. At non-toxic concentrations, PHY potently decreased migration, proliferation, and tumorigenesis of BC cells in vitro. Metabolic studies revealed that PHY treatment significantly reduced the bioenergetic profile by decreasing respiration, ATP production, and glycolysis capacity. In addition, PHY significantly altered the levels of mitochondrial (PGC-1α) and glycolysis (GLUT1, HK2 and PKM2) markers, and downregulated transcriptional regulators involved in cancer cell metabolism, including ß-catenin, c-Myc, HIF-1α, and NF-κB. An orthotopic implantation mouse model of BC confirmed that PHY treatment suppressed BC growth in vivo and target genes were consistently suppressed in tumor specimens. CONCLUSION: The findings from our in vitro as well as in vivo studies exhibit that PHY suppresses energy metabolism as well as tumorigenesis in BC. Especially, PHY represents a promising therapeutic effect against hormone-insensitive BC (triple negative) by targeting energy metabolism.
Assuntos
Neoplasias da Mama , Oxepinas/farmacologia , Neoplasias de Mama Triplo Negativas , Animais , Apoptose , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica , Feminino , Glicólise , Humanos , Camundongos , Neoplasias de Mama Triplo Negativas/tratamento farmacológicoRESUMO
A novel aromatic compound, grandiuvarone B (5-acetoxy-3-benzoyloxymethyl-5H-oxepin-4-one), along with a known compound grandiuvarone A (5-acetoxy-6-benzoyloxymethyl-5H-oxepin-4-one) were isolated from methanol extracts of Desmos chinensis leaves. Their structures were determined by various spectroscopic techniques including nuclear magnetic resonance (NMR), high-resolution electrospray ionisation mass spectrometry (HR-ESI-MS) and circular dichroism (CD). Grandiuvarone A and grandiuvarone B are isomers and the S configuration of grandiuvarone B was reported for the first time. We then determined their antifungal activity against Aspergillus flavus. Results revealed that grandiuvarone B exhibited better antifungal activity against A. flavus, with MIC values of 0.01 mg/mL compared to grandiuvarone A (MIC values of 0.02 mg/mL). In the presence of each active compound at 160 µg/g of aquafeed, A. flavus growth was completely inhibited. Grandiuvarone B also showed antibacterial activity against the plant pathogen Ralstonia solanacearum.
Assuntos
Annonaceae/química , Antibacterianos/isolamento & purificação , Antifúngicos/isolamento & purificação , Oxepinas/isolamento & purificação , Folhas de Planta/química , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Aspergillus flavus/efeitos dos fármacos , Isomerismo , Testes de Sensibilidade Microbiana , Estrutura Molecular , Oxepinas/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Análise EspectralRESUMO
Four new flavonoids (1-4), a new benzyl benzoate derivative (5), five new oxepinones (6-10), and 14 known compounds (11-24) were isolated from the leaf and twig extracts of Desmos cochinchinensis. Their structures were established by spectroscopic methods. The structure of 1 was also confirmed by X-ray diffraction data. The absolute configurations of 3, 4, and 6-10 were determined from comparisons of their ECD spectra with those of relevant reported compounds. Compounds 1, 2, 6, 8, 10, 12-15, and 17 showed α-glucosidase inhibitory activities with IC50 values ranging from 0.2 to 4.9 µM.
Assuntos
Annonaceae/química , Flavonoides/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Oxepinas/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , alfa-Glucosidases/efeitos dos fármacos , Flavonoides/química , Inibidores de Glicosídeo Hidrolases/química , Estrutura Molecular , Oxepinas/química , Extratos Vegetais/química , Análise Espectral/métodos , Difração de Raios XRESUMO
BACKGROUND: Lichens, which represent symbiotic associations of fungi and algae, are potential sources of numerous natural products. Physciosporin (PHY) is a potent secondary metabolite found in lichens and was recently reported to inhibit the motility of lung cancer cells via novel mechanisms. PURPOSE: The present study investigated the anticancer potential of PHY on colorectal cancer (CRC) cells. METHODS: PHY was isolated from lichen extract by preparative TLC. The effect of PHY on cell viability, motility and tumourigenicity was elucidated by MTT assay, hoechst staining, flow cytometric analysis, transwell invasion and migration assay, soft agar colony formation assay, Western blotting, qRT-PCR and PCR array in vitro as well as tumorigenicity study in vivo. RESULTS: PHY decreased the viability of various CRC cell lines (Caco2, CT26, DLD1, HCT116 and SW620). Moreover, PHY elicited cytotoxic effects by inducing apoptosis at toxic concentrations. At non-toxic concentrations, PHY dose-dependently suppressed the invasion, migration and colony formation of CRC cells. PHY inhibited the motility of CRC cells by suppressing epithelial-mesenchymal transition and downregulating actin-based motility markers. In addition, PHY downregulated ß-catenin and its downstream target genes cyclin-D1 and c-Myc. Moreover, PHY modulated KAI1 C-terminal-interacting tetraspanin and KAI1 expression, and downregulated the downstream transcription factors c-jun and c-fos. Finally, PHY administration showed considerable bioavailability and effectively decreased the growth of CRC xenografts in mice without causing toxicity. CONCLUSION: PHY suppresses the growth and motility of CRC cells via novel mechanisms.
Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Oxepinas/farmacologia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Líquens/química , Masculino , Camundongos Endogâmicos BALB C , Oxepinas/administração & dosagem , Oxepinas/farmacocinética , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/genética , beta Catenina/metabolismoRESUMO
The phytochemical study of Stereocaulon montagneanum harvested in Sumatra (Indonesia) led to the isolation of 11 known compounds including two metabolites not previously described in the genus Stereocaulon, peristictic acid (8) and menegazziaic acid (10). The complete 1H and 13C NMR spectral assignments of stictic acid derivatives are reported with some revisions. Five depsidones belonging to the stictic acid chemosyndrome were superoxide anion scavengers as potent as ascorbic acid and with no toxicity on two human cell lines.
Assuntos
Antioxidantes/farmacologia , Sequestradores de Radicais Livres/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Líquens/química , Oxepinas/farmacologia , Protetores contra Radiação/farmacologia , Superóxidos/metabolismo , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/isolamento & purificação , Compostos Heterocíclicos de 4 ou mais Anéis/química , Compostos Heterocíclicos de 4 ou mais Anéis/isolamento & purificação , Humanos , Indonésia , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Melanoma Experimental , Camundongos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Oxepinas/química , Oxepinas/isolamento & purificação , Protetores contra Radiação/química , Protetores contra Radiação/isolamento & purificação , Solventes , Raios UltravioletaRESUMO
The review chronologically considers the main classes of the currently available anthelminthic substances: early anthelmintic compounds, benzimidazoles, imidazolthiazoles, tetrahydropyrimidines, avermectins and milbemycins, and salicylanilides. Great attention is paid to novel substances (emodepside, monepantel, derquantel, tribendimidine) and promising developments. Some aspects of the molecular mechanisms of action of anthelmintics, their resistance, and alternative dehelmintization methods are discussed.
Assuntos
Anti-Helmínticos/classificação , Cestoides/efeitos dos fármacos , Desenho de Fármacos , Nematoides/efeitos dos fármacos , Trematódeos/efeitos dos fármacos , Aminoacetonitrila/análogos & derivados , Aminoacetonitrila/síntese química , Aminoacetonitrila/farmacologia , Animais , Anti-Helmínticos/síntese química , Anti-Helmínticos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Cestoides/fisiologia , Infecções por Cestoides/diagnóstico , Infecções por Cestoides/tratamento farmacológico , Infecções por Cestoides/parasitologia , Depsipeptídeos/síntese química , Depsipeptídeos/farmacologia , Humanos , Indóis/síntese química , Indóis/farmacologia , Medicina Tradicional , Nematoides/fisiologia , Infecções por Nematoides/diagnóstico , Infecções por Nematoides/tratamento farmacológico , Infecções por Nematoides/parasitologia , Oxepinas/síntese química , Oxepinas/farmacologia , Fenilenodiaminas/síntese química , Fenilenodiaminas/farmacologia , Trematódeos/fisiologia , Infecções por Trematódeos/diagnóstico , Infecções por Trematódeos/tratamento farmacológico , Infecções por Trematódeos/parasitologiaRESUMO
Two new dibenz[b,f]oxepins, empetroxepins A and B (1 and 2), and seven known compounds (3-9) were isolated from an extract of the Canadian medicinal plant Empetrum nigrum that significantly inhibited the growth of Mycobacterium tuberculosis H37Ra. The structures of 1 and 2 were established through analysis of NMR and MS data. The antimycobacterial activity of the plant extract was attributed primarily to the presence of two chalcone derivatives (6 and 7) that exhibited selective antimycobacterial activity (IC50 values of 23.8 and 32.8 µM, respectively) in comparison to mammalian (HEK 293) cells (IC50 values of 109 and 249 µM, respectively).
Assuntos
Antituberculosos/isolamento & purificação , Antituberculosos/farmacologia , Benzoxepinas/isolamento & purificação , Benzoxepinas/farmacologia , Chalcona/isolamento & purificação , Chalcona/farmacologia , Ericaceae/química , Mycobacterium tuberculosis/efeitos dos fármacos , Oxepinas/isolamento & purificação , Oxepinas/farmacologia , Animais , Antituberculosos/química , Benzoxepinas/química , Canadá , Chalcona/química , Células HEK293 , Humanos , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Oxepinas/químicaRESUMO
Lichens produce various unique chemicals that can be used for pharmaceutical purposes. To screen for novel lichen secondary metabolites showing inhibitory activity against lung cancer cell motility, we tested acetone extracts of 13 lichen samples collected in Chile. Physciosporin, isolated from Pseudocyphellaria coriacea (Hook f. & Taylor) D.J. Galloway & P. James, was identified as an effective compound and showed significant inhibitory activity in migration and invasion assays against human lung cancer cells. Physciosporin treatment reduced both protein and mRNA levels of N-cadherin with concomitant decreases in the levels of epithelial-mesenchymal transition markers such as snail and twist. Physciosporin also suppressed KITENIN (KAI1 C-terminal interacting tetraspanin)-mediated AP-1 activity in both the absence and presence of epidermal growth factor stimulation. Quantitative real-time PCR analysis showed that the expression of the metastasis suppressor gene, KAI1, was increased while that of the metastasis enhancer gene, KITENIN, was dramatically decreased by physciosporin. Particularly, the activity of 3'-untranslated region of KITENIN was decreased by physciosporin. Moreover, Cdc42 and Rac1 activities were decreased by physciosporin. These results demonstrated that the lichen secondary metabolite, physciosporin, inhibits lung cancer cell motility through novel mechanisms of action.
Assuntos
Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Movimento Celular/efeitos dos fármacos , Líquens/metabolismo , Neoplasias Pulmonares/patologia , Oxepinas/metabolismo , Oxepinas/farmacologia , Acetona/química , Antineoplásicos/isolamento & purificação , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Proteína Kangai-1/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Invasividade Neoplásica , Metástase Neoplásica , Oxepinas/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Fator de Transcrição AP-1/metabolismo , Proteínas rho de Ligação ao GTP/metabolismoRESUMO
Three new depsidones ( 1, 3, and 4), a new diaryl ether ( 5), and a new natural pyrone ( 9) (synthetically known), together with three known depsidones, nidulin ( 6), nornidulin ( 7), and 2-chlorounguinol ( 8), were isolated from the marine-derived fungus ASPERGILLUS UNGUIS CRI282-03. Aspergillusidone C ( 4) showed the most potent aromatase inhibitory activity with the IC (50) value of 0.74 µM, while depsidones 1, 3, 6- 8 inhibited aromatase with IC (50) values of 1.2-11.2 µM. It was found that the structural feature of depsidones, not their corresponding diaryl ether derivatives (e.g. 5), was important for aromatase inhibitory activity. Aspergillusidones A ( 1) and B ( 3) showed radical scavenging activity in the XXO assay with IC (50) values of 16.0 and < 15.6 µM, respectively. Compounds 1 and 3- 7 were mostly inactive or showed only weak cytotoxic activity against HuCCA-1, HepG2, A549, and MOLT-3 cancer cell lines.
Assuntos
Inibidores da Aromatase/farmacologia , Aspergillus/química , Depsídeos/química , Depsídeos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Lactonas/farmacologia , Oxepinas/química , Animais , Inibidores da Aromatase/química , Inibidores da Aromatase/isolamento & purificação , Aspergillus/classificação , Aspergillus/isolamento & purificação , Sequência de Bases , Linhagem Celular Tumoral , Sobrevivência Celular , DNA Fúngico/química , DNA Fúngico/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Depsídeos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/isolamento & purificação , Humanos , Concentração Inibidora 50 , Lactonas/química , Lactonas/isolamento & purificação , Espectroscopia de Ressonância Magnética , Dados de Sequência Molecular , Estrutura Molecular , Oxepinas/isolamento & purificação , Oxepinas/farmacologia , Poríferos/microbiologia , Análise de Sequência de DNARESUMO
Two new depsidones, livistones A (1) and B (2), and a new benzofurane, livistone C (3), together with the 11 known compounds including three stilbenes (4-6), four steroids, three flavan-3-ols, and an alkaloid were isolated from the fruits of Livistona chinensis. The structures of the new compounds were determined by spectroscopic methods. Compounds 1, 4-6 exhibited remarkable cell protective activities against H(2)O(2)-induced SH-SY5Y cell damage.
Assuntos
Arecaceae/química , Benzofuranos/isolamento & purificação , Benzofuranos/farmacologia , Depsídeos/isolamento & purificação , Depsídeos/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Lactonas/isolamento & purificação , Lactonas/farmacologia , Oxepinas/isolamento & purificação , Oxepinas/farmacologia , Fenóis/isolamento & purificação , Fenóis/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Benzofuranos/química , Depsídeos/química , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Frutas/química , Humanos , Peróxido de Hidrogênio/farmacologia , Lactonas/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Oxepinas/química , Fenóis/química , Fitosteróis/química , Fitosteróis/isolamento & purificação , Estereoisomerismo , Estilbenos/química , Estilbenos/isolamento & purificaçãoRESUMO
Two new beta-orcinol depsidones, 1 and 2, together with 13 known compounds were isolated from the lichen Usnea articulata. The structures of 1 and 2 were elucidated by spectroscopic analyses and those of known compounds by comparison of their spectroscopic data with literature values or by direct comparison with authentic standards. Compounds 1, 2, and 5 exhibited moderate antiradical activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The depsidones 4 and 5 showed better superoxide anion scavenging activity (IC50 = 566 and 580 microM, respectively) than quercetin (IC50 = 754 microM).
Assuntos
Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Depsídeos/isolamento & purificação , Depsídeos/farmacologia , Sequestradores de Radicais Livres/isolamento & purificação , Compostos Heterocíclicos de 4 ou mais Anéis/isolamento & purificação , Lactonas/isolamento & purificação , Lactonas/farmacologia , Oxepinas/isolamento & purificação , Usnea/química , Antioxidantes/química , Compostos de Bifenilo , Depsídeos/química , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/química , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Indonésia , Concentração Inibidora 50 , Lactonas/química , Estrutura Molecular , Oxepinas/química , Oxepinas/farmacologia , Picratos/farmacologia , Quercetina/farmacologia , Superóxidos/farmacologiaRESUMO
Grandiuvarone A (1) and grandiuvarins A-C (2-4) were isolated from the bark of Uvaria grandiflora. The structures of these new aromatic compounds were elucidated on the basis of spectroscopic analyses, especially 2D NMR techniques. Only compound 1 exhibited antileishmanial activity, with IC(50)/IC(90) values of 0.7/1.5 microg/mL. The positive controls pentamidine and amphotericin B had IC(50)/IC(90) values of 1.6/6.6 and 0.17/0.34 microg/mL, respectively.
Assuntos
Antiprotozoários , Leishmania/efeitos dos fármacos , Oxepinas , Plantas Medicinais/química , Uvaria/química , Anfotericina B/farmacologia , Animais , Antiprotozoários/química , Antiprotozoários/isolamento & purificação , Antiprotozoários/farmacologia , Concentração Inibidora 50 , Nova Guiné , Oxepinas/química , Oxepinas/isolamento & purificação , Oxepinas/farmacologia , Pentamidina/farmacologia , Casca de Planta/químicaAssuntos
Antiparkinsonianos/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Pargilina/análogos & derivados , Doença de Parkinson/tratamento farmacológico , Selegilina/uso terapêutico , Anfetaminas/metabolismo , Animais , Antiparkinsonianos/farmacologia , Apoptose/efeitos dos fármacos , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Haplorrinos , Humanos , Inativação Metabólica , Indanos/farmacologia , Indanos/uso terapêutico , Camundongos , Camundongos Transgênicos , Modelos Neurológicos , Inibidores da Monoaminoxidase/farmacologia , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Oxepinas/farmacologia , Oxepinas/uso terapêutico , Estresse Oxidativo , Pargilina/química , Pargilina/farmacologia , Doença de Parkinson/enzimologia , Doença de Parkinson/patologia , Propilaminas/química , Propilaminas/farmacologia , Selegilina/farmacocinética , Selegilina/farmacologiaRESUMO
The psychotropic effects of "Hokkai-Kisso", i.e. roots of Japanese valerian, were compared with those of diazepam and imipramine. Both 30% EtOH extract of valerian root (11.2 g/kg) and diazepam (3 mg/kg) significantly prolonged hexobarbital-induced sleep in mice. Spontaneous ambulation and rearing during an open field test were significantly decreased by valerian extract (11.2 g/kg), but kessyl glycol diacetate (KGD, 400 mg/kg) and diazepam (3 mg/kg) significantly increased ambulation. Diazepam (10 mg/kg) significantly decreased approach-avoidance conflict in mice in a water-lick conflict test, but valerian extract and KGD did not. By contrast, valerian extract (4.1 g/kg) and imipramine (20 mg/kg) significantly inhibited immobility induced by a forced swimming test in rats, but did not increase spontaneous motor activity during an open field test just before the forced swimming test. In addition, valerian extract and imipramine significantly reversed reserpine-induced hypothermia in mice. These results indicate that valerian extract acts on the central nervous system and may be an antidepressant.
Assuntos
Comportamento Animal/efeitos dos fármacos , Plantas Medicinais , Psicotrópicos/farmacologia , Valeriana , Animais , Diazepam/farmacologia , Imipramina/farmacologia , Camundongos , Oxepinas/farmacologia , Extratos Vegetais/farmacologia , Ratos , Ratos Endogâmicos , Sono/efeitos dos fármacosRESUMO
16 alpha-Hydroxy-ent-kauran-19-oic acid was isolated from Montanoa hibiscifolia. The effects of this acid and its methyl ester on the contractile activity of rat and guinea pig uterine horns were studied. Both inhibited spontaneous, oxytocin-induced and potassium-induced contractile activities. The inhibitory effect produced by the methyl ester was greater than that observed with the acid. The methyl ester was 2-5 times more potent than the acid upon spontaneous and potassium-induced contractions and 11-15 times more potent than the acid upon the contractile activity of uterine smooth muscle induced by oxytocin. Such effects were observed using bath concentrations of 6, 15, 30 and 60 microM of each compound.
Assuntos
Diterpenos/farmacologia , Oxepinas/farmacologia , Plantas Medicinais/análise , Contração Uterina/efeitos dos fármacos , Animais , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Feminino , Cobaias , Montanoa , Ocitocina/antagonistas & inibidores , Ocitocina/farmacologia , Extratos Vegetais/farmacologia , Potássio/antagonistas & inibidores , Potássio/farmacologia , RatosRESUMO
The zoapatle plant, Montanoa tomentosa, has an extensive ethnomedical history of use in fertility regulation. Several fractions and isolates of this plant were evaulated in in vitro and in vivo tests to identify and characterize active constituents which may be responsible for its antifertility effects. The guinea pig was the animal model. Two types of in vitro activity were observed, a uterotonic type effect and an inhibition of spontaneous contractions of the uterine muscle. The in vivo effects appear to correlate with the ability of a fraction/isolate to inhibit the spontaneous contractions in in vitro testing. The non-polar fractions/isolates accounted for the inhibition of spontaneous contraction effects and the in vivo activity. The more polar fractions/isolates accounted for the uterine stimulant activity.
Assuntos
Abortivos não Esteroides , Abortivos , Oxepinas/farmacologia , Contração Uterina/efeitos dos fármacos , Aminoácidos/análise , Aminoácidos/farmacologia , Animais , Feminino , Cobaias , Técnicas In Vitro , Montanoa , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Plantas Medicinais/análise , Gravidez , Estados UnidosRESUMO
Intrauterine administration of zoapatle aqueous crude extract (ZACE) from Montanoa frutescens on the fourth day of rat pregnancy, at concentrations equivalent to 50 mg and 5 mg of dry leaves, was associated with total inhibition of implantation sites. On the other hand, ZACE from Montanoa tomentosa equivalent to 50 and/or 100 mg of dry leaves, prepared and administered in the same fashion, did not inhibit the number of implants by day 11 of pregnancy. However, most implants were found abnormal, of blue color, poor orientation or spacing; these morphological changes could be considered as reabsorption sites.
Assuntos
Implantação do Embrião/efeitos dos fármacos , Oxepinas/farmacologia , Extratos Vegetais/farmacologia , Prenhez/efeitos dos fármacos , Animais , Fracionamento Químico/métodos , Perda do Embrião/induzido quimicamente , Feminino , Montanoa , Oxepinas/administração & dosagem , Oxepinas/isolamento & purificação , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Plantas Medicinais/análise , Gravidez , Ratos , Ratos Endogâmicos , Especificidade da Espécie , TemperaturaRESUMO
Intrauterine administration of Zoapatle aqueous crude extract (ZACE) prepared from Montanoa tomentosa s.s.p. tomentosa, on day 4 of pregnancy, did not alter the normal uterine morphological changes by days 5 and 8 of pregnancy in the rat. On the other hand, ZACE made from Montanoa frutescens caused profound alterations on the uterine structures, such as: focal loss of epithelial lining, thickened blood vessels and alterations in stroma cells in rat endometrium. Morphological alterations correlate well with the antiimplantation effect associated with the intrauterine administration of these plant extracts. Scanning electron micrographs of leaves from Montanoa tomentosa and Montanoa frutescens revealed striking differences in glandular secretion and trichomes.
Assuntos
Endométrio/efeitos dos fármacos , Oxepinas/farmacologia , Extratos Vegetais/farmacologia , Plantas Medicinais/análise , Prenhez/efeitos dos fármacos , Animais , Endométrio/irrigação sanguínea , Endométrio/ultraestrutura , Feminino , Microscopia Eletrônica de Varredura , Montanoa , Oxepinas/administração & dosagem , Oxepinas/isolamento & purificação , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Plantas Medicinais/ultraestrutura , Gravidez , Ratos , Especificidade da Espécie , Contração Uterina/efeitos dos fármacosRESUMO
The effect of zoapatle aqueous crude extract (ZACE) was further studied and partially characterized upon human and rabbit spermatozoa. ZACE prepared from Montanoa tomentosa s.s.p tomentosa did not influence sperm motility or viability in a wide range of ZACE concentrations tested; on the other hand, ZACE prepared from Montanoa frutescens had immediate and constant inhibitory effect upon motility and decreased cell viability. Red cell lysis was readily observed with ZACE-frutescens, but not with ZACE-tomentosa. The effect of time on ZACE-frutescens potency for inducing red cell lysis was observed.