RESUMEN
BACKGROUND AND OBJECTIVE: Even though herbal medicines have played an important role in disease management and health for many centuries, their present frequent use is challenged by the necessity to determine their complex composition and their multitarget mode of action. In the present study, modern methods were investigated towards their potential in the characterization of herbal substances. As a model the herbal substance Chelidonii herba was used, for which several reports on liver toxicities exist. Extracts of Chelidonii herba with different solvents were characterized phytochemically and functionally by experiments with HepG2 liver cells. METHODS: Chelidonii herba was extracted with four solvents of different polarity (dichloromethane, water, ethanol, and ethanol 50% (V/V); four replicates each). The different extracts were characterized metabolomically by (1)H-NMR fingerprinting analysis and principal component analysis (PCA). The content of alkaloids was additionally determined by RP-HPLC. Functional characterization was achieved by the determination of cell proliferation and by transcriptomics techniques (Whole Genome Gene Expression Microarrays v2, Agilent Technologies) in HepG2 cells after exposure to the different extracts (four experimental replicates each). RESULTS: Based on data from (1)H-NMR fingerprints and RP-HPLC analyses the different extracts showed a divergent composition of constituents depending on the solvent used. HepG2 liver cells responded differentially to the four extracts. Microarray analysis revealed a significant regulation of genes and signal cascades related to biotransformation. Also liver-toxic signal cascades were activated. Neither the activated genes nor the proliferation response could be clearly related to the differing alkaloid content of the extracts. CONCLUSION: Different manufacturing processes lead to different herbal preparations. A systems biology approach combining a metabolomic plant analysis with a functional characterization by gene expression profiling in HepG2 cells is an appropriate strategy to characterize variations in plant extracts. Safety assessments of herbal substances may benefit from such complementary analyses.
Asunto(s)
Alcaloides/química , Chelidonium/química , Metabolómica , Extractos Vegetales/química , Proliferación Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Perfilación de la Expresión Génica , Células Hep G2 , Humanos , Espectroscopía de Resonancia Magnética , Análisis de Secuencia por Matrices de Oligonucleótidos , Componentes Aéreos de las Plantas/química , Plantas Medicinales/químicaRESUMEN
Ethnobotanical investigations led to the selection of 19 plant species, used traditionally in Sudan against malaria and other similar tropical diseases, for further studies. Pamianthe peruviana (Amaryllidaceae) exhibited significant activity against a chloroquine-resistant Plasmodium falciparum strain (K1) and a chloroquine-sensitive strain (NF54) with IC(50) values of 0.6 and 1.1 microg/ml, respectively. Additionally, P. peruviana showed considerable activities against Trypanosoma brucei rhodesiense (IC(50) 1.5 microg/ml) and T. cruzi (IC(50) 11.8 microg/ml). The antiplasmodial activity of the different extracts of Salvadora persica (Salvadoraceae) against P. falciparum NF54 strain were found to be 0.6 microg/ml (stems) and 0.7 microg/ml (leaves). Extracts of different parts of Combretum hartmannianum (Combretaceae) possessed significant activity against the chloroquine-sensitive P. falciparum strain (NF54) with IC(50) values of 0.2 microg/ml (bark), 0.4 microg/ml (stem) and 4.3 microg/ml (leaves). Most interestingly, the extracts of the leaves of C. hartmannianum totally inhibited the enzyme HIV-1 reverse transcriptase (HIV-1 RT) at a concentration of 66 microg/ml. A comparably strong activity against p56(lck) tyrosine kinase was also seen for this extract.
Asunto(s)
Antimaláricos/farmacología , Antineoplásicos Fitogénicos/farmacología , Bacterias/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Transcriptasa Inversa del VIH/antagonistas & inhibidores , Proteína Tirosina Quinasa p56(lck) Específica de Linfocito/antagonistas & inhibidores , Extractos Vegetales/farmacología , Plantas Medicinales , Tripanocidas/farmacología , Animales , Células HT29 , Humanos , Leishmania donovani/efectos de los fármacos , SudánRESUMEN
A series of mainly marine derived natural products were tested for their activities against Mycobacterium tuberculosis and M. avium. Of the thirty-nine compounds tested fifteen demonstrated minimum inhibition concentrations (MICs) of 32 micrograms/ml or less, and eleven had MICs of 16 micrograms/ml or less. The most active compound found in this study was the sponge derived metabolite axisonitrile-3 (MIC 2 micrograms/ml).
Asunto(s)
Antibacterianos/farmacología , Mycobacterium avium/efectos de los fármacos , Mycobacterium tuberculosis/efectos de los fármacos , Células Cultivadas , Humanos , Pruebas de Sensibilidad MicrobianaRESUMEN
Inhibitors of HIV reverse transcriptase (RT) are important drugs for the treatment of acquired immuno-deficiency syndrome (AIDS). One approach to identify novel inhibitors of HIV-1-RT is the screening of natural compounds. Many natural products have been shown to be active as RT inhibitors. These compounds belong to a wide range of different structural classes, e.g., coumarins, flavonoids, tannins, alkaloids, lignans, terpenes, naphtho- and anthraquinones, and polysaccharides. The life forms from which the bioactive compounds were isolated are as equally diverse and comprise terrestrial and marine plants, micro-organisms, and marine animals. From the most extensive screening effort, carried out by the NCl, calanolide A, isolated from the terrestrial plant Calophyllum lanigerum (Guttiferae), has been discovered as the most interesting natural RT inhibitor. The promise of this natural product probably relates to a novel mechanism of action. The current review describes natural products from various sources that are able to inhibit HIV-RT.
Asunto(s)
Transcriptasa Inversa del VIH/antagonistas & inhibidores , Plantas Medicinales , Inhibidores de la Transcriptasa Inversa/química , Inhibidores de la Transcriptasa Inversa/aislamiento & purificación , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Humanos , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Relación Estructura-ActividadRESUMEN
The 3-hydroxy-3-methylglutaric acid (HMG) containing flavonoid glucoside chamaemeloside, has been determined to have in vivo hypoglycaemic activity comparable to that of free HMG. An improved isolation scheme for obtaining chamaemeloside from Chamaemelum nobile is presented.
Asunto(s)
Asteraceae/química , Glucósidos/farmacología , Hipoglucemiantes/farmacología , Plantas Medicinales/química , Animales , Glucemia/análisis , Línea Celular , Prueba de Tolerancia a la Glucosa , Glucósidos/química , Glucósidos/aislamiento & purificación , Hipoglucemiantes/química , Hipoglucemiantes/aislamiento & purificación , Masculino , RatonesRESUMEN
From a Maltese sample of the marine sponge Agelas oroides, five compounds: oroidin (1), 2-cyano-4,5-dibromopyrrole (2), 4,5-dibromopyrrole-2-carboxylic acid (3), 4,5-dibromopyrrole-2-carboxylic acid methyl ester (4), and 4 alpha-methyl-5 alpha-cholest-8-en-3 beta-ol (5) have been isolated. For compounds 1-5, completely assigned 1H- and 13C-NMR data are reported for the first time. For 2 a single crystal X-ray crystallographic analysis proved its structure unambiguously. The X-ray analysis of 2 indicated it to crystallise in an unexpected polar space group. Biological activity assessment of all isolates indicate 5 to have moderate antiplasmodial activity, as well as being cytotoxic, and 2 to be moderately cytotoxic towards several cancer cell lines.
Asunto(s)
Antimaláricos/aislamiento & purificación , Antineoplásicos/aislamiento & purificación , Plasmodium/efectos de los fármacos , Poríferos/química , Animales , Antimaláricos/química , Antineoplásicos/química , Cristalografía por Rayos X , Análisis EspectralRESUMEN
Further investigation into the natural product chemistry of the tropical marine sponge Agelas oroides has yielded the new compound 2,4,6,6-tetramethyl-3(6 H)-pyridone (1), and 2,2,6,6-tetramethyl-4-piperidone (2). Both compounds are volatile. The structures of 1 and 2 were determined from the interpretation of their 1D and 2D NMR, UV, IR, and mass spectral data.
RESUMEN
For a sample of Laurencia obtusa, collected from the Caribbean island of Dominica, allolaurinterol was isolated for the first time and found to be responsible for the biological activity of the dichloromethane extract. For allolaurinterol, complete and assigned 1H- and 13C-NMR data are given, together with an assessment of its antibacterial, antifungal, and antialgal activities.
RESUMEN
Natural products research is increasingly turning to marine animals, plants, and microbes as source organisms. Several marine natural products are currently in preclinical and clinical evaluation, others show promising biological activities in in vitro and in vivo assays. Investigations of biological and chemical ecological phenomena in the marine world will contribute to a better understanding of marine habitats, and also provide a more founded basis regarding the search for pharmaceutically useful marine natural products.
Asunto(s)
Bacterias , Hongos , Plantas Medicinales , Animales , Antibacterianos , Antiinfecciosos/aislamiento & purificación , Antineoplásicos/aislamiento & purificación , Antivirales/aislamiento & purificación , Biotecnología , Inmunosupresores/aislamiento & purificación , Estructura Molecular , Poríferos , Agua de Mar , Simbiosis , Microbiología del AguaRESUMEN
A series of monogalactosyl diacylglycerols was isolated from lipophilic extracts of Fischerella ambigua. These glycolipids were identified on the basis of chemical and spectroscopic analyses.
RESUMEN
A total of 80 lipophilic and hydrophilic extracts obtained from 20 samples of cultured freshwater and terrestrial cyanobacteria were investigated for their biological activities. Of all the extracts, 26% exhibited a significant lethal effect against brine shrimp. Out of 54 extracts tested for antimicrobial activity, 78% showed antibacterial and 45% antifungal activities. Of 30 extracts tested for cytotoxicity against KB cells, none was found to be active. Bioassay-guided fractionation of the lipophilic extracts of Fischerella ambigua led to the isolation of three compounds; ambigols A (1) and B (2), and tjipanazole D (3). Compounds 1 and 2 exhibited antibacterial, antifungal, cytotoxic, molluscicidal, and anti-inflammatory, and antiviral activities. Tjipanazole D (3) showed moderate antibacterial properties.
Asunto(s)
Antibacterianos/farmacología , Antifúngicos/farmacología , Compuestos de Bifenilo/farmacología , Cianobacterias , Fenoles/farmacología , Éteres Fenílicos/farmacología , Extractos Vegetales/farmacología , Animales , Antibacterianos/aislamiento & purificación , Antifúngicos/aislamiento & purificación , Artemia , Biomphalaria , Compuestos de Bifenilo/aislamiento & purificación , Carbazoles/aislamiento & purificación , Carbazoles/farmacología , Supervivencia Celular/efectos de los fármacos , Humanos , Células KB , Pruebas de Sensibilidad Microbiana , Fenoles/aislamiento & purificación , Éteres Fenílicos/aislamiento & purificaciónRESUMEN
Sixty-nine natural products derived from Phaeophyta (brown algae), Rhodophyta (red algae), Porifera (sponges), Cnidaria (soft corals), and Mollusca (nudibranchs) were investigated for their cytotoxic, antimalarial, and antimicrobial effects. Fifty-six were found to mediate a positive response in one or more of these test systems.
Asunto(s)
Productos Biológicos/farmacología , Cnidarios/química , Eucariontes/química , Moluscos/química , Animales , Antiinfecciosos/farmacología , Antimaláricos/farmacología , Antineoplásicos/farmacología , Humanos , Estructura Molecular , Células Tumorales CultivadasRESUMEN
The marine brown alga, DICTYOTA VOLUBILIS, was found to contain four unusually substituted hydroazulenoid diterpenes ( 1 - 4) as well as the known compounds dictyol G acetate ( 5) and dilophol. The structures of all isolates were secured by detailed analysis of their spectroscopic data; IR, MS, and NMR.