RESUMEN
Progression of non-alcoholic fatty liver disease (NAFLD) in the context of metabolic syndrome (MetS) is only partially explored due to the lack of preclinical models. In order to study the alterations in hepatic metabolism that accompany this condition, we developed a model of MetS accompanied by the onset of steatohepatitis (NASH) by challenging golden hamsters with a high-fat diet low in vitamin E and selenium (HFD), since combined deficiency results in hepatic necroinflammation in rodents. Metabolomics and transcriptomics integrated analyses of livers revealed an unexpected accumulation of hepatic S-Adenosylmethionine (SAM) when compared with healthy livers likely due to diminished methylation reactions and repression of GNMT. SAM plays a key role in the maintenance of cellular homeostasis and cell cycle control. In agreement, analysis of over-represented transcription factors revealed a central role of c-myc and c-Jun pathways accompanied by negative correlations between SAM concentration, MYC expression and AMPK phosphorylation. These findings point to a drift of cell cycle control toward senescence in livers of HFD animals, which could explain the onset of NASH in this model. In contrast, hamsters with NAFLD induced by a conventional high-fat diet did not show SAM accumulation, suggesting a key role of selenium and vitamin E in SAM homeostasis. In conclusion, our results suggest that progression of NAFLD in the context of MetS can take place even in a situation of hepatic SAM excess and that selenium and vitamin E status might be considered in current therapies against NASH based on SAM supplementation.
Asunto(s)
Hígado/metabolismo , Síndrome Metabólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , S-Adenosilmetionina/metabolismo , Selenio/deficiencia , Vitamina E/metabolismo , Quinasas de la Proteína-Quinasa Activada por el AMP , Animales , Cricetinae , Dieta Alta en Grasa/efectos adversos , Progresión de la Enfermedad , Humanos , Masculino , Mesocricetus , Síndrome Metabólico/genética , Enfermedad del Hígado Graso no Alcohólico/genética , Proteína Oncogénica p55(v-myc)/genética , Proteína Oncogénica p55(v-myc)/metabolismo , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , Selenio/análisis , Vitamina E/análisisRESUMEN
Euclea natalensis A.DC., Knowltonia vesicatoria (L.f) Sims, and Pelargonium sidoides DC. are South African plants traditionally used to treat tuberculosis. Extracts from these plants were used in combination with isoniazid (INH) to investigate the possibility of synergy with respect to antimycobacterial activity. The ethanol extract of K. vesicatoria was subjected to fractionation to identify the active compounds. The activity of the Knowltonia extract remained superior to the fractions with a minimum inhibitory concentration (MIC) of 625.0 µg/mL against Mycobacterium smegmatis and an MIC of 50.00 µg/mL against M. tuberculosis. The K. vesicatoria extract was tested against two different drug-resistant strains of M. tuberculosis, which resulted in an MIC of 50.00 µg/mL on both strains. The combination of K. vesicatoria with INH exhibited the best synergistic antimycobacterial activity with a fractional inhibitory concentration index of 0.25 (a combined concentration of 6.28 µg/mL). A fifty percent inhibitory concentration of this combination against U937 cells was 121.0 µg/mL. Two compounds, stigmasta-5,23-dien-3-ol (1) and 5-(hydroxymethyl)furan-2(5H)-one (2), were isolated from K. vesicatoria as the first report of isolation for both compounds from this plant and the first report of antimycobacterial activity. Compound (1) was active against drug-sensitive M. tuberculosis with an MIC of 50.00 µg/mL.
RESUMEN
The intense blue fluorescence of the infusion of Lignum nephriticum (Eysenhardtia polystachya), first observed in the sixteenth century, is due to a novel four-ring tetrahydromethanobenzofuro[2,3-d]oxacine which is not present in the plant but is the end product of an unusual, very efficient iterative spontaneous oxidation of at least one of the tree's flavonoids.
Asunto(s)
Colorantes Fluorescentes/química , Compuestos Heterocíclicos de 4 o más Anillos/química , Plantas Medicinales/química , Flavonoides/química , Fluorescencia , Colorantes Fluorescentes/aislamiento & purificación , Colorantes Fluorescentes/metabolismo , Compuestos Heterocíclicos de 4 o más Anillos/aislamiento & purificación , Compuestos Heterocíclicos de 4 o más Anillos/metabolismo , Estructura Molecular , Relación Estructura-ActividadRESUMEN
Four acyloxy-isopimarane derivatives along with two known isopimarane diterpenoids, the flavone cirsimaritin and the sterols beta-sitosterol and stigmasterol were isolated from the aerial parts of Aeollanthus rydingianus. The structures of the compounds were established on the basis of spectroscopic analysis and chemical evidence. The isolated substances were screened for antimicrobial activity against Gram-positive and Gram-negative bacteria and a yeast strain. 19-Acetoxy-7,15-isopimaradien-3beta-ol and 7,15-isopimaradien-19-ol showed minimum inhibitory concentration (MIC) values of 3.90-15.62 microg/ml for Staphylococcus aureus and of 7.81microg/ml for Enterococcus hirae.
Asunto(s)
Antibacterianos , Diterpenos , Lamiaceae/química , Plantas Medicinales/química , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Diterpenos/química , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Enterococcus/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Sitoesteroles , Staphylococcus aureus/efectos de los fármacos , Vancomicina/farmacologíaRESUMEN
Further studies on Plectranthus sp. (Lamiaceae) led to the isolation of terpenes and phenol esters from Plectranthus strigosus Benth. ent-16-Kauren-19-ol (1), ent-16-kauren-19-oic acid (2), xylopic acid (3), xylopinic acid (4), hinokiol (5), 4 beta,6 beta-dihydroxy-1 alpha,5 beta(H)-guai-9-ene (6) 4 beta,6 beta-dihydroxy-1 alpha,5 beta(H)-guai-10(14)-ene (7), mixtures of hexacosan-1,26-diol and octacosan-1,28-diol ferulate diesters (8), of esters from ferulic acid and fatty alcohols (9) and of esters from fatty acids and 2-(4-hydroxyphenyl)-ethanol (10) were for the first time isolated from this genus. Supplementary spectral data for 3,8 and parvifloron D (11) metabolites are also presented. A bioactivity study revealed herpetic inhibitory properties for (1) and (2), and antioxidant ability for (5) and (8) phenolic constituents.
Asunto(s)
Fenoles/química , Fenoles/farmacología , Plectranthus/química , Terpenos/química , Terpenos/farmacología , Abietanos/química , Abietanos/aislamiento & purificación , Abietanos/farmacología , Animales , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Antivirales/química , Antivirales/aislamiento & purificación , Antivirales/farmacología , Compuestos de Bifenilo/química , Proliferación Celular/efectos de los fármacos , Chlorocebus aethiops , Diterpenos de Tipo Kaurano/química , Diterpenos de Tipo Kaurano/aislamiento & purificación , Diterpenos de Tipo Kaurano/farmacología , Herpesvirus Humano 1/fisiología , Herpesvirus Humano 2/fisiología , Humanos , Hidrazinas/química , Fenoles/aislamiento & purificación , Picratos , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Terpenos/aislamiento & purificación , Células Vero , Replicación Viral/efectos de los fármacosRESUMEN
The known (+)-trans-ozic acid (1) and two new labdane diterpenoids (2 and 3) have been isolated from an ethanol extract of Orthosiphon labiatus. The structures of 2 and 3 were established mainly by 1D and 2D NMR spectroscopic means. The ethanolic extract of Salvia africana-lutea afforded the known abietane diterpenoids carnosol (4), rosmadial (5), and carnosic acid (characterized as its derivative 6). Compounds 3 and 6 exhibited MICs of 157 and 28 microM, respectively, against Mycobacterium tuberculosis, while 2 and 6 showed cytotoxic activity with IC50 82 and 69 microM, respectively, against a breast (MCF-7) human cancer cell line.
Asunto(s)
Antineoplásicos Fitogénicos , Antituberculosos , Diterpenos , Orthosiphon/química , Plantas Medicinales/química , Salvia/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Antituberculosos/química , Antituberculosos/aislamiento & purificación , Antituberculosos/farmacología , Diterpenos/química , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Concentración 50 Inhibidora , Estructura Molecular , Mycobacterium tuberculosis/efectos de los fármacosRESUMEN
Four new clerodane diterpenoids, salvisplendins A-D (1-4), have been isolated from an acetone extract of the flowers of Salvia splendens, together with an artifact (5), arising from salvisplendin D (4) by addition of diazomethane, and the already known clerodane olearin (6). The structures of the new compounds (1-5) were established mainly by 1D and 2D NMR spectroscopic studies and, in the case of salvisplendin A (1), by chemical correlation with splenolide B (7). Complete 1H and 13C NMR assignments for olearin (6), not published hitherto, are also reported.
Asunto(s)
Diterpenos de Tipo Clerodano/aislamiento & purificación , Plantas Medicinales/química , Salvia/química , Diterpenos de Tipo Clerodano/química , Flores/química , Italia , Estructura Molecular , Resonancia Magnética Nuclear BiomolecularRESUMEN
A new 9alpha-(2-oxopropyl)abietane derivative (1) has been isolated from an acetone extract of Plectranthus grandidentatus. Extraction of the plant material and analytical processes carried out in the absence of acetone also revealed the presence of 1 in the plant, thus suggesting that it is a natural product rather than an artifact. Attempts at obtaining Michael adducts between acetone and para-quinone abietane diterpenoids were unsuccessful, whereas treatment of the ortho-quinone cryptotanshinone (3) with acetone under basic conditions yielded compound 2. The structures of 1 and 2 were established by 1D and 2D NMR spectroscopic studies.
Asunto(s)
Abietanos/química , Abietanos/aislamiento & purificación , Fenantrenos/química , Plantas Medicinales/química , Plectranthus/química , Acetona/química , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Quinonas/química , Sudáfrica , EstereoisomerismoRESUMEN
Three labdane diterpenoids were isolated from an acetone extract of Plectranthus ornatus. Their structures, closely related to that of forskolin, were determined by NMR studies. Unambiguous and complete assignments of the 1H and 13C NMR chemical shifts for these substances are presented. The assignments are based on 2D shift-correlated [1H, 1H-COSY, 1H, 13C-gHSQC-1J (C,H), 1H, 13C-gHMBC-(n)J (C,H) (n = 2 and 3)] and NOE experiments.
Asunto(s)
Diterpenos/química , Espectroscopía de Resonancia Magnética/métodos , Extractos Vegetales/química , Plectranthus/metabolismo , Isótopos de Carbono , Colforsina/análisis , Colforsina/química , Diterpenos/análisis , Conformación Molecular , Extractos Vegetales/análisis , ProtonesRESUMEN
From the bark of Drimys winterii Forst., the drimane derivatives drimendiol, polygodial, isotadeonal and isodrimeninol were isolated. Complete and unambiguous 1H and 13C NMR chemical shift assignments of these compounds were achieved by COSY experiments, 13C/1H shift correlation diagrams and NOE experiments. Isotadeonal and isodrimeninol were found for the first time in this plant species.
Asunto(s)
Magnoliopsida/química , Sesquiterpenos/química , Isótopos de Carbono , Hidrógeno , Espectroscopía de Resonancia Magnética/métodos , Extractos Vegetales/química , Plantas Medicinales , Sesquiterpenos/aislamiento & purificaciónRESUMEN
From an acetone extract of Staehelina dubia, large quantities of the previously known germacranolide artemisiifolin were isolated. The conformations of the 10-membered germacra-1(10)E,4Z-diene ring system of this compound and those of its derivatives 11,13-dihydroartemisiifolin, isabelin and 6alpha-hydroxy-15-oxogermacra-1(10)E,4Z,11(13)-trien-12,8alpha-olide were studied by NMR spectroscopic methods. Low-energy conformations were obtained by quantum mechanical calculations. An x-ray diffraction analysis of artemisiifolin established that, in the crystalline state, it possesses a unique conformation that corresponds to the majority one existing in acetone-d6 solution.
Asunto(s)
Furanos/análisis , Furanos/química , Espectroscopía de Resonancia Magnética/métodos , Modelos Moleculares , Extractos Vegetales/análisis , Extractos Vegetales/química , Difracción de Rayos X/métodos , Algoritmos , Conformación MolecularRESUMEN
Six new diterpenoids, three labdane and three kaurane derivatives, have been isolated from an acetone extract of Plectranthus fruticosus together with other already known substances. The structures of these compounds (1-5 and 7) were established mainly by spectroscopic means, particularly by 1D and 2D NMR studies, as well as by some chemical correlations with known diterpenoids. The physical and spectroscopic data of the derivative 11, obtained by hydrolysis of the labdane 2, were identical to those reported for a compound previously isolated from Croton joufra, to which structure 12 had been established erroneously by other authors. Several of the isolated compounds were tested as antimicrobial agents against three bacteria strains and one yeast strain, but only 4 showed a moderate inhibitory activity against Staphylococcus aureus.
Asunto(s)
Antibacterianos/aislamiento & purificación , Diterpenos/aislamiento & purificación , Plantas Medicinales/química , Plectranthus/química , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/química , Antibacterianos/farmacología , Croton/química , Diterpenos/química , Diterpenos/farmacología , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Portugal , EstereoisomerismoRESUMEN
A new triterpenoid, 1beta,2beta;21,23-diepoxy-7alpha-hydroxy-24,25,26,27-tetranor-apotirucalla-14,20,22-trien-3-one (1), has been isolated from an acetone extract of seeds of Trichilia havanensis, along with other known limonoids. The structure of 1 was established by spectroscopic methods, particularly by 1D and 2D NMR studies. Compound 1 was tested as an antifeedant agent against Leptinotarsa decemlineata larvae, showing a significant antifeedant activity at 300 ppm.
Asunto(s)
Limoninas/aislamiento & purificación , Meliaceae/química , Plantas Medicinales/química , Animales , Escarabajos/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Larva/efectos de los fármacos , Limoninas/química , Limoninas/farmacología , México , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Semillas/química , EstereoisomerismoRESUMEN
Five known abietane diterpenes, fatty acid esters of 7alpha-acyloxy-6beta-hydroxyroyleanone (1), grandidone A (2), 7alpha-acetoxy-6beta-hydroxyroyleanone (3), 6beta,7alpha-dihydroxyroyleanone (4), and coleon U (5), isolated from Plectranthus grandidentatus Gürke, were evaluated for their in vitro antiproliferative activity against five human cancer cell lines MCF-7, NCI-H460, SF-268, TK-10, and UACC-62. Coleon U (5) exhibited the strongest effect among all the assayed compounds. The abietane 3 revealed also a strong inhibitory effect while diterpenes 2 and 4 inhibited only slightly the growth of all cancer cell lines.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Diterpenos/farmacología , Plectranthus , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , División Celular/efectos de los fármacos , Diterpenos/química , Diterpenos/aislamiento & purificación , Humanos , Concentración 50 Inhibidora , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
Mediante un estudio descriptivo de corte transversal, se realizo una investigacion en 155 mujeres embarazadas en la zona rural como urbana del municipio de Padre las Casas en el ano 1990 con el proposito de determinar la situacion de la atencion prenatal. Los Resultados son: las embarazadas eran basicamente jovenes (menos de 20 ano) (58.7 por ciento ). Estas se habian chequeado en un gran porcentaje (41.4 por ciento ), menos de 3 veces y el 39.5 por ciento nunca habia visitado un medico en el curso de su embarazo. El 64.6 por ciento , en ningun momentose habia administrado dosis alguna de toxoide tetanica. El 29.1 por ciento de este grupo prioritario de salud presento uno o varios signos y/o sintomas de patologias propias del embarazo