RESUMEN
Two previously undescribed caryophyllane-related sesquiterpenoids, antipacids A (1) and B (2), with a novel bicyclo[5.2.0] core skeleton, and known compound clovane-2ß,9α-diol (3), along with rumphellolide L (4), an esterified product of 1 and 3, were isolated from the organic extract of octocoral Rumphella antipathes. Their structures, including the absolute configurations were elucidated by spectroscopic and chemical experiments. In vivo anti-inflammatory activity analysis indicated that antipacid B (2) inhibited the generation of superoxide anions and the release of elastase by human neutrophils, with IC50 values of 11.22 and 23.53 µM, respectively, while rumphellolide L (4) suppressed the release of elastase with an IC50 value of 7.63 µM.
Asunto(s)
Antozoos/metabolismo , Antiinflamatorios/farmacología , Neutrófilos/efectos de los fármacos , Sesquiterpenos Policíclicos/farmacología , Animales , Antiinflamatorios/aislamiento & purificación , Humanos , Elastasa de Leucocito/metabolismo , Estructura Molecular , Neutrófilos/metabolismo , Sesquiterpenos Policíclicos/aislamiento & purificación , Relación Estructura-Actividad , Superóxidos/metabolismoRESUMEN
Integrating multifactor blood analysis is a key step toward a precise diagnosis of the health status of marine mammals. Variations in the circulating lipid profile reflect changes in the metabolism and physiology of an individual. To demonstrate the practicability of lipid profiling for physiological assessment, the phosphorylcholine-containing lipids in the plasma of long-term managed beluga whales (Delphinapterus leucas) were profiled using a lipidomics methodology. Using a multivariate analysis, the mean corpuscular volume, cholesterol, potassium, and γ-glutamyltranspeptidase levels were well modeled with the lipid profile of the female whales. In the models, the correlated lipids provided information about blood parameter-related metabolism and physiological regulation, in particular relating to cholesterol and inflammation. In the males, the levels of cholesterol, triglycerides, blood urea nitrogen, creatinine, plasma iron, and segmented neutrophil were well modeled with the lipid profile. In addition to providing information about the related metabolism and regulation, through a cross-linked analysis of the blood parameters, the correlated lipids indicated a parallel regulation involved in the energy metabolism of the male whales. Lipidomics as a method for revealing the context of physiological change shows practical potential for the health care of managed whales.
Asunto(s)
Crianza de Animales Domésticos/métodos , Animales de Zoológico , Metabolismo de los Lípidos/fisiología , Lípidos/análisis , Ballenas/fisiología , Animales , Lípidos/genéticaRESUMEN
A known norcembranoidal diterpene, 5-episinuleptolide (1), along with a new analogue, 4α-hydroxy-5-episinuleptolide (2), were isolated from a cultured-type soft coral Sinularia numerosa. The structures of 1 and 2 were elucidated on the basis of spectroscopic methods and by comparison of the data with those of the related metabolites. Cytotoxicity of metabolites 1 and 2 against a panel of tumor cells is also described. Compound 2 exhibited moderate cytotoxicity toward CCRF-CEM cells with an IC50 value 4.21 µg/mL. Preliminary SAR (structure activity relationship) information was obtained from these two compounds.
Asunto(s)
Antozoos/química , Diterpenos/química , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Estructura Molecular , Resonancia Magnética Nuclear BiomolecularRESUMEN
BACKGROUND: The burst size of a phage is important prior to phage therapy and probiotic usage. The efficiency for a phage to burst its host bacterium can result from molecular domino effects of the phage gene expressions which dominate to control host machinery after infection. We found two Podoviridae phages, ÏA318 and ÏAs51, burst a common host V. alginolyticus with different efficiencies of 72 and 10 PFU/bacterium, respectively. Presumably, the genome sequences can be compared to explain their differences in burst sizes. RESULTS: Among genes in 42.5 kb genomes with a GC content of 43.5%, 16 out of 47 open-reading frames (ORFs) were annotated to known functions, including RNA polymerase (RNAP) and phage structure proteins. 11 strong phage promoters and three terminators were found. The consensus sequence for the new vibriophage promoters is AATAAAGTTGCCCTATA, where the AGTTG bases of -8 through -12 are important for the vibriophage specificity, especially a consensus T at -9 position eliminating RNAP of K1E, T7 and SP6 phages to transcribe the genes. ÏA318 and ÏAs51 RNAP shared their own specific promoters. In comparing ÏAs51 with ÏA318 genomes, only two nucleotides were deleted in the RNAP gene and three mutating nucleotides were found in the major capsid genes. CONCLUSION: Subtle analyses on the residue alterations uncovered the effects of five nucleotide mutations on the functions of the RNAP and capsid proteins, which account for the host-bursting efficiency. The deletion of two nucleotides in RNAP gene truncates the primary translation due to early stop codon, while a second translational peptide starting from GTG just at deletion point can remediate the polymerase activity. Out of three nucleotide mutations in major capsid gene, H53N mutation weakens the subunit assembly between capsomeres for the phage head; E313K reduces the fold binding between ß-sheet and Spine Helix inside the peptide.
Asunto(s)
Bacteriófagos/genética , Proteínas de la Cápside/genética , ARN Polimerasas Dirigidas por ADN/genética , Mutación Puntual , Vibrio alginolyticus/virología , Secuencia de Aminoácidos , Bacteriófagos/enzimología , Secuencia de Bases , Genoma Viral , Especificidad del Huésped , Anotación de Secuencia Molecular , Datos de Secuencia Molecular , Regiones Promotoras Genéticas , Análisis de Secuencia de ADN , Liberación del VirusRESUMEN
Five new 7α-hydroxyeunicellin-based diterpenoids, designated as cladieunicellins M-Q (1-5), were isolated from a Formosan octocoral Cladiella sp. The structures of 1-5 were elucidated on the basis of spectroscopic methods and by comparison of the data with those of the related metabolites. Cytotoxicity of metabolites 1-5 against the human leukemia Molt 4 and HL 60 is also described. Among them, compounds 1, 3 and 5 exhibited moderate cytotoxicity toward Molt 4 cells with IC50 values 16.43, 14.17 and 15.55 µM, respectively. Preliminary SAR (structure activity relationship) information was obtained from these compounds and their analogues.
Asunto(s)
Antozoos/metabolismo , Antineoplásicos/farmacología , Diterpenos/farmacología , Leucemia/tratamiento farmacológico , Animales , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Línea Celular Tumoral , Diterpenos/química , Diterpenos/aislamiento & purificación , Células HL-60 , Humanos , Concentración 50 Inhibidora , Leucemia/patología , Análisis Espectral , Relación Estructura-ActividadRESUMEN
A novel sesquiterpenoid, rumphellaoic acid A (1), was isolated from the gorgonian coral Rumphella antipathies, and was found to possess a carbon skeleton that was obtained for the first time from a natural sources. The structure of 1 was elucidated by spectroscopic methods and this compound and was found to exert a moderate inhibitory effect on the release of elastase by human neutrophils.
Asunto(s)
Antozoos/química , Sesquiterpenos/química , Sesquiterpenos/farmacología , Animales , Humanos , Neutrófilos/efectos de los fármacos , Elastasa Pancreática/metabolismo , Análisis Espectral/métodos , TaiwánRESUMEN
Two novel diterpenoids, sinularbols A (1) and B (2), which were found to possess a new carbon skeleton were isolated from the soft coral Sinularia arborea. The structures of compounds 1 and 2 were elucidated by spectroscopic methods and 2 displayed a moderately inhibitory effect on the generation of superoxide anion by human neutrophils.
Asunto(s)
Antozoos/química , Diterpenos/química , Animales , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Conformación Molecular , Espectrometría de Masa por Ionización de Electrospray , Espectrofotometría Infrarroja , Superóxidos/químicaRESUMEN
The structures, names, bioactivities and references of 138 briarane-type diterpenoids, including 87 new compounds, are summarized in this review. All the briarane-type compounds mentioned in this review article were obtained from gorgonian corals including the genus Briareum, Dichotella, Junceella and Verrucella. Some of these compounds showed potential bioactivities.
Asunto(s)
Antozoos/metabolismo , Diterpenos/aislamiento & purificación , Animales , Diterpenos/química , Diterpenos/farmacología , HumanosRESUMEN
Three new 8-alkylcoumarins, 7-O-methylphellodenol-B (1), 7-methoxy-8-(3-methyl- 2,3-epoxy-1-oxobutyl)chromen-2-one (2), and 3'-O-methylvaginol (3), together with seven known compounds (4-10) were isolated from the fruits of Cnidium monnieri. Their structures were determined by detailed analysis of spectroscopic data and comparison with the data of known analogues. All the isolates were evaluated the cytoprotective activity by MTS cell proliferation assay and the results showed that all the three new 8-alkylcoumarins exhibited cytoprotective effect on Neuro-2a neuroblastoma cells injured by hydrogen peroxide.
Asunto(s)
Apiaceae/química , Cumarinas/farmacología , Frutas/química , Peróxido de Hidrógeno/toxicidad , Estrés Oxidativo/efectos de los fármacos , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cumarinas/química , Cumarinas/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Ratones , Estructura Molecular , Neuroblastoma/patología , Oxidantes/toxicidad , Sustancias Protectoras/química , Sustancias Protectoras/aislamiento & purificación , Sustancias Protectoras/farmacologíaRESUMEN
Two new marine-derived caryophyllene-type sesquiterpenoids, rumphellols A and B (1 and 2), were obtained from the gorgonian coral, Rumphella antipathies, collected off the waters of Taiwan. Although caryophyllene-type sesquiterpenes are rarely found in marine organisms, compounds of this type could be principal components of R. antipathies. The structures of new Compounds 1 and 2 were determined by analysis of their spectroscopic data, including 1D and 2D NMR experiments. Caryophyllene 1 and 2 were evaluated in terms of their anti-inflammatory activity by examining their inhibitory effects on the generation of superoxide anions and the release of elastase by human neutrophils.
Asunto(s)
Antozoos/química , Antiinflamatorios no Esteroideos/química , Extractos Celulares/química , Sesquiterpenos/química , Sesterterpenos/química , Animales , Antiinflamatorios no Esteroideos/farmacología , Extractos Celulares/farmacología , Humanos , Neutrófilos/efectos de los fármacos , Neutrófilos/enzimología , Elastasa Pancreática/metabolismo , Sesquiterpenos Policíclicos , Sesquiterpenos/farmacología , Sesterterpenos/farmacología , Superóxidos/metabolismoRESUMEN
Wild bitter gourd (Momordica charantia L. var. abbreviate Seringe), a common vegetable in Asia, is used in traditional medicine to treat various diseases, including inflammation. Extant literature indicates that wild bitter gourds have components that activate PPARα and PPARγ. This research probed the influence of adding wild bitter gourd to diets on inflammation responses in mice with sepsis induced by intraperitoneal injection of LPS. Male BALB/c mice were divided normal, sepsis, positive control, and three experimental groups. The latter ate diets with low (1%), moderate (2%), and high (10%) ratios of wild bitter gourd lyophilized powder. Before mice were sacrificed, with the exception of the normal group, intraperitoneal injection of LPS induced sepsis in each group; positive control group was injected with LPS after PDTC. This experiment revealed starkly lower weights in groups with added wild bitter gourd than those of the remaining groups. Blood lipids (TG, cholesterol, and NEFA) were also lower in comparison to the sepsis group, and blood glucose concentrations recovered and approached normal levels. Blood biochemistry values related to inflammation reactions indicated GOT, GPT, C-RP, and NO concentrations of groups with added wild bitter gourd were all lower than those of the sepsis group. Secretion levels of the spleen pro-inflammatory cytokines IL-1, IL-6, and TNF-α tallied significantly lower in comparison to the sepsis group, whereas secretion levels of IL-10 anti-inflammatory cytokine increased. Expression level of proteins NF-κB, iNOS, and COX-2 were significantly inhibited. Results indicate wild bitter gourd in diets promoted lipid metabolism, reducing fat accumulation, and improving low blood glucose in sepsis. Addition of wild bitter gourd can reduce inflammation biochemical markers or indicators and pro-inflammatory cytokines in the body, hence improving the inflammation responses in mice with sepsis.
Asunto(s)
Antiinflamatorios/farmacología , Momordica charantia/química , Extractos Vegetales/farmacología , Sepsis/tratamiento farmacológico , Animales , Antiinflamatorios/uso terapéutico , Citocinas/metabolismo , Evaluación Preclínica de Medicamentos , Mediadores de Inflamación/sangre , Lipopolisacáridos/farmacología , Masculino , Ratones Endogámicos BALB C , Extractos Vegetales/uso terapéutico , Sepsis/sangre , Sepsis/inmunología , Bazo/efectos de los fármacos , Bazo/inmunología , Bazo/metabolismoRESUMEN
Two new 4,5-seco-caryophyllane sesquiterpenoids, rumphellaones B (1) and C (2), which were found to possess unprecedented γ-lactone moieties, were obtained from the gorgonian coral Rumphella antipathies. The structures of 1 and 2 were elucidated by spectroscopic methods and compound 2 was found to display modest inhibitory effects on the generation of superoxide anions and the release of elastase by human neutrophils at a concentration of 10 µg/mL.
Asunto(s)
Antozoos/química , Antiinflamatorios/aislamiento & purificación , Sesquiterpenos/aislamiento & purificación , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Células Cultivadas , Humanos , Neutrófilos/efectos de los fármacos , Neutrófilos/enzimología , Elastasa Pancreática/metabolismo , Sesquiterpenos/química , Sesquiterpenos/farmacología , Superóxidos/metabolismoRESUMEN
Two new 13-hydroxycembrane diterpenoids, arbolides A (1) and B (2), along with a known trihydroxysteroid, crassarosterol A (3), were isolated from the soft coral Sinularia arborea. The structures of new cembranes 1 and 2 were elucidated by spectroscopic methods. Steroid 3 was found to exhibit cytotoxicity toward K562 and MOLT-4 leukemia.
Asunto(s)
Antozoos/química , Antozoos/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacología , Diterpenos/química , Diterpenos/farmacología , Animales , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales/métodos , Humanos , Células K562 , Leucemia/tratamiento farmacológicoRESUMEN
A new norcembranoidal diterpene, 1-epi-sinulanorcembranolide A (1), and a new cembranoidal diterpene, flexibilin D (2), were isolated from the soft corals, Sinularia gaweli and Sinularia flexibilis, respectively. The structures of new metabolites 1 and 2 were elucidated by spectroscopic methods, and compound 2 was found to significantly inhibit the accumulation of the pro-inflammatory iNOS and COX-2 proteins of the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. In addition, S. flexibilis yielded a known cembrane, 5-dehydrosinulariolide (3); the structure, including its absolute stereochemistry, was further confirmed by single-crystal X-ray diffraction analysis.
Asunto(s)
Antozoos/química , Diterpenos/farmacología , Macrófagos/efectos de los fármacos , Animales , Ciclooxigenasa 2/efectos de los fármacos , Ciclooxigenasa 2/metabolismo , Diterpenos/química , Diterpenos/aislamiento & purificación , Lipopolisacáridos/farmacología , Macrófagos/metabolismo , Ratones , Óxido Nítrico Sintasa de Tipo II/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo II/metabolismo , Análisis Espectral , Difracción de Rayos XRESUMEN
Three new cembrane-type diterpenoids, flexibilins A-C (1-3), along with a known cembrane, (-)-sandensolide (4), were isolated from the soft coral, Sinularia flexibilis. The structures of cembranes 1-4 were elucidated by spectroscopic methods. The structure of 4, including its absolute stereochemistry, was further confirmed by single-crystal X-ray diffraction analysis. Cembrane 2 displayed a moderate inhibitory effect on the release of elastase by human neutrophils.
Asunto(s)
Antozoos/química , Diterpenos/farmacología , Neutrófilos/efectos de los fármacos , Elastasa Pancreática/efectos de los fármacos , Animales , Diterpenos/química , Diterpenos/aislamiento & purificación , Humanos , Neutrófilos/metabolismo , Elastasa Pancreática/metabolismo , Análisis Espectral , Taiwán , Difracción de Rayos XRESUMEN
A new quinone derivative, flexibilisquinone (1), was isolated from the cultured soft coral Sinularia flexibilis, originally distributed in the waters of Taiwan. The structure of quinone 1 was established by extensive spectroscopic methods, particularly 1D and 2D NMR experiments. In the in vitro anti-inflammatory effects test, quinone 1 was found to significantly inhibit the accumulation of the pro-inflammatory iNOS and COX-2 proteins of the LPS-stimulated RAW264.7 macrophage cells.
Asunto(s)
Antozoos/metabolismo , Antiinflamatorios no Esteroideos/farmacología , Inflamación/tratamiento farmacológico , Quinonas/farmacología , Animales , Antiinflamatorios no Esteroideos/química , Línea Celular , Ciclooxigenasa 2/efectos de los fármacos , Inflamación/inducido químicamente , Lipopolisacáridos , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Ratones , Óxido Nítrico Sintasa de Tipo II/efectos de los fármacos , Quinonas/químicaRESUMEN
The widespread use of hexabromocyclododecane (HBCD), a brominated flame retardant, is a major public health concern because of the toxic, persistent, and bioaccumulative nature of HBCD. However, there is limited information available regarding the distribution and transportation of HBCD in sediments across various environmental settings, spanning from riverine to marine environments in the Kaohsiung area of Taiwan. In this study, we comprehensively investigated the level and distribution of and potential ecological risk posed by HBCD in surface sediments in the Kaohsiung area of Taiwan. In sediment samples from stations on the Love River and Kaohsiung Port area, the concentrations of HBCD ranged from 10.6 to 320.1 µg/kg dry weight (dw) and nondetectable (n.d.) to 58.4 µg/kg dw, respectively. The concentrations of HBCD in sediment collected from the M1, M2, and M3 sites, located in the Cijin coastal area, were 896.2 µg/kg dw, 3.2 µg/kg dw (
Asunto(s)
Retardadores de Llama , Hidrocarburos Bromados , Contaminantes Químicos del Agua , Taiwán , Monitoreo del Ambiente , Hidrocarburos Bromados/análisis , Sedimentos Geológicos , Ríos , Retardadores de Llama/análisis , Contaminantes Químicos del Agua/análisisRESUMEN
A fast reversed-phase liquid chromatography-electrospray ionization triple quadrupole mass spectrometry method was developed for the molecular species profiling of glycerophosphocholine (GPC) and sphingomyelin (SM) in total lipid extracts. A two-stage mass spectrometry strategy was adopted to analyze in detail the composition of lipid molecular species. Precursor ion analysis was first conducted to obtain the preliminary composition profile of the phosphorylcholine-containing lipid. The product ion spectra were sequentially acquired for each recorded signal to determine the molecular structure of the lipid. A total of 150 GPCs and 12 SMs were identified in the fetal mouse lung with relative amounts ranging from 13.7% to less than 0.002% (normalizing by the total signal response). A column packed with core-shell particles was used to obtain excellent chromatographic separation with a shorter time demand in a conventional high-performance liquid chromatography system. Considering the compromise between the chromatographic efficiency and the electrospray signal response, the optimization of the mobile phase improves the chromatographic plate number to approximately 40,000 and the detection limits to less than 0.001 mg/L. The applicability of the method was validated through a study of chemically induced early lung maturation. The metabolic alteration in the fetal mouse lung was clearly reflected in the GPC and SM composition with several characteristics of the molecular structure that related to the character of the phospholipid layer upon the epithelial lining of alveoli and the relevant cell function. The results indicated that this analytical strategy is reliable for comprehensive molecular species profiling of GPC and SM and might be extended to the analysis of other phospholipids.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Pulmón/química , Pulmón/embriología , Fosforilcolina/análisis , Espectrometría de Masa por Ionización de Electrospray/métodos , Esfingomielinas/análisis , Animales , Femenino , Límite de Detección , Lípidos/análisis , Ratones , Espectrometría de Masas en Tándem/métodosRESUMEN
A new labdane-type diterpenoid, echinolabdane A (1), and a new sterol, 6-epi-yonarasterol B (2), were isolated from a gorgonian coral identified as Echinomuricea sp. The structures of metabolites 1 and 2 were elucidated by spectroscopic methods. Echinolabdane A (1) possesses a novel tetracyclic skeleton with an oxepane ring jointed to an α,ß-unsaturated-γ-lactone ring by a hemiketal moiety, and this compound is the first labdane-type diterpenoid to be obtained from marine organisms belonging to the phylum Cnidaria. 6-epi-Yonarasterol B (2) is the first steroid derivative to be isolated from gorgonian coral belonging to the genus Echinomuricea, and this compound displayed significant inhibitory effects on the generation of superoxide anions and the release of elastase by human neutrophils.
Asunto(s)
Antozoos/química , Productos Biológicos/química , Productos Biológicos/aislamiento & purificación , Diterpenos/química , Diterpenos/aislamiento & purificación , Animales , Organismos Acuáticos/química , Productos Biológicos/farmacología , Cnidarios/química , Diterpenos/farmacología , Humanos , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Elastasa Pancreática/antagonistas & inhibidores , Elastasa Pancreática/metabolismo , Análisis Espectral/métodos , Esteroles/química , Esteroles/aislamiento & purificación , Esteroles/farmacología , Superóxidos/antagonistas & inhibidores , Superóxidos/metabolismoRESUMEN
A new halimane-type diterpenoid, echinohalimane A (1), was isolated from a gorgonian, identified as Echinomuricea sp. The structure of 1 was determined by spectroscopic methods and this compound was found to exhibit cytotoxicity toward various tumor cells and display an inhibitory effect on the release of elastase by human neutrophils. Echinohalimane A (1) is the first halimane analogue from the marine organisms belonging to phylum Cnidaria.