RESUMEN
Suaeda glauca, a halophyte in the Amaranthaceae family, exhibits remarkable resilience to high salt and alkali stresses despite the absence of salt glands or vesicles in its leaves. While there is growing pharmacological interest in S. glauca, research on its secondary metabolites remains limited. In this study, chemical constituents of the aerial parts of S. glauca were identified using 1D- and 2D-NMR experiments, and its biological activity concerning hair loss was newly reported. Eight compounds, including alkaloids (1~3), flavonoids (4~6), and phenolics (7 and 8), were isolated. The compounds, except the flavonoids, were isolated for the first time from S. glauca. In the HPLC chromatogram, quercetin-3-O-ß-d-glucoside, kaempferol-3-O-ß-d-glucoside, and kaempferol were identified as major constituents in the extract of S. glauca. Additionally, the therapeutic potential of the extract of S. glauca and the isolated compounds 1~8 on the expressions of VEGF and IGF-1, as well as the regulation of Wnt/ß-catenin signaling, were evaluated in human follicle dermal papilla cells (HFDPCs) and human umbilical vein endothelial cells (HUVECs). Among the eight compounds, compound 4 was the most potent in terms of increasing the expression of VEGF and IGF-1 and the regulation of Wnt/ß-catenin. These findings suggest that S. glauca extract and its compounds are potential new candidates for preventing or treating hair loss.
Asunto(s)
Chenopodiaceae , Factor I del Crecimiento Similar a la Insulina , Humanos , Animales , Plantas Tolerantes a la Sal , beta Catenina , Factor A de Crecimiento Endotelial Vascular , Alopecia , Flavonoides/farmacología , Células Endoteliales de la Vena Umbilical Humana , Extractos Vegetales/farmacologíaRESUMEN
Benign prostatic hyperplasia (BPH), characterized by the enlargement of the prostate gland and subsequent lower urinary tract symptoms, poses a significant health concern for aging men with increasing prevalence. Extensive efforts encompassing in vitro and in vivo models are underway to identify novel and effective agents for the management and treatment of BPH. Research endeavors are primarily channeled toward assessing the potential of compounds to inhibit cell proliferation, curb inflammation, and display anti-androgenic activity. Notably, through screening aimed at inhibiting 5-alpha reductase type 2 (5αR2) in human prostatic cells, two acyl compounds (1 and 2) were isolated from a bioactive fraction sourced from an association of marine sponges Poecillastra sp. and Jaspis sp. The complete structure of 1 was determined as (Z)-dec-3-enony (2S, 3S)-capreomycidine, ascertained by JBCA and ECD comparison. While the absolute configurations of 2 remained unassigned, it was identified as a linkage of a 2, 7S*-dihydoxy-9R*-methyloctadecanoyl group with the 2-amino position of a tramiprosate moiety referred to as homotaurine. Evaluation of both compounds encompassed the assessment of their inhibitory effects on key biomarkers (5αR2, AR, PSA, and PCNA) associated with BPH in testosterone propionate (TP)-activated LNCap and RWPE-1 cells.
RESUMEN
There were five sesquiterpene lactones, belonging to the eudesmanolide class, isolated from the halophyte Sonchus brachyotus DC. The structures of the compounds were determined using spectroscopic methods, including 1D and 2D NMR spectra, MS data, and optical rotation values. Compounds 4 and 5 were characterized by the position of p-hydroxyphenylacetyl group in the sugar moiety. In the evaluation of anti-inflammatory effects on LPS-activated RAW264.7 macrophages, compound 1, 5α,6ßH-eudesma-3,11(13)-dien-12,6α-olide, potently suppressed the expression of iNOS and COS-2, as well as the production of TNF-α, IL-6, and IL-10. Treatment of 1 regulates the Nrf2/HO-1 pathway.
Asunto(s)
Sesquiterpenos , Sonchus , Plantas Tolerantes a la Sal , Sesquiterpenos/química , Extractos Vegetales/química , Lactonas/químicaRESUMEN
Three voratin compounds (1-3) were isolated from the symbiotic marine dinoflagellate Effrenium voratum. The planar structures of 1-3 were determined by 1D and 2D NMR spectroscopy and HRESIMS, and the relative and absolute configurations were established using ROESY correlations, Mosher's method, and quantum calculations. All of the compounds are zwitterionic and contain a dihydroindolizinium ring and a spiroketal moiety. Compounds 1-3 were found to exhibit therapeutic effects against benign prostatic hyperplasia (BPH), as evaluated using testosterone propionate-treated LNCap and RWPE-1 human prostate cells. This excellent activity suggests that 1-3 are promising for the development of BPH treatments.
Asunto(s)
Alcaloides , Dinoflagelados , Hiperplasia Prostática , Alcaloides/farmacología , Alcaloides/uso terapéutico , Animales , Biomarcadores , Humanos , Masculino , Extractos Vegetales/farmacología , Hiperplasia Prostática/tratamiento farmacológico , Ratas , Ratas Sprague-DawleyRESUMEN
Ovataline (1), which is a polar metabolite containing a hexahydroquinoline moiety, was isolated from cultures of the marine dinoflagellate Ostreopsis cf. ovata. 1 was characterized as a zwitterionic compound with hexahydroquinoline and tetrahydropyran rings. The configurations of the chiral centers in 1 were established using ROESY correlations, J-based configurational and Mosher reaction analyses, and density functional theory calculations. 1 exhibited a 78% (1 µM) inhibition of type II 5α-reductase in testosterone propionate-induced RWPE-1 human prostatic cells.
Asunto(s)
Dinoflagelados , Policétidos , Colestenona 5 alfa-Reductasa/metabolismo , Humanos , Policétidos/metabolismoRESUMEN
Densazalin, a polycyclic alkaloid, was isolated from the marine sponge Haliclona densaspicula collected in Korea. The complete structure of the compound was determined by spectroscopic methods, including 1D and 2D nuclear magnetic resonance techniques, high-resolution mass spectrometry, and comparison of the calculated and measured electronic circular dichroism spectra. Densazalin possesses a unique 5,11-diazatricyclo[7.3.1.02,7]tridecan-2,4,6-triene moiety, which is connected by two linear carbon chains. This compound was derived from the biogenetic precursor bis-1,3-dialkylpyridnium. Densazalin exhibited cytotoxic activity on two human tumor cell lines (AGS and HepG2) in the Cell Counting Kit-8 (CCK-8) bioassay, with IC50 values ranging from 15.5 to 18.4 µM.
Asunto(s)
Alcaloides/aislamiento & purificación , Biología Marina , Poríferos/química , Alcaloides/química , Alcaloides/farmacología , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Análisis Espectral/métodosRESUMEN
By activity-guided fractionation based on inhibition of nitric oxide (NO) and prostaglandin E2 (PGE2), six fistularin compounds (1-6) were isolated from the marine sponge Ecionemia acervus (order Astrophorida). Based on stereochemical structure determination using Mosher's method, fistularin-3 was assigned as a new stereoisomer. On the basis of the stereochemistry of fistularin-3, the stereochemical homogeneity of all six compounds was established by comparing carbon and proton chemical shifts. For fistularin-1 (1) and -2 (2), quantum calculations were performed to confirm their stereochemistry. In a co-culture system of human epithelial Caco-2 cells and THP-1 macrophages, all six isolated compounds showed potent anti-inflammatory activities. These bioactive fistularins inhibited the production of NO, PGE2, TNF-α, IL-1ß, and IL-6 induced by lipopolysaccharide and interferon gamma. Inducible NO synthase and cyclooxygenase-2 expression and MAPK phosphorylation were downregulated in response to the inhibition of NF-κB nuclear translocation. Among the compounds tested, fistularin-1 (1) and 19-deoxyfistularin-3 (4) showed the highest activity. These findings suggest the potential use of the marine sponge E. acervus and its metabolites as pharmaceuticals for the treatment of inflammation-related diseases including inflammatory bowel disease.
Asunto(s)
Antiinflamatorios/farmacología , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Isoxazoles/farmacología , Poríferos/metabolismo , Tirosina/análogos & derivados , Animales , Antiinflamatorios/aislamiento & purificación , Células CACO-2 , Técnicas de Cocultivo , Citocinas/metabolismo , Dinoprostona/metabolismo , Humanos , Mediadores de Inflamación/metabolismo , Enfermedades Inflamatorias del Intestino/inmunología , Enfermedades Inflamatorias del Intestino/metabolismo , Isoxazoles/aislamiento & purificación , Estructura Molecular , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Transducción de Señal , Estereoisomerismo , Relación Estructura-Actividad , Células THP-1 , Tirosina/aislamiento & purificación , Tirosina/farmacologíaRESUMEN
Using bio-guided fractionation and based on the inhibitory activities of nitric oxide (NO) and prostaglandin E2 (PGE2), eight isoquinolinequinone derivatives (1-8) were isolated from the marine sponge Haliclona sp. Among these, methyl O-demethylrenierate (1) is a noble ester, whereas compounds 2 and 3 are new O-demethyl derivatives of known isoquinolinequinones. Compound 8 was assigned as a new 21-dehydroxyrenieramycin F. Anti-inflammatory activities of the isolated compounds were tested in a co-culture system of human epithelial Caco-2 and THP-1 macrophages. The isolated derivatives showed variable activities. O-demethyl renierone (5) showed the highest activity, while 3 and 7 showed moderate activities. These bioactive isoquinolinequinones inhibited lipopolysaccharide and interferon gamma-induced production of NO and PGE2. Expression of inducible nitric oxide synthase, cyclooxygenase-2, and the phosphorylation of MAPKs were down-regulated in response to the inhibition of NF-κB nuclear translocation. In addition, nuclear translocation was markedly promoted with a subsequent increase in the expression of HO-1. Structure-activity relationship studies showed that the hydroxyl group in 3 and 5, and the N-formyl group in 7 may be key functional groups responsible for their anti-inflammatory activities. These findings suggest the potential use of Haliclona sp. and its metabolites as pharmaceuticals treating inflammation-related diseases including inflammatory bowel disease.
Asunto(s)
Antiinflamatorios/farmacología , Haliclona/química , Isoquinolinas/farmacología , Transporte Activo de Núcleo Celular , Animales , Células CACO-2 , Hemo-Oxigenasa 1/genética , Humanos , Interferón gamma/farmacología , Isoquinolinas/química , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Relación Estructura-Actividad , Células THP-1RESUMEN
Hyperammonemia is a deleterious and inevitable consequence of liver failure. However, no adequate therapeutic agent is available for hyperammonemia. Although recent studies showed that the pharmabiotic approach could be a therapeutic option for hyperammonemia, its development is clogged with poor identification of etiological microbes and low transplantation efficiency of candidate microbes. In this study, we developed a pharmabiotic treatment for hyperammonemia that employs a symbiotic pair of intestinal microbes that are both able to remove ammonia from the surrounding environment. By a radioactive tracing experiment in mice, we elucidated how the removal of ammonia by probiotics in the intestinal lumen leads to lower blood ammonia levels. After determination of the therapeutic mechanism, ammonia-removing probiotic strains were identified by high-throughput screening of gut microbes. The symbiotic partners of ammonia-removing probiotic strains were identified by screening intestinal microbes of a human gut, and the pairs were administrated to hyperammonemic mice to evaluate therapeutic efficacy. Blood ammonia was in a chemical equilibrium relationship with intestinal ammonia. Lactobacillus reuteri JBD400 removed intestinal ammonia to shift the chemical equilibrium to lower the blood ammonia level. L. reuteri JBD400 was successfully transplanted with a symbiotic partner, Streptococcus rubneri JBD420, improving transplantation efficiency 2.3×103 times more compared to the sole transplantation while lowering blood ammonia levels significantly. This work provides new pharmabiotics for the treatment of hyperammonemia as well as explains its therapeutic mechanism. Also, this approach provides a concept of symbiotic pairs approach in the emerging field of pharmabiotics.
Asunto(s)
Hiperamonemia , Limosilactobacillus reuteri , Probióticos , Amoníaco , Animales , Hiperamonemia/terapia , RatonesRESUMEN
Turbinaria ornata is a tropical brown algae (seaweed) known to have anti-inflammatory properties. In this study, we analyzed T. ornata extract (TOE) using liquid chromatography quadrupole time of flight mass spectrometry (LC-QTOF-MS) and nuclear magnetic resonance (NMR) and evaluated the in vivo efficacy of TOE against dextran sulfate sodium-induced chronic colitis in C57BL/6 mice. The bioactive fraction of TOE was administered orally daily for 6 weeks to mice under different treatments normal, colitis, and colitis + conventional drug (5-aminosalicylic acid, 5-ASA). Regarding clinical manifestation, the disease activity index and colon length of the colitis + TOE group were significantly reduced compared to those of the colitis group. The results of myeloperoxidase activity and histopathological examination showed similar results. Western blot analysis of colon tissues revealed that cyclooxygenase-2, tumor necrosis factor alpha (TNF-α), and phosphorylated signal transducer and activator of transcription-3 (p-STAT3) were significantly decreased in the colitis + 5-ASA group, whereas forkhead box P3 (FOXP3) was increased. qPCR results showed changes in T cell subsets; the administration of TOE upregulated regulatory T cell (Treg) expression, although T helper 17 cell (Th17) expression did not change significantly. Interestingly, the colitis + TOE group showed high levels of both Th1 and Th2 transcription factors, but the secreted cytokine interferon (IFN)-γ and interleukin (IL)-4 remained unchanged and somewhat reduced. Additionally, TNF-α gene expression was significantly reduced in the colitis + TOE group. IL-6 mRNA levels were also decreased, although not significantly. Four compounds were structurally elucidated using 1D- and 2D-NMR spectroscopy, and five compounds were fully identified or tentatively characterized using LC-QTOF-MS. In conclusion, TOE could alleviate chronic colitis via upregulation of Foxp3+ Treg cells and production of the anti-inflammatory cytokine IL-10, which directly inhibits macrophages and pro-inflammatory cytokine synthesis, leading to reduced colitis.
Asunto(s)
Colitis/tratamiento farmacológico , Factores de Transcripción Forkhead/genética , Phaeophyceae/química , Factor de Transcripción STAT3/genética , Animales , Colitis/inducido químicamente , Colitis/genética , Colitis/inmunología , Colon/efectos de los fármacos , Colon/patología , Sulfato de Dextran/toxicidad , Humanos , Interferón gamma/genética , Interleucina-17/genética , Ratones , Linfocitos T Reguladores/efectos de los fármacos , Células Th17/efectos de los fármacosRESUMEN
This study aimed to investigate the beneficial effects of A. melanocarpa on testosterone propionate (TP)-induced benign prostatic hyperplasia (BPH) in Wistar rats. Moreover, the bioactive constituents in the extract were determined using LC/MS and HPLC analyses. The dried fruits of A. melanocarpa were extracted using accelerated solvent extraction (ASE) under different extract conditions (temperature, 30 C or 100 C; extract solvent, 60% or 100% ethanol) to yield four extracts (T1~T4). Of the four A. melanocarpa extracts, T1 extracted under the condition of 100% ethanol/low temperature (30 C) exhibited the greatest inhibitory activity on TP-induced prostatic hyperplasia in rats. The administration of T1 (100 mg/kg body weight, p.o.) for six weeks attenuated TP-induced prostate enlargement and reduced the levels of dihydrotestosterone (DHT) and 5α-reductase in both serum and prostate tissue. The suppression of PCNA mRNA expression in prostate tissue was remarkable in T1-treated rats. In LC/MS analysis, the levels of main anthocyanins and phenolics were significantly higher in T1 than in the other extracts. Furthermore, the quantitative study showed that the contents of cyanidin-3-glucose and cyanidin-3-xylose in T1 exhibited 1.27~1.67 and 1.10~1.26 folds higher compared to those in the other extracts. These findings demonstrated that A. melanocarpa extract containing anthocyanins as bioactive constituents attenuated the development of testosterone-induced prostatic hyperplasia, and suggested that this extract has therapeutic potential to treat prostate enlargement and BPH.
Asunto(s)
Antocianinas/farmacología , Extracción Líquido-Líquido/métodos , Photinia/química , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Hiperplasia Prostática/tratamiento farmacológico , Testosterona/efectos adversos , Animales , Antocianinas/aislamiento & purificación , Colestenona 5 alfa-Reductasa/sangre , Colestenona 5 alfa-Reductasa/metabolismo , Dihidrotestosterona/sangre , Dihidrotestosterona/metabolismo , Expresión Génica/efectos de los fármacos , Masculino , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Antígeno Nuclear de Célula en Proliferación/genética , Antígeno Nuclear de Célula en Proliferación/metabolismo , Próstata/metabolismo , Hiperplasia Prostática/inducido químicamente , Hiperplasia Prostática/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Wistar , TemperaturaRESUMEN
Prorocentrolide and its analogs, the novel naturally derived antitumor agents, have recently been identified in the dinoflagellate Prorocentrum lima. In the current study, the underlying inhibitory mechanisms of 4-hydroxyprorocentrolide (1) and prorocentrolide C (2) on the proliferation of human carcinoma cells were determined. 1 and 2 arrested the cell cycle at the S phase in A549 cells and G2/M phase in HT-29 cells, leading to apoptotic cell death, as determined using fluorescence-activated cell sorting analysis with Annexin V/PI double staining. Apoptosis induced by these compounds was associated with alterations in the expression of cell cycle-regulating proteins (cyclin D1, cyclin E1, CDK2, and CDK4), as well as alterations in the levels of apoptosis-related proteins (PPAR, Bcl-2, Bcl-xl, and survivin). These findings provide new insights into the antitumor mechanisms of 4-hydroxyprorocentrolide and prorocentrolide C and a basis for future investigations assessing prorocentrolide analogs as prospective therapeutic drugs.
Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Neoplasias del Colon/tratamiento farmacológico , Dinoflagelados/metabolismo , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Células A549 , Antineoplásicos/aislamiento & purificación , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas de Ciclo Celular/metabolismo , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Células HT29 , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Transducción de SeñalRESUMEN
The inflammatory bowel diseases (IBD) cause chronic inflammation of the gastrointestinal tract and include ulcerative colitis (UC) and Crohn's disease (CD). The prevalence of IBD has been increasing worldwide, and has sometimes led to irreversible impairment of gastrointestinal structure and function. In the present study, we successfully isolated a new phylloketal derivative, deacetylphylloketal (1) along with four known compounds from the sponge genus Phyllospongia. The anti-inflammatory properties of deacetylphylloketal (1) and phyllohemiketal A (2) were evaluated using an in vitro co-culture system that resembles the intestinal epithelial environment. A co-culture system was established that consisted of human epithelial Caco-2 cells and phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophage cells. The treatment of co-cultured THP-1 cells with compounds 1 or 2 significantly suppressed the production and/or gene expression of lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2), Interleukin-6 (IL-6), IL-1ß and Tumor Necrosis Factor alpha (TNF-α). The expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 were down-regulated in response to inhibition of NF-kB translocation into the nucleus in cells. In addition, we observed that 1 and 2 markedly promoted the nuclear translocation of Nrf2 and subsequent increase in the expression of heme oxygernase (HO)-1. These findings suggest the potential use of sponge genus Phyllospongia and its metabolites as a pharmaceutical aid in the treatment of inflammation-related diseases including IBD.
Asunto(s)
Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico , Poríferos/química , Sesterterpenos/farmacología , Animales , Antiinflamatorios/aislamiento & purificación , Células CACO-2 , Línea Celular , Técnicas de Cocultivo , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Inflamación/patología , Intestinos/efectos de los fármacos , Intestinos/patología , Lipopolisacáridos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , FN-kappa B/metabolismo , Sesterterpenos/aislamiento & purificaciónRESUMEN
Crohn's disease (CD) and ulcerative colitis (UC), collectively referred to as inflammatory bowel disease (IBD), are autoimmune diseases characterized by chronic inflammation within the gastrointestinal tract. Debromohymenialdisine is an active pyrrole alkaloid that is well known to serve as a stable and effective inhibitor of Chk2. In the present study, we attempted to investigate the anti-inflammatory properties of (10Z)-debromohymenialdisine (1) isolated from marine sponge Stylissa species using an intestinal in vitro model with a transwell co-culture system. The treatment with 1 attenuated the production and gene expression of lipopolysaccharide (LPS)-induced Interleukin (IL)-6, IL-1ß, prostaglandin E2 (PGE2), and tumor necrosis factor-α in co-cultured THP-1 macrophages at a concentration range of 1-5 µM. The protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 were down-regulated in response to the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) translocation into the nucleus in cells. In addition, we observed that 1 markedly promoted the nuclear translocation of nuclear factor erythroid 2 related factor 2 (Nrf2) and subsequent increase of heme oxygenase-1 (HO-1) expression. These findings suggest the potential use of 1 as a pharmaceutical lead in the treatment of inflammation-related diseases including IBD.
Asunto(s)
Organismos Acuáticos/química , Azepinas/farmacología , Colitis Ulcerosa , Enfermedad de Crohn , Intestinos/patología , Poríferos/química , Pirroles/farmacología , Animales , Azepinas/química , Células CACO-2 , Técnicas de Cocultivo , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/patología , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/metabolismo , Enfermedad de Crohn/patología , Dinoprostona/metabolismo , Humanos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Pirroles/química , Células THP-1RESUMEN
Herein, we clarify the structure and relative configurations of two prorocentrolide analogues (1 and 2) isolated from the benthic marine dinoflagellate Prorocentrum lima. The results of NMR spectroscopy show that 1 is prorocentrolide substituted by a hydroxy group at C-4, while the newly isolated compound 2 can be thought of as 1 lacking one ether ring and having one extra double bond. The relative configurations of all stereogenic centers and the configurations of the double bonds in 1 and 2 were determined utilizing ROESY correlations and J-based configuration analysis. Furthermore, 2 was shown to exhibit cytotoxicity against HCT-116 and Neuro-2a cells (IC50 2.2 and 5.2 µM, respectively.
Asunto(s)
Dinoflagelados/química , Toxinas Marinas/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Toxinas Marinas/química , Relación Estructura-ActividadRESUMEN
Gukulenin A is a bis-tropolone tetraterpenoid isolated from the marine sponge Phorbas gukhulensis. In this study, we examined the anticancer activities of gukulenin A in ovarian cancer cell lines (A2780, SKOV3, OVCAR-3, and TOV-21G) and in an ovarian cancer mouse model generated by injecting A2780 cells. We found that gukulenin A suppressed tumor growth in A2780-bearing mice. Gukulenin A markedly inhibited cell viability in four ovarian cancer cell lines, including the A2780 cell line. Gukulenin A treatment increased the fraction of cells accumulated at the sub G1 phase in a dose-dependent manner and the population of annexin V-positive cells, suggesting that gukulenin A induces apoptotic cell death in ovarian cancer cells. In addition, gukulenin A triggered the activation of caspase-3, -8, and -9, and caspase inhibitors attenuated gukulenin A-induced A2780 cell death. The results suggest that gukulenin A may be a potential therapeutic agent for ovarian cancer.
Asunto(s)
Neoplasias Ováricas/tratamiento farmacológico , Poríferos/química , Terpenos/farmacología , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Caspasa 8/metabolismo , Caspasa 9/metabolismo , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Distribución Aleatoria , Terpenos/aislamiento & purificación , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Black-fruited chokeberries (Aronia melanocarpa), growing mainly in the Central and Eastern European countries, have health benefits due to the high concentrations of polyphenolic compounds. However, a strong bitter taste of chokeberries limits its usage as functional food. We hypothesized that the fermented A. melanocarpa with a reduced bitter taste would improve insulin sensitivity and/or ameliorate weight gain induced by high-fat diet (HFD) in male C57BL/6J mice. The mice were administered with HFD together with the 100 mg/kg of natural A. melanocarpa (T1) or the fermented A. melanocarpa (T2) for 8 weeks. The treatment with T2 (100 mg/kg body weight, p.o.) markedly attenuated the weight gain and the increase in serum triglyceride level induced by HFD. The T2-treated group had better glucose tolerance and higher insulin sensitivity as measured by oral glucose tolerance test and intraperitoneal insulin tolerance test in comparison to the T1-treated group. Phytochemical analysis revealed that the main constituents of T2 were cyanidin-3-xyloside and 1-(3',4'-dihydroxycinnamoyl)cyclopenta-2,3-diol, and the content of cyanidin glycosides (3-glucoside, 3-xyloside) was significantly reduced during the fermentation process. From the above results, we postulated that antiobesity effect of black chokeberry was not closely correlated with the cyanidin content. Fermented chokeberry might be a viable dietary supplement rich in bioactive compounds useful in preventing obesity.
Asunto(s)
Acetobacter/metabolismo , Fármacos Antiobesidad/metabolismo , Alimentos Fermentados/análisis , Obesidad/dietoterapia , Photinia/microbiología , Extractos Vegetales/metabolismo , Saccharomyces/metabolismo , Animales , Antocianinas/administración & dosificación , Antocianinas/química , Antocianinas/metabolismo , Fármacos Antiobesidad/química , Dieta Alta en Grasa/efectos adversos , Fermentación , Alimentos Fermentados/microbiología , Frutas/química , Frutas/metabolismo , Frutas/microbiología , Humanos , Insulina/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/etiología , Obesidad/metabolismo , Photinia/química , Photinia/metabolismo , Extractos Vegetales/químicaRESUMEN
Berries of Aronia melanocarpa (chokeberry) are known to be a rich source of biologically active polyphenols. In the present study, the effects of seven anti-adipogenic polyphenolic phytochemicals isolated from A. melanocarpa methanol extract on adipogenic transcription factors were investigated. Amygdalin and prunasin were found to inhibit 3T3-L1 adipocyte differentiation by suppressing the expressions of PPARγ (peroxisome proliferator-activated receptor γ), C/EBPα (CCAAT/enhancer binding protein α), SREBP1c (sterol regulatory element binding protein 1c), FAS (fatty acid synthase), and aP2 (adipocyte fatty-acidâ»binding protein). A. melanocarpa extract-treated (100 or 200 mg/kg/day on body weight) high fat diet (HFD)-induced obese mice showed significant decreases in body weight, serum triglyceride (TG), and low-density lipoprotein cholesterol (LDLC) levels and improved insulin sensitivity as compared with HFD controls. This research shows A. melanocarpa extract is potentially beneficial for the suppression of HFD-induced obesity.
Asunto(s)
Adipogénesis/efectos de los fármacos , Tejido Adiposo/metabolismo , Dieta Alta en Grasa/efectos adversos , Resistencia a la Insulina , Obesidad/tratamiento farmacológico , Photinia/química , Polifenoles/uso terapéutico , Células 3T3-L1 , Adipocitos/fisiología , Tejido Adiposo/citología , Animales , Peso Corporal , LDL-Colesterol/sangre , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/etiología , Obesidad/metabolismo , Obesidad/fisiopatología , Fitoterapia , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Polifenoles/farmacología , Triglicéridos/sangreRESUMEN
BACKGROUND: In traditional folk medicine, Limonium tetragonum is used in the treatment of uterine hemorrhage, tinnitus, and oligomenorrhea. OBJECTIVE: This study aimed to identify the therapeutic effect of L. tetragonum EtOAc extract (EALT) on liver of mice with chronic alcohol poisoning. MATERIALS AND METHODS: C57BL/6J mice were administered 100 mg/kg of EALT with a single binge ethanol/Lieber-DeCarli liquid diet for 8 weeks. RESULTS: The chronic-binge ethanol diet induced a significant increase in liver marker enzyme activities. Coadministration of EALT reversed the elevation of serum total cholesterol and triglyceride as well as aspartate aminotransferase and alanine aminotransferase due to chronic alcohol consumption. Histologic findings including markedly attenuated fat accumulation in hepatocytes were observed in EALT-treated mice. EALT supplementation prevented alcoholic liver injury through attenuation of inflammatory mediators such as toll-like receptor-4, cytochrome P4502E1, and cyclooxygenase-2, and inflammatory cytokine interleukin-6. CONCLUSION: Results provided direct experimental evidence for the hepatoprotective effect of EALT in the NIAAA mouse model. Therapeutic attempts with the L. tetragonum extract might be useful in the management of alcoholic liver disease. SUMMARY: Halophyte Limonium tetragonum has recently been of interest in Korea for its nutritional value and salty taste which made it an ideal vegetablePhytochemical analysis of L. tetragonum EtOAc extract (EALT) resulted in nine compounds including catechins and myricetin glycosides as main componentsAdministration of EALT for 8 weeks showed hepatoprotective effect on Lieber-DeCarli diet-fed mouse modelA significant decrease in liver marker enzymes and inflammatory mediators was also detected. Abbreviations used: EALT: L. tetragonum EtOAc extract; TC: Total cholesterol; TG: Triglyceride; ROS: Reactive oxygen species; CYP2E1: Cytochrome P4502E1; TLR-4: Toll-like receptor-4; COX-2: Cyclooxygenase-2.
RESUMEN
Following isolation of the polyhydroxy compound, ostreol B, from cultivated cells of the toxic dinoflagellate Ostreopsis cf. ovata collected in South Korea, 1D and 2D NMR spectroscopy were employed to determine the planar chemical structure of this compound, which contained a tetrahydropyran ring, two terminal double bonds, and 21 hydroxyl groups. The absolute configurations of all stereogenic carbon centers in ostreol B were then determined through a combination of the J-based configuration analysis, rotating frame Overhauser effect correlations, and the modified Mosher method following cleavage of the 1,2-diol bonds. Ostreol B was also found to exhibit moderate cytotoxicity in HepG2, Neuro-2a and HCT-116 cells.