RESUMEN
The objective of this study was to evaluate the effect of yellow mealworm (Tenebrio molitor L.) exuviae (ME) given as a prebiotic in 20% of the diet fed to BALB/c mice. Analysis of the ME revealed that it was mostly composed of crude protein (52.94%), crude fiber (10.70%), and moisture (10.54%). When ME was fed to mice for 8 weeks, the number of intestinal lactic acid bacteria increased, reaching similar numbers (4.50 ± 0.80 CFU/mL) to those (4.70 ± 0.80 CFU/mL) of the control group not fed ME. Microbiome analysis showed that 8 weeks feeding of ME promoted the growth of Bifidobacteriaceae and Lactobacillaceae compared to the POS group, indicating the positive effects of feeding 20% ME on the intestinal microbiota of mice. These results suggest that ME can be considered as a dietary prebiotics to improve human gut microbial population, but further application study to human is necessary.
RESUMEN
The objective of this study was to evaluate probiotic effects of two Lactobacillus plantarum strains (GBL16 and 17) isolated from black raspberry. Results revealed that the number of GBL16 was gradually decreased as bile salt concentration was increased from 0.3 to 1%. However, GBL17 did not show any difference when GBL17 was applied to 1% bile salt, and it indicates that GBL17 is more tolerant to bile salt than GBL16. GBL17 exhibited higher heat resistance and adhesion ability to Caco-2 cells than GBL16. Regarding gut microbiome, no significant change in the number of total bacteria in intestines of mice after treatment with GBLs was determined. However, the combination of GBL16 and GBL17 significantly increased the number of total bacteria in intestines of mice after they were orally administered. Therefore, the results suggest that both GBL16 and 17 strains could be one of major probiotics that can improve human gut health.
RESUMEN
Two new lignans, (2 R,3 R)-2 ß-(4''-hydroxy-3''-methoxybenzyl)-3 α-(4'-hydroxy-3'-methoxybenzyl)-γ-butyrolactone 2-O-( ß-D-glucopyranoside) (1) and (1 S,2 R,3 S)-dimethyl-1,2,3,4-tetrahydro-3,6,7-trihydroxy-1-(3',4'-dihydroxyphenyl)naphthalene-2,3-dicarboxylate (2) together with nine known compounds (3-11) were isolated from the ethyl acetate fraction of the roots of Pulsatilla koreana. Their chemical structures were established based on physicochemical and spectroscopic data analyses. All isolates were investigated for their inhibition effects against the classical pathway of the complement system. Among them, compound 6 showed significant inhibitory activity with an IC (50) value of 75.9 µM, compounds 8 and 9 had moderate effects with IC (50) values of 182.2 and 166.5 µM, respectively.
Asunto(s)
Lignanos/farmacología , Pulsatilla/química , Fraccionamiento Químico , Proteínas del Sistema Complemento/química , Lignanos/química , Lignanos/aislamiento & purificación , Extractos Vegetales/química , Raíces de Plantas/químicaRESUMEN
In the course of screening plants used in folk medicine as memory enhancers, a 70% ethanolic extract of Stephania rotunda roots showed significant AChE inhibitory activity. Repeated column chromatography led to the isolation of a new protoberberine alkaloid, which we named stepharotudine (1), and seven known compounds (2-8). The chemical structures of the isolated compounds were elucidated based on extensive 1D and 2D NMR spectroscopic data. Compounds 1-8 were investigated in vitro for their anticholinesterase activity using a rat cortex AChE enzyme.
Asunto(s)
Alcaloides/farmacología , Inhibidores de la Colinesterasa/farmacología , Stephania/química , Acetilcolinesterasa/aislamiento & purificación , Alcaloides/química , Alcaloides/aislamiento & purificación , Animales , Alcaloides de Berberina/química , Alcaloides de Berberina/aislamiento & purificación , Alcaloides de Berberina/farmacología , Encéfalo/enzimología , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/aislamiento & purificación , Proteínas Ligadas a GPI/antagonistas & inhibidores , Proteínas Ligadas a GPI/aislamiento & purificación , Raíces de Plantas/química , RatasRESUMEN
The hexane-soluble fraction of the roots of Aceriphyllum rossii was used to isolate seven new oleanane-type triterpenoids, aceriphyllic acids C-I (1-7), together with seven known triterpenoids. The structures of aceriphyllic acids C-I were determined as 3alpha-hydroxyolean-12-en-23,29-dioic acid (1), 3beta-hydroxyolean-12-en-23,29-dioic acid (2), 3beta,23-dihydroxyolean-12-en-29-oic acid (3), 3alpha-O-acetylolean-12-en-23,27-dioic acid (4), 3alpha-O-caffeoylolean-12-en-27-oic acid (5), 3alpha-O-acetylolean-12-en-23,29-dioic acid (6), and 3alpha-hydroxyolean-12-en-23-al-27-oic acid (7) by spectroscopic analyses. In the evaluation of the in vitro cytotoxicity of these compounds against the MCF-7 and LLC cancer cell lines, compounds 10 and 13 exhibited cytotoxic activity against the LLC cancer cell line with IC(50) values of 7.63 and 6.56 microM, respectively.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Ácido Oleanólico/aislamiento & purificación , Ácido Oleanólico/farmacología , Plantas Medicinales/química , Saxifragaceae/química , Antineoplásicos Fitogénicos/química , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Corea (Geográfico) , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Ácido Oleanólico/química , Raíces de Plantas/químicaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Gynostemma pentaphyllum (Thunb.) tea was used in Vietnamese folk medicine as anti-diabetic agent. AIM OF THE STUDY: This study was aimed to investigate the inhibitory activities of fractions and constituents isolated from Gynostemma pentaphyllum on protein tyrosine phosphatase 1B (PTP1B) since it has been proposed as a treatment therapy for type 2 diabetes and obesity. MATERIALS AND METHODS: The 70% EtOH extract, CHCl3 fraction, EtOAc fraction, BuOH fraction, and seven isolated dammarane triterpenes were evaluated for their inhibitory activity in protein phosphatase enzymes (PTP1B and VHR). RESULTS: CHCl3-soluble fraction showed a dose-dependent inhibitory activity of the PTP1B enzyme with the IC50 value of 30.5 microg/mL. Among seven tested compounds, compounds 6 showed the most potent PTP1B inhibitory activity with IC50 value of 5.3+/-0.4 microM compared to a range 15.7-28.5 microM for the other six compounds. The inhibition mode of 6 was competitive toward p-NPP with a K(i) value of 2.8 microM. CONCLUSION: These study results suggested that the PTP1B inhibitory activity of these dammaranes may enable this plant to play an important role in the treatment of diabetes.
Asunto(s)
Gynostemma/química , Extractos Vegetales/farmacología , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Triterpenos/farmacología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Humanos , Concentración 50 Inhibidora , Medicina Tradicional de Asia Oriental , Nitrofenoles/metabolismo , Compuestos Organofosforados/metabolismo , Fitoterapia , Componentes Aéreos de las Plantas , Extractos Vegetales/química , Triterpenos/aislamiento & purificación , DamaranosRESUMEN
Yeast-based functional screening for inhibitors of Bcl-2-associated X protein (Bax)-induced cell death in yeast identified ADP-ribosylation factor 4 (ARF4) as a novel anti-apoptotic gene in human glioblastoma-derived U373MG cells. Yeast or U373MG cells that overexpressed ARF4 exhibited reduced reactive oxygen species (ROS) generation in response to Bax or N-(4-hydroxyphenyl)retinamide (4-HPR), respectively, which suggests that ROS play a role in the inhibition of cell death by ARF4. The 4-HPR-mediated phosphorylation of c-JUN N-terminal kinase, p38, and extracellular signal-regulated kinase was markedly suppressed in U373MG cells that stably expressed ARF4. Stable ARF4 transfectants were also refractory to 4-HPR-induced mitochondrial translocation of Bax, release of mitochondrial cytochrome c, and activation of caspase-3. Our results suggest that ARF4 participates in the regulation of glioblastoma apoptosis through the inhibition of stress-mediated apoptotic signals.
Asunto(s)
Factores de Ribosilacion-ADP/genética , Antineoplásicos/farmacología , Apoptosis/genética , Fenretinida/farmacología , Glioblastoma/genética , Factores de Ribosilacion-ADP/metabolismo , Western Blotting , Línea Celular Tumoral , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Citometría de Flujo , Expresión Génica , Biblioteca de Genes , Glioblastoma/metabolismo , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Mutagénesis Sitio-Dirigida , Estrés Oxidativo/genética , Especies Reactivas de Oxígeno/metabolismo , Transfección , Técnicas del Sistema de Dos Híbridos , Proteína X Asociada a bcl-2/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Four new flavonoids, 3'-formyl-4',6',4-trihydroxy-2'-methoxy-5'-methylchalcone (1), 3'-formyl-6',4-dihydroxy-2'-methoxy-5'-methylchalcone 4'-O-beta-D-glucopyranoside (2), (2S)-8-formyl-6-methylnaringenin (3), and (2S)-8-formyl-6-methylnaringenin 7-O-beta-D-glucopyranoside (4) were isolated from the buds of Cleistocalyx operculatus (Myrtaceae). The structures of the new metabolites (1-4) were determined on the basic of spectroscopic analyses including 2 dimensional NMR. Compounds 1 and 3 exhibited 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity with IC(50) values of 22.8 and 27.1 microM, respectively.
Asunto(s)
Antioxidantes/farmacología , Flavonoides/farmacología , Myrtaceae/química , Antioxidantes/aislamiento & purificación , Compuestos de Bifenilo , Dicroismo Circular , Flavonoides/química , Flavonoides/aislamiento & purificación , Flores/química , Hidrólisis , Espectroscopía de Resonancia Magnética , Complejos Multienzimáticos/química , Picratos/química , Extractos Vegetales/química , Espectrometría de Masa por Ionización de Electrospray , Espectrofotometría Infrarroja , Espectrofotometría Ultravioleta , beta-Glucosidasa/químicaRESUMEN
Yeast-based functional screening of a human glioblastoma cDNA library identified ras-related nuclear protein (Ran) as a novel suppressor of Bcl-2-associated X protein (Bax), a pro-apoptotic member of the Bcl-2 family of proteins. Yeast cells that expressed human Ran were resistant to Bax-induced cell death. In U373MG glioblastoma cells, stable overexpression of Ran significantly attenuated apoptotic cell death induced by the chemotherapeutic agent paclitaxel. FACS analysis demonstrated that Ran is involved in paclitaxel-induced cell cycle arrest. Stable overexpression of Ran also markedly inhibited the phosphorylation of Bcl-2 by paclitaxel, and inhibited the translocation of Bax, the release of cytochrome c and activation of caspase-3. Paclitaxel-induced phosphorylation of c-JUN N-terminal kinase (JNK), but not p38, extracellular signal-regulated kinase and Akt, was markedly suppressed in U373MG cells that stably expressed Ran. These results suggest that Ran suppresses paclitaxel-induced cell death through the downregulation of JNK-mediated signal pathways.
Asunto(s)
Apoptosis/efectos de los fármacos , Glioblastoma/patología , Paclitaxel/farmacología , Proteína de Unión al GTP ran/metabolismo , Proteínas Reguladoras de la Apoptosis/metabolismo , Línea Celular Tumoral , Activación Enzimática/efectos de los fármacos , Fase G1/efectos de los fármacos , Biblioteca de Genes , Glioblastoma/enzimología , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Modelos Biológicos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Saccharomyces cerevisiae/citología , Saccharomyces cerevisiae/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Human cytochrome c oxidase subunit VIa polypeptide 1 (COX6A1) was identified as a novel suppressor of Bcl-2-associated X protein (Bax)-mediated cell death using yeast-based functional screening of a mammalian cDNA library. The overexpression of COX6A1 significantly suppressed Bax- and N-(4-hydroxyphenyl)retinamide (4-HPR)-induced apoptosis in yeast and human glioblastoma-derived U373MG cells, respectively. The generation of reactive oxygen species (ROS) in response to Bax or 4-HPR was inhibited in yeast and U373MG cells that expressed COX6A1, indicating that COX6A1 exerts a protective effect against ROS-induced cell damage. 4-HPR-induced mitochondrial translocation of Bax, release of mitochondrial cytochrome c, and activation of caspase-3 were markedly attenuated in U373MG cells that stably expressed COX6A1. Our results demonstrate that yeast-based functional screening of human genes for inhibitors of Bax-sensitivity in yeast identified a protein that not only suppresses the toxicity of Bax in yeast, but also has a potential role in protecting mammalian cells from 4-HPR-induced apoptosis.
Asunto(s)
Apoptosis , Complejo IV de Transporte de Electrones/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Antineoplásicos/farmacología , Línea Celular Tumoral , Complejo IV de Transporte de Electrones/genética , Fenretinida/farmacología , Biblioteca de Genes , Humanos , Especies Reactivas de Oxígeno/metabolismo , Saccharomyces cerevisiae/citología , Saccharomyces cerevisiae/genética , Técnicas del Sistema de Dos Híbridos , Proteína X Asociada a bcl-2/genéticaRESUMEN
To elucidate the molecular mechanisms underlying the up-regulation of aldose reductase observed in many cancer cells, we investigated the signal transduction pathways mediating induction of aldose reductase gene expression by 12-O-tetradecanoylphorbol-13-acetate, a potent tumor promoter. A maximum of four-fold induction in aldose reductase mRNA was demonstrated in HeLa cells treated with 12-O-tetradecanoylphorbol-13-acetate. The increased level of aldose reductase transcript was accompanied by the elevated level of enzyme activity, and completely abolished in the presence of actinomycin D. Inhibitors of protein kinase C, bisindolylmaleimide I and calphostin C, as well as inhibitors of tyrosine kinase, genistein and tyrphostin A23, significantly attenuated 12-O-tetradecanoylphorbol-13-acetate-induced increase in aldose reductase mRNA. Blockade of the p38 mitogen-activated protein kinase pathway by SB203580 also suppressed 12-O-tetradecanoylphorbol-13-acetate-induced aldose reductase expression. The promoter activity of aldose reductase gene was significantly augmented in the cells treated with 12-O-tetradecanoylphorbol-13-acetate, but attenuated in the presence of bisindolylmaleimide I, tyrphostin A23 or SB203580. Pyrrolidinedithiocarbamate, a nuclear factor kappaB inhibitor, dose-dependently suppressed 12-O-tetradecanoylphorbol-13-acetate-induced increase in aldose reductase mRNA. 12-O-tetradecanoylphorbol-13-acetate augmented the DNA binding activity of nuclear factor kappaB and nuclear factor kappaB-dependent gene transcription, and these effects were attenuated by bisindolylmaleimide I or tyrphostin A23, but not by SB203580. Taken together, activation of protein kinase C and tyrosine kinase by 12-O-tetradecanoylphorbol-13-acetate elicits increased promoter activity of aldose reductase gene via nuclear factor kappaB. A p38 mitogen-activated protein kinase pathway, distinct from the tyrosine kinase pathway, may also take part in 12-O-tetradecanoylphorbol-13-acetate-induced increase in aldose reductase gene expression.