RESUMEN
There is an almost unlimited interest in searching and developing new drugs, especially when we are in an era that are witnessing more and more emerging pathogens. Natural products from traditional medicines represent a large library for searching lead compounds with novel bioactivities. Sodium houttuyfonate is such one bioactive compound derived from Houttuynia cordata Thunb which has been employed in traditional medicine for treating infectious and inflammatory diseases. Sodium houttuyfonate has demonstrated multiple kinds of pharmacological effects, including antifungal, antibacterial, anti-inflammatory, and cardiovascular protective activities, which are discussed here to provide insights into our understanding of the pharmacological effects of SH and the underlying mechanisms.
Asunto(s)
Alcanos/farmacología , Antibacterianos/farmacología , Antiinflamatorios/farmacología , Antifúngicos/farmacología , Cardiotónicos/farmacología , Sulfitos/farmacología , Alcanos/efectos adversos , Alcanos/química , Alcanos/uso terapéutico , Animales , Antibacterianos/efectos adversos , Antibacterianos/química , Antibacterianos/uso terapéutico , Antiinflamatorios/efectos adversos , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Antifúngicos/efectos adversos , Antifúngicos/química , Antifúngicos/uso terapéutico , Cardiotónicos/efectos adversos , Cardiotónicos/química , Cardiotónicos/uso terapéutico , Houttuynia/química , Humanos , Sulfitos/efectos adversos , Sulfitos/química , Sulfitos/uso terapéuticoRESUMEN
Inflammatory bowel disease (IBD) including Crohn's disease and ulcerative colitis is a chronic intestinal disease most likely associated with gut dysbiosis. Candida related mycobiota has been demonstrated to play a role in IBD progression. Traditional Chinese herbal medicines (TCHMs) with antifungal activity have a potential in prevention and treatment of fungi-related IBD. Sodium houttuyfonate (SH) is a promising anti-Candida TCHMs. In this study, a dextran sulfate sodium induced colitis model with Candida albicans precolonization is established. SH gavage can significantly decrease the fungal burdens in feces and colon tissues, reduce disease activity index score, elongate colon length, and attenuate colonic damages. Moreover, SH markedly inhibits the levels of anti-Saccharomyces cerevisiae antibodies, ß-glucan, and proinflammatory cytokine (IL-1ß, IL-6, IL-8, TNF-α), and increases anti-inflammatory factor IL-10 level in serum and colon tissue. Further experiments demonstrate that SH could induce ß-glucan exposure, priming intestinal macrophages to get rid of colonized C. albicans through the collaboration of Dectin-1 and TLR2/4. With the decreased fungal burden, the protein levels of Dectin-1, TLR2, TLR4, and NF-κBp65 are fallen back, indicating the primed macrophages calm down and the colitis is alleviated. Collectively, these results manifest that SH can attenuate C. albicans associated colitis via ß-glucan exposure, deepening our understanding of TCHMs in the prevention and treatment of fungi associated IBD.
Asunto(s)
Alcanos/farmacología , Candida albicans/efectos de los fármacos , Colitis/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Sulfitos/farmacología , Animales , Colitis/inducido químicamente , Sulfato de Dextran/toxicidad , Disbiosis/microbiología , Ratones , beta-GlucanosRESUMEN
BACKGROUND: The potential of onion juice, as well as extracts of waste (tunic) (5%) and fleshy scale leaves (25%), to inhibit enzymatic browning of frozen Agaricus bisporus was investigated. The onion materials were used for blanching and their effectiveness in conserving integrity and appearance of mushroom fruiting bodies was compared with the currently accepted method of blanching in a sodium metabisulfite (SM) solution. RESULTS: It was observed that l-phenylalanine content may be a useful indicator of the changes in enzymatic activity during frozen storage, and l-tyrosine may be an indicator of a loss of lightness in color (parameter L*). The enzymes responsible for color changes were mainly monophenolase (MON) and, to a lesser degree, diphenolase (DIP). After being stored frozen for 8 months, these enzymes were detected at a 29:1 (DIP:MON) ratio in untreated mushrooms and a 2:1 (DIP:MON) ratio in mushrooms treated with onion juice. CONCLUSION: Onion products may be a good alternative to an SM solution. The most effective method to conserve the light color of fruiting bodies was blanching in juice or in an extract of the fleshy scale leaves. The least effective inhibitor of MON was tunic extract, which did, however, cause a favourable increase in the reducing capacity (total polyphenols) and flavonoids. Although the onion waste (tunic) extract changed the color of mushrooms from white to creamy orange, the color of these products was attractive and positively evaluated by panellists. © 2020 Society of Chemical Industry.
Asunto(s)
Agaricus/enzimología , Conservación de Alimentos/métodos , Conservantes de Alimentos/farmacología , Proteínas Fúngicas/metabolismo , Cebollas/química , Extractos Vegetales/farmacología , Agaricus/química , Agaricus/efectos de los fármacos , Color , Proteínas Fúngicas/química , Sulfitos/farmacologíaRESUMEN
Both plants and animals are living things made up of similar cells as well as organelles, and their essence of life is the same. However, plants face more environmental stress than animals and generate excessive reactive oxygen species (ROS), a group of small molecules that can harm proteins, necessitating distinctive metabolic processes. Secondary metabolites in plants are a group of chemical components that can eliminate ROS and can also exhibit medicinal properties; therefore, herbal medicines are often closely linked to the ecological significance of secondary metabolites. Why plants contain so many, not few, active medicinal ingredients is unknown. The root of Scutellaria baicalensis, a popular herbal medicine, is rich in various flavonoids with diverse structural features. Sodium hydrosulfite (Na2S2O4) can produce OË-2 radicals and induce physical conditions under environmental stress. Using UHPLC-ESI-Q-TOF-MS/MS analysis, a total of 25 different compounds were identified in the roots of S. baicalensis between the Na2S2O4 groups and suitable conditions. Based on the results of the t-test (P<0.05) performed for the groups and ions with values of VIP ≥ 2, the most significantly different chemical markers with Na2S2O4 treatment were shikimic acid, citric acid, baicalin, wogonoside, baicalein, wogonin, 3,5,7,2',6'-pentahydroxyflavanone, 5,2',6'-trihydroxy-7,8-dimethoxy flavone, chrysin, eriodictyol, 5,8-dihydroxy-6,7 -dimethoxy flavone, skullcapflavone â ¡, and 5,7-dihydroxy-6,8,2',3'-tetrame thoxyflavone, and most of them were free flavonoids with many phenolic hydroxyl or methoxyl groups and characteristically high antioxidant activities. S. baicalensis roots modified their ability to eliminate ROS and maintained the equilibrium of ROS through the multitudinous biosynthesis and conversion of flavonoids, which is similar to the equilibrium established by an intricate buffer solution and perfectly explains the diversity and complexity of medicinal plant ingredients.
Asunto(s)
Scutellaria baicalensis/química , Metabolismo Secundario/efectos de los fármacos , Sulfitos/farmacología , Medicamentos Herbarios Chinos/análisis , Flavonoides/análisis , Metabolómica , Raíces de Plantas/química , Scutellaria baicalensis/efectos de los fármacos , Estrés FisiológicoRESUMEN
Traditional herbal monomers (THMs) are widely distributed in many traditional Chinese formulas (TCFs) and decoctions (TCDs) and are frequently used for the prevention and treatment of fungal infections. The antifungal activities of five common THMs, including sodium houttuyfonate (SH), berberine (BER), palmatine (PAL), jatrorrhizine (JAT) and cinnamaldehyde (CIN), and their potential for inducing cell wall remodeling (CWR), were evaluated against Candida albicans SC5314 and Candida auris 12372. SH/CIN plus BER/PAL/JAT showed synergistic antifungal activity against both Candida isolates. Furthermore, SH-associated combinations (SH plus BER/PAL/JAT) induced stronger exposure of ß-glucan and chitin than their counterparts, while CIN triggered more marked exposure compared with CIN-associated combinations (CIN plus BER/PAL/JAT). Collectively, this study demonstrated the anti-Candida effect and the CWR induction potential of the five THMs and their associated combinations, providing a possibility of their in vivo application against fungal-associated infections.
Asunto(s)
Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Candida/efectos de los fármacos , Pared Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Acroleína/análogos & derivados , Acroleína/farmacología , Alcanos/farmacología , Berberina/análogos & derivados , Berberina/farmacología , Alcaloides de Berberina/farmacología , Humanos , Pruebas de Sensibilidad Microbiana , Sulfitos/farmacologíaRESUMEN
A 10-week feeding experiment was carried out examining the effects of deoxynivalenol (DON)-contaminated maize treated with different sodium sulphite (SoS) concentrations on performance, health and DON-plasma concentrations in fattening pigs. Two maize batches were used: background-contaminated (CON, 0.73 mg/kg maize) and Fusarium-toxin contaminated (DON, 44.45 mg/kg maize) maize. Both were wet preserved at 20% moisture content, with one of three (0.0, 2.5, 5.0 g/kg maize) sodium sulphite concentrations and propionic acid (15%). Each maize batch was then mixed into a barley-wheat-based diet at a proportion of 10%, resulting in the following 6 feeding groups: CON- (CON + 0.0 g SoS/kg maize), CON2.5 (CON + 2.5 g SoS/kg maize), CON5.0 (CON + 5.0 g SoS/kg maize), DON- (DON + 0.0 g SoS/kg maize), DON2.5 (DON + 2.5 g SoS/kg maize) and DON5.0 (DON + 5.0 g SoS/kg maize). Dietary DON concentration was reduced by ~ 36% in group DON2.5 and ~ 63% in group DON5.0. There was no impact on ZEN concentration in the diets due to SoS treatment. Pigs receiving diet DON- showed markedly lower feed intake (FI) compared to those fed the control diets. With SoS-treatment of maize, FI of pigs fed the DON diet (DON5.0: 3.35 kg/d) were comparable to that control (CON-: 3.30 kg/day), and these effects were also reflected in live weight gain. There were some effects of SoS, DON or their interaction on serum urea, cholesterol and albumin, but always within the physiological range and thus likely negligible. SoS wet preservation of Fusarium-toxin contaminated maize successfully detoxified DON to its innocuous sulfonates, thus restoring impaired performance in fatteners.
Asunto(s)
Alimentación Animal/análisis , Contaminación de Alimentos/prevención & control , Sulfitos/farmacología , Tricotecenos/análisis , Aumento de Peso/efectos de los fármacos , Albúminas/análisis , Crianza de Animales Domésticos , Animales , Colesterol/sangre , Fusarium/patogenicidad , Porcinos , Urea/sangre , Zea mays/químicaRESUMEN
Folate deficiency in early development leads to disturbance in multiple processes, including neurogenesis during which fibroblast growth factor (FGF) pathway is one of the crucial pathways. Whether folic acid (FA) directly affects FGF pathways to influence neurodevelopment and the possible mechanism remains unclear. In this study, we presented evidence that in human FA-insufficient encephalocele, the FGF pathway was interfered. Furthermore, in Brachyury knockout mice devoid of such T-box transcription factors regulating embryonic neuromesodermal bipotency and a key component of FGF pathway, change in expression of Brachyury downstream targets, activator Fgf8 and suppressor dual specificity phosphatase 6 was detected, along with the reduction in expression of other key FGF pathway genes. By using a FA-deficient cell model, we further demonstrated that decrease in Brachyury expression was through alteration in hypermethylation at the Brachyury promoter region under FA deficiency conditions, and suppression of Brachyury promoted the inactivation of the FGF pathway. Correspondingly, FA supplementation partially reverses the effects seen in FA-deficient embryoid bodies. Lastly, in mice with maternal folate-deficient diets, aberrant FGF pathway activity was found in fetal brain dysplasia. Taken together, our findings highlight the effect of FA on FGF pathways during neurogenesis, and the mechanism may be due to the low expression of Brachyury gene via hypermethylation under FA-insufficient conditions.-Chang, S., Lu, X., Wang, S., Wang, Z., Huo, J., Huang, J., Shangguan, S., Li, S., Zou, J., Bao, Y., Guo, J., Wang, F., Niu, B., Zhang, T., Qiu, Z., Wu, J., Wang, L. The effect of folic acid deficiency on FGF pathway via Brachyury regulation in neural tube defects.
Asunto(s)
Proteínas Fetales/metabolismo , Factores de Crecimiento de Fibroblastos/metabolismo , Deficiencia de Ácido Fólico/metabolismo , Ácido Fólico/uso terapéutico , Defectos del Tubo Neural/tratamiento farmacológico , Defectos del Tubo Neural/metabolismo , Proteínas de Dominio T Box/metabolismo , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Inmunoprecipitación de Cromatina , Encefalocele/metabolismo , Femenino , Deficiencia de Ácido Fólico/fisiopatología , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Humanos , Inmunohistoquímica , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Regiones Promotoras Genéticas , Transducción de Señal/efectos de los fármacos , Sulfitos/farmacologíaRESUMEN
Biofilm dispersion is the last step in the development of biofilms, and allows bacteria to spawn novel biofilms in new locales. In the previous studies, we found that sodium houttuyfonate (SH) is effective at inhibiting biofilm formation and motility of Pseudomonas aeruginosa. Here, we investigated the effect of SH against the biofilm dispersion of P. aeruginosa by an in vitro model. The results show that the plant derivative, SH, could effectively inhibit both biofilm dispersion of P. aeruginosa, and gene and protein expression of the key biofilm regulator BdlA in a dose-dependent manner. Furthermore, our presented results suggest that SH can penetrate into the biofilm of P. aeruginosa to repress the biofilm life cycle. Therefore, these results indicate that the antimicrobial activity of SH may be partially due to its ability to disrupt biofilm dispersion in P. aeruginosa.
Asunto(s)
Alcanos/farmacología , Biopelículas/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Sulfitos/farmacología , Alcanos/metabolismo , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Pseudomonas aeruginosa/metabolismo , Sulfitos/metabolismoRESUMEN
The existing investigation was directed to consider the protective role of vitamin C and E alone and in combination on sodium metabisulphite-induced damage on testicular. Experimental animals were received sodium metabisulphite (520 mg/kg) alone and in combination with vitamin E (100 mg/kg), vitamin C (100 mg/kg) and vitamin E + C, while the control groups received 0.9% saline solution and olive oil (the solvent of the vitamin E). Finally, the changes in the testis histology were examined stereologically. Lipid peroxidation was assessed through the measurement of malondialdehyde (MDA) levels in testis tissues. Also, serum testosterone concentrations were measured. The results indicated that 80%-90% (spermatogonia A and B, spermatocyte and Leydig) and 40% of the Sertoli cells were missed in the rats that received sodium metabisulphite, respectively, compared with the controls. The co-supplementation of vitamin E with vitamin C significantly decreased MDA (p = 0.006) and increased testosterone (p = 0.001) concentrations in the rats received SMB which were as much as control and olive groups. Co-supplementation of vitamin E and vitamin C due to their synergistic effects could be an appropriate strategy in preventing testicular from sodium metabisulphite-induced damage.
Asunto(s)
Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Sustancias Protectoras/farmacología , Sulfitos/farmacología , Testículo/efectos de los fármacos , Vitamina E/farmacología , Animales , Células Intersticiales del Testículo/efectos de los fármacos , Células Intersticiales del Testículo/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Ratas , Ratas Wistar , Células de Sertoli/efectos de los fármacos , Células de Sertoli/metabolismo , Testículo/metabolismo , Testosterona/sangreRESUMEN
The in vitro susceptibility to sodium metabisulphite (NaMBS) was investigated in 10 different food spoilage filamentous fungi, namely Aspergillus flavus, A. carbonarius, A. niger, A. ochraceus, A. tubingensis, A. westerdijkiae, Cladosporium cladosporioides, Fusarium oxysporum, Penicillium commune and P. expansum. The fungi were inoculated in sterile 96-well microtiter plates containing Yeast-extract Sucrose (YES) semi-solid agar supplemented with NaMBS in concentrations ranging from 2000 to 3.9â¯mgâ¯l-1 and incubated at 25⯰C. Growth was monitored by absorbance measurements at 600â¯nm using a multi-spectrophotometer. The surface areas under the optical density (OD) vs. time growth curves obtained were used to calculate the fractional area f(a), from which the non-inhibitory (NIC) and minimum inhibitory concentrations (MIC) of the antifungal agent were calculated for each fungus using the Gompertz model for decay. Most Aspergillus species showed remarkable resistance to NaMBS, presenting NIC and MIC values higher than 250 and 2500â¯mgâ¯l-1, respectively. The most susceptible fungi were the two Penicillium species and A. carbonarius, which presented very low NIC (<100â¯mgâ¯l-1) and MIC (<1300â¯mgâ¯l-1) values, whereas C. cladosporioides and F. oxysporum presented intermediate values. The method has the advantage of good repeatability and accuracy, rapid results within 48-72â¯h, growth detection and susceptibility to the antifungal agent for several fungi at the same time, and optimal use of microbiological media by using small volumes of consumables.
Asunto(s)
Antifúngicos/farmacología , Aspergillus/efectos de los fármacos , Pruebas de Sensibilidad Microbiana/métodos , Nefelometría y Turbidimetría/métodos , Penicillium/efectos de los fármacos , Sulfitos/farmacología , Microbiología de Alimentos , Espectrofotometría/métodosRESUMEN
Quorum sensing of bacteria and its specific gene expression regulation have a very important role in bacterial biofilm formation. LuxS and agr are the key regulatory genes in quorum sensing of Staphylococcus epidermidis, and RNA â ¢ is the effector molecule of agr system. In order to evaluate the effects of sodium houttuyfonate in combination with erythromycin on the transcription level of S. epidermidis, serial dilution method was used to determine the MIC of sodium houttuyfonate, erythromycin and vancomycin on S. epidermidis, and fluorescent quantitative PCR method was used to detect the transcription levels of luxS, agr/RNAâ ¢ in different time periods after treatment on S. epidermidis by sodium houttuyfonate in combination with erythromycin, vancomycin, and erythromycin alone. Our results showed that in treatment by 1/2MIC, 1/4MIC sodium houttuyfonate, 1/2MIC sodium houttuyfonate +1/2MIC erythromycin, 1/4MIC sodium houttuyfonate+1/4MIC erythromycin, and 1/8MIC sodium houttuyfonate+1/8MIC erythromycin for ATCC 35984, they could rapidly up-regulate the expression of luxS of S. epidermidis from the beginning as compared with negative control, with significant differences (P<0.05); furthermore, sodium houttuyfonate can still up-regulate the expression of luxS even after treatment for 6, 12 and 48 h. Sodium houttuyfonate in MIC and 1/2MIC concentration can significantly down-regulate the expression of agr (P<0.05); 1/2MIC sodium houttuyfonate+1/2MIC erythromycin, 1/4MIC sodium houttuyfonate+1/4MIC erythromycin, can also significantly down-regulate the expression of agr in 6 h, 12 h and 24 h(P<0.05). Sodium houttuyfonate in MIC, can significantly down-regulate the expression of RNA â ¢ (P<0.05), and 1/2MIC sodium houttuyfonate+1/2MIC erythromycin can also significantly down-regulate the expression of RNAâ ¢(P<0.05). Therefore, our presented results showed that sodium houttuyfonate in combination with erythromycin can rapidly up-regulate the transcription of luxS of S. epidermidis, and can down-regulate the expression of agr/RNA â ¢ in certain concentrations, and suggested that sodium houttuyfonate in combination of erythromycin could inhibit mutual aggregation between S. epidermidis and biofilm bacteria, inhibit membrane nutrition and formation of water transport channels, prevent separation of bacterial cells in biofilm, and inhibit the formation of bacterial exotoxin of S. epidermidis.
Asunto(s)
Alcanos/farmacología , Eritromicina/farmacología , Staphylococcus epidermidis/efectos de los fármacos , Sulfitos/farmacología , Proteínas Bacterianas/metabolismo , Biopelículas , Liasas de Carbono-Azufre/metabolismo , Pruebas de Sensibilidad Microbiana , ARN Bacteriano/metabolismo , Vancomicina/farmacologíaRESUMEN
Hydrogen sulfide is formed in the human intestinal tract as the end product of the anaerobic microbial degradation of sulfur compounds present in mucus, bile or proteins. Since human gut microbial sulfur metabolism has been poorly characterized, we aimed to identify and isolate the microorganisms involved in sulfide formation. Fresh fecal samples from one healthy donor and one diagnosed with irritable bowel syndrome were used as inocula for enrichments that were supplemented with sulfate or sulfite as electron acceptors in combination with different electron donors. After two transfers, cultures with high sulfide production were selected and the phylogenetic composition of the enriched microbial communities was determined. Sulfite respiration and cysteine degradation were the dominant sulfidogenic processes, and the most abundant bacteria enriched belonged to Bilophila and Clostridium cluster XIVa. Different isolates were obtained and remarkably included a novel sulfite reducer, designated strain 2C. Strain 2C belongs to the Veillonellaceae family of Firmicutes phylum and showed limited (91%) 16S rRNA gene sequence similarity with that of known Sporomusa species and hence may represent a novel genus. This study indicates that bacteria that utilize sulfite and organic sulfur compounds rather than merely sulfate are relevant for human intestinal sulfur metabolism.
Asunto(s)
Bacterias/aislamiento & purificación , Bacterias/metabolismo , Intestinos/microbiología , Sulfatos/metabolismo , Azufre/metabolismo , Bacterias/clasificación , Bacterias/genética , Clostridium/efectos de los fármacos , Clostridium/genética , Clostridium/aislamiento & purificación , ADN Bacteriano/genética , Heces/microbiología , Firmicutes/efectos de los fármacos , Firmicutes/genética , Firmicutes/aislamiento & purificación , Microbioma Gastrointestinal/genética , Humanos , Intestinos/química , Síndrome del Colon Irritable/microbiología , Filogenia , ARN Ribosómico 16S , Análisis de Secuencia de ADN , Sulfatos/farmacología , Sulfuros/metabolismo , Sulfitos/metabolismo , Sulfitos/farmacología , Taurina/metabolismoRESUMEN
A maternal high-fat diet (HFD) alters the offspring's feeding regulation, leading to obesity. This phenomenon is partially mediated by aberrant expression of the hypothalamic anorexigenic neuropeptide proopiomelanocortin (POMC). Nevertheless, although some individual offspring suffer from morbid obesity, others escape the malprogramming. It is suggested that this difference is due to epigenetic programming. In this study, we report that in lean offspring of non-HFD-fed dams, essential promoter regions for Pomc expression were enriched with 5-hydroxymethylcytosine (5hmC) together with a reduction in the level of 5-methylcytosine (5mC). Moreover, 5hmC was negatively correlated whereas 5mC was positively correlated with body weight in offspring from both HFD- and control-fed dams. We further found that Pomc expression in obese offspring is determined by a two-step epigenetic inhibitory mechanism in which CpG methylation is linked with histone posttranslational modifications. An increase in CpG methylation at the Poxmc promoter enables binding of methyl-binding domain 1 (MBD1) to 5mC, but not to its derivative 5hmC. MBD1 then interacts with SET domain bifurcated 1 methyltransferase to promote bimethylation on the histone 3 lysine 9 residue, reducing Pomc mRNA expression. These results suggest an epigenetic regulatory mechanism that affects obesity-prone or resilient traits.
Asunto(s)
5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Histonas/metabolismo , Proopiomelanocortina/genética , Regiones Promotoras Genéticas/genética , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Islas de CpG/genética , Metilación de ADN/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Obesidad/metabolismo , Ratas , Ratas Wistar , Sulfitos/farmacología , Delgadez/metabolismoRESUMEN
Sodium houttuyfonate (SH) is a derivative of effective component of a Chinese material medica, Houttuynia cordata, which is applied in anti-infection of microorganism. But, the antimicrobial mechanisms of SH still remain unclear. Here, we firstly discovered that SH effectively inhibits the three types of virulence related motility of.Pseudomonas aeruginosa, i.e., swimming, twitching and swarming. The plate assay results showed that the inhibitory action of SH against swimming and twitching in 24 h and swarming in 48 h is dose-dependent; and bacteria nearly lost all of the motile activities under the concentration of 1 x minimum inhibitory concentration (MIC) (512 mg x L(-1) same as azithromycin positive group (1 x MIC, 16 mg x L(-1)). Furthermore, we found that the expression of structural gene flgB and pilG is down-regulated by SH, which implies that inhibitory mechanism of SH against motility of P. aeruginosa may be due to the inhibition of flagella and pili bioformation of P. aeruginosa by SR Therefore, our presented results firstly demonstrate that SH effectively inhibits the motility activities of P. aeruginosa, and suggest that SH could be a promising antipseudomonas agents in clinic.
Asunto(s)
Alcanos/farmacología , Medicamentos Herbarios Chinos/farmacología , Houttuynia/química , Pseudomonas aeruginosa/citología , Pseudomonas aeruginosa/efectos de los fármacos , Sulfitos/farmacología , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Biopelículas/efectos de los fármacos , Fimbrias Bacterianas/efectos de los fármacos , Fimbrias Bacterianas/genética , Fimbrias Bacterianas/metabolismo , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/patogenicidad , Virulencia/efectos de los fármacosRESUMEN
BACKGROUND: The inhibitory effect of andrographolide sodium bisulphite (ASB) on jack bean urease (JBU) and Helicobacter pylori urease (HPU) was performed to elucidate the inhibitory potency, kinetics and mechanism of inhibition in 20 mM phosphate buffer, pH 7.0, 2 mM EDTA, 25 °C. METHODS: The ammonia formations, indicator of urease activity, were examined using modified spectrophotometric Berthelot (phenol-hypochlorite) method. The inhibitory effect of ASB was characterized with IC50 values. Lineweaver-Burk and Dixon plots for JBU inhibition of ASB was constructed from the kinetic data. SH-blocking reagents and competitive active site Ni2+ binding inhibitors were employed for mechanism study. Molecular docking technique was used to provide some information on binding conformations as well as confirm the inhibition mode. RESULTS: The IC50 of ASB against JBU and HPU was 3.28±0.13 mM and 3.17±0.34 mM, respectively. The inhibition proved to be competitive and concentration- dependent in a slow-binding progress. The rapid formation of initial ASB-JBU complex with an inhibition constant of Ki=2.86×10(-3) mM was followed by a slow isomerization into the final complex with an overall inhibition constant of Ki*=1.33×10(-4) mM. The protective experiment proved that the urease active site is involved in the binding of ASB. Thiol reagents (L-cysteine and dithiothreithol) strongly protect the enzyme from the loss of enzymatic activity, while boric acid and fluoride show weaker protection, indicating that the active-site sulfhydryl group of JBU was potentially involved in the blocking process. Moreover, inhibition of ASB proved to be reversible since ASB-inactivated JBU could be reactivated by dithiothreitol application. Molecular docking assay suggested that ASB made contacts with the important sulfhydryl group Cys-592 residue and restricted the mobility of the active-site flap. CONCLUSIONS: ASB was a competitive inhibitor targeting thiol groups of urease in a slow-binding manner both reversibly and concentration-dependently, serving as a promising urease inhibitor for the treatment of urease-related diseases.
Asunto(s)
Diterpenos/farmacología , Sulfitos/farmacología , Ureasa , Canavalia/enzimología , Cinética , Simulación del Acoplamiento Molecular , Ureasa/química , Ureasa/efectos de los fármacos , Ureasa/metabolismoRESUMEN
BACKGROUND: Sodium metabisulfite is commonly used as preservative in foods but can oxidize to sulfite radicals initiating molecular oxidation. Ghrelin is a peptide hormone primarily produced in the stomach and has anti-inflammatory effects in many organs. This study aimed to assess endogenous omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) in rat peripheral organs following sodium metabisulfite treatment and determine the possible effect of ghrelin on changes in n-6 inflammatory pathway. METHODS: Male Wistar rats included in the study were allowed free access to standard rat chow. Sodium metabisulfite was given by gastric gavage and ghrelin was administered intraperitoneally for 5 weeks. Levels of arachidonic acid (AA, C20:4n-6), dihomo-gamma-linolenic acid (DGLA, C20:3n-6), eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3) in liver, heart and kidney tissues were determined by an optimized multiple reaction monitoring (MRM) method using ultra fast-liquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Cyclooxygenase (COX) and prostaglandin E2 (PGE2) were measured in tissue samples to evaluate changes in n-6 inflammatory pathway. RESULTS: Omega-6 PUFA levels, AA/DHA and AA/EPA ratio were significantly increased in liver tissue following sodium metabisulfite treatment compared to controls. No significant change was observed in heart and kidney PUFA levels. Tissue activity of COX and PGE2 levels were also significantly increased in liver tissue of sodium metabisulfite treated rats compared to controls. Ghrelin treatment decreased n-6 PUFA levels and reduced COX and PGE2 levels in liver tissue of sodium metabisulfite treated rats. CONCLUSION: Current results suggest that ghrelin exerts anti-inflammatory action through modulation of n-6 PUFA levels in hepatic tissue.
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Ácidos Grasos Omega-6/biosíntesis , Ghrelina/farmacología , Inflamación/metabolismo , Hígado/efectos de los fármacos , Sulfitos/farmacología , Ácido 8,11,14-Eicosatrienoico/análisis , Animales , Ácido Araquidónico/análisis , Dinoprostona/análisis , Ácidos Docosahexaenoicos/análisis , Ácido Eicosapentaenoico/análisis , Ácidos Grasos Omega-3/análisis , Ácidos Grasos Omega-3/biosíntesis , Ácidos Grasos Omega-6/análisis , Riñón/química , Hígado/metabolismo , Masculino , Miocardio/química , Prostaglandina-Endoperóxido Sintasas/análisis , Ratas , Ratas Wistar , Espectrometría de Masa por Ionización de Electrospray , Sulfitos/antagonistas & inhibidoresRESUMEN
Walter Álvarez Quispe, terapeuta kallawaya y biomédico especializado en cirugía general y ginecología, presenta la lucha de los terapeutas tradicionales y alternativos por la depenalización de estos sistemas médicos andinos realizada entre 1960 y 1990. Bolivia se torna el primer país en América Latina y el Caribe en despenalizar la medicina tradicional antes de los planteamientos de la Conferencia Internacional sobre Atención Primaria de Salud (Alma-Ata, 1978). Los datos aportados por el entrevistado aseguran que los logros alcanzados, principalmente por los kallawayas, responden a un proyecto propio y autónomo. Estas conquistas no se deben a las políticas oficiales de interculturalidad en salud, aunque busquen atribuirse para sí los logros alcanzados.
Walter Álvarez Quispe, a Kallawaya healer and biomedical practitioner specializing in general surgery and gynecology, presents the struggle of traditional and alternative healers to get their Andean medical systems depenalized between 1960 and 1990. Bolivia was the first country in Latin America and the Caribbean to decriminalize traditional medicine before the proposals of the International Conference on Primary Health Care (Alma-Ata, 1978). The data provided by the interviewee show that the successes achieved, mainly by the Kallawayas, stem from their own independent initiative. These victories are not the result of official policies of interculturality in healthcare, although the successes achieved tend to be ascribed to them.
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Animales , Cobayas , Masculino , Bronquios/inervación , Broncoconstricción/efectos de los fármacos , Broncoconstrictores/farmacología , Ácido Cítrico/farmacología , Neuronas Aferentes/fisiología , Sulfitos/farmacología , Administración por Inhalación , Acetilcolina/farmacología , Resistencia de las Vías Respiratorias/efectos de los fármacos , Autacoides/farmacología , Bradiquinina/farmacología , Péptido Relacionado con Gen de Calcitonina/metabolismo , Ácido Cítrico/administración & dosificación , Concentración de Iones de Hidrógeno , Histamina/farmacología , Técnicas In Vitro , Rendimiento Pulmonar/efectos de los fármacos , Pulmón/inervación , Pulmón/metabolismo , Neuroquinina A/farmacología , Neuronas Aferentes/efectos de los fármacos , Serotonina/farmacología , Sustancia P/farmacología , Sulfitos/administración & dosificaciónRESUMEN
OBJECTIVE: To investigate the resistant effect of houttuyfonate sodium (SH) combined with imipenem (IMP) against Pseudomonas aeruginosa (Pa) biofilms. METHOD: The two-fold dilution method was used to examine the minimum inhibitory concentration (MIC) of the tested drug. The crystal violet staining was applied to detect the effect of the combination of 1/2MIC, 1MIC, 2MIC of SH, single IMP, 1/2MIC of SH and IMP of various concentrations on the clearance rate of adherent bacteria, growth of biofilms and alginate production. Fluorescein diacetate (FDA)-propidium iodide (PI) doubling staining assay was employed to observe the bacterial viability and morphological changes after membrane dispersion of each drug group. RESULT: Sodium houttuyfonate could enhance the effect of IMP against pseudomonas aeruginosa biofilms. Particularly, the combination group with the concentration of 2MIC showed the highest effect, with P < 0.001 compared with the negative control group. The above results were proved by the bacterial viability and biofilm morphology under fluorescence microscope. CONCLUSION: After being combined with imipenem, sodium houttuyfonate shows a higher effect against biofilms. It is expected that the combination of the two drugs could improve the clinical efficacy of associated infections.
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Alcanos/farmacología , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Imipenem/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/fisiología , Sulfitos/farmacología , Sinergismo Farmacológico , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacosRESUMEN
SUMMARY: We present methylC track, an efficient mechanism for visualizing single-base resolution DNA methylation data on a genome browser. The methylC track dynamically integrates the level of methylation, the position and context of the methylated cytosine (i.e. CG, CHG and CHH), strand and confidence level (e.g. read coverage depth in the case of whole-genome bisulfite sequencing data). Investigators can access and integrate these information visually at specific locus or at the genome-wide level on the WashU EpiGenome Browser in the context of other rich epigenomic datasets. AVAILABILITY AND IMPLEMENTATION: The methylC track is part of the WashU EpiGenome Browser, which is open source and freely available at http://epigenomegateway.wustl.edu/browser/. The most up-to-date instructions and tools for preparing methylC track are available at http://epigenomegateway.wustl.edu/+/cmtk. CONTACT: twang@genetics.wustl.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Metilación de ADN , Epigenómica/métodos , Navegador Web , Metilación de ADN/efectos de los fármacos , Bases de Datos Genéticas , Genoma Humano/genética , Humanos , Análisis de Secuencia de ADN , Sulfitos/farmacologíaRESUMEN
OBJECTIVE: To observe the effect of the combination of sub-MIC sodium houttuyfonate and erythromycin on biofilm of Staphylococcus epidermidis. METHOD: The serial dilution method was adopted to determine MIC of the combination of sodium houttuyfonate and erythromycin on S. epidermidis; the checkerboard method was used to evaluate the combination of sodium houttuyfonate and erythromycin on suspended bacteria of S. epidermidis; S. epidermidis biofilm was built in vitro, and XTT reduction assay was used to evaluate the effect of the combination of sub-MIC sodium houttuyfonate and erythromycin on the adhesion of S. epidermidis and bacterial metabolism inside the biofilm. Microscope was applied to observe the impact the single administration and combination of the two medicines under sub-MIC on biofilm morphology of S. epidermidis. RESULT: The MIC of sodium houttuyfonate and erythromycin were 62.5, 7.812 5 mg x L(-1), respectively. The combination of 1/8MIC sodium houttuyfonate and 1/2MIC erythronmycin showed a synergistic effect on S. epidermidis. Sodium houttuyfonate, erythromycin and their combination had an inhibitory effect on the adhesion and metabolism of S. epidermidis biofilm bacteria, and made impact on the morphology of S. epidermidis biofilm. CONCLUSION: The sub-MIC sodium houttuyfonate and erythromycin have an inhibitory effect on S. epidermidis biofilm. The combination of sodium houttuyfonate and erythromycin shows a synergistic effect in inhibiting suspended bacteria and biofilm of S. epidermidis, particularly in inhibiting the metabolism of S. epidermidis biofilm bacteria and impacting the morphology of biofilm.