RESUMEN
Pseudomonas aeruginosa is an opportunistic pathogen responsible for acute and chronic infections in immunocompromised hosts. This organism is known to compete efficiently against coinfecting microorganisms, due in part to the secretion of antimicrobial molecules and the synthesis of siderophore molecules with high affinity for iron. P. aeruginosa possess a large repertoire of TonB-dependent transporters for the uptake of its own, as well as xenosiderophores released from other bacteria or fungi. Here, we show that P. aeruginosa is also capable of utilizing plant-derived polyphenols as an iron source. We found that exclusively plant-derived phenols containing a catechol group (i.e., chlorogenic acid, caffeic acid, quercetin, luteolin) induce the expression of the TonB-dependent transporters PiuA or PirA. This induction requires the two-component system PirR-PirS. Chlorogenic acid in its Fe(III)-loaded form was actively transported by PiuA and PirA and supported growth under iron-limiting conditions. Coincidentally, PiuA and PirA are also the main TonB transporters for the recently approved siderophore-drug conjugate cefiderocol. Surprisingly, quercetin supplementation increased the susceptibility of P. aeruginosa to siderophore-drug conjugates, due to induction of piuA and pirA expression mediated by the PirR-PirS two-component system. These findings suggest a potential novel therapeutic application for these biologically active dietary polyphenols. IMPORTANCE Iron is an essential element for living organisms. Most bacteria synthesize species-specific iron chelators, called siderophores, able to capture iron from their host or the environment. Pseudomonas aeruginosa, an opportunistic pathogen, produces two endogenous siderophores but is able to acquire iron also via xenosiderophores, produced by other bacteria or fungi, using a set of conserved TonB transporters. Here, we show that P. aeruginosa is also able to use plant metabolites, like quercetin and chlorogenic acid, as siderophores. These metabolites possess an iron-chelating catechol group and are recognized and transported by the TonB transporters PirA and PiuA. Since these transporters also promote the specific uptake of siderophore-drug conjugates, P. aeruginosa exposed to these plant catechols becomes hypersusceptible to this novel class of antibiotics. This unexpected finding suggests a potential therapeutic application for quercetin and chlorogenic acid, which were mainly investigated for their antioxidant and anti-inflammatory properties.
Asunto(s)
Pseudomonas aeruginosa , Sideróforos , Antibacterianos/farmacología , Proteínas Bacterianas/metabolismo , Catecoles/metabolismo , Catecoles/farmacología , Ácido Clorogénico/metabolismo , Ácido Clorogénico/farmacología , Compuestos Férricos/metabolismo , Hierro/metabolismo , Quelantes del Hierro/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Pseudomonas aeruginosa/metabolismo , Quercetina/metabolismo , Sideróforos/metabolismoRESUMEN
Date was considered a high nutritional value fruit due to its high content of active ingredients. Frequent exposure to cosmetic radiations including UVC caused deleterious effects and tissue damage and organ affection. This study investigated the efficacy of Ajwa date extract (ADE) in protection against UVC-induced kidney injury in rats. Five groups of rats were included in this study. Group I: Rats were exposed to UVC radiation at a dose 5 kJ (1 h/day) for 28 days. Group II: Rats were pretreated orally with ADE (10 mg/kg/day) 1 h before exposure to UVC radiation with dose 5 kJ. Group III: Rats were pretreated with ADE (15 mg/kg) 1 h before exposure to UVC radiation. Group IV: Rats were exposed to UVC radiation then treated with ADE (10 mg/kg). Group V: Rats exposed to UV radiation then treated with ADE (15 mg/kg) after 1 h from exposure. Analyzing the active constituents of ADE by GC/MS showed that, quercetin, myricetin kaempferol, thymine, and catechol are the most active ingredients. Biochemical markers obtained showed that, serum 8-oxoguanine as marker for DNA damage was increased, and total antioxidant activity and glutathione reduced were decreased (p < 0.01), while neutrophil (p < 0.001), conjugated diene (p < 0.05), and interferon-γ (p < 0.01) were increased after exposure to UVC. However, all the parameters changed were reversed by ADE-treated rats compared with untreated; the higher dose was more effective and protective effect was better than treated effect. Kidney total proteins and reduced glutathione and procollagen levels were decreased while malondialdehyde was increased after exposure to UVC (p < 0.01). These abnormalities were normalized by ADE treatment and protected. It was concluded that, flavonoids from Ajwa extract protected against deleterious effects of UVC by enhancing antioxidant activities and reducing infiltration of neutrophils that caused kidney injury.
Asunto(s)
Antioxidantes , Rayos Ultravioleta , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Biomarcadores/metabolismo , Catecoles/metabolismo , Flavonoides/metabolismo , Flavonoides/farmacología , Glutatión/metabolismo , Interferón gamma/metabolismo , Interferón gamma/farmacología , Quempferoles/metabolismo , Quempferoles/farmacología , Riñón/metabolismo , Malondialdehído/metabolismo , Neutrófilos/metabolismo , Estrés Oxidativo , Extractos Vegetales/metabolismo , Extractos Vegetales/farmacología , Procolágeno , Quercetina/farmacología , Ratas , Timina/metabolismo , Timina/farmacologíaRESUMEN
Recently, the numbers of studies on natural products have considerably increased owing to their exceptional biological activities and health benefits. Their pharmacological attributes have played an immense role in detecting natural and safe alternative therapeutics, consequently extending their industrial applications. In this line, ginger (Zingiber officinale) has been gaining wide attention owing to its bioactive compounds, such as phenolic and terpene compounds. Ginger has a great pharmacological and biological potential in the prevention and treatment of various diseases, namely colds, nausea, arthritis, migraines and hypertension. However, these bioactive compounds are unstable and susceptible to degradation, volatilization and oxidation during extraction and processing, mainly owing to their exposure to environments with adverse conditions, such as high temperature, the presence of O2 and light. In this sense, this current review covers a wide range of topics, starting from the chemical profile and biological properties of ginger bioactive compounds (GBCs), their clinical effectiveness for the treatment of diseases and the application of different encapsulation methods (molecular inclusion, spray drying, complex coacervation, ionic strength and nanoemulsions) to protect and improve their application in food products. This work summarizes the fundamental principles of, recent progress in and effectiveness of different methods regarding the physicochemical, structural and functional properties of encapsulated GBCs. The potential use of encapsulated GBCs as a promising active ingredient to be applied in different food products is discussed in detail.
Asunto(s)
Náusea/tratamiento farmacológico , Extractos Vegetales/metabolismo , Extractos Vegetales/farmacología , Zingiber officinale/metabolismo , Catecoles/metabolismo , Ensayos Clínicos como Asunto , Alcoholes Grasos/metabolismo , Humanos , Náusea/metabolismoRESUMEN
BACKGROUND: Polygonatum kingianum Coll. et Hemsl. is an important plant in Traditional Chinese Medicine. The extracts from its tubers are rich in polysaccharides and other metabolites such as saponins. It is a well-known concept that growing medicinal plants in semi-arid (or drought stress) increases their natural compounds concentrations. This study was conducted to explore the morpho-physiological responses of P. kingianum plants and transcriptomic signatures of P. kingianum tubers exposed to mild, moderate, and severe drought and rewatering. RESULTS: The stress effects on the morpho-physiological parameters were dependent on the intensity of the drought stress. The leaf area, relative water content, chlorophyll content, and shoot fresh weight decreased whereas electrolyte leakage increased with increase in drought stress intensity. A total of 53,081 unigenes were obtained; 59% of which were annotated. We observed that 1352 and 350 core genes were differentially expressed in drought and rewatering, respectively. Drought stress driven differentially expressed genes (DEGs) were enriched in phenylpropanoid biosynthesis, flavonoid biosynthesis, starch and sucrose metabolism, and stilbenoid diarylheptanoid and gingerol biosynthesis, and carotenoid biosynthesis pathways. Pathways such as plant-pathogen interaction and galactose metabolism were differentially regulated between severe drought and rewatering. Drought reduced the expression of lignin, gingerol, and flavonoid biosynthesis related genes and rewatering recovered the tubers from stress by increasing the expression of the genes. Increased expression of carotenoid biosynthesis pathway related genes under drought suggested their important role in stress endurance. An increase in starch and sucrose biosynthesis was evident from transcriptomic changes under drought stress. Rewatering recovered the drought affected tubers as evident from the contrasting expression profiles of genes related to these pathways. P. kingianum tuber experiences an increased biosynthesis of sucrose, starch, and carotenoid under drought stress. Drought decreases the flavonoids, phenylpropanoids, gingerol, and lignin biosynthesis. These changes can be reversed by rewatering the P. kingianum plants. CONCLUSIONS: These results provide a transcriptome resource for P. kingianum and expands the knowledge on the effect of drought and rewatering on important pathways. This study also provides a large number of candidate genes that could be manipulated for drought stress tolerance and managing the polysaccharide and secondary metabolites' contents in P. kingianum.
Asunto(s)
Polygonatum/metabolismo , Transcriptoma/genética , Carotenoides/metabolismo , Catecoles/metabolismo , Sequías , Alcoholes Grasos/metabolismo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Polygonatum/genéticaRESUMEN
In this study, three psychrotolerant phenol-degrading yeast strains Candida subhashii (strain A011), Candida oregonenis (strain B021) and Schizoblastosporion starkeyi-henricii (strain L012) isolated from Rucianka peatland were examined to determine which alternative metabolic pathway for phenol biodegradation is used by these microorganisms. All yeast strains were cultivated in minimal salt medium supplemented with phenol at 500, 750 and 1000â¯mgâ¯l-1 concentration with two ways of conducting phenol biodegradation experiments: with and without the starving step of yeast cells. For studied yeast strains, no catechol 2,3-dioxygenase activities were detected by enzymatic assay and no products of catechol meta-cleavage in yeast cultures supernatants (GC-MS analysis), were detected. The detection of catechol 1,2-dioxygenase activity and the presence of cis,cis-muconic acid in the analyzed samples revealed that all studied psychrotolerant yeast strains were able to metabolize phenol via the ortho-cleavage pathway. Therefore, they may be tested in terms of their use to develop biotechnology for the production of cis,cis-muconic acid, a substrate used in the production of plastics (PET) and other valuable goods.
Asunto(s)
Redes y Vías Metabólicas , Fenol/metabolismo , Saccharomycetales/metabolismo , Microbiología del Suelo , Biodegradación Ambiental , Catecol 1,2-Dioxigenasa/metabolismo , Catecoles/análisis , Catecoles/metabolismo , Polonia , Saccharomycetales/clasificación , Saccharomycetales/enzimología , Saccharomycetales/aislamiento & purificación , Ácido Sórbico/análogos & derivados , Ácido Sórbico/análisis , Ácido Sórbico/metabolismoRESUMEN
Isocordoin (1), a chalcone isolated from different plants, has been found to present a range of interesting biological properties. This study aimed to evaluate the anti-hypersensitive and anti-inflammatory effects of isocordoin (1) and several natural and semisynthetic derivatives (2-10). Initial evaluation of (1), dihydroisocordoin (2) and six semisynthetic derivatives (3-8) in the inhibition of abdominal writhes induced by acetic acid model showed that only isocordoin dimethylether (5) caused more than 70% of inhibition. Further evaluation of 5 for its anti-oedematogenic activity and anti-hypersensitivity effect induced by carrageenan, lipopolysaccharide (LPS), bradykinin (BK), prostaglandin E2 (PGE2), and epinephrine showed that isocordoin dimethylether (5) presented a discrete inhibition of carrageenan- and LPS-induced hypersensitivity, and of carrageenan-induced paw oedema, and that it was able to significantly reduce both the oedema and hypersensitivity induced by BK. Furthermore, when tested in the PGE2 model, 5 interfered only with the paw-oedema, without showing any effect against the paw-hypersensitivity. Evaluation of the natural isocordoin (1), together with the semisynthetic derivatives isocordoin dimethylether (5), isocordoin methylether (9), and dihydroisocordoin methylether (10) in the BK-induced oedema and hypersensitivity showed that the monoalkylated derivatives 10 and 9 had the strongest antinociceptive activity. The results of this investigation indicate that both monoalkylation of the C-4' phenolic hydroxyl group and reduction of the double bond in the α,ß-unsaturated system of the chalcone skeleton favor activity.
Asunto(s)
Catecoles/síntesis química , Catecoles/farmacología , Analgésicos/farmacología , Animales , Antiinflamatorios/farmacología , Antihipertensivos/farmacología , Catecoles/metabolismo , Chalcona/farmacología , Chalconas/farmacología , Edema/tratamiento farmacológico , Fabaceae/metabolismo , Femenino , Hiperalgesia/tratamiento farmacológico , Masculino , Ratones , Extractos Vegetales/farmacologíaRESUMEN
In this study, metabolomics and proteomics were employed to investigate the change mechanism of nonvolatile compounds during white tea processing. A total of 99 nonvolatile compounds were identified, among which the contents of 13 free amino acids, caffeine, theaflavins, 7 nucleosides and nucleotides, and 5 flavone glycosides increased significantly, while the contents of theanine, catechins, theasinesins, 3 proanthocyanidins, and phenolic acids decreased significantly during the withering period. The results of proteomics indicated that the degradation of proteins accounted for the increase in free amino acid levels; the weakened biosynthesis, in addition to oxidation, also contributed to the decrease in flavonoid levels; the degradation of ribonucleic acids contributed to the increase in nucleoside and nucleotide levels during the withering period. In addition, the drying process was found to slightly promote the formation of white tea taste. Our study provides a novel characterization of white tea taste formation during processing.
Asunto(s)
Camellia sinensis/química , Metabolómica/métodos , Té/química , Alcaloides/análisis , Alcaloides/metabolismo , Camellia sinensis/metabolismo , Catecoles/análisis , Catecoles/metabolismo , Flavonoides/análisis , Flavonoides/metabolismo , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Proteínas de Plantas/metabolismo , Análisis de Componente Principal , Proteómica , Té/metabolismoRESUMEN
Ginger (Zingiber officinale Roscoe) is a valuable culinary and medicinal plant. The compound 6-gingerol is the main gingerol in ginger rhizomes and it possesses interesting pharmacological and physiological properties. Mutation breeding involved using low doses of gamma radiation (5-30 Gy) to increase the genetic variability in ginger rhizomes (M1 generation). Ginger plants selected from the next generation (M2) were characterized and subjected to quantitative analysis for 6-gingerol content using HPLC of ginger extracts. M2 offspring from a parent ginger rhizome irradiated with 20 Gy was found to have a high 6-gingerol content (38.4 ± 0.01 mg/g methanol extract in comparison to 22.1 ± 0.03 mg/g methanol extract in non-irradiated control samples). Radiation induced genetic variability was also probed and confirmed using RAPD-PCR analysis. This research demonstrates the potential for ginger improvement and to our knowledge is the first to report the use of gamma radiation in breeding ginger plants with enhanced 6-gingerol content.
Asunto(s)
Catecoles/metabolismo , Alcoholes Grasos/metabolismo , Rayos gamma , Mutación , Fitomejoramiento , Rizoma/metabolismo , Zingiber officinale/metabolismo , Cromatografía Líquida de Alta Presión , Reacción en Cadena de la Polimerasa/métodos , Técnica del ADN Polimorfo Amplificado AleatorioRESUMEN
The number of patients with Alzheimer's disease (AD) and type 2 diabetes (T2D) is increasing rapidly, and thus more research has been focused on the relationship between these two age-related chronic diseases. According to the amyloid hypothesis, prevention of the aggregation of amyloid ß (Aß) and human islet amyloid polypeptide (hIAPP) is a promising strategy for AD and T2D. In this study, thioflavin-T assay and transmission electron microscopy were performed to evaluate the inhibitory effect of three phenylpropanoids isolated from Lycopus lucidus-schizotenuin A and lycopic acids A and B-on both Aß and hIAPP fibrillization. All tested compounds exhibited similarly strong inhibitory activity toward amyloid aggregation. These results suggested that catechol moieties play important roles in the inhibition of amyloid plaque formation.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/antagonistas & inhibidores , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Polipéptido Amiloide de los Islotes Pancreáticos/antagonistas & inhibidores , Lycopus/química , Catecoles/metabolismo , Humanos , Extractos Vegetales/farmacologíaRESUMEN
Dermatophytosis is a dermic disease caused by fungi. The aim of this study was to search anti-dermatophyte bioactive compounds in Piper umbellatum leaves. Cytotoxicity evaluation was performed against MRC-5 and HepG2 as a selectivity parameter. Crude ethanol extract presented MIC value of 39.1 µg/mL against M. canis and no cytotoxicity to Hep G2 (human liver cancer) and MRC-5 (normal lung fibroblast). 4-nerolydilcatechol was isolated from P. umbellatum ethanolic extract. MIC values for 4-NC were 7.6µM to M. canisand 15.6µM to Trichophyton rubrum. 4-NC presented activity against M. canis14 times lower than to MRC-5 (non-tumoral human cell line), which suggest selective activity for this fungus. Molecular modeling suggests 4-NC could bind to CYP51, present in lanosterol synthesis, blocking fungi development. In conclusion, P. umbellatum crude ethanol extract and 4-NC demonstrated high and selective in vitro antifungal activity.[Formula: see text].
Asunto(s)
Antifúngicos/farmacología , Arthrodermataceae/efectos de los fármacos , Catecoles/farmacología , Microsporum/efectos de los fármacos , Piper/química , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Bioensayo , Dominio Catalítico , Catecoles/química , Catecoles/metabolismo , Dermatomicosis/microbiología , Evaluación Preclínica de Medicamentos/métodos , Etanol/química , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Células Hep G2 , Humanos , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Extractos Vegetales/química , Hojas de la Planta/química , Esterol 14-Desmetilasa/química , Esterol 14-Desmetilasa/metabolismoRESUMEN
Xiao Chai Hu Tang (XCHT) is sold as traditional medicine or dietary supplement in worldwide. To understand metabolism profile of traditional medicine is key point in their logical pharmacological research and clinical application. Based on our previous research of the chemical and absorption signature of XCHT in vitro, we proposed a novel strategy to identify the bioactive components of XCHT in vivo. This strategy have two steps: firstly, based on the parents' database in vitro, built-in and editable biotransformations for phase I and phase II metabolism reactions with MassHunter Metabolite ID software (building metabolites database). Secondly, mouse plasma, bile and urine samples were analyzed by UHPLC-ESI-Q-TOF/MS technique, and the absorbed parents and metabolites were compared and identified with the XCHT's digital library using MassHunter Metabolite ID software. In total, 27 parent compounds and 26 metabolites of XCHT were identified in vivo, 2'-O-xylosyl saikosaponin b2 or b1 was reported for the first time. Saponins and their related metabolites were predominantly excreted into the bile, but flavonoids were excreted by both hepatic as well as renal excretion. Flavonoids, saponins, gingerol and their related metabolites were the absorbed components in cardiovascular system and bioactive components of XCHT. Phase I reactions (hydrolysis, hydroxylation and oxidation) and phase II reactions (glucuronidation) were identified and involved in the mouse metabolism of XCHT.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Animales , Bilis/química , Bilis/metabolismo , Catecoles/análisis , Catecoles/química , Catecoles/metabolismo , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/química , Alcoholes Grasos/análisis , Alcoholes Grasos/química , Alcoholes Grasos/metabolismo , Flavonoides/análisis , Flavonoides/química , Flavonoides/metabolismo , Masculino , Ratones , Saponinas/análisis , Saponinas/química , Saponinas/metabolismoRESUMEN
Metabolic syndrome is a cluster of medical conditions that increases the risk of developing cardiovascular disease and type 2 diabetes. Numerous studies have shown that inflammation is directly involved in the onset of metabolic syndrome and related pathologies. In this study, in silico techniques were applied to a natural products database containing molecules isolated from mushrooms from the Catalan forests to predict molecules that can act as human nuclear-factor κß kinase 2 (IKK-2) inhibitors. IKK-2 is the main component responsible for activating the nuclear-factor κß transcription factor (NF-κß). One of these predicted molecules was o-orsellinaldehyde, a molecule present in the mushroom Grifola frondosa. This study shows that o-orsellinaldehyde presents anti-inflammatory and pro-apoptotic properties by acting as IKK-2 inhibitor. Additionally, we suggest that the anti-inflammatory and pro-apoptotic properties of Grifola frondosa mushroom could partially be explained by the presence of o-orsellinaldehyde on its composition.
Asunto(s)
Aldehídos/química , Antiinflamatorios/química , Catecoles/química , Grifola/química , Inhibidores de Proteínas Quinasas/química , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Aldehídos/metabolismo , Aldehídos/uso terapéutico , Animales , Antiinflamatorios/metabolismo , Antiinflamatorios/uso terapéutico , Apoptosis/efectos de los fármacos , Productos Biológicos/química , Productos Biológicos/metabolismo , Catecoles/metabolismo , Catecoles/uso terapéutico , Supervivencia Celular/efectos de los fármacos , Simulación por Computador , Bases de Datos de Compuestos Químicos , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Fosforilación/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/metabolismo , Extractos Vegetales/uso terapéutico , Inhibidores de Proteínas Quinasas/metabolismo , Inhibidores de Proteínas Quinasas/uso terapéutico , Células RAW 264.7 , Transducción de Señal/efectos de los fármacos , Quinasa de Factor Nuclear kappa BRESUMEN
Ginger, a popular functional food, has been widely used throughout the world for centuries. However, its metabolic behaviors remain unclear, which entails an obstacle to further understanding of its functional components. In this study, the metabolic profiles of ginger in rats were systemically investigated by UPLC-Q/TOF-MS. The results included the characterization of 92 components of ginger based on the summarized fragmentation patterns and self-building chemical database. Furthermore, four representative compounds were selected to explore the typical metabolic pathways of ginger. Consequently, 141 ginger-related xenobiotics were characterized, following the metabolic spots of the pungent phytochemicals were summarized. These findings indicated that the in vivo effective components of ginger were mainly derived from [6]-gingerol and [6]-shogaol. Meanwhile, hydrogenation, demethylation, glucuronidation, sulfation, and thiolation were their major metabolic reactions. These results expand our knowledge about the metabolism of ginger, which will be important for discovering its functional components and the further mechanism research.
Asunto(s)
Agentes Aversivos/química , Alimentos Funcionales/análisis , Extractos Vegetales/química , Zingiber officinale/química , Animales , Agentes Aversivos/metabolismo , Catecoles/análisis , Catecoles/metabolismo , Cromatografía Líquida de Alta Presión , Alcoholes Grasos/análisis , Alcoholes Grasos/metabolismo , Zingiber officinale/metabolismo , Masculino , Metaboloma , Extractos Vegetales/metabolismo , Ratas , Ratas Sprague-Dawley , Espectrometría de Masas en Tándem , Xenobióticos/química , Xenobióticos/metabolismoRESUMEN
O-methyltransferases (OMTs) have been demonstrated to play key roles in the biosynthesis of plant secondary metabolites, such as alkaloids, isoprenoids, and phenolic compounds. Here, we isolated and characterized an OMT gene from Lycoris aurea (namely LaOMT1), based on our previous transcriptome sequencing data. Sequence alignment and phylogenetic analysis showed that LaOMT1 belongs to the class I OMT, and shares high identity to other known plant OMTs. Also, LaOMT1 is highly identical in its amino acid sequence to NpN4OMT, a norbelladine 4'-OMT from Narcissus sp. aff. pseudonarcissus involved in the biosynthesis of Amaryllidaceae alkaloids. Biochemical analysis indicated that the recombinant LaOMT1 displayed both para and metaO-methylation activities with caffeic acid and 3,4-dihydroxybenzaldehyde, and showed a strong preference for the meta position. Besides, LaOMT1 also catalyzes the O-methylation of norbelladine to form 4'-O-methylnorbelladine, which has been demonstrated to be a universal precursor of all the primary Amaryllidaceae alkaloid skeletons. The results from quantitative real-time PCR assay indicated that LaOMT1 was ubiquitously expressed in different tissues of L. aurea, and its highest expression level was observed in the ovary. Meanwhile, the largest concentration of lycorine and galanthamine were found in the ovary, whereas the highest level of narciclasine was observed in the bulb. In addition, sodium chloride (NaCl), cold, polyethylene glycol (PEG), sodium nitroprusside (SNP), and methyl jasmonate (MeJA) treatments could significantly increase LaOMT1 transcripts, while abscisic acid (ABA) treatment dramatically decreased the expression level of LaOMT1. Subcellular localization showed that LaOMT1 is mainly localized in cytoplasm and endosome. Our results in this study indicate that LaOMT1 may play a multifunctional role, and lay the foundation for Amaryllidaceae alkaloid biosynthesis in L. aurea.
Asunto(s)
Clonación Molecular , Metiltransferasas/metabolismo , Proteínas de Plantas/metabolismo , Plantas Medicinales/metabolismo , Alcaloides de Amaryllidaceae/metabolismo , Benzaldehídos/metabolismo , Ácidos Cafeicos/metabolismo , Catecoles/metabolismo , Metiltransferasas/genética , Proteínas de Plantas/genética , Plantas Medicinales/genéticaRESUMEN
Chlorpropham [isopropyl N-(3-chlorophenyl) carbamate] (CIPC), an important phenyl carbamate herbicide, has been used as a plant growth regulator and potato sprout suppressant (Solanum tuberosum L) during long-term storage. A bacterium capable of utilizing the residual herbicide CIPC as a sole source of carbon and energy was isolated from herbicide-contaminated soil samples employing selective enrichment method. The isolated bacterial strain was identified as Bacillus licheniformis NKC-1 on the basis of its morphological, cultural, biochemical characteristics and also by phylogenetic analysis based on 16S rRNA gene sequences. The organism degraded CIPC through its initial hydrolysis by CIPC hydrolase enzyme to yield 3-chloroaniline (3-CA) as a major metabolic product. An inducible 3-CA dioxygenase not only catalyzes the incorporation of molecular oxygen but also removes the amino group by the deamination yielding a monochlorinated catechol. Further, degradation of 4-chlorocatechol proceeded via ortho- ring cleavage through the maleylacetate process. 3-Chloroaniline and 4-chlorocatechol are the intermediates in the CIPC degradation which suggested that dechlorination had occurred after the aromatic ring cleavage. The presence of these metabolites has been confirmed by using ultra-violet (UV), high-performance liquid chromatography (HPLC), thin layer chromatography (TLC), Fourier transmission-infrared (FT-IR), proton nuclear magnetic resonance (1H NMR) and gas chromatography-mass (GC-MS) spectral analysis. Enzyme activities of CIPC hydrolase, 3-CA dioxygenase and chlorocatechol 1, 2-dioxygenase were detected in the cell-free-extract of the CIPC culture and are induced by cells of NKC-1 strain. These results demonstrate the biodegradation pathways of herbicide CIPC and promote the potential use of NKC-1 strain to bioremediate CIPC-contaminated environment with subsequent release of ammonia, chloride ions and carbon dioxide.
Asunto(s)
Bacillus licheniformis/metabolismo , Clorprofam/metabolismo , Compuestos de Amonio/análisis , Compuestos de Anilina/metabolismo , Bacillus licheniformis/clasificación , Bacillus licheniformis/genética , Bacillus licheniformis/aislamiento & purificación , Biodegradación Ambiental , Catecoles/metabolismo , Cloruros/análisis , Clorprofam/química , Dioxigenasas , Herbicidas/metabolismo , Redes y Vías Metabólicas , Organofosfatos/análisis , Fenilcarbamatos/metabolismo , Filogenia , Reguladores del Crecimiento de las Plantas/metabolismo , ARN Ribosómico 16S/genética , Microbiología del Suelo , Solanum tuberosum , Especificidad de la EspecieRESUMEN
As one of the main bioactive compounds of dried ginger, 6-shogaol has been widely used to alleviate many ailments. It is also a major pungent flavor component, and its precursor prior to dehydration is 6-gingerol, which is reported to be responsible for the pungent flavor and biological activity of fresh ginger. Structurally, gingerols including 6-gingerol have a ß-hydroxyl ketone moiety and is liable to dehydrate to generate an α,ß-unsaturated ketone under heat and/or acidic conditions. The conjugation of the α,ß-unsaturated ketone skeleton in the chemical structure of 6-shogaol explicates its higher potency and efficacy than 6-gingerol in terms of antioxidant, anti-inflammatory, anticancer, antiemetic and other bioactivities. Research on the health benefits of 6-shogaol has been conducted and results have been reported recently; however, scientific data are scattered due to a lack of systematic collection. In addition, action mechanisms of the preventive and/or therapeutic actions of 6-shogaol remain obscurely non-collective. Herein, we review the preparations, biological activity and mechanisms, and metabolism of 6-shogaol as well as the properties of 6-shogaol metabolites.
Asunto(s)
Catecoles/metabolismo , Catecoles/farmacología , Extractos Vegetales/metabolismo , Extractos Vegetales/farmacología , Zingiber officinale/química , Animales , Catecoles/análisis , Humanos , Extractos Vegetales/análisisRESUMEN
Vibrio spp. are pathogens of many bacterial diseases which have caused great economic losses in marine aquaculture. The strategy of alternative medical treatment that is utilised by herbalists has expanded in the past decade. The aim of our study is to discover the antibacterial molecules against Vibrio spp. Bacterial growth inhibition, membrane permeabilisation assessment and DNA interaction assays, as well as agarose gel electrophoresis, were employed to elucidate the antibacterial activity of hydroxytyrosol acetate. Results showed that hydroxytyrosol acetate had antibacterial activity against Vibrio spp. and it played the role via increasing bacterial membrane permeabilisation. The DNA interaction assay and agarose gel electrophoresis revealed that hydroxytyrosol acetate interacted with DNA. Hydroxytyrosol acetate enhanced the fluorescent intensity of DNA binding molecules and mediated supercoiled DNA relaxation. The present study provides more evidence that hydroxytyrosol acetate is a novel antibacterial candidate against Vibrio spp.
Asunto(s)
Acetatos/aislamiento & purificación , Antibacterianos/aislamiento & purificación , Catecoles/aislamiento & purificación , Olea/química , Extractos Vegetales/farmacología , Acetatos/química , Acetatos/metabolismo , Acetatos/farmacología , Antibacterianos/metabolismo , Antibacterianos/farmacología , Catecoles/metabolismo , Catecoles/farmacología , Permeabilidad de la Membrana Celular/efectos de los fármacos , ADN Bacteriano/metabolismo , Alcohol Feniletílico/análogos & derivados , Extractos Vegetales/química , Vibrio/efectos de los fármacos , Vibrio/ultraestructuraRESUMEN
The objective of the present study was to characterize the role of novel resveratrol (Res) analogs: 4-(E)-{(4-hydroxyphenylimino)-methylbenzene, 1, 2-diol} (HPIMBD) and 4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol} (TIMBD) as potent antioxidants against breast cancer. Non-neoplastic breast epithelial cell lines MCF-10A and MCF-10F were treated with 17ß-estradiol (E2), Res, HPIMBD, and TIMBD for up to 72 h. mRNA and protein levels of antioxidant genes, superoxide dismutase 3 (SOD3) and N-quinoneoxidoreductase-1 (NQO1) and transcription factors, nuclear factor erythroid 2-related factor (Nrf) 1, 2 and 3 were quantified after the above treatments. Generation of reactive oxygen species (ROS) was measured by CM-H2-DCFDA and oxidative-DNA damage was determined by measuring 8-hydroxy-2-deoxyguanosine (8-OHdG). HPIMBD and TIMBD scavenged cellular ROS production, attenuated oxidative DNA damage, increased mRNA and protein expression levels of SOD3 and NQO1 and activated Nrf signaling pathway. Our studies demonstrate that HPIMBD and TIMBD have the potential as novel antioxidants to prevent development of breast cancer.
Asunto(s)
Anticarcinógenos/metabolismo , Antioxidantes/metabolismo , Neoplasias de la Mama/prevención & control , Mama/metabolismo , Catecoles/metabolismo , Bases de Schiff/metabolismo , Estilbenos/metabolismo , 8-Hidroxi-2'-Desoxicoguanosina , Anticarcinógenos/efectos adversos , Antioxidantes/efectos adversos , Mama/citología , Mama/patología , Neoplasias de la Mama/etiología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Catecoles/efectos adversos , Línea Celular , Proliferación Celular , Supervivencia Celular , Daño del ADN , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Suplementos Dietéticos/efectos adversos , Inducción Enzimática , Estradiol/efectos adversos , Femenino , Humanos , NAD(P)H Deshidrogenasa (Quinona)/química , NAD(P)H Deshidrogenasa (Quinona)/genética , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Estrés Oxidativo , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Resveratrol , Bases de Schiff/efectos adversos , Transducción de Señal , Estilbenos/efectos adversos , Superóxido Dismutasa/química , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismoRESUMEN
Three series of novel urushiol derivatives were designed by introducing a hydroxamic acid moiety into the tail of an alkyl side chain and substituents with differing electronic properties or steric bulk onto the benzene ring and alkyl side chain. The compounds' binding affinity toward HDAC8 was screened by Glide docking. The highest-scoring compounds were processed further with molecular docking, MD simulations, and binding free energy studies to analyze the binding modes and mechanisms. Ten compounds had Glide scores of -8.2 to -10.2, which revealed that introducing hydroxy, carbonyl, amino, or methyl ether groups into the alkyl side chain or addition of -F, -Cl, sulfonamide, benzamido, amino, or hydroxy substituents on the benzene ring could significantly increase binding affinity. Molecular docking studies revealed that zinc ion coordination, hydrogen bonding, and hydrophobic interactions contributed to the high calculated binding affinities of these compounds toward HDAC8. MD simulations and binding free energy studies showed that all complexes possessed good stability, as characterized by low RMSDs, low RMSFs of residues, moderate hydrogen bonding and zinc ion coordination and low values of binding free energies. Hie147, Tyr121, Phe175, Hip110, Phe119, Tyr273, Lys21, Gly118, Gln230, Leu122, Gly269, and Gly107 contributed favorably to the binding; and Van der Waals and electrostatic interactions provided major contributions to the stability of these complexes. These results show the potential of urushiol derivatives as HDAC8 binding lead compounds, which have great therapeutic potential in the treatment of various malignancies, neurological disorders, and human parasitic diseases.
Asunto(s)
Catecoles/química , Inhibidores de Histona Desacetilasas/química , Histona Desacetilasas/química , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Proteínas Represoras/química , Biocatálisis/efectos de los fármacos , Catecoles/metabolismo , Catecoles/farmacología , Diseño de Fármacos , Evaluación Preclínica de Medicamentos/métodos , Inhibidores de Histona Desacetilasas/metabolismo , Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/metabolismo , Humanos , Enlace de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Ácidos Hidroxámicos/química , Estructura Molecular , Unión Proteica , Conformación Proteica , Proteínas Represoras/metabolismo , Electricidad EstáticaRESUMEN
[6]-Shogaol (6S), one of the major bioactive components in dry ginger, is attracting considerable attention because of its wide spectrum of biological activities, but its metabolic fate is still not fully understood. In the present study, the microbial metabolism of 6S was examined for the first time in in vitro batch fecal fermentation system and in mice. Two major microbial metabolites were detected and identified as 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-ol (M9) and 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-one (M11). Our results indicated that reductions of the double bond and the ketone group are the major metabolic pathways of 6S by the human gut microbiota. We also observed the interindividual variability in the metabolism of M11 to M9 by human gut microbiota. In addition, we demonstrated that the glucuronidated form of 6S and its metabolites could be rapidly deconjugated by human gut microbiota and in mice, which can be regarded as a reactive process taking place in the intestinal tract. To our knowledge, this is the first report involving the identification of the microbial metabolites of 6S in an in vitro fermentation system, and the first demonstration of the critical role of gut microbiota in producing the bioactive free form of 6S and its metabolites in the intestinal tract in mice.