RESUMO
O-GlcNAcylation is a dynamic, reversible and atypical O-glycosylation that regulates various cellular physiological processes via conformation, stabilisation, localisation, chaperone interaction or activity of target proteins. The O-GlcNAcylation cycle is precisely controlled by collaboration between O-GlcNAc transferase and O-GlcNAcase. Uridine-diphosphate-N-acetylglucosamine, the sole donor of O-GlcNAcylation produced by the hexosamine biosynthesis pathway, is controlled by the input of glucose, glutamine, acetyl coenzyme A and uridine triphosphate, making it a sensor of the fluctuation of molecules, making O-GlcNAcylation a pivotal nutrient sensor for the metabolism of carbohydrates, amino acids, lipids and nucleotides. O-GlcNAcylation, particularly prevalent in liver, is the core hub for controlling systemic glucose homeostasis due to its nutritional sensitivity and precise spatiotemporal regulation of insulin signal transduction. The pathology of various liver diseases has highlighted hepatic metabolic disorder and dysfunction, and abnormal O-GlcNAcylation also plays a specific pathological role in these processes. Therefore, this review describes the unique features of O-GlcNAcylation and its dynamic homeostasis maintenance. Additionally, it explains the underlying nutritional sensitivity of O-GlcNAcylation and discusses its mechanism of spatiotemporal modulation of insulin signal transduction and liver metabolic homeostasis during the fasting and feeding cycle. This review emphasises the pathophysiological implications of O-GlcNAcylation in nonalcoholic fatty liver disease, nonalcoholic steatohepatitis and hepatic fibrosis, and focuses on the adverse effects of hyper O-GlcNAcylation on liver cancer progression and metabolic reprogramming.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Transdução de Sinais , Humanos , Glicosilação , Processamento de Proteína Pós-Traducional , Insulina , GlucoseRESUMO
Three new phenylpropanoid glycosides, piperpubelide (1), 1-propionyl-3-hydroxy-phenyl-4-O-ß-D-glucopyranoside (2), and 1-propionyl-4-hydroxy-phenyl-3-O-ß-D-glucopyranoside (3), a new tyramine-type alkamide, puberulumine L (4), together with thirteen known compounds (5-17) were isolated from Piper puberulum (Benth.) Maxim. Their structures were elucidated by analysis of spectroscopic data involving NMR, IR, UV, and HRESIMS data. Calculated and experimental ECD was used to confirm the configuration of compound 1. Compounds 14, 16, and 17 exhibited relatively positive DPPH radical scavenging activities, with corresponding EC50 of 10.23, 24.12, and 21.83 µM, respectively. In addition, compound 5 inhibited LPS-induced NO production in BV-2 microglia with an IC50 value of 18.05 µM.
Assuntos
Glucosídeos , Piper , Glucosídeos/farmacologia , Glucosídeos/química , Piper/química , Tiramina/farmacologia , Tiramina/química , Estrutura Molecular , Glicosídeos/farmacologia , Glicosídeos/químicaRESUMO
Twenty-four new phenylpropanoid esters of sucrose, phanerosides A-X (1-24), were isolated from an EtOH extract of the rattans of Phanera championii Benth. (Fabaceae). Their structures were elucidated on the basis of comprehensive spectroscopic data analysis. A wide range of structural analogues were presented due to the different numbers and positions of acetyl substituents and the structures of phenylpropanoid moieties. Phenylpropanoid esters of sucrose were isolated from the Fabaceae family for the first time. Biologically, the inhibitory effects of compounds 6 and 21 on NO production in LPS-induced BV-2 microglial cells were better than that of the positive control, with IC50 values of 6.7 and 5.2 µM, respectively. The antioxidant activity assay showed that compounds 5, 15, 17, and 24 displayed moderate DPPH radical scavenging activity, with IC50 values ranging from 34.9 to 43.9 µM.
Assuntos
Bauhinia , Sacarose , Sacarose/química , Ésteres/química , Antioxidantes/farmacologia , Antioxidantes/química , Estrutura MolecularRESUMO
Two pairs of cycloneolignane enantiomers, piperhancins A and B (1 and 2, respectively), along with two enantiomeric pairs of biosynthetic related neolignanes, hancinone C (3) and piperhancin C (4), were isolated from the stems of Piper hancei. Compound 1 is an unprecedented 1',2:1,2'-dicyclo-8,3'-neolignane. Their structures and absolute configurations were elucidated by spectroscopic analyses, X-ray diffraction, and electronic circular dichroism calculations. Among all of the isolates, compounds (+)-1, (-)-1, (+)-2, (-)-2, and (+)-3 could significantly inhibit the production of nitric oxide secreted by lipopolysaccharide (LPS)-induced neuroinflammation in BV-2 microglial cells, with IC50 values of 1.1-26.3 µM. In addition, compound (-)-1 could decrease the mRNA levels of iNOS, IL-6, and TNF-α induced by LPS in BV-2 microglial cells.
Assuntos
Piper , Lipopolissacarídeos , Microglia , Estrutura Molecular , Óxido Nítrico , EstereoisomerismoRESUMO
The lignin-carbohydrate complex (LCC) was isolated from milled wood lignin of 2- and 24-month-old crude bamboo (Neosinocalamus affinis) culms using acetic acid (AcOH) and then characterized. The results have shown that the LCC preparation from 2-month-old bamboo (L2) exhibited a slightly lower molecular weight than the LCC preparation from the 24-month-old bamboo (L24). Further studies using Fourier transform infrared spectroscopy (FT-IR) and heteronuclear single quantum coherence (2D-HSQC) NMR spectra analyses indicate that the LCC preparations included glucuronoarabinoxylan and G-S-H lignin-type with G>S>>H. The content of the S lignin units of LCC in the mature bamboo was always higher than in the young bamboo. Combined with sugar composition analysis, the contents of phenyl glycoside and ether linkages in the L24 preparation were higher than in the L2 preparation; however, there was a reverse relationship of ester LCC bonds in L2 and L24. Lignin-xylan was the main type of LCC linkage in bamboo LCCs. Lignin-lignin linkages in the LCC preparations included ß-ß, ß-5 and ß-1 carbon-to-carbon, as well as ß-O-4 ether linkages, but ß-1 linkages were not present in L2.
Assuntos
Bambusa/química , Carboidratos/química , Lignina/química , Substâncias Macromoleculares/química , Madeira/química , Ácido Acético/química , Configuração de Carboidratos , Estrutura Molecular , Peso Molecular , Xilanos/químicaRESUMO
Three new phenolic glycosides (1-3) and a new lignan glycoside (4), together with five known compounds (5-9) were isolated from the ethanol extract of the aerial part of Gaultheria leucocarpa var. yunnanensis (Franch.) T.Z.Hsu & R.C.Fang. Their structures were determined on the basis of spectroscopic techniques, experimental and calculated ECD spectra, acid hydrolysis, and enzymatic hydrolysis experiments. All the isolates were evaluated for their anti-inflammatory and antioxidant activities. Compounds 7 and 8 exhibited inhibitory effects against the LPS-induced production of NO with IC50 of 63.71 and 10.66 µM, respectively, compared to L-NMMA having an IC50 of 6.95 µM. Besides, compound 7 also represented significant DPPH radical scavenging activity with EC50 of 18.75 µM, comparable with vitamin C (EC50 = 15.77 µM).
Assuntos
Glicosídeos Cardíacos , Gaultheria , Lignanas , Glicosídeos/química , Lignanas/farmacologia , Gaultheria/química , Estrutura Molecular , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/químicaRESUMO
Five undescribed eudesmane methyl esters (1-5), three undescribed eudesmane-12,6-olides (6-8), and 21 known analogues (9-29) were isolated from the aerial part of Artemisia princeps Pamp. Their structures were established by detailed analysis of the NMR and HRESIMS data. The absolute configurations of 1-8 were determined based on single-crystal X-ray diffraction analysis and ECD calculations. Moreover, the inhibitory effects on LPS-induced NO production in BV-2 microglial cells of all the isolated compounds were assessed. Except for compounds 2, 4, 10, and 11, the others showed significant inhibitory activities, with IC50 values of 0.73-18.66 µM, wherein the potential structure-activity relationship was also discussed.
Assuntos
Artemisia , Sesquiterpenos de Eudesmano , Sesquiterpenos , Artemisia/química , Estrutura Molecular , Sesquiterpenos/química , Relação Estrutura-Atividade , Sesquiterpenos de Eudesmano/farmacologia , Sesquiterpenos de Eudesmano/químicaRESUMO
Seven undescribed polyoxygenated ursane-type triterpenoids (vitnegundins A-G), three undescribed triterpenoid saponins (vitnegundins H-J), and 17 known ones were isolated from an EtOH extract of the aerial parts of Vitex negundo L. The structures of the undescribed compounds were established by extensive spectroscopic analysis. The absolute configurations of vitnegundins A, B, and E were determined by single-crystal X-ray diffraction data. Vitnegundins B-D are pentacyclic triterpenoids possessing rare cis-fused C/D rings and vitnegundins C-H represent undescribed ursane-type triterpenoids with 12,19-epoxy moiety. In the biological activity assay, vitnegundin A, vitnegundin E, and swinhoeic acid displayed inhibitory effects against LPS-induced NO release in BV-2 microglial cells, with IC50 values of 11.8, 44.2, and 19.6 µM, respectively.
Assuntos
Anti-Inflamatórios , Extratos Vegetais , Saponinas , Triterpenos , Vitex , Vitex/química , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Saponinas/química , Saponinas/isolamento & purificação , Saponinas/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Etanol/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Difração de Raios X , Concentração Inibidora 50 , Microglia/efeitos dos fármacos , Linhagem CelularRESUMO
OBJECTIVE: To investigate the expression of 3-mercaptopyruvate sulfurtransferase (3MST) in medulla oblongata of neonatal rats and effects of intrauterine cigarette exposure on its expression. METHODS: Sprague Dawley pregnant rats were randomly divided into 2 groups, control group and cigarette smoke exposure group (n = 8). 3MST mRNA and protein expression in medulla oblongata of neonatal rats were analysed by RT-PCR and Western blot, respectively, and the expression of 3MST in the neurons of respiratory-related nuclei in medulla oblongata of neonatal rats was investigated with immunohistochemical technique. RESULTS: The RT-PCR and Western blot analyses showed that 3MST mRNA and protein were expressed in the medulla oblogata of neonatal rats and intrauterine cigarette exposure promoted their expression (P < 0.05). Immunohistochemical staining indicated that 3MST existed in the neurons of pre-Bötzinger complex (pre-BötC), hypoglossal nucleus (12N), ambiguous nucleus (Amb), facial nucleus (FN) and nucleus tractus solitarius (NTS) in control group of the animals and the mean optical densities of 3MST-positive neurons in the pre-BötC, 12N, Amb and FN, but not NTS, were significantly increased in cigarette smoke exposure group (P < 0.05). CONCLUSIONS: 3MST exists in the neurons of medullary respiratory nuclei of neonatal rats and its expression can be up-regulated by intrauterine cigarette exposure, suggesting that the 3MST-H2S pathway may be involved in protection of medullary respiratory centers against injury induced by intrauterine cigarette exposure.
Assuntos
Bulbo/enzimologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Sulfurtransferases/metabolismo , Poluição por Fumaça de Tabaco/efeitos adversos , Animais , Animais Recém-Nascidos , Feminino , Masculino , Bulbo/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Ratos Sprague-Dawley , Sulfurtransferases/genética , Regulação para Cima/efeitos dos fármacosRESUMO
Six new compounds, including three lignans (1a, 1b, and 2), two abietane-type diterpenoids (3 and 4), and a triterpenoid (5), together with 13 known compounds (6a, 6b, and 7-17) were isolated from the aerial parts of Gaultheria leucocarpa var. yunnanensis. Their structures were elucidated by analysis of spectroscopic data involving NMR, IR, UV, and HRESIMS. The absolute configurations of lignans were confirmed by experimental and calculated ECD spectra. The anti-inflammatory and antioxidant activities of the isolates were evaluated. Compounds 12, 13, and 15 showed inhibitory effects against the LPS-induced production of NO in BV-2 microglial cells with the IC50 values of 30.50, 23.26, and 13.02 µM, respectively. In addition, compounds 2 and 7 performed moderate DPPH radical scavenging activities.
Assuntos
Gaultheria , Lignanas , Triterpenos , Abietanos , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Gaultheria/química , Lignanas/química , Lignanas/farmacologia , Lipopolissacarídeos , Estrutura Molecular , Terpenos , Triterpenos/químicaRESUMO
O-GlcNAcylation is a highly dynamic, reversible and atypical glycosylation that regulates the activity, biological function, stability, sublocation and interaction of target proteins. O-GlcNAcylation receives and coordinates different signal inputs as an intracellular integrator similar to the nutrient sensor and stress receptor, which target multiple substrates with spatio-temporal analysis specifically to maintain cellular homeostasis and normal physiological functions. Our review gives a brief description of O-GlcNAcylation and its only two processing enzymes and HBP flux, which will help to better understand its physiological characteristics of sensing nutrition and environmental cues. This nutritional and stress-sensitive properties of O-GlcNAcylation allow it to participate in the precise regulation of skeletal muscle metabolism. This review discusses the mechanism of O-GlcNAcylation to alleviate metabolic disorders and the controversy about the insulin resistance of skeletal muscle. The level of global O-GlcNAcylation is precisely controlled and maintained in the "optimal zone", and its abnormal changes is a potential factor in the pathogenesis of cancer, neurodegeneration, diabetes and diabetic complications. Although the essential role of O-GlcNAcylation in skeletal muscle physiology has been widely studied and recognized, it still is underestimated and overlooked. This review highlights the latest progress and potential mechanisms of O-GlcNAcylation in the regulation of skeletal muscle contraction and structural properties.
Assuntos
Complicações do Diabetes , Resistência à Insulina , Complicações do Diabetes/metabolismo , Glicosilação , Humanos , Contração Muscular , Músculo Esquelético/metabolismoRESUMO
Seven undescribed abietane-type diterpenoids, gauleucins A-G, and 11 known ones were isolated from an EtOH extract of the aerial parts of Gaultheria leucocarpa var. yunnanensis. These isolates could be classified into four subtypes: abietanes, 16-nor-abietanes, 16,18-di-nor-abietanes, and 3,4-seco-16-nor-abietane. Their structures were established by extensive spectroscopic analysis, and the absolute configurations of an undescribed and two known diterpenoids were determined by single-crystal X-ray diffraction data. Four compounds showed moderate inhibitory effects against the LPS-induced production of nitric oxide in BV-2 microglial cells. In an α-glucosidase inhibitory assay, gauleucin E and margoclin displayed inhibitory activities with IC50 values of 319.3 and 327.9 µM, respectively, while the IC50 value of the positive control (acarbose) was 387.8 µM.
Assuntos
Diterpenos , Gaultheria , Abietanos/química , Abietanos/farmacologia , Diterpenos/análise , Gaultheria/química , Estrutura Molecular , Óxido Nítrico , Componentes Aéreos da Planta/químicaRESUMO
O-GlcNAcylation is an atypical, reversible, and dynamic glycosylation that plays a critical role in maintaining the normal physiological functions of cells by regulating various biological processes such as signal transduction, proteasome activity, apoptosis, autophagy, transcription, and translation. It can also respond to environmental changes and physiological signals to play the role of "stress receptor" and "nutrition sensor" in a variety of stress responses and biological processes. Even, a homeostatic disorder of O-GlcNAcylation may cause many diseases. Therefore, O-GlcNAcylation and its regulatory role in stress response are reviewed in this paper.
Assuntos
Estresse do Retículo Endoplasmático , Proteínas/metabolismo , Estresse Fisiológico , Acilação , Homeostase , HumanosRESUMO
Amino cellulose (AC) is a cellulose derivative with biodegradability, biocompatibility, and excellent film-forming property, but AC film exhibits poor mechanical property and thermal stability. To improve the performance of AC film and further promote application, a novel composite film prepared from AC and bisphenol A-type-benzoxazine (BATB) are reported. In this paper, AC and BATB were firstly synthesized and characterized, then AC-BATB composite films were prepared with different weight ratios (AC/BATB) and temperatures by the synergistic interactions of chemical cross-linking and hydrogen bonds. Based on the results of tensile test and thermal analysis, BATB played a vital role in improving the mechanical and thermal properties of composite films, and the enhancement effect was more remarkable at elevated temperature. The maximum tensile strength and tensile modulus of composite films were 2.86 times and 7.26 times higher than that of AC control film, thus promoting the functional application of composite films.
RESUMO
A facile and green route is introduced to fabricate antimicrobial composite films in this article from xylan (XL) and hydroxyethyl cellulose (HEC) with citric acid (CA) and polyethylene glycol 400 (PEG-400) as crosslinker and plasticizer, respectively. XL was obtained by precipitating wood hydrolysate (WH) produced during pulping process with ethanol. Antimicrobial activity was constructed by incorporating ß-cyclodextrin/sodium benzoate (ß-CD/NaBz) complex into the composite matrix. The interactions, including hydrogen bonds and covalent bonds, between the polymers were confirmed by FT-IR spectroscopy. Morphology and crystallinity of composite films at different curing time were investigated by AFM and XRD, respectively. The composite film cured for 40â¯min exhibits tensile strength up to 62.3â¯MPa and oxygen permeability (OP) as low as 1.0â¯cm3·µmâ¯m-2·d-1·kPa-1. Finally, the antimicrobial test against Staphylococcus aureus reveals superior antimicrobial activity of composite films with complex. In conclusion, the XL/HEC antimicrobial film has great potential in the field of sustainable food packing materials.
Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Embalagem de Alimentos , Membranas Artificiais , Xilanos/química , Fenômenos Químicos , Fenômenos Mecânicos , Microscopia de Força Atômica , Estrutura Molecular , Solubilidade , Análise EspectralRESUMO
To study the differences in chemical composition analysis and spatial distribution of young Neosinocalamus affinis bamboo, we used the methods of standard of National Renewable Energy Laboratory and confocal Raman microscopy, respectively. It was found that the acid-soluble lignin and acid-insoluble lignin content showed an inverse relationship with the increasing bamboo age. Raman analysis revealed that Raman signal intensity of lignin in both the secondary cell wall and the compound middle lamella regions showed a similar increase trend with growth of bamboo. In addition, eight hemicellulosic fractions were obtained by successively treating holocellulose of the 2-, 4-, 8-, and 12-month-old Neosinocalamus affinis bamboo culms with DMSO and alkaline solution. The ratio of arabinose to xylose of hemicelluloses was increased with the growth of bamboo. FT-IR and NMR analyses revealed that DMSO-soluble hemicelluloses of young bamboo culms are mainly composed of highly substituted xylans and ß-d-glucans.
Assuntos
Bambusa/química , Extratos Vegetais/química , Bambusa/crescimento & desenvolvimento , Parede Celular/química , Lignina/química , Lignina/isolamento & purificação , Espectroscopia de Ressonância Magnética , Extratos Vegetais/isolamento & purificação , Brotos de Planta/química , Brotos de Planta/crescimento & desenvolvimento , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Wood auto-hydrolysates (WAH) are obtained in the pulping process by the hydrothermal extraction, which contains lots of hemicelluloses and slight lignin. WAH and chitosan (CS) were introduced into this study to construct WAH-based films by the casting method. The FT-IR results revealed the crosslinking interaction between WAH and CS due to the Millard reaction. The morphology, transmittance, thermal properties and mechanical properties of composite WAH/CS films were investigated. As the results showed, the tensile strength, light transmittances and thermal stability of the WAH-based composite films increased with the increment of WAH/CS content ratio. In addition, the results of oxygen transfer rate (OTR) and water vapor permeability (WVP) suggested that the OTR and WVP values of the films decreased due to the addition of CS. The maximum value of tensile strengths of the composite films achieved 71.2 MPa and the OTR of the films was low as 0.16 cm³·µm·m-2·24 h-1·kPa-1, these properties are better than those of other hemicelluloses composite films. These results suggested that the barrier composite films based on WAH and CS will become attractive in the food packaging application for great mechanical properties, good transmittance and low oxygen transfer rate.