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Vortex beams carrying orbital angular momentum (OAM) provide a new degree of freedom for light waves in addition to the traditional degrees of freedom, such as intensity, phase, frequency, time, and polarization. Due to the theoretically unlimited orthogonal states, the physical dimension of OAM is capable of addressing the problem of low information capacity. With the advancement of the OAM optical communication technology, OAM router devices (OAM-RDs) have played a key role in significantly improving the flexibility and practicability of communication systems. In this review, major breakthroughs in the OAM-RDs are summarized, and the latest technological standing is examined. Additionally, a detailed account of the recent works published on techniques related to the OAM-RDs has been categorized into five areas: channel multicasting, channel switching, channel filtering, channel hopping, and channel adding/extracting. Meanwhile, the principles, research methods, advantages, and disadvantages are discussed and summarized in depth while analyzing the future development trends and prospects of the OAM-RDs.
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Polyunsaturated fatty acids (PUFAs) have beneficial roles in a variety of human pathologies and disorders. Owing to the limited source of PUFAs in animals and plants, microorganisms, especially fungi, have become a new source of PUFAs. In fungi, fatty acid desaturases (F-FADS) are the main enzymes that convert saturated fatty acids (SFAs) into PUFAs. Their catalytic activities and substrate specificities, which are directly dependent on the structure of the FADS proteins, determine their efficiency to convert SFAs to PUFAs. Catalytic mechanisms underlying F-FADS activities can be determined from the findings of the relationship between their structure and function. In this review, the advances made in the past decade in terms of catalytic activities and substrate specificities of the fungal FADS cluster are summarized. The relationship between the key domain(s) and site(s) in F-FADS proteins and their catalytic activity is highlighted, and the FADS cluster is analyzed phylogenetically. In addition, subcellular localization of F-FADS is discussed. Finally, we provide prospective crystal structures of F-FADSs. The findings may provide a reference for the resolution of the crystal structures of F-FADS proteins and facilitate the increase in fungal PUFA production for human health.
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Ácidos Graxos Dessaturases , Ácidos Graxos Insaturados , Animais , Humanos , Estudos Prospectivos , Ácidos Graxos Insaturados/metabolismo , Ácidos Graxos Dessaturases/metabolismo , Ácidos Graxos , Plantas/metabolismoRESUMO
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with complicated interrelationships responsible for initiating its pathogenesis. Novel strategies for the treatment of this devastating disease have attracted increasing attention worldwide. Anthocyanins are bioactive compounds that are widely distributed in the plant kingdom, and multiple studies have elucidated their beneficial role in preventing and managing T2DM. This review summarizes and comments on the hypoglycemic actions of anthocyanins from the perspective of molecular mechanisms and different target-related signaling pathways in vitro, in vivo, and clinical trials. Anthocyanins can ameliorate T2DM by functioning as carbohydrate digestive enzyme inhibitors, facilitating glucose transporter 4 (GLUT4) translocation, suppressing the effectiveness of dipeptidyl peptidase IV (DPP-IV), promoting glucagon-like peptide-1 (GLP-1) secretion, inhibiting protein tyrosine phosphatase 1B (PTP1B) overexpression, and interacting with sodium-glucose co-transporter (SGLT) to delay glucose absorption in various organs and tissues. In summary, anthocyanin is a promising and practical small molecule that can hyperglycemic symptoms and accompanying complications suffered by patients with diabetes. However, rational and potent doses for daily intake and clinical studies are required in the future.
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Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Humanos , Hipoglicemiantes/farmacologia , Antocianinas/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/farmacologia , Glicemia/metabolismoRESUMO
Extracellular vesicles (EVs) are naturally occurring non-replicating particles released from cells, known for their health-promoting effects and potential as carriers for drug delivery. Extensive research has been conducted on delivery systems based on culture-cell-derived EVs. Nevertheless, they have several limitations including low production yield, high expenses, unsuitability for oral administration, and safety concerns in applications. Conversely, food-derived EVs (FDEVs) offer unique advantages that cannot be easily substituted. This review provides a comprehensive analysis of the biogenesis pathways, composition, and health benefits of FDEVs, as well as the techniques required for constructing oral delivery systems. Furthermore, it explores the advantages and challenges associated with FDEVs as oral nanocarriers, and discusses the current research advancements in delivering active phytoconstituents. FDEVs, functioning as a nanocarrier platform for the oral delivery of active molecules, present numerous benefits such as convenient administration, high biocompatibility, low toxicity, and inherent targeting. Nevertheless, numerous unresolved issues persist in the isolation, characterization, drug loading, and application of FDEVs. Technical innovation and standardization of quality control are the key points to promote the development of FDEVs. The review aimed to provide frontier ideas and basic quality control guidelines for developing new functional food based on FDEVs oral drug delivery system.
Extracellular vesicles (EVs) are excellent nano-carriers for active molecules.Food-derived EVs (FDEVs) are better sources of EVs in delivery applications.Active phytoconstituents could be protected by loading them into FDEVs.The development of FDEVs-based delivery system is promising in new functional food.
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Potential roles for anthocyanins in preventing various chronic diseases have been reported. These compounds are highly sensitive to external conditions and are susceptible to degradation, which increases the complexity of their metabolism in vivo. This review discusses anthocyanin metabolism in the digestive tract, phase I and II metabolism, and enterohepatic circulation (EHC), as well as their distribution of anthocyanins in blood, urine, and several organs. In the oral cavity, anthocyanins are partly hydrolyzed by microbiota into aglycones which are then conjugated by glucuronidase. In stomach, anthocyanins are absorbed without deglycosylation via specific transporters, such as sodium-dependent glucose co-transporter 1 and facilitative glucose transporters 1, while in small intestine, they are mainly absorbed as aglycones. High polymeric anthocyanins are easily degraded into low-polymeric forms or smaller phenolic acids by colonic microbiota, which improves their absorption. Anthocyanins and their derivatives are modified by phase I and II metabolic enzymes in cells and are released into the blood via the gastrovascular cavity into EHC. Notably, interconversion can be occurred under the action of enzymes such as catechol-O-methyltransferase. Taking together, differences in anthocyanin absorption, distribution, metabolism, and excretion largely depend on their glycoside and aglycone structures.
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Antocianinas , Catecol O-Metiltransferase , Antocianinas/metabolismo , Trato Gastrointestinal/metabolismo , Intestino Delgado/metabolismo , GlucoseRESUMO
The incidence of the intestinal disease is globally increasing, and the intestinal mucosa immune system is an important defense line. A potential environmental cause to regulate gut health is diet. Cyanidin-3-O-glucoside is a natural plant bioactive substance that has shown rising evidence of improving intestinal disease and keeping gut homeostasis. This review summarized the intestinal protective effect of Cyanidin-3-O-glucoside in vivo and in vitro and discussed the potential mechanisms by regulating the intestinal mucosal immune system. Cyanidin-3-O-glucoside and phenolic metabolites inhibited the presence and progression of intestinal diseases and explained from the aspects of repairing the intestinal wall, inhibiting inflammatory reaction, and regulating the gut microbiota. Although the animal and clinical studies are inadequate, based on the accumulated evidence, we propose that the interaction of Cyanidin-3-O-glucoside with the intestinal mucosal immune system is at the core of most mechanisms by which affect host gut diseases. This review puts forward the potential mechanism of action and targeted treatment strategies.
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Glucosídeos , Enteropatias , Animais , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Mucosa Intestinal , Antocianinas/uso terapêutico , Sistema ImunitárioRESUMO
With the continuous growth of global energy demand and the late stage of conventional oilfield exploitation, the demand for developing and utilizing low-permeability heavy oil reservoirs is becoming increasingly urgent. However, the exploitation of low-permeability heavy oil reservoirs faces many challenges due to their high viscosity, low permeability, and complex geological conditions. To overcome these challenges, researchers have gradually introduced SC-CO2 as an oil displacement agent in the exploitation of heavy oil reservoirs. However, the oil displacement mechanism of SC-CO2 in low-permeability heavy oil reservoirs and its improvement mechanism are still not completely understood. The article provides a detailed study and understanding of the oil displacement mechanism of SC-CO2, which involves the expansion of heavy oil volume through SC-CO2 dissolution. This mechanism reduces the capillary resistance and flow resistance during the oil flow process. The permeation of CO2 disrupts the internal structure and arrangement of heavy oil, reducing its viscosity. CO2 extracts both light and heavy components from the heavy oil, reducing the residual oil saturation. In addition, the mechanism of improving the effect of oil displacement agents such as nanoparticles, polymers, and surfactants on SC-CO2 displacement was also explored. By further exploring the mechanisms and improvement mechanisms of SC-CO2 displacement for heavy oil, it can guide the selection and optimization of oil displacement agents. Furthermore, understanding the mechanism can also provide a theoretical basis for engineering practice and technical innovation. While the research on CO2 flooding is analyzed and evaluated, the obstacles and challenges that still exist at this stage are indicated, and future research work on CO2 in low-permeability heavy oil reservoirs is proposed.
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As an emerging digital production technology, 3D food printing intends to meet the demand for customized food design, personalized nutrition, simplification of the food supply chain system, and greater food material diversity. Most 3D food printing studies focus on the development of materials for extrusion-based food printing. Plant-based foods are essential for a healthy diet, and they are growing in popularity as their positive effects on human health gain wider recognition. The number of original studies on plant-based printable materials has increased significantly in the past few years. Currently, there is an absence of a comprehensive systematic review on the applications of plant-based materials in extrusion-based food printing. Thus, this review aims to provide a more intuitive overview and guidance for future research on 3D printing of plant-based materials. The requirements, classifications, and binding mechanisms of extrusion-based food printing materials are first summarized. Additionally, notable recent achievements and emerging trends involving the use of plant-based materials in extrusion-based food printing are reviewed across three categories, namely, hot-melt (e.g., chocolate), hydrogel, and soft (e.g., cereal- and fruit/vegetable-based) materials. Finally, the challenges facing 3D food printing technology as well as its future prospects are discussed.
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Chocolate , Impressão Tridimensional , Alimentos , Tecnologia de Alimentos , Humanos , HidrogéisRESUMO
PURPOSE: Anthocyanins are well-characterized by anti-oxidative and anti-inflammatory potentials. Peptic ulcers contribute to the development of severe gastric disorders. In the current study, the effects of blueberry anthocyanin extracts (BE) on the Helicobacter pylori lipopolysaccharide (LPS)-induced peptic epithelium injures were assessed and the associated mechanism driving the effects was explored by focusing on MAPK/NF-κB pathway. METHODS: Peptic injures were induced in a mouse model using LPS plus ligation method and then the mice were treated with BE. Then changes in gastric histology, inflammatory response, and MAPK/NF-κB axis were detected. To reveal the role of MAPK/NF-κB axis in the effects of BE, human gastric epithelial cells (HGECs) were further subjected to co-treatment of BE, LPS, and MAPK activator. RESULTS: The assays of mouse model showed that BE attenuated gastric epithelial injuries by improving epithelial structure and suppressing gastric inflammatory response, which was associated with the inhibition of MAPK/NF-κB axis. In in vitro assays, BE suppressed viability and production of cytokines, and induced apoptosis in LPS-treated HGECs. The re-activation of MAPK pathway counteracted the effects of BE by re-inducing cell viability and suppressing cell apoptosis. CONCLUSIONS: The protective effects of BE against LPS-induced injuries in mouse stomach depended on the inhibition of both MAPK pathway and the downstream NF-κB signaling.
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Mirtilos Azuis (Planta) , Helicobacter pylori , Animais , Antocianinas/farmacologia , Epitélio/metabolismo , Humanos , Lipopolissacarídeos/farmacologia , Camundongos , NF-kappa B/metabolismoRESUMO
PURPOSE: Hidden blood loss (HBL) is a growing area of interest for spinal surgeons. Simultaneously, spine surgeons' pursuit of minimally invasive spine surgery has never ceased, as evidenced by the increasing number of articles comparing percutaneous endoscopic transforaminal lumbar interbody fusion (Endo-TLIF) and minimally invasive transforaminal lumbar interbody fusion (Mis-TLIF). However, there has been no comparison of HBL between Endo-TLIF and Mis-TLIF. This study aimed to compare HBL, visible blood loss (VBL), and total blood loss (TBL) following Endo-TLIF and Mis-TLIF and evaluate the clinical significance of these procedures. METHODS: Between October 2017 and October 2019, 370 patients underwent lumbar interbody fusion at our institution and were followed up for at least 24 months. Our study included 41 Endo-TLIF and 43 Mis-TLIF cases. We recorded each patient's age, height, weight, and haematocrit and calculated the TBL, which was used to indirectly obtain the HBL. Additionally, we compared the clinical outcomes of these two groups, including visual analogue scores for the lumbar spine and leg (VAS-Back; VAS-Leg), Oswestry Disability Index (ODI), Japanese Orthopaedic Association (JOA) scores, disease type, operative segment, and intervertebral fusion and complication rates. RESULTS: Endo-TLIF had significantly lower HBL, VBL, and TBL values than Mis-TLIF (P < 0.05 for all). Although Endo-TLIF contained significantly less HBL than Mis-TLIF, the HBL to TBL ratio was statistically greater in Endo-TLIF (91%) than in Mis-TLIF (87%). Concerning clinical outcomes, VAS-Back, VAS-Leg, ODI, JOA, and Endo-TLIF demonstrated greater improvement rates than Mis-TLIF one week post-operatively. However, at the final follow-up, VAS-Back, VAS-Leg, ODI, and JOA scores all demonstrated a trend toward sustained improvement, with no statistically significant between-procedure difference. There were no statistically significant between-procedure differences in disease type, surgical segment, and complication or fusion rates. CONCLUSION: Endo-TLIF significantly reduced HBL, VBL, and TBL compared to Mis-TLIF and improved short-term clinical outcomes; however, long-term clinical outcomes and fusion rates remained comparable between the two groups, as did the incidence of peri-operative complications.
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Fusão Vertebral , Humanos , Vértebras Lombares/cirurgia , Região Lombossacral , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Treatment by ozone water is an emerging technology for the degradation of pesticide residues in vegetables. The ozone dissolved in water generates hydroxyl radicals (· OH), which are highly effective in decomposing organic substances, such as malathion and carbosulfan. RESULTS: We found that washing pak choi with 2.0 mg L-1 ozone water for 30 min resulted in 58.3% and 38.2% degradation of the malathion and carbosulfan contents respectively, and the degradation rates of these pure pesticides were 83.0% and 66.3% respectively. In addition, the 'first + first'-order reaction kinetic model was found to predict the trend in the pesticide content during ozone water treatment. Based on investigations by gas chromatography-mass spectrometry combined with the structures of the pesticides, the by-products generated were identified. More specifically, the ozonation-based degradation of carbosulfan generated carbofuran and benzofuranol, whereas malathion produced succinic acid and phosphoric acid. Although some new harmful compounds were formed during degradation of the parent pesticides, these were only present in trace quantities and were transient intermediates that eventually disappeared during the reaction. CONCLUSION: Our results, therefore, indicate that ozone water treatment technology for pesticide residue degradation is worthy of popularization and application. © 2022 Society of Chemical Industry.
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Ozônio , Resíduos de Praguicidas , Praguicidas , Poluentes Químicos da Água , Purificação da Água , Ozônio/química , Malation/análise , Carbamatos/análise , Purificação da Água/métodos , Praguicidas/análise , Resíduos de Praguicidas/análise , Poluentes Químicos da Água/química , OxirreduçãoRESUMO
BACKGROUND: Free fractions of different blackberry varieties' extracts are high in phenolic compounds with antioxidant activities. However, the phenolic profiles and antioxidant activities against peroxyl radicals of bound fractions of different blackberry varieties' extracts have not been previously reported. In addition, what the key antioxidant phenolic compounds are in free and bound fractions of blackberry extracts remain unknown. This study aimed to investigate the phenolic profiles and antioxidant activities of free and bound fractions of eight blackberry varieties' extracts and reveal the key antioxidant phenolic compounds by boosted regression trees. RESULTS: Fifteen phenolics (three anthocyanins, four flavonols, three phenolic acids, two proanthocyanidins, and three ellagitannins) were identified in blackberry by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Ferulic acid, ellagic acid, procyanidin C1, kaempferol-O-hexoside, ellagitannins hex, and gallic acid were major bound phenolics. Bound fractions of eight blackberry varieties' extracts were high in phenolics and showed great antioxidant activity. Boosted regression trees analysis showed that cyanidin-3-O-glucoside and chlorogenic acid were the most significant compounds, contributing 48.4% and 15.9% respectively to the antioxidant activity of free fraction. Ferulic acid was the most significant antioxidant compound in bound fraction, with a contribution of 61.5%. Principal component analysis showed that Kiowa was the best among the eight varieties due to its phenolic profile and antioxidant activity. CONCLUSION: It was concluded that blackberry varieties contained high amounts of bound phenolics, which confer health benefits through reducing oxidative stress. Ferulic acid was the key compound to explain the antioxidant activities of bound fractions. © 2021 Society of Chemical Industry.
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Antioxidantes/química , Fenóis/química , Extratos Vegetais/química , Rubus/química , Antocianinas/química , Cromatografia Líquida de Alta Pressão , Frutas/química , Taninos Hidrolisáveis/química , Hidroxibenzoatos/química , Espectrometria de Massas , Proantocianidinas/química , Rubus/classificaçãoRESUMO
The health benefits of anthocyanins are compromised by their chemical instability and susceptibility to external stress. Researchers found that the interaction between anthocyanins and macromolecular components such as proteins and polysaccharides substantially determines the stability of anthocyanins during food processing and storage. The topic thus has attracted much attention in recent years. This review underlines the new insights gained in our current study of physical and chemical properties and functional properties in complex food systems. It examines the interaction between anthocyanins and food proteins or polysaccharides by focusing on the "structure-stability" relationship. Furthermore, multispectral and molecular computing simulations are used as the chief instruments to explore the interaction's mechanism. During processing and storage, the stability of anthocyanins is generally influenced by the adverse characteristics of food and beverage, including temperature, light, oxygen, enzymes, pH. While the action modes and types between protein/polysaccharide and anthocyanins mainly depend on their structures, the noncovalent interaction between them is the key intermolecular force that increases the stability of anthocyanins. Our goal is to provide the latest understanding of the stability of anthocyanins under food processing conditions and further improve their utilization in food industries. Practical Application: This review provides support for the steady-state protection of active substances.
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Antocianinas , Polissacarídeos , Antocianinas/química , Bebidas , Alimentos , Oxigênio , Polissacarídeos/químicaRESUMO
Aflatoxin B1 (AFB1) causes oxidative stress and hepatocyte apoptosis through its epoxidized metabolite AFBO, which is catalyzed by CYP450 enzymes. Ferulic acid (FA) is a phenolic acid commonly found in plants and is known for its antioxidant capacity. However, the role of FA in AFB1-induced liver injury is still elusive. In this study, rats were exposed to AFB1 and simultaneously treated with FA for 30 days. The results showed that I) FA alleviated the histopathological changes induced by AFB1, inhibited the elevation of serological indexes induced by AFB1, and reduced the production of AFBO in liver. II) AFB1-induced increase in CYP450 expression was significantly reduced by FA. The molecular docking results of FA and CYP2A6 showed high fitness score and interaction. III) FA obviously inhibited the production of MDA, and significantly activated the Nrf2/GST pathway and antioxidant enzymes (SOD and GST). IV) AFB1-induced hepatocyte apoptosis, the high expression of p53, bax, cyt-c, caspase-9, caspase-3, and the low expression of bcl-2 were all restored by FA. It has been suggested from these results that FA proved effective against AFB1-induced liver damage in rats via inhibiting CYP450 enzyme, promoting antioxidant pathway Nrf2/GST, activating antioxidant enzymes (SOD and GST), and regulating the mitochondrial pathway.
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Protein tyrosine phosphatase 1B (PTP1B) has recently been identified as a potential target of Norathyriol. Unfortunately, Norathyriol is not a potent PTP1B inhibitor, which somewhat hinders its further application. Based on the fact that no study on the relationship of chemical structure and PTP1B inhibitory activity of Norathyriol has been reported so far, we attempted to perform structural optimization so as to improve the potency for PTP1B. Via structure-based drug design (SBDD), a rational strategy based on the binding mode of Norathyriol to PTP1B, we designed 26 derivatives with substitutions at the four phenolic hydroxyl groups of Norathyriol. By chemical synthesis and in vitro bioassay, we identified seven PTP1B inhibitors that were more potent than Norathyriol, of which XWJ24 showed the highest potency (IC50: 0.6⯵M). We also found out that XWJ24 was a competitive inhibitor and showed the 4.5-fold selectivity over its close homolog, TC-PTP. Through molecular docking of XWJ24 against PTP1B, we highlighted the essential role of its hydrogen bond with Asp181 for PTP1B inhibition and identified a potential halogen bond with Asp48 that was not observed for Norathyriol. The current data indicate that our SBDD strategy is effective to discover potent PTP1B-targeted Norathyriol derivatives, and XWJ24 is a promising lead compound for further development.
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Descoberta de Drogas , Inibidores Enzimáticos/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Xantenos/farmacologia , Bioensaio , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Relação Estrutura-Atividade , Xantenos/síntese química , Xantenos/químicaRESUMO
Phytochemical investigation of Croton crassifolius roots afforded five sesquiterpenes (1-5), including two new sesquiterpenes 6S-hydroxy-cyperenoic acid (1) and crassifterpenoid A (5), together with three known compounds (2-4). The structures of the new compounds were determined by comprehensive spectroscopic methods, and their absolute configurations were determined by quantum chemical ECD calculation. Crassifterpenoid A (5) is the first germacrane-type sesquiterpene isolated from C. crassifolius, which enriched the diversity of chemical constituents in Croton crassifolius. In addition, the cytotoxicities of all compounds against human liver cancer lines HepG2 and Hep3B were determined, but none showed significant activity.
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Croton/química , Raízes de Plantas/química , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Dicroísmo Circular , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Resultados Negativos , Extratos Vegetais/químicaRESUMO
Clerodane diterpenoids are the main bioactive constituents of Croton crassifolius and are proved to have multiple biological activities. However, quality control (QC) research on the constituents are rare. Thus, the major research purpose of the current study was to establish an efficient homogenate extraction (HGE) process combined with a sensitive and specific ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLCâ»MS) technique together for the rapid extraction and determination of clerodane diterpenoids in C. crassifolius. All calibration curves showed good linearity (r > 0.9943) within the test ranges and the intra- and inter-day precisions and repeatability were all within required limits. This modified HGEâ»UHPLCâ»MS method only took 5 min to extract nine clerodane diterpenoids in C. crassifolius and another 12 min to quantify these components. The results indicated that the quantitative analysis based on UHPLCâ»MS was a feasible method for QC of clerodane diterpenoids in C. crassifolius, and the findings outlined in the current study also inferred the potential of the method in the QC of clerodane diterpenoids in other complex species of plants.
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Cromatografia Líquida de Alta Pressão , Croton/química , Diterpenos/química , Espectrometria de Massas , Extratos Vegetais/química , Fracionamento Químico , Diterpenos/análise , Diterpenos/farmacologia , Estrutura Molecular , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
A novel and practical copper-catalyzed strategy for intermolecular cyanosulfonylation and cyanotrifluoromethylation of unactivated alkenes in water-containing solvents is described. The methodology developed provides an efficient and convenient access to a variety of ß-sulfonyl nitriles and ß-trifluoromethyl nitriles, which would have wide applications in chemical and pharmaceutical industries.
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Chemical investigation of the roots of Croton crassifolius led to the isolation of five pyran-2-one derivatives, including two brand new compounds (1-2), one new natural product (3) and two known compounds (4-5). Their structures and absolute configurations were established by spectroscopic analyses as well as comparison between the calculated optical rotation (OR) values with the experimental data. Interestingly, the new compound 1 showed an unusual negative chemical shift at H-11. It is well known that negative chemical shift values of 1H NMR spectrum are extremely rare in natural products. Such a negative chemical shift of 1H NMR spectrum was reproduced by density functional theory (DFT) calculations and explained by the shielding effect from the pyran-2-one ring over the hydrogen atom in the 3D conformations. Then, MTT assay was applied to evaluate the cytotoxicity of the isolated compounds (1-5) against two liver cancer cell lines (HepG2 and MHCC97H). The results suggested that compound 1 displayed the highest cytotoxicity with an IC50 value of 9.8⯵M against HepG2 cells. Moreover, there was no obvious cytotoxicity of compounds 1-5 on normal liver cell line LO2. Furthermore, the mechanism of apoptosis induction in compound 1-treated HepG2 cells was investigated. The results showed that compound 1 could induce apoptosis via p53-mediated Ras/Raf/ERK suppression in HepG2 cells.
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Antineoplásicos Fitogênicos/farmacologia , Croton/química , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Pironas/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Quinases raf/metabolismo , Proteínas ras/metabolismo , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Raízes de Plantas/química , Pironas/química , Pironas/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
Hepatocellular carcinoma (HCC) is the most common type of liver cancer, and treatment options for HCC are limited. In addition, the discovery of new natural compounds with anti-hepatocarcinoma activity is attracting increasing attention. For this reason, phytochemical investigation of Croton crassifolius led to the isolation of 17 diterpenoids, including three new clerodane diterpenoids, named crassifolius A-C (1-3), along with 14 known ones (4-17). Their structures were established by 1D, 2D NMR, HR-ESI-MS, detailed calculated electronic circular dichroism (ECD) spectra and the assistance of quantum chemical predictions (QCP) of 13C NMR chemical shifts. The cytotoxicities of all these compounds against human liver cancer lines (HepG2 and Hep3B) were determined. Among them, compound 1 exhibited good cytotoxicity with IC50 value of 17.91µM against human liver tumor cells Hep3B. Following further studies of the anti-tumor mechanism of compound 1-induced cell growth inhibition, we found that compound 1 caused apoptotic cell death in Hep3B cells by detecting morphologic changes and Western blotting analysis.