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Molecules, Volume 23, Issue 12 (December 2018)

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Open AccessArticle High-Pressure Homogenization Pre-Treatment Improved Functional Properties of Oyster Protein Isolate Hydrolysates
Molecules 2018, 23(12), 3344; https://doi.org/10.3390/molecules23123344 (registering DOI)
Received: 14 November 2018 / Revised: 14 December 2018 / Accepted: 15 December 2018 / Published: 17 December 2018
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Abstract
The effects of HPH (high-pressure homogenization) pre-treatment on the functional properties of OPIH (oyster protein isolates hydrolysates) were studied. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis profiles, solubility, particle size distribution, zeta potential, surface hydrophobicity, emulsifying activity index and microstructure of emulsions were analyzed. Results
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The effects of HPH (high-pressure homogenization) pre-treatment on the functional properties of OPIH (oyster protein isolates hydrolysates) were studied. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis profiles, solubility, particle size distribution, zeta potential, surface hydrophobicity, emulsifying activity index and microstructure of emulsions were analyzed. Results indicated that HPH pre-treatment increased the accessibility of OPI to trypsin hydrolysis, resulting in decease in particle size, increase in solubility, absolute zeta potential, surface hydrophobicity and emulsifying activity index. In addition, HPH pre-treated OPIH emulsions became more uniform and the particle size of droplets decreased. These results revealed that HPH pre-treatment has the potential to modify the functional properties of OPIH. Full article
Open AccessArticle Comparison and Identification for Rhizomes and Leaves of Paris yunnanensis Based on Fourier Transform Mid-Infrared Spectroscopy Combined with Chemometrics
Molecules 2018, 23(12), 3343; https://doi.org/10.3390/molecules23123343 (registering DOI)
Received: 29 November 2018 / Revised: 12 December 2018 / Accepted: 14 December 2018 / Published: 17 December 2018
PDF Full-text (1152 KB) | Supplementary Files
Abstract
Paris polyphylla, as a traditional herb with long history, has been widely used to treat diseases in multiple nationalities of China. Nevertheless, the quality of P. yunnanensis fluctuates among from different geographical origins, so that a fast and accurate classification method was
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Paris polyphylla, as a traditional herb with long history, has been widely used to treat diseases in multiple nationalities of China. Nevertheless, the quality of P. yunnanensis fluctuates among from different geographical origins, so that a fast and accurate classification method was necessary for establishment. In our study, the geographical origin identification of 462 P. yunnanensis rhizome and leaf samples from Kunming, Yuxi, Chuxiong, Dali, Lijiang, and Honghe were analyzed by Fourier transform mid infrared (FT-MIR) spectra, combined with partial least squares discriminant analysis (PLS-DA), random forest (RF), and hierarchical cluster analysis (HCA) methods. The obvious cluster tendency of rhizomes and leaves FT-MIR spectra was displayed by principal component analysis (PCA). The distribution of the variable importance for the projection (VIP) was more uniform than the important variables obtained by RF, while PLS-DA models obtained higher classification abilities. Hence, a PLS-DA model was more suitably used to classify the different geographical origins of P. yunnanensis than the RF model. Additionally, the clustering results of different geographical origins obtained by HCA dendrograms also proved the chemical information difference between rhizomes and leaves. The identification performances of PLS-DA and the RF models of leaves FT-MIR matrixes were better than those of rhizomes datasets. In addition, the model classification abilities of combination datasets were higher than the individual matrixes of rhizomes and leaves spectra. Our study provides a reference to the rational utilization of resources, as well as a fast and accurate identification research for P. yunnanensis samples. Full article
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Open AccessArticle Quantum Mechanical/Molecular Mechanical Analysis of the Catalytic Mechanism of Phosphoserine Phosphatase
Molecules 2018, 23(12), 3342; https://doi.org/10.3390/molecules23123342 (registering DOI)
Received: 14 November 2018 / Revised: 11 December 2018 / Accepted: 13 December 2018 / Published: 17 December 2018
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Abstract
Phosphoserine phosphatase (PSP), a member of the haloacid dehalogenase (HAD) superfamily that comprises the vast majority of phosphotransferases, is likely a steady-state regulator of the level of d-serine in the brain. The proposed catalytic cycle of PSP consists of a two-step mechanism:
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Phosphoserine phosphatase (PSP), a member of the haloacid dehalogenase (HAD) superfamily that comprises the vast majority of phosphotransferases, is likely a steady-state regulator of the level of d-serine in the brain. The proposed catalytic cycle of PSP consists of a two-step mechanism: formation of a phospho-enzyme intermediate by phosphate transfer to Asp11 and its subsequent hydrolysis. Our combined quantum mechanical/molecular mechanical (QM/MM) calculations of the reaction pathways favour a dissociative mechanism of nucleophilic substitution via a trigonal-planar metaphosphate-like configuration for both steps, associated with proton transfer to the leaving group or from the nucleophile. This proton transfer is facilitated by active site residue Asp13 that acts as both a general base and a general acid. Free energy calculation on the reaction pathways further support the structural role of the enzymatic environment and the active site architecture. The choice of a proper reaction coordinate along which to bias the free energy calculations can be guided by a projection of the canonical reaction coordinate obtained from a chain-of-state optimisation onto important internal coordinates. Full article
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Open AccessFeature PaperArticle Quantum Chemical Calculations on CHOP Derivatives—Spanning the Chemical Space of Phosphinidenes, Phosphaketenes, Oxaphosphirenes, and COP Isomers
Molecules 2018, 23(12), 3341; https://doi.org/10.3390/molecules23123341 (registering DOI)
Received: 16 November 2018 / Revised: 6 December 2018 / Accepted: 16 December 2018 / Published: 17 December 2018
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Abstract
After many decades of intense research in low-coordinate phosphorus chemistry, the advent of Na[OCP] brought new stimuli to the field of CHOP isomers and derivatives thereof. The present theoretical study at the CCSD(T)/def2-TZVPP level describes the chemical space of CHOP isomers in terms
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After many decades of intense research in low-coordinate phosphorus chemistry, the advent of Na[OCP] brought new stimuli to the field of CHOP isomers and derivatives thereof. The present theoretical study at the CCSD(T)/def2-TZVPP level describes the chemical space of CHOP isomers in terms of structures and potential energy surfaces, using oxaphosphirene as the starting point, but also covering substituted derivatives and COP isomers. Bonding properties of the P–C, P–O, and C–O bonds in all neutral and anionic isomeric species are discussed on the basis of theoretical calculations using various bond strengths descriptors such as WBI and MBO, but also the Lagrangian kinetic energy density per electron as well as relaxed force constants. Ring strain energies of the superstrained 1H-oxaphosphirene and its barely strained oxaphosphirane-3-ylidene isomer were comparatively evaluated with homodesmotic and hyperhomodesmotic reactions. Furthermore, first time calculation of the ring strain energy of an anionic ring is described for the case of oxaphosphirenide. Full article
(This article belongs to the Special Issue Main Group Elements in Synthesis)
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Open AccessArticle Modulation of ERK1/2 and Akt Pathways Involved in the Neurotrophic Action of Caffeic Acid Alkyl Esters
Molecules 2018, 23(12), 3340; https://doi.org/10.3390/molecules23123340 (registering DOI)
Received: 19 November 2018 / Revised: 9 December 2018 / Accepted: 13 December 2018 / Published: 17 December 2018
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Abstract
Neurodegenerative diseases affect millions of human lives all over the world. The number of afflicted patients is rapidly growing, and disease-modifying agents are urgently needed. Caffeic acid, an important member of the hydroxycinnamic acid family of polyphenols, has considerable neurotrophic effects. We have
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Neurodegenerative diseases affect millions of human lives all over the world. The number of afflicted patients is rapidly growing, and disease-modifying agents are urgently needed. Caffeic acid, an important member of the hydroxycinnamic acid family of polyphenols, has considerable neurotrophic effects. We have previously shown how caffeate alkyl ester derivatives significantly promote survival and differentiation in neuronal cells. In this study, the mechanisms by which these ester derivatives exert their neurotrophic effects are examined. A series of eight caffeic acid esters with different alkyl chain lengths, ranging from methyl (CAF1) to dodecyl esters (CAF8), were synthesized and studied for their influence on neurotrophic signaling pathways. Caffeate esters did not induce tropomyosin-receptor kinase A (TrkA) phosphorylation, which was assessed by immunoblotting up to a concentration of 25 µM. NIH/3T3 cells overexpressing TrkA were generated to further examine phosphorylation of this receptor tyrosine kinase. None of the esters induced TrkA phosphorylation in these cells either. Assessment of the effect of caffeate derivatives on downstream neurotrophic pathways by immunoblotting showed that the most potent esters, decyl caffeate (CAF7) and dodecyl caffeate (CAF8) caused extracellular signal-regulated kinase (ERK1/2) and Akt serine threonine kinase phosphorylation in PC12 cells at 5 and 25 µM concentrations. In conclusion, this study shows that caffeate esters exert their neurotrophic action by modulation of ERK1/2 and Akt signaling pathways in neuronal cells, and further demonstrates the potential therapeutic implications of these derivatives for neurodegenerative diseases. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle In Vitro Neuroprotection of Rat Hippocampal Neurons by Manninotriose and Astragaloside IV Against Corticosterone-Induced Toxicity
Molecules 2018, 23(12), 3339; https://doi.org/10.3390/molecules23123339 (registering DOI)
Received: 20 September 2018 / Revised: 12 December 2018 / Accepted: 13 December 2018 / Published: 17 December 2018
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Abstract
A chronically elevated glucocorticoid level impairs memory and cognition. Manninotriose is the main oligosaccharide of Prepared Radix Rehmanniae, and Astragaloside IV (AS-IV) is the primary ingredient of Astragali Radix; they have been reported to possess neuroprotective effects. The aim of the present study
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A chronically elevated glucocorticoid level impairs memory and cognition. Manninotriose is the main oligosaccharide of Prepared Radix Rehmanniae, and Astragaloside IV (AS-IV) is the primary ingredient of Astragali Radix; they have been reported to possess neuroprotective effects. The aim of the present study was to investigate the protective effects of Manninotriose and AS-IV on corticosterone (CORT) induced neurotoxicity and the underlying mechanisms. Primary cultured hippocampal neurons from newborn Sprague Dawley rats were treated with CORT in the absence or presence of Manninotriose and AS-IV. Cell Counting Kit-8 experiments and fluorescein diacetate (FDA)/propidium iodide (PI) double staining were conducted to assess the activity and survival rate of neurons. Quantitative Real-time PCR (qRT-PCR) and western blot analysis were performed to detect the expression of glucocorticoid receptor (GR), zinc finger protein (Zif268) and synapsin 1 (SYN1). DNA methylation of the gene promoter was assessed by bisulfite sequencing (BSP) analysis. The results demonstrated that pre-treatment with Manninotriose and AS-IV significantly improved cell viability and survival rate, and ameliorated the downregulation of GR, Zif268 and SYN1 genes in CORT injured neurons. BSP analysis revealed that CORT was able to improve the CpG island methylation rate of SYN1. AS-IV was observed to decrease the hypermethylation of the SYN1 gene induced by CORT. The results of the present study indicated that Manninotriose and AS-IV may have a protective effect against CORT-induced damage and the downregulation of learning and memory associated genes in hippocampal neurons. Regulation of DNA methylation may be important in the pharmaceutical activities of AS-IV. Thus, Manninotriose and AS-IV may be effective agents against learning and memory impairment. Full article
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Open AccessArticle Temporal Filtering to Improve Single Molecule Identification in High Background Samples
Molecules 2018, 23(12), 3338; https://doi.org/10.3390/molecules23123338 (registering DOI)
Received: 30 October 2018 / Revised: 6 December 2018 / Accepted: 13 December 2018 / Published: 17 December 2018
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Abstract
Single molecule localization microscopy is currently revolutionizing the life sciences as it offers, for the first time, insights into the organization of biological samples below the classical diffraction limit of light microscopy. While there have been numerous examples of new biological findings reported
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Single molecule localization microscopy is currently revolutionizing the life sciences as it offers, for the first time, insights into the organization of biological samples below the classical diffraction limit of light microscopy. While there have been numerous examples of new biological findings reported in the last decade, the technique could not reach its full potential due to a set of limitations immanent to the samples themselves. Particularly, high background signals impede the proper performance of most single-molecule identification and localization algorithms. One option is to exploit the characteristic blinking of single molecule signals, which differs substantially from the residual brightness fluctuations of the fluorescence background. To pronounce single molecule signals, we used a temporal high-pass filtering in Fourier space on a pixel-by-pixel basis. We evaluated the performance of temporal filtering by assessing statistical parameters such as true positive rate and false discovery rate. For this, ground truth signals were generated by simulations and overlaid onto experimentally derived movies of samples with high background signals. Compared to the nonfiltered case, we found an improvement of the sensitivity by up to a factor 3.5 while no significant change in the localization accuracy was observable. Full article
(This article belongs to the Special Issue Single-Molecule Fluorescence Spectroscopy)
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Open AccessArticle Fluorine-Containing Dibenzoanthracene and Benzoperylene-Type Polycyclic Aromatic Hydrocarbons: Synthesis, Structure, and Basic Chemical Properties
Molecules 2018, 23(12), 3337; https://doi.org/10.3390/molecules23123337 (registering DOI)
Received: 20 November 2018 / Revised: 10 December 2018 / Accepted: 11 December 2018 / Published: 16 December 2018
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Abstract
Intramolecular photocyclization of stilbene derivatives (Mallory reaction) is one of the efficient methods for building polycyclic aromatic hydrocarbon (PAH) frameworks, and is also expected to be applicable to synthesis of fluorine-containing PAHs (F-PAHs). In this study, dibenzoanthracene-type (4a) and benzoperylene-type (
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Intramolecular photocyclization of stilbene derivatives (Mallory reaction) is one of the efficient methods for building polycyclic aromatic hydrocarbon (PAH) frameworks, and is also expected to be applicable to synthesis of fluorine-containing PAHs (F-PAHs). In this study, dibenzoanthracene-type (4a) and benzoperylene-type (4b) F-PAHs were synthesized using the Mallory reaction of the 1,4-distyrylbenzene-type π-conjugated molecule (3a), which was prepared by addition-defluorination of available octafluorocyclopentene (OFCP) and aryllithium in three steps. The structure of 4a originating from π–π interaction was characterized by X-ray crystallographic analysis. The absorption maxima of UV-Vis spectra and emission maxima of photoluminescence spectra of the PAHs were positioned at a longer wavelength compared to those of the corresponding unsubstituted PAHs, presumably due to the electron-withdrawing nature of perfluorocyclopentene (PFCP) units. The effect of PFCP units in F-PAHs was also studied by time-dependent density functional theory (TD-DFT) calculation. Full article
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Open AccessArticle Influence of N2 on Formation Conditions and Guest Distribution of Mixed CO2 + CH4 Gas Hydrates
Molecules 2018, 23(12), 3336; https://doi.org/10.3390/molecules23123336 (registering DOI)
Received: 15 November 2018 / Revised: 6 December 2018 / Accepted: 12 December 2018 / Published: 15 December 2018
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Abstract
In this contribution, a method based on a solid solution theory of clathrate hydrate for multiple cage occupancy, host lattice relaxation, and guest-guest interactions is presented to estimate hydrate formation conditions of binary and ternary gas mixtures. We performed molecular modeling of the
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In this contribution, a method based on a solid solution theory of clathrate hydrate for multiple cage occupancy, host lattice relaxation, and guest-guest interactions is presented to estimate hydrate formation conditions of binary and ternary gas mixtures. We performed molecular modeling of the structure, guest distribution, and hydrate formation conditions for the CO2 + CH4 and CO2 + CH4 + N2 gas hydrates. In all considered systems with and without N2, at high and medium content of CO2 in the gas phase, we found that CO2 was more favorable in occupying clathrate hydrate cavities than CH4 or N2. The addition of N2 to the gas phase increased the ratio concentration of CO2 in comparison with the concentration of CH4 in clathrate hydrates and made gas replacement more effective. The mole fraction of CO2 in the CO2 + CH4 + N2 gas hydrate rapidly increased with the growth of its content in the gas phase, and the formation pressure of the CO2 + CH4 + N2 gas hydrate rose in comparison to the formation pressure of the CO2 + CH4 gas hydrate. The obtained results agreed with the known experimental data for simple CH4 and CO2 gas hydrates and the mixed CO2 + CH4 gas hydrate. Full article
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Open AccessArticle A Comparative Study of Advanced Stationary Phases for Fast Liquid Chromatography Separation of Synthetic Food Colorants
Molecules 2018, 23(12), 3335; https://doi.org/10.3390/molecules23123335 (registering DOI)
Received: 8 November 2018 / Revised: 9 December 2018 / Accepted: 13 December 2018 / Published: 15 December 2018
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Abstract
Food analysis demands fast methods for routine control and high throughput of samples. Chromatographic separation enables simultaneous determination of numerous compounds in complex matrices, several approaches increasing separation efficiency and speed of analysis were involved. In this work, modern types of column with
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Food analysis demands fast methods for routine control and high throughput of samples. Chromatographic separation enables simultaneous determination of numerous compounds in complex matrices, several approaches increasing separation efficiency and speed of analysis were involved. In this work, modern types of column with monolithic rod or superficially porous particles were employed and compared for determination of eight synthetic food dyes, their chromatographic performance was evaluated. During method optimization, cyano stationary phase Chromolith Performance CN 100 × 4.6 mm and Ascentis Express ES-CN 100 × 4.6 mm, 5 µm were selected for the separation of polar colorants. The separation was performed by gradient elution of acetonitrile/methanol and 2% water solution of ammonium acetate at flow rate 2.0 mL min−1. Mobile phase composition and the gradients were optimized in order to enable efficient separation on both columns. The method using fused-core particle column provided higher separation efficiency, narrow peaks of analytes resulted in increased peak capacity and shortening of analysis time. After the validation, the method was applied for analysis of coloured beers, soft drinks and candies. Full article
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Open AccessReview Looking at Marine-Derived Bioactive Molecules as Upcoming Anti-Diabetic Agents: A Special Emphasis on PTP1B Inhibitors
Molecules 2018, 23(12), 3334; https://doi.org/10.3390/molecules23123334 (registering DOI)
Received: 30 November 2018 / Revised: 10 December 2018 / Accepted: 13 December 2018 / Published: 15 December 2018
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Abstract
Diabetes mellitus (DM) is a chronic metabolic disease with high morbimortality rates. DM has two types: type 1, which is often associated with a total destruction of pancreatic beta cells, and non-insulin-dependent or type 2 diabetes mellitus (T2DM), more closely associated with obesity
[...] Read more.
Diabetes mellitus (DM) is a chronic metabolic disease with high morbimortality rates. DM has two types: type 1, which is often associated with a total destruction of pancreatic beta cells, and non-insulin-dependent or type 2 diabetes mellitus (T2DM), more closely associated with obesity and old age. The main causes of T2DM are insulin resistance and/or inadequate insulin secretion. Protein-tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signaling pathways and plays an important role in T2DM, as its overexpression may induce insulin resistance. Thus, since PTP1B may be a therapeutic target for both T2DM and obesity, the search for novel and promising natural inhibitors has gained much attention. Hence, several marine organisms, including macro and microalgae, sponges, marine invertebrates, sea urchins, seaweeds, soft corals, lichens, and sea grasses, have been recently evaluated as potential drug sources. This review provides an overview of the role of PTP1B in T2DM insulin signaling and treatment, and highlights the recent findings of several compounds and extracts derived from marine organisms and their relevance as upcoming PTP1B inhibitors. In this systematic literature review, more than 60 marine-derived metabolites exhibiting PTP1B inhibitory activity are listed. Their chemical classes, structural features, relative PTP1B inhibitory potency (assessed by IC50 values), and structure–activity relationships (SARs) that could be drawn from the available data are discussed. The upcoming challenge in the field of marine research—metabolomics—is also addressed. Full article
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Open AccessArticle Metabolomics Research Reveals the Mechanism of Action of Astragalus Polysaccharide in Rats with Digestive System Disorders
Molecules 2018, 23(12), 3333; https://doi.org/10.3390/molecules23123333 (registering DOI)
Received: 24 November 2018 / Revised: 10 December 2018 / Accepted: 14 December 2018 / Published: 15 December 2018
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Abstract
With the diversity of modern dietary lifestyles, digestive system disorders (DSD) have become a frequently occurring disease in recent years. Astragalus polysaccharide (APS) is a homogeneous polysaccharide extracted from Astragalus, which might ameliorate the digestive and absorptive functions. However, the treatment mechanisms
[...] Read more.
With the diversity of modern dietary lifestyles, digestive system disorders (DSD) have become a frequently occurring disease in recent years. Astragalus polysaccharide (APS) is a homogeneous polysaccharide extracted from Astragalus, which might ameliorate the digestive and absorptive functions. However, the treatment mechanisms remain unclear. In this study, rats with DSD were fed a high-fat–low-protein diet and subjected to weight-bearing swimming until exhaustion. When body weight and autonomous activities of the rats decreased, they were administered APS. After two weeks, serum metabolomics analysis based on LC-MS was performed to validate the therapeutic effect of APS and explore its mechanism. APS pharmacodynamics was determined in this study, and serum metabolomics analysis discovered and identified 16 significant, differentially produced metabolites involved in energy, amino acid, and lipid metabolism, including citric acid, lactic acid, alanine, phosphatidylcholine, phenylalanine. After treatment with APS, the levels of the above small-molecule metabolites were reversed. Our results show the efficacy of APS in DSD treatment through the regulation of perturbed metabolic pathways related to energy, amino acid, and lipid metabolism. Full article
(This article belongs to the Section Chemical Biology)
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Open AccessFeature PaperArticle Quantitative Assessment of rPM6 for Fluorine- and Chlorine-Containing Metal Complexes: Comparison with Experimental, First-Principles, and Other Semiempirical Results
Molecules 2018, 23(12), 3332; https://doi.org/10.3390/molecules23123332 (registering DOI)
Received: 30 November 2018 / Revised: 12 December 2018 / Accepted: 14 December 2018 / Published: 15 December 2018
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Abstract
We report a reparameterization of PM6 parameters for fluorine and chlorine using our training set containing transition metal complexes. Spin unrestricted calculations with the resulting rPM6 (UrPM6) were examined quantitatively using two test sets: (i) the description of magnetic interactions in 25 dinuclear
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We report a reparameterization of PM6 parameters for fluorine and chlorine using our training set containing transition metal complexes. Spin unrestricted calculations with the resulting rPM6 (UrPM6) were examined quantitatively using two test sets: (i) the description of magnetic interactions in 25 dinuclear metal complexes and (ii) the prediction of barrier heights and reaction energies for epoxidation and fluorination reactions catalyzed by high-valent manganese-oxo species. The conventional UPM6 and UPM7 methods were also evaluated for comparison on the basis of either experimental or computational (the UB3LYP/SVP level) outcomes. The merits of UrPM6 are highlighted by both the test sets. As regards magnetic exchange coupling constants, the UrPM6 method had the smallest mean absolute errors from the experimental data (19 cm−1), followed by UPM7 (119 cm−1) and UPM6 (373 cm−1). For the epoxidation and fluorination reactions, all of the transition state searches were successful using UrPM6, while the success rates obtained by UPM6 and UPM7 were only 50%. The UrPM6-optimized stationary points also agreed well with the reference UB3LYP-optimized geometries. The accuracy for estimating reaction energies was also greatly remedied. Full article
(This article belongs to the Special Issue Open-Shell Systems for Functional Materials)
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Open AccessArticle Deuterated Arachidonic Acids Library for Regulation of Inflammation and Controlled Synthesis of Eicosanoids: An In Vitro Study
Molecules 2018, 23(12), 3331; https://doi.org/10.3390/molecules23123331 (registering DOI)
Received: 26 November 2018 / Revised: 10 December 2018 / Accepted: 10 December 2018 / Published: 15 December 2018
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Abstract
The synthesis of signal lipids, including eicosanoids, is not fully understood, although it is key to the modulation of various inflammatory states. Recently, isotopologues of essential polyunsaturated fatty acids (PUFAs) deuterated at bis-allylic positions (D-PUFAs) have been proposed as inhibitors of non-enzymatic lipid
[...] Read more.
The synthesis of signal lipids, including eicosanoids, is not fully understood, although it is key to the modulation of various inflammatory states. Recently, isotopologues of essential polyunsaturated fatty acids (PUFAs) deuterated at bis-allylic positions (D-PUFAs) have been proposed as inhibitors of non-enzymatic lipid peroxidation (LPO) in various disease models. Arachidonic acid (AA, 20:4 n-6) is the main precursor to several classes of eicosanoids, which are produced by cyclooxygenases (COX) and lipoxygenases (LOX). In this study we analyzed the relative activity of human recombinant enzymes COX-2, 5-LOX, and 15-LOX-2 using a library of arachidonic acids variably deuterated at the bis-allylic (C7, C10, and C13) positions. Kinetic parameters (KM, Vmax) and isotope effects calculated from kH/kD for seven deuterated arachidonic acid derivatives were obtained. Spectroscopic methods have shown that deuteration at the 13th position dramatically affects the kinetic parameters of COX-2 and 15-LOX-2. The activity of 5-LOX was evaluated by measuring hydroxyeicosatetraenoic acids (8-HETE and 5-HETE) using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Deuteration at the seventh and 10th positions affects the performance of the 5-LOX enzyme. A flowchart is proposed suggesting how to modulate the synthesis of selected eicosanoids using the library of deuterated isotopologues to potentially fine-tune various inflammation stages. Full article
(This article belongs to the Section Chemical Biology)
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Open AccessArticle Metabolomics of Solanum lycopersicum Infected with Phytophthora infestans Leads to Early Detection of Late Blight in Asymptomatic Plants
Molecules 2018, 23(12), 3330; https://doi.org/10.3390/molecules23123330 (registering DOI)
Received: 28 October 2018 / Revised: 3 December 2018 / Accepted: 3 December 2018 / Published: 15 December 2018
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Abstract
Tomato crops suffer attacks of various pathogens that cause large production losses. Late blight caused by Phytophthora infestans is a devastating disease in tomatoes because of its difficultly to control. Here, we applied metabolomics based on liquid chromatography–mass spectrometry (LC-MS) and metabolic profiling
[...] Read more.
Tomato crops suffer attacks of various pathogens that cause large production losses. Late blight caused by Phytophthora infestans is a devastating disease in tomatoes because of its difficultly to control. Here, we applied metabolomics based on liquid chromatography–mass spectrometry (LC-MS) and metabolic profiling by matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) in combination with multivariate data analysis in the early detection of late blight on asymptomatic tomato plants and to discriminate infection times of 4, 12, 24, 36, 48, 60, 72 and 96 h after inoculation (hpi). MALDI-MS and LC-MS profiles of metabolites combined with multivariate data analysis are able to detect early-late blight-infected tomato plants, and metabolomics based on LC-MS discriminates infection times in asymptomatic plants. We found the metabolite tomatidine as an important biomarker of infection, saponins as early infection metabolite markers and isocoumarin as early and late asymptomatic infection marker along the post infection time. MALDI-MS and LC-MS analysis can therefore be used as a rapid and effective method for the early detection of late blight-infected tomato plants, offering a suitable tool to guide the correct management and application of sanitary defense approaches. LC-MS analysis also appears to be a suitable tool for identifying major metabolites of asymptomatic late blight-infected tomato plants. Full article
(This article belongs to the Special Issue Biological Sample Analysis by Liquid Chromatography)
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Open AccessArticle RNA–Protein Interactions Prevent Long RNA Duplex Formation: Implications for the Design of RNA-Based Therapeutics
Molecules 2018, 23(12), 3329; https://doi.org/10.3390/molecules23123329 (registering DOI)
Received: 19 November 2018 / Revised: 12 December 2018 / Accepted: 13 December 2018 / Published: 15 December 2018
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Abstract
Cells frequently simultaneously express RNAs and cognate antisense transcripts without necessarily leading to the formation of RNA duplexes. Here, we present a novel transcriptome-wide experimental approach to ascertain the presence of accessible double-stranded RNA structures based on sequencing of RNA fragments longer than
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Cells frequently simultaneously express RNAs and cognate antisense transcripts without necessarily leading to the formation of RNA duplexes. Here, we present a novel transcriptome-wide experimental approach to ascertain the presence of accessible double-stranded RNA structures based on sequencing of RNA fragments longer than 18 nucleotides that were not degraded by single-strand cutting nucleases. We applied this approach to four different cell lines with respect to three different treatments (native cell lysate, removal of proteins, and removal of ribosomal RNA and proteins). We found that long accessible RNA duplexes were largely absent in native cell lysates, while the number of RNA duplexes was dramatically higher when proteins were removed. The majority of RNA duplexes involved ribosomal transcripts. The duplex formation between different non-ribosomal transcripts appears to be largely of a stochastic nature. These results suggest that cells are—via RNA-binding proteins—mostly devoid of long RNA duplexes, leading to low “noise” in the molecular patterns that are utilized by the innate immune system. These findings have implications for the design of RNA interference (RNAi)-based therapeutics by imposing structural constraints on designed RNA complexes that are intended to have specific properties with respect to Dicer cleavage and target gene downregulation. Full article
(This article belongs to the Special Issue Therapeutic Nucleic Acids: Past, Present, and Future)
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Open AccessArticle Tetra-glucopyranosyl Diterpene ent-Kaur-16-en-19-oic Acid and ent-13(S)-Hydroxyatisenoic Acid Derivatives from a Commercial Extract of Stevia rebaudiana (Bertoni) Bertoni
Molecules 2018, 23(12), 3328; https://doi.org/10.3390/molecules23123328 (registering DOI)
Received: 29 November 2018 / Revised: 13 December 2018 / Accepted: 14 December 2018 / Published: 15 December 2018
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Abstract
Stevia rebaudiana and its diterpene glycosides are one of the main focuses of food companies interested in developing novel zero calorie sugar substitutes since the recognition of steviol glycosides as Generally Recognized as Safe (GRAS) by the United States Food and Drug Administration.
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Stevia rebaudiana and its diterpene glycosides are one of the main focuses of food companies interested in developing novel zero calorie sugar substitutes since the recognition of steviol glycosides as Generally Recognized as Safe (GRAS) by the United States Food and Drug Administration. Rebaudioside A, one of the major steviol glycosides of the leaves is more than 200 times sweeter than sucrose. However, its lingering aftertaste makes it less attractive as a table-top sweetener, despite its human health benefits. Herein, we report the purification of two novel tetra-glucopyranosyl diterpene glycosides 1 and 3 (rebaudioside A isomers) from a commercial Stevia rebaudiana leaf extract compounds, their saponification products compounds 2 and 4, together with three known compounds isolated in gram quantities. Compound 1 was determined to be 13-[(2-O-β-d-glucopyranosyl-6-O-β-d-glucopyranosyl-β-d-glucopyranosyl) oxy]ent-kaur-16-en-19-oic acid-β-d-glucopyranosy ester (rebaudioside Z), whereas compound 3 was found to be 13-[(2-O-β-d-glucopyranosyl-3-O-β-d-glucopyranosyl-β-d-glucopyranosyl) oxy]ent-hydroxyatis-16-en-19-oic acid -β-d-glucopyranosy ester. Two new tetracyclic derivatives with no sugar at position C-19 were prepared from rebaudiosides 1 and 3 under mild alkaline hydrolysis to afford compounds 2 13-[(2-O-β-d-glucopyranosyl-6-O-β-d-glucopyranosyl-β-d-glucopyranosyl) oxy]ent-kaur-16-en-19-oic acid (rebaudioside Z1) and 4 13-[(2-O-β-d-glucopyranosyl-3-O-β-d-glucopyranosyl-β-d-glucopyranosyl) oxy]ent-hydroxyatis-16-en-19-oic acid. Three known compounds were purified in gram quantities and identified as rebaudiosides A (5), H (6) and J (7). Chemical structures were unambiguously elucidated using different approaches, namely HRESIMS, HRESI-MS/MS, and 1D-and 2D-NMR spectroscopic data. Additionally, a high-quality crystal of iso-stevioside was grown in methanol and its structure confirmed by X-ray diffraction. Full article
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Open AccessArticle Evaluation of the Inhibitory Effects of Genipin on the Fluoxetine-Induced Invasive and Metastatic Model in Human HepG2 Cells
Molecules 2018, 23(12), 3327; https://doi.org/10.3390/molecules23123327
Received: 16 November 2018 / Revised: 10 December 2018 / Accepted: 13 December 2018 / Published: 14 December 2018
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Abstract
Metastasis of hepatocellular carcinoma (HCC) is usually unrecognized before any pathological examination, resulting in time-taking treatment and poor prognosis. As a consequence, HCC patients usually show symptoms of depression. In order to suppress such psychiatric disorders and to facilitate better treatment outcome, antidepressants
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Metastasis of hepatocellular carcinoma (HCC) is usually unrecognized before any pathological examination, resulting in time-taking treatment and poor prognosis. As a consequence, HCC patients usually show symptoms of depression. In order to suppress such psychiatric disorders and to facilitate better treatment outcome, antidepressants are prescribed. Up to present, information about the effect of antidepressants on HCC is still lacking. Therefore, we chose fluoxetine (FXT), one of the top five psychiatric prescriptions in the United States, together with the HepG2 cell model to explore its effect on HCC. Our study found that FXT (5 µM) increased the migratory distance of HepG2 cells by a factor of nearly 1.7 compared to control. In addition, our study also investigated the effect of genipin (GNP), which is an active compound from Gardenia jasminoides Ellis fruit (family Rubiaceae), on the FXT-induced HepG2 cells. Our study found that 30 and 60 µM GNP reduced the migratory distance by 42% and 74% respectively, compared to FXT treatment alone. Furthermore, we also found that FXT upregulated matrix metalloproteinases (MMPs) genes, increased the protein expression of MMPs, urokinase-type plasminogen activator (uPA), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), activator protein 1 (AP-1), phosphorylated mitogen-activated protein kinase (P-p38), phosphorylated protein kinase B (P-Akt), downregulated tissue inhibitor metalloproteinases (TIMPs) genes and decreased the TIMPs proteins expression whereas, GNP fully counteracted the action of FXT. Conclusively, this study has provided valuable information regarding the possible molecular mechanisms through which FXT affects the metastatic invasiveness of HepG2 cells and evidences to support that GNP counteracts such effect via the same molecular mechanisms. Full article
Open AccessFeature PaperArticle Development of an LC–Tandem Mass Spectrometry Method for the Quantitative Analysis of Hercynine in Human Whole Blood
Molecules 2018, 23(12), 3326; https://doi.org/10.3390/molecules23123326
Received: 23 November 2018 / Revised: 13 December 2018 / Accepted: 13 December 2018 / Published: 14 December 2018
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Abstract
Given that the peculiar redox behavior of ergothioneine involves a rapid regeneration process, the measurement of its precursor and redox metabolite hercynine could be particularly useful in assessing its role in oxidative stress or other biological processes. Thus, a LC-MS/MS method for the
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Given that the peculiar redox behavior of ergothioneine involves a rapid regeneration process, the measurement of its precursor and redox metabolite hercynine could be particularly useful in assessing its role in oxidative stress or other biological processes. Thus, a LC-MS/MS method for the determination of hercynine concentrations in whole blood was developed. After lysis of red blood cells by cold water, samples were filtered on micro concentrators at a controlled temperature of 4 °C. The clear filtered fluid was then treated with diethylpyrocarbonate to derivatize hercynine for the analysis by LC-MS/MS. The derivatized analyte was isocratically separated as a carbethoxy derivative on a C18 column with a mobile phase of an aqueous 0.1% v/v formic acid and acetonitrile (95:5). Effluents were monitored by MRM transitions at m/z 270.28→95 and 273.21→95 for hercynine and its deuterated counterpart, respectively. No cross-talk between MRM transitions was observed and a good linearity was found within a range of 35–1120 nmol/L. The LOD and LOQ were, respectively, 10.30 and 31.21 nmol/L with an intraday and intermediate precision below 7%. The average hercynine concentration in whole blood from 30 healthy male volunteers (aged 77 ± 12 years) was 178.5 ± 118.1 nmol/L. Overall, the method is easy to perform, allowing a rapid and accurate assessment of whole blood concentrations of hercynine. Full article
(This article belongs to the Special Issue Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry-II)
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Open AccessArticle [2+2+2] Annulation of N-(1-Naphthyl)acetamide with Two Alkynoates via Cleavage of Adjacent C–H and C–N Bonds Catalyzed by an Electron-Deficient Rhodium(III) Complex
Molecules 2018, 23(12), 3325; https://doi.org/10.3390/molecules23123325
Received: 21 November 2018 / Revised: 7 December 2018 / Accepted: 12 December 2018 / Published: 14 December 2018
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Abstract
It has been established that an electron-deficient cationic CpE-rhodium(III) complex catalyzes the non-oxidative [2+2+2] annulation of N-(1-naphthyl)acetamide with two alkynoates via cleavage of the adjacent C–H and C–N bonds to give densely substituted phenanthrenes under mild conditions (at 40 °C
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It has been established that an electron-deficient cationic CpE-rhodium(III) complex catalyzes the non-oxidative [2+2+2] annulation of N-(1-naphthyl)acetamide with two alkynoates via cleavage of the adjacent C–H and C–N bonds to give densely substituted phenanthrenes under mild conditions (at 40 °C under air). In this reaction, a dearomatized spiro compound was isolated, which may support the formation of a cationic spiro rhodacycle intermediate in the catalytic cycle. The use of N-(1-naphthyl)acetamide in place of acetanilide switched the reaction pathway from the oxidative [2+2+2] annulation-lactamization via C–H/C–H cleavage to the non-oxidative [2+2+2] annulation via C–H/C–N cleavage. This chemoselectivity switch may arise from stabilization of the carbocation in the above cationic spiro rhodacycle by the neighboring phenyl and acetylamino groups, resulting in the nucleophilic C–C bond formation followed by β-nitrogen elimination. Full article
(This article belongs to the Special Issue Amide Bond Activation)
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Open AccessArticle Analysis of Targeted Metabolites and Molecular Structure of Starch to Understand the Effect of Glutinous Rice Paste on Kimchi Fermentation
Molecules 2018, 23(12), 3324; https://doi.org/10.3390/molecules23123324
Received: 21 November 2018 / Revised: 13 December 2018 / Accepted: 13 December 2018 / Published: 14 December 2018
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Abstract
Bachu (Chinese cabbage) kimchi, a Korean traditional fermented dish, were prepared with or without the addition of glutinous (waxy) rice paste and their characteristics including pH, total bacteria count, total starch content, sugar metabolites, and molecular structure of starch were examined periodically for
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Bachu (Chinese cabbage) kimchi, a Korean traditional fermented dish, were prepared with or without the addition of glutinous (waxy) rice paste and their characteristics including pH, total bacteria count, total starch content, sugar metabolites, and molecular structure of starch were examined periodically for 20 days to investigate the effect of adding glutinous rice paste to kimchi during fermentation. The pH and total bacteria count showed that the fermentation of kimchi added with glutinous rice paste (GRP kimchi) progressed a little more quickly than that of control kimchi without glutinous rice paste. The GRP kimchi had higher glucose content but lower fructose content than control kimchi. Interestingly, maltose was only detected in GRP kimchi during fermentation. The GRP kimchi contained much greater amount of mannitol throughout fermentation than control kimchi. Total starch content in GRP kimchi gradually decreased during fermentation, which might have contributed to its greater glucose content and the larger amount of maltose production. In GRP kimchi, peak height and area for all degrees of polymerization (DP) of starch decreased during fermentation and its average chain length decreased while the proportion of short chains increased as fermentation processed, indicating degradation of starch chains by enzymes presented in the kimchi. Full article
(This article belongs to the Special Issue Carbohydrate Chemistry)
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Open AccessArticle An Assessment of Computational Methods for Calculating Accurate Structures and Energies of Bio-Relevant Polysulfur/Selenium-Containing Compounds
Molecules 2018, 23(12), 3323; https://doi.org/10.3390/molecules23123323
Received: 27 November 2018 / Revised: 12 December 2018 / Accepted: 12 December 2018 / Published: 14 December 2018
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Abstract
The heavier chalcogens sulfur and selenium are important in organic and inorganic chemistry, and the role of such chalcogens in biological systems has recently gained more attention. Sulfur and, to a lesser extent selenium, are involved in diverse reactions from redox signaling to
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The heavier chalcogens sulfur and selenium are important in organic and inorganic chemistry, and the role of such chalcogens in biological systems has recently gained more attention. Sulfur and, to a lesser extent selenium, are involved in diverse reactions from redox signaling to antioxidant activity and are considered essential nutrients. We investigated the ability of the DFT functionals (B3LYP, B3PW91, ωB97XD, M06-2X, and M08-HX) relative to electron correlation methods MP2 and QCISD to produce reliable and accurate structures as well as thermochemical data for sulfur/selenium-containing systems. Bond lengths, proton affinities (PA), gas phase basicities (GPB), chalcogen–chalcogen bond dissociation enthalpies (BDE), and the hydrogen affinities (HA) of thiyl/selenyl radicals were evaluated for a range of small polysulfur/selenium compounds and cysteine per/polysulfide. The S–S bond length was found to be the most sensitive to basis set choice, while the geometry of selenium-containing compounds was less sensitive to basis set. In mixed chalcogens species of sulfur and selenium, the location of the sulfur atom affects the S–Se bond length as it can hold more negative charge. PA, GPB, BDE, and HA of selenium systems were all lower, indicating more acidity and more stability of radicals. Extending the sulfur chain in cysteine results in a decrease of BDE and HA, but these plateau at a certain point (199 kJ mol−1 and 295 kJ mol−1), and PA and GPB are also decreased relative to the thiol, indicating that the polysulfur species exist as thiolates in a biological system. In general, it was found that ωB97XD/6-311G(2d,p) gave the most reasonable structures and thermochemistry relative to benchmark calculations. However, nuances in performance are observed and discussed. Full article
(This article belongs to the Section Computational and Theoretical Chemistry)
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Open AccessArticle Cardioprotective Effects of Puerarin-V on Isoproterenol-Induced Myocardial Infarction Mice Is Associated with Regulation of PPAR-Υ/NF-κB Pathway
Molecules 2018, 23(12), 3322; https://doi.org/10.3390/molecules23123322
Received: 12 November 2018 / Revised: 10 December 2018 / Accepted: 13 December 2018 / Published: 14 December 2018
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Abstract
Puerarin is a well-known traditional Chinese medicine which has been used for the treatment of cardiovascular diseases. Recently, a new advantageous crystal form of puerarin, puerarin-V, has been developed. However, the cardioprotective effects of puerarin-V on myocardial infarction (MI) heart failure are still
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Puerarin is a well-known traditional Chinese medicine which has been used for the treatment of cardiovascular diseases. Recently, a new advantageous crystal form of puerarin, puerarin-V, has been developed. However, the cardioprotective effects of puerarin-V on myocardial infarction (MI) heart failure are still unclear. In this research, we aim to evaluate the cardioprotective effects of puerarin-V on the isoproterenol (ISO)-induced MI mice and elucidate the underlying mechanisms. To induce MI in C57BL/6 mice, ISO was administered at 40 mg/kg subcutaneously every 12 h for three times in total. The mice were randomly divided into nine groups: (1) control; (2) ISO; (3) ISO + puerarin injection; (4–9) ISO + puerarin-V at different doses and timings. After treatment, cardiac function was evaluated by electrocardiogram (ECG), biochemical and histochemical analysis. In vitro inflammatory responses and apoptosis were evaluated in human coronary artery endothelial cells (HCAECs) challenged by lipopolysaccharide (LPS). LPS-induced PPAR-Υ/NF-κB and subsequently activation of cytokines were assessed by the western blot and real-time polymerase chain reaction (PCR). Administration of puerarin-V significantly inhibits the typical ST segment depression compared with that in MI mice. Further, puerarin-V treatment significantly improves ventricular wall infarction, decreases the incidence of mortality, and inhibits the levels of myocardial injury markers. Moreover, puerarin-V treatment reduces the inflammatory milieu in the heart of MI mice, thereby blocking the upregulation of proinflammatory cytokines (TNF-α, IL-1β and IL-6). The beneficial effects of puerarin-V might be associated with the normalization in gene expression of PPAR-Υ and PPAR-Υ/NF-κB /ΙκB-α/ΙΚΚα/β phosphorylation. In the in vitro experiment, treatment with puerarin-V (0.3, 1 and 3 μM) significantly reduces cell death and suppresses the inflammation cytokines expression. Likewise, puerarin-V exhibits similar mechanisms. The cardioprotective effects of puerarin-V treatment on MI mice in the pre + post-ISO group seem to be more prominent compared to those in the post-ISO group. Puerarin-V exerts cardioprotective effects against ISO-induced MI in mice, which may be related to the activation of PPAR-γ and the inhibition of NF-κB signaling in vivo and in vitro. Taken together, our research provides a new therapeutic option for the treatment of MI in clinic. Full article
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)
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Open AccessArticle Evaluation of the Absorption Behavior of Main Component Compounds of Salt-Fried Herb Ingredients in Qing’e Pills by Using Caco-2 Cell Model
Molecules 2018, 23(12), 3321; https://doi.org/10.3390/molecules23123321
Received: 31 October 2018 / Revised: 7 December 2018 / Accepted: 12 December 2018 / Published: 14 December 2018
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Abstract
Qing’e Pills is a Chinese traditional herbal product, which is often used to strengthen muscles and bones in TCM (traditional Chinese Medicine) practice. Its two main component herbs, namely, Cortex Eucommiae and Fructus Psoraleae are both required to be salt-fried according to TCM
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Qing’e Pills is a Chinese traditional herbal product, which is often used to strengthen muscles and bones in TCM (traditional Chinese Medicine) practice. Its two main component herbs, namely, Cortex Eucommiae and Fructus Psoraleae are both required to be salt-fried according to TCM theory. We have evaluated the effects of salt-frying treated herbs on Caco-2 cell uptake behavior for those active ingredients of Qing’e Pills. By investigating of various variables, including MTT, temperature, inhibitors, pH, salt concentration and herb processing methods, we tried to clarify whether the salt-processing on herbs was necessary or not. Results showed that, compared to other processing methods, the salt-frying process significantly (p < 0.01) enhanced the absorption of effective components of Qing’e Pills. The way that psoralen, isopsoralen, psoralenoside and geniposide acid entered Caco-2 cells at low concentrations was via passive diffusion. These components were not substrates of P-glycoprotein. It demonstrated that the salt-frying process not only enhanced the concentration of active components in herb extract, but also changed their absorption behaviors. Nevertheless, the mechanism of absorption behavior changing needs to be further investigated. Full article
(This article belongs to the collection Herbal Medicine Research)
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Open AccessArticle Design, Synthesis and Antibacterial Evaluation of 3-Substituted Ocotillol-Type Derivatives
Molecules 2018, 23(12), 3320; https://doi.org/10.3390/molecules23123320 (registering DOI)
Received: 30 November 2018 / Revised: 12 December 2018 / Accepted: 13 December 2018 / Published: 14 December 2018
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Abstract
Antibiotic resistance has become a serious global problem that threatens public health. In our previous work, we found that ocotillol-type triterpenoid saponin showed good antibacterial activity. Based on preliminary structure-activity relationship, novel serious C-3 substituted ocotillol-type derivatives 726 were designed and
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Antibiotic resistance has become a serious global problem that threatens public health. In our previous work, we found that ocotillol-type triterpenoid saponin showed good antibacterial activity. Based on preliminary structure-activity relationship, novel serious C-3 substituted ocotillol-type derivatives 726 were designed and synthesized. The in vitro antibacterial activity was tested on five bacterial strains (B. subtilis 168, S. aureus RN4220, E. coli DH5α, A. baum ATCC19606 and MRSA USA300) and compared with the tests on contrast. Among these derivatives, C-3 position free hydroxyl substituted compounds 714, showed good antibacterial activity against Gram-positive bacteria. Furthermore, compound 22 exhibited excellent antibacterial activity with minimum inhibitory concentrations (MIC) values of 2 μg/mL against MRSA USA300 and 4 μg/mL against B. subtilis. The structure-activity relationships of all current ocotillol-type derivatives our team synthesised were summarized. In addition, the prediction of absorption, distribution, metabolism, and excretion (ADME) properties and the study of pharmacophores were also conducted. These results can provide a guide to further design and synthesis works. Full article
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Open AccessArticle Schisandra Chinensis Lignans Suppresses the Production of Inflammatory Mediators Regulated by NF-κB, AP-1, and IRF3 in Lipopolysaccharide-Stimulated RAW264.7 Cells
Molecules 2018, 23(12), 3319; https://doi.org/10.3390/molecules23123319
Received: 23 November 2018 / Revised: 9 December 2018 / Accepted: 10 December 2018 / Published: 14 December 2018
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Abstract
Schisandra Fructus (SF) is a traditional Chinese herb used in the treatment of inflammatory disorders like hepatitis. One of the main anti-inflammatory components of SF is the lignans. However, the underlying anti-inflammatory mechanism of Schisandra Chinensis lignans (SCL) remains unclear. This study aims
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Schisandra Fructus (SF) is a traditional Chinese herb used in the treatment of inflammatory disorders like hepatitis. One of the main anti-inflammatory components of SF is the lignans. However, the underlying anti-inflammatory mechanism of Schisandra Chinensis lignans (SCL) remains unclear. This study aims to investigate the effects of SCL on inflammatory mediators in lipopolysaccharide-stimulated RAW264.7 cells and explore the underlying mechanism. The production of nitric oxide (NO) was determined by Griess reaction. ELISA was used to determine cytokine levels and chemokines secretion. To estimate protein levels and enzyme activities, we employed Western blotting. Nuclear localization of NF-κB, AP-1, and IRF3 was detected using immunofluorescence analyses. The results showed that SCL significantly reduced the release of inflammatory mediators, including NO and PGE2, which may be related to down-regulation of iNOS and COX-2 expression. The production of cytokines and chemokines was suppressed by SCL treatment. SCL also decreased the phosphorylation of IKKα/β, IκB-α, Akt, TBK1, ERK, p38, JNK, NF-κB (p65), AP-1 (c-Jun), and IRF3 in RAW264.7 macrophages activated with LPS. The nuclear protein levels and nuclear translocation of AP-1, NF-κB and IRF3 were suppressed by SCL. These results indicated that SCL suppressed the IKKα/β/NF-κB, MAPKs/AP-1 and TBK1/IRF3 signaling pathways in LPS-stimulated RAW264.7 macrophages. Full article
(This article belongs to the Special Issue Bioactive Plant Compounds for Sustainable Health)
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Open AccessArticle Enhancement of Berberine Hypoglycemic Activity by Oligomeric Proanthocyanidins
Molecules 2018, 23(12), 3318; https://doi.org/10.3390/molecules23123318
Received: 29 November 2018 / Revised: 10 December 2018 / Accepted: 12 December 2018 / Published: 14 December 2018
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Abstract
This study investigated the possible enhancement of berberine’s (BB) hypoglycemic activity by oligomeric proanthocyanidins (OPCs) and its underlying mechanism. The hypoglycemic activity of the studied compounds was evaluated in diabetic db/db mice. The cellular uptake and efflux of BB with or
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This study investigated the possible enhancement of berberine’s (BB) hypoglycemic activity by oligomeric proanthocyanidins (OPCs) and its underlying mechanism. The hypoglycemic activity of the studied compounds was evaluated in diabetic db/db mice. The cellular uptake and efflux of BB with or without OPCs were investigated using Caco-2 intestinal cells. A pharmacokinetic study of BB and OPCs was performed in Sprague Dawley (SD) mice by oral administration of the study compounds. Liquid chromatography–tandem mass spectrometry (LC–MS/MS) was employed to determine the cellular efflux, retention, and the serum concentrations of the compounds. The results revealed that OPCs considerably potentiated the hypoglycemic efficacy of BB in diabetic db/db mice. In the in vitro experiments, OPCs significantly inhibited the efflux and increased the uptake of the P-glycoprotein (P-gp) substrate rhodamine-123 (R123) and BB in Caco-2 intestinal cells. Moreover, OPCs substantially reduced the expression of P-gp in Caco-2 cells. The inhibition of BB efflux by OPCs was translated into the improved pharmacokinetics in vivo. When co-administered, OPCs obviously increased the average maximum concentration of BB in mice. In summary, this study demonstrated that combination of BB with OPCs could significantly improve the pharmacokinetics and hypoglycemic efficacy of BB, which is valuable for future exploration of the combination of BB and OPCs as oral hypoglycemic agents. Full article
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Open AccessArticle HFIP-Promoted Bischler Indole Synthesis under Microwave Irradiation
Molecules 2018, 23(12), 3317; https://doi.org/10.3390/molecules23123317
Received: 27 November 2018 / Revised: 10 December 2018 / Accepted: 11 December 2018 / Published: 14 December 2018
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Abstract
1,1,1,3,3,3-Hexafluoropropan-2-ol (HFIP) was found to be effective for the Bischler indole synthesis under microwave irradiation in the absence of a metal catalyst. Under the catalysis of HFIP, a wide range of α-amino arylacetones were successfully transformed into indole derivatives with moderate to good
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1,1,1,3,3,3-Hexafluoropropan-2-ol (HFIP) was found to be effective for the Bischler indole synthesis under microwave irradiation in the absence of a metal catalyst. Under the catalysis of HFIP, a wide range of α-amino arylacetones were successfully transformed into indole derivatives with moderate to good yields. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle Simultaneous Determination of Nε-(carboxymethyl) Lysine and Nε-(carboxyethyl) Lysine in Different Sections of Antler Velvet after Various Processing Methods by UPLC-MS/MS
Molecules 2018, 23(12), 3316; https://doi.org/10.3390/molecules23123316
Received: 13 November 2018 / Revised: 9 December 2018 / Accepted: 12 December 2018 / Published: 14 December 2018
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Abstract
Nε-(Carboxymethyl) lysine (CML) and Nε-(carboxyethyl) advanced glycation end-products (AGEs) and are frequently used as markers of AGE formation. AGEs, such as CML and CEL, have harmful effects in the human body and have been closely linked to many diseases
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Nε-(Carboxymethyl) lysine (CML) and Nε-(carboxyethyl) advanced glycation end-products (AGEs) and are frequently used as markers of AGE formation. AGEs, such as CML and CEL, have harmful effects in the human body and have been closely linked to many diseases such as diabetes and uremia. However, details on the contents of CML and CEL after applying different antler velvet processing methods are lacking. In this research, a robust lysine (CEL) are two typical UPLC-MS/MS method has been developed for the simultaneous determination of CML and CEL in various sections of antler velvet processed with different methods. In addition, factors affecting the CML and CEL contents are discussed. The CML contents of antler velvet after freeze-drying, boiling, processing without blood, and processing with blood were 74.55–458.59, 119.44–570.69, 75.36–234.92, and 117.11–456.01 μg/g protein, respectively; the CEL contents were 0.74–12.66, 11.33–35.93, 0.00–6.75, and 0.00–23.41 μg/g protein, respectively. The different contents of CML and CEL in the different samples of antler velvet result from the different interactions of the protein and lysine at different temperatures. These data can be used to estimate the potential consumer intake of CML and CEL from antler velvet and for guiding producers on how to reduce the production of CML and CEL. Full article
(This article belongs to the Special Issue Method Development and Validation in Food and Pharmaceutical Analysis)
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Open AccessArticle Chenodeoxycholic Acid from Bile Inhibits Influenza A Virus Replication via Blocking Nuclear Export of Viral Ribonucleoprotein Complexes
Molecules 2018, 23(12), 3315; https://doi.org/10.3390/molecules23123315
Received: 19 October 2018 / Revised: 10 December 2018 / Accepted: 12 December 2018 / Published: 14 December 2018
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Abstract
Influenza A virus (IAV) infection is still a major global threat for humans, especially for the risk groups: young children and the elderly. The currently licensed antiviral drugs target viral factors and are prone to viral resistance. In recent years, a few endogenous
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Influenza A virus (IAV) infection is still a major global threat for humans, especially for the risk groups: young children and the elderly. The currently licensed antiviral drugs target viral factors and are prone to viral resistance. In recent years, a few endogenous small molecules from host, such as estradiol and omega-3 polyunsaturated fatty acid (PUFA)-derived lipid mediator protection D1 (PD1), were demonstrated to be capable of inhibiting IAV infection. Chenodeoxycholic acid (CDCA), one of the main primary bile acids, is synthesized from cholesterol in the liver and classically functions in emulsification and absorption of dietary fats. Clinically, CDCA has been used in the treatment of patients with cholesterol gallstones for more than five decades. In this study, we showed that CDCA attenuated the replication of three subtypes of influenza A virus, including a highly pathogenic H5N1 strain, in A549 and MDCK cell cultures with IC50 ranging from 5.5 to 11.5 μM. Mechanistically, CDCA effectively restrained the nuclear export of viral ribonucleoprotein (vRNP) complexes. In conclusion, as an endogenous physiological small molecule, CDCA can inhibit IAV replication in vitro, at least in part, by blocking vRNP nuclear export, and affords further studies for development as a potential antiviral agent against IAV infections. Full article
(This article belongs to the Special Issue Recent Advances in the Development of Antiviral Agents)
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