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Molecules, Volume 24, Issue 8 (April-2 2019)

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Open AccessArticle Microwave-Assisted Synthesis of Trazodone and Its Derivatives as New 5-HT1A Ligands: Binding and Docking Studies
Molecules 2019, 24(8), 1609; https://doi.org/10.3390/molecules24081609 (registering DOI)
Received: 12 March 2019 / Revised: 13 April 2019 / Accepted: 19 April 2019 / Published: 23 April 2019
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Abstract
Trazodone, a well-known antidepressant drug widely used throughout the world, works as a 5-hydroxytryptamine (5-HT2) and α1-adrenergic receptor antagonist and a serotonin reuptake inhibitor. Our research aimed to develop a new method for the synthesis of trazodone and its [...] Read more.
Trazodone, a well-known antidepressant drug widely used throughout the world, works as a 5-hydroxytryptamine (5-HT2) and α1-adrenergic receptor antagonist and a serotonin reuptake inhibitor. Our research aimed to develop a new method for the synthesis of trazodone and its derivatives. In the known methods of the synthesis of trazodone and its derivatives, organic and toxic solvents are used, and the synthesis time varies from several to several dozen hours. Our research shows that trazodone and its derivatives can be successfully obtained in the presence of potassium carbonate as a reaction medium in the microwave field in a few minutes. As a result of the research work, 17 derivatives of trazodone were obtained, including compounds that exhibit the characteristics of 5-HT1A receptor ligands. Molecular modeling studies were performed to understand the differences in the activity toward 5-HT1A and 5-HT2A receptors between ligand 10a (2-(6-(4-(3-chlorophenyl)piperazin-1-yl)hexyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one) (5-HT1A Ki = 16 nM) and trazodone. The docking results indicate the lack of the binding of ligand 10a to 5-HT2AR, which is consistent with the in vitro studies. On the other hand, the docking results for the 5-HT1A receptor indicate two possible binding modes. Crystallographic studies support the hypothesis of an extended conformation. Full article
(This article belongs to the Special Issue Sustainable Synthesis)
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Open AccessArticle Cytotoxic Withanolides from the Whole Herb of Physalis angulata L.
Molecules 2019, 24(8), 1608; https://doi.org/10.3390/molecules24081608 (registering DOI)
Received: 7 March 2019 / Revised: 16 April 2019 / Accepted: 20 April 2019 / Published: 23 April 2019
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Abstract
Physalis angulata L. is a medicinal plant of the Solanaceae family, which is used to produce a variety of steroids. The present study reports on the cytotoxic withanolides of this plant. The species of Physalis angulata L. was identified by DNA barcoding techniques. [...] Read more.
Physalis angulata L. is a medicinal plant of the Solanaceae family, which is used to produce a variety of steroids. The present study reports on the cytotoxic withanolides of this plant. The species of Physalis angulata L. was identified by DNA barcoding techniques. Two new withanolides (12), together with six known analogues (38), were isolated from the whole plant of Physalis angulata L. The structures of these new compounds were determined on the basis of extensive spectroscopic data analyses and electronic circular dichroism (ECD) calculations. The withanolides exhibited strong cytotoxic activities against A549, Hela and p388 cell lines. Furthermore, compounds 1 and 2 induced typical apoptotic cell death in A549 cell line according to the evaluation of the apoptosis-inducing activity by flow cytometric analysis. Full article
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Open AccessArticle Soluble Heparin and Heparan Sulfate Glycosaminoglycans Interfere with Sonic Hedgehog Solubilization and Receptor Binding
Molecules 2019, 24(8), 1607; https://doi.org/10.3390/molecules24081607 (registering DOI)
Received: 2 April 2019 / Revised: 14 April 2019 / Accepted: 19 April 2019 / Published: 23 April 2019
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Abstract
Sonic hedgehog (Shh) signaling plays a tumor-promoting role in many epithelial cancers. Cancer cells produce soluble a Shh that signals to distant stromal cells that express the receptor Patched (Ptc). These receiving cells respond by producing other soluble factors that promote cancer cell [...] Read more.
Sonic hedgehog (Shh) signaling plays a tumor-promoting role in many epithelial cancers. Cancer cells produce soluble a Shh that signals to distant stromal cells that express the receptor Patched (Ptc). These receiving cells respond by producing other soluble factors that promote cancer cell growth, generating a positive feedback loop. To interfere with reinforced Shh signaling, we examined the potential of defined heparin and heparan sulfate (HS) polysaccharides to block Shh solubilization and Ptc receptor binding. We confirm in vitro and in vivo that proteolytic cleavage of the N-terminal Cardin–Weintraub (CW) amino acid motif is a prerequisite for Shh solubilization and function. Consistent with the established binding of soluble heparin or HS to the Shh CW target motif, both polysaccharides impaired proteolytic Shh processing and release from source cells. We also show that HS and heparin bind to, and block, another set of basic amino acids required for unimpaired Shh binding to Ptc receptors on receiving cells. Both modes of Shh activity downregulation depend more on HS size and overall charge than on specific HS sulfation modifications. We conclude that heparin oligosaccharide interference in the physiological roles of HS in Shh release and reception may be used to expand the field of investigation to pharmaceutical intervention of tumor-promoting Shh functions. Full article
(This article belongs to the Special Issue Glycosaminoglycans and Glycomimetics)
Open AccessCommunication Lanostane-Type Saponins from Vitaliana primuliflora
Molecules 2019, 24(8), 1606; https://doi.org/10.3390/molecules24081606 (registering DOI)
Received: 1 April 2019 / Revised: 20 April 2019 / Accepted: 22 April 2019 / Published: 23 April 2019
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Abstract
The phytochemistry of the genera Androsace, Cortusa, Soldanella, and Vitaliana, belonging to the Primulaceae family is not well studied so far. Hence, in this paper, we present the results of UHPLC-MS/MS analysis of several primrose family members as well as [...] Read more.
The phytochemistry of the genera Androsace, Cortusa, Soldanella, and Vitaliana, belonging to the Primulaceae family is not well studied so far. Hence, in this paper, we present the results of UHPLC-MS/MS analysis of several primrose family members as well as isolation and structure determination of two new saponins from Vitaliana primuliflora subsp. praetutiana. These two nor-triterpenoid saponins were characterized as (23S)-17α,23-epoxy-29-hydroxy-3β-[(O-β-d-glucopyranosyl-(1→2)-O-α-l-rhamnopyranosyl-(1→2)-O-β-d-glucopyranosyl-(1→2)-O-α-l-arabinopyranosyl-(1→6)-β-d-glucopyranosyl)oxy]-27-nor-lanost-8-en-25-one and (23S)-17α,23-epoxy-29-hydroxy-3β-[(O-α-l-rhamnopyranosyl-(1→2)-O-β-d-glucopyranosyl-(1→2)-O-α-l-arabinopyranosyl-(1→6)-β-d-glucopyranosyl)oxy]-27-nor-lanost-8-en-25-one, respectively. Their structures were determined by high resolution mass spectrometry (HRMS), tandem mass spectrometry (MS/MS), one- and two-dimensional nuclear magnetic resonance spectroscopy (1D-, and 2D-NMR) analyses. So far, the 27-nor-lanostane monodesmosides were rarely found in dicotyledon plants. Therefore their presence in Vitaliana and also in Androsace species belonging to the Aretia section is unique and reported here for the first time. Additionally, eleven other saponins were determined by HRMS and MS/MS spectra. The isolated lanostane saponins can be considered as chemotaxonomic markers of the family Primulaceae. Full article
(This article belongs to the Special Issue Natural Product Isolation, Identification and Biological Activity)
Open AccessArticle Microwave-Assisted Extraction, Purification, Partial Characterization, and Bioactivity of Polysaccharides from Panax ginseng
Molecules 2019, 24(8), 1605; https://doi.org/10.3390/molecules24081605 (registering DOI)
Received: 30 March 2019 / Revised: 18 April 2019 / Accepted: 18 April 2019 / Published: 23 April 2019
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Abstract
Polysaccharides are a main active substance in Panax ginseng; however, microwave-assisted extraction used to prepare P. ginseng polysaccharides (MPPG) has rarely been reported, and knowledge of the bactericidal activity of P. ginseng polysaccharides remains low. Thus, this study was designed to investigate [...] Read more.
Polysaccharides are a main active substance in Panax ginseng; however, microwave-assisted extraction used to prepare P. ginseng polysaccharides (MPPG) has rarely been reported, and knowledge of the bactericidal activity of P. ginseng polysaccharides remains low. Thus, this study was designed to investigate the extraction of P. ginseng polysaccharides by using two methods—hot water extraction and microwave-assisted extraction—and compare their chemical composition and structure. In addition, their antibacterial and antioxidant activities were also determined. The data implied that P. ginseng polysaccharides extracted by microwave-assisted extraction possessed a higher extraction yield than hot water extraction (WPPG) under optimized conditions, and the actual yields were 41.6% ± 0.09% and 28.5% ± 1.62%, respectively. Moreover, the preliminary characterization of polysaccharides was identified after purification. The WPPG with the molecular weight (Mw) of 2.07 × 105 Da was composed of Man, Rib, Rha, GalA, Glu, Gal, and Arab, and the typical characteristics of polysaccharides were determined by IR spectra. Compared with WPPG, MPPG had a higher Mw, uronic acid content, and Glu content. More importantly, the antioxidant activity of MPPG was higher than WPPG, which was probably ascribed to its highly Mw and abundant uronic acid content. Besides, both of them exhibited high bactericidal activity. These results demonstrate that microwave-assisted extraction is an effective method for obtaining P. ginseng polysaccharides, and MPPG could be applied as an antioxidant and antibacterial agent. Full article
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Open AccessArticle Improving the Utility of the Tox21 Dataset by Deep Metadata Annotations and Constructing Reusable Benchmarked Chemical Reference Signatures
Molecules 2019, 24(8), 1604; https://doi.org/10.3390/molecules24081604 (registering DOI)
Received: 20 March 2019 / Revised: 16 April 2019 / Accepted: 19 April 2019 / Published: 23 April 2019
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Abstract
The Toxicology in the 21st Century (Tox21) project seeks to develop and test methods for high-throughput examination of the effect certain chemical compounds have on biological systems. Although primary and toxicity assay data were readily available for multiple reporter gene modified cell lines, [...] Read more.
The Toxicology in the 21st Century (Tox21) project seeks to develop and test methods for high-throughput examination of the effect certain chemical compounds have on biological systems. Although primary and toxicity assay data were readily available for multiple reporter gene modified cell lines, extensive annotation and curation was required to improve these datasets with respect to how FAIR (Findable, Accessible, Interoperable, and Reusable) they are. In this study, we fully annotated the Tox21 published data with relevant and accepted controlled vocabularies. After removing unreliable data points, we aggregated the results and created three sets of signatures reflecting activity in the reporter gene assays, cytotoxicity, and selective reporter gene activity, respectively. We benchmarked these signatures using the chemical structures of the tested compounds and obtained generally high receiver operating characteristic (ROC) scores, suggesting good quality and utility of these signatures and the underlying data. We analyzed the results to identify promiscuous individual compounds and chemotypes for the three signature categories and interpreted the results to illustrate the utility and re-usability of the datasets. With this study, we aimed to demonstrate the importance of data standards in reporting screening results and high-quality annotations to enable re-use and interpretation of these data. To improve the data with respect to all FAIR criteria, all assay annotations, cleaned and aggregate datasets, and signatures were made available as standardized dataset packages (Aggregated Tox21 bioactivity data, 2019). Full article
(This article belongs to the Special Issue High Throughput Screening II)
Open AccessArticle Profiling of Seed Proteome in Pea (Pisum sativum L.) Lines Characterized with High and Low Responsivity to Combined Inoculation with Nodule Bacteria and Arbuscular Mycorrhizal Fungi
Molecules 2019, 24(8), 1603; https://doi.org/10.3390/molecules24081603 (registering DOI)
Received: 17 March 2019 / Revised: 14 April 2019 / Accepted: 18 April 2019 / Published: 23 April 2019
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Abstract
Legume crops represent the major source of food protein and contribute to human nutrition and animal feeding. An essential improvement of their productivity can be achieved by symbiosis with beneficial soil microorganisms—rhizobia (Rh) and arbuscular mycorrhizal (AM) fungi. The efficiency of these interactions [...] Read more.
Legume crops represent the major source of food protein and contribute to human nutrition and animal feeding. An essential improvement of their productivity can be achieved by symbiosis with beneficial soil microorganisms—rhizobia (Rh) and arbuscular mycorrhizal (AM) fungi. The efficiency of these interactions depends on plant genotype. Recently, we have shown that, after simultaneous inoculation with Rh and AM, the productivity gain of pea (Pisum sativum L) line K-8274, characterized by high efficiency of interaction with soil microorganisms (EIBSM), was higher in comparison to a low-EIBSM line K-3358. However, the molecular mechanisms behind this effect are still uncharacterized. Therefore, here, we address the alterations in pea seed proteome, underlying the symbiosis-related productivity gain, and identify 111 differentially expressed proteins in the two lines. The high-EIBSM line K-8274 responded to inoculation by prolongation of seed maturation, manifested by up-regulation of proteins involved in cellular respiration, protein biosynthesis, and down-regulation of late-embryogenesis abundant (LEA) proteins. In contrast, the low-EIBSM line K-3358 demonstrated lower levels of the proteins, related to cell metabolism. Thus, we propose that the EIBSM trait is linked to prolongation of seed filling that needs to be taken into account in pulse crop breeding programs. The raw data have been deposited to the ProteomeXchange with identifier PXD013479. Full article
(This article belongs to the Special Issue CZE/LC-MS-based Proteomics)
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Open AccessFeature PaperReview Red Beetroot and Betalains as Cancer Chemopreventative Agents
Molecules 2019, 24(8), 1602; https://doi.org/10.3390/molecules24081602 (registering DOI)
Received: 8 March 2019 / Revised: 19 April 2019 / Accepted: 20 April 2019 / Published: 23 April 2019
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Abstract
Carcinogenesis is the process whereby a normal cell is transformed into a neoplastic cell. This action involves several steps starting with initiation and followed by promotion and progression. Driving these stages are oxidative stress and inflammation, which in turn encompasses a myriad of [...] Read more.
Carcinogenesis is the process whereby a normal cell is transformed into a neoplastic cell. This action involves several steps starting with initiation and followed by promotion and progression. Driving these stages are oxidative stress and inflammation, which in turn encompasses a myriad of aberrant gene expressions, both within the transforming cell population and the cells within the surrounding lesion. Chemoprevention of cancer with bioreactive foods or their extracted/purified components occurs via normalizing these inappropriate gene activities. Various foods/agents have been shown to affect different gene expressions. In this review, we discuss whereby the chemoprevention activities of the red beetroot itself may disrupt carcinogenesis and the activities of the water-soluble betalains extracted from the plant. Full article
(This article belongs to the Special Issue Natural Products for Cancer Chemoprevention)
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Open AccessArticle Complex Tannins Isolated from Jelly Fig Achenes Affect Pectin Gelation through Non-Specific Inhibitory Effect on Pectin Methylesterase
Molecules 2019, 24(8), 1601; https://doi.org/10.3390/molecules24081601 (registering DOI)
Received: 28 March 2019 / Revised: 15 April 2019 / Accepted: 22 April 2019 / Published: 23 April 2019
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Abstract
Jelly fig (Ficus awkeotsang Makino) is used to prepare drinks and desserts in Asia, owing to the gelling capability of its pectin via endogenous pectin methylesterase (PE) catalyzation. Meanwhile, substances with PE inhibitory activity (SPEI) in jelly fig achenes (JFA) [...] Read more.
Jelly fig (Ficus awkeotsang Makino) is used to prepare drinks and desserts in Asia, owing to the gelling capability of its pectin via endogenous pectin methylesterase (PE) catalyzation. Meanwhile, substances with PE inhibitory activity (SPEI) in jelly fig achenes (JFA) residue were noticed to be able to impede the gelation. In this study, we characterized and isolated SPEI from JFA by a series of PE inhibition-guided isolations. Crude aqueous extract of JFA residue was mixed with acetone, and 90% acetone-soluble matter was further fractionated by Diaion HP-20 chromatography. The retained fraction with dominant PE inhibitory activity was collected from 100% methanol eluate. Results from high-performance liquid chromatography mass spectrometry (HPLC/MS) and hydrolysis-induced chromogenic transition revealed the SPEI as complex tannins. Total tannins content was determined in each isolated fraction, and was closely related to PE inhibitory activity. In addition, SPEI in this study could inhibit activities of digestive enzymes in vitro and may, therefore, be assumed to act as non-specific protein binding agent. Full article
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Open AccessArticle Search for New Aggregable Fragments of Human Insulin
Molecules 2019, 24(8), 1600; https://doi.org/10.3390/molecules24081600 (registering DOI)
Received: 18 March 2019 / Revised: 18 April 2019 / Accepted: 20 April 2019 / Published: 23 April 2019
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Abstract
In this study, three independent methods were used to identify short fragment of both chains of human insulin which are prone for aggregation. In addition, circular dichroism (CD) research was conducted to understand the progress of aggregation over time. The insulin fragments (deca- [...] Read more.
In this study, three independent methods were used to identify short fragment of both chains of human insulin which are prone for aggregation. In addition, circular dichroism (CD) research was conducted to understand the progress of aggregation over time. The insulin fragments (deca- and pepta-peptides) were obtained by solid-phase synthesis using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate (DMT/NMM/TosO-) as a coupling reagent. Systematic studies allowed identification of the new fragments, expected to be engaged in triggering aggregation of the entire structure of human insulin under physiological conditions. It was found that the aggregation process occurs through various structural conformers and may favor the formation of a fibrous structure of aggregate. Full article
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Open AccessArticle Analysis of Gaseous By-Products of CF3I and CF3I-CO2 after High Voltage Arcing Using a GCMS
Molecules 2019, 24(8), 1599; https://doi.org/10.3390/molecules24081599 (registering DOI)
Received: 26 March 2019 / Revised: 17 April 2019 / Accepted: 20 April 2019 / Published: 23 April 2019
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Abstract
Increasing demand for an alternative insulation medium to sulphur hexafluoride (SF6) has led to the investigation of new environmentally friendly insulation gases which could be used in high voltage equipment on the electrical power network. One such alternative, which is currently [...] Read more.
Increasing demand for an alternative insulation medium to sulphur hexafluoride (SF6) has led to the investigation of new environmentally friendly insulation gases which could be used in high voltage equipment on the electrical power network. One such alternative, which is currently being explored by researchers, is Trifluoroiodomethane (CF3I) which could potentially be used in a gas mixture with carbon dioxide (CO2) as an insulation medium. In this paper an analysis of gaseous by-products detected as a result of high voltage breakdown through pure CF3I and a CF3I-CO2 gas mixture across a sphere-sphere electrode arrangement is given. Gas chromatography and mass spectrometry (GCMS) is used to identify the gaseous by-products produced as a result of high voltage arcing which causes the gas between the electrodes to dissociate. Analysing these gas by-products helps to identify the long-term behaviour of the gas mixture in high voltage equipment. Full article
(This article belongs to the Section Analytical Chemistry)
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Open AccessArticle Full Structural Characterization of Homoleptic Complexes of Diacetylcurcumin with Mg, Zn, Cu, and Mn: Cisplatin-level Cytotoxicity in Vitro with Minimal Acute Toxicity in Vivo
Molecules 2019, 24(8), 1598; https://doi.org/10.3390/molecules24081598 (registering DOI)
Received: 3 April 2019 / Revised: 17 April 2019 / Accepted: 21 April 2019 / Published: 23 April 2019
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Abstract
At the present time, scientists place a great deal of effort worldwide trying to improve the therapeutic potential of metal complexes of curcumin and curcuminoids. Herein, the synthesis of four homoleptic metal complexes with diacetylcurcumin (DAC), using a ligand designed to prevent the [...] Read more.
At the present time, scientists place a great deal of effort worldwide trying to improve the therapeutic potential of metal complexes of curcumin and curcuminoids. Herein, the synthesis of four homoleptic metal complexes with diacetylcurcumin (DAC), using a ligand designed to prevent the interaction of phenolic groups, rendering metal complexes through the β-diketone functionality, is reported. Due to their physiological relevance, we used bivalent magnesium, zinc, copper, and manganese for complexation with DAC. The resulting products were characterized by ultraviolet-visible (UV-Vis), fluorescence spectroscopy, infrared spectroscopy (IR), liquid and solid-state nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), magnetic moment, mass spectrometry (MS), single crystal, and powder X-ray diffraction (SCXRD and PXRD). Crystallization was achieved in dimethylsulfoxide (DMSO) or N,N-dimethylformamide (DMF) as triclinic systems with space group P-1, showing the metal bound to the β-diketone function, while the 1H-NMR confirmed the preference of the enolic form of the ligand. Single crystal data demonstrated a 1:2 metal:ligand ratio. The inhibition of lipid peroxidation was evaluated using the thiobarbituric acid reactive substance assay (TBARS). All four metal complexes (Mg, Zn, Cu, and Mn) exhibited good antioxidant effect (IC50 = 2.03 ± 0.27, 1.58 ± 0.07, 1.58 ± 0.15 and 1.24 ± 0.10 μM respectively) compared with butylated hydroxytoluene (BHT) and α-tocopherol. The cytotoxic activity in human cancer cell lines against colon adenocarcinoma (HCT-15), mammary adenocarcinoma (MCF-7), and lung adenocarcinoma (SKLU-1) was found comparable ((DAC)2Mg), or ca. 2-fold higher ((DAC)2Zn) than cisplatin. The acute toxicity assays indicate class 5 toxicity, according to the Organization for Economic Co-operation and Development (OECD) guidelines at doses of 3 g/kg for all complexes. No mortality or changes in the behavior of animals in any of the treated groups was observed. A therapeutic potential can be envisaged from the relevant cytotoxic activity upon human cancer cell lines in vitro and the undetected in vivo acute toxicity of these compounds. Full article
(This article belongs to the Section Organic Chemistry)
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Open AccessArticle Comparative Phytochemical Profile, Antioxidant, Antimicrobial and In Vivo Anti-Inflammatory Activity of Different Extracts of Traditionally Used Romanian Ajuga genevensis L. and A. reptans L. (Lamiaceae)
Molecules 2019, 24(8), 1597; https://doi.org/10.3390/molecules24081597 (registering DOI)
Received: 19 March 2019 / Revised: 17 April 2019 / Accepted: 20 April 2019 / Published: 23 April 2019
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Abstract
Several Ajuga species are used in Romanian folk medicine for their antioxidant, antimicrobial and anti-inflammatory properties, to treat pain, fever or arthritis. Still, the active compounds responsible for these effects and their mechanism of action are scarcely known. This research was designed to [...] Read more.
Several Ajuga species are used in Romanian folk medicine for their antioxidant, antimicrobial and anti-inflammatory properties, to treat pain, fever or arthritis. Still, the active compounds responsible for these effects and their mechanism of action are scarcely known. This research was designed to investigate the phytochemical profile (e.g. iridoids, polyphenolic compounds, phytosterols), as well as the biological potential (antioxidant, antibacterial, antifungal, anti-inflammatory properties) of two selected Ajuga species collected from different regions of Romanian spontaneous flora. The main compounds identified in A. reptans aerial parts extracts were 8-O-acetylharpagide, isoquercitrin and β-sitosterol, whilst in A. genevensis were 8-O-acetylharpagide, luteolin and campesterol. The extracts were screened for their antioxidant potential using different methods (DPPH, TEAC, EPR) and the results showed a good activity, in accordance with the polyphenol content (18–26 mg GAE/g dw). The antifungal activity on the tested strains was good. The determination of few parameters linked with the inflammatory mechanism allowed the assessment of in vivo anti-inflammatory potential. Ajuga reptans and A. genevensis ethanol extracts had anti-inflammatory activity through lowering the oxidative stress, phagocytosis, PMN and total leukocytes. The best anti-oxidative and anti-inflammatory activity was observed for the Ajuga reptans 100 mg dw/mL extract when compared with diclofenac, thus the dose could be correlated with the pharmacological effect. These findings provide substantial evidence that both selected Ajuga species have the potential to be valued as sources of phytochemicals in effective anti-inflammatory herbal preparations. Full article
(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)
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Open AccessArticle Anthocyanin Encapsulated by Ferulic Acid-Grafted-Maltodextrin (FA-g-MD) Microcapsules Potentially Improved its Free Radical Scavenging Capabilities Against H2O2-Induced Oxidative Stress
Molecules 2019, 24(8), 1596; https://doi.org/10.3390/molecules24081596 (registering DOI)
Received: 12 March 2019 / Revised: 12 April 2019 / Accepted: 19 April 2019 / Published: 23 April 2019
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Abstract
This study aimed to investigate the antioxidant activity and release behavior of anthocyanin (ANC) loaded within FA-g-MD wall (ANC-FA-g-MD microcapsule) in vitro. The microencapsulation of ANC was prepared by spray drying and displayed a biphasic release profile. The combination of ANC and FA-g-MD [...] Read more.
This study aimed to investigate the antioxidant activity and release behavior of anthocyanin (ANC) loaded within FA-g-MD wall (ANC-FA-g-MD microcapsule) in vitro. The microencapsulation of ANC was prepared by spray drying and displayed a biphasic release profile. The combination of ANC and FA-g-MD (0.0625–1 mg/mL) showed a higher antioxidant activity than that of both individuals. A possible intermolecular interaction between ANC and FA-g-MD was studied by UV-vis spectra. Intracellular reactive oxygen species (ROS), 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test, and protein expression of quinone oxidoreductase 1(NQO1), glutathione reductase (GSR) and γ-glutamate cysteine ligase catalytic subunit (γ-GCLC) were measured through human colon cancer cells (HT-29). After a 24-hour incubation of the HT-29, the combinations (0–60 μg/mL) exhibited a high potential to diminish the ROS level. And the distinct upregulated expressions of GCLC and NQO1 of HT-29 were detected after treatment with combinations compared to those of single ones. These results suggested that the ANC-FA-g-MD microcapsules exerts enhanced antioxidant effect with capability of the modulation of GCLC and NQO1. Full article
(This article belongs to the Special Issue Anthocyanins: Recent Progress in Health Benefits Studies)
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Open AccessArticle Gypenoside LXXV Promotes Cutaneous Wound Healing In Vivo by Enhancing Connective Tissue Growth Factor Levels Via the Glucocorticoid Receptor Pathway
Molecules 2019, 24(8), 1595; https://doi.org/10.3390/molecules24081595 (registering DOI)
Received: 8 April 2019 / Revised: 18 April 2019 / Accepted: 22 April 2019 / Published: 23 April 2019
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Abstract
Cutaneous wound healing is a well-orchestrated event in which many types of cells and growth factors are involved in restoring the barrier function of skin. In order to identify whether ginsenosides, the main active components of Panax ginseng, promote wound healing, the [...] Read more.
Cutaneous wound healing is a well-orchestrated event in which many types of cells and growth factors are involved in restoring the barrier function of skin. In order to identify whether ginsenosides, the main active components of Panax ginseng, promote wound healing, the proliferation and migration activities of 15 different ginsenosides were tested by MTT assay and scratched wound closure assay. Among ginsenosides, gypenoside LXXV (G75) showed the most potent wound healing effects. Thus, this study aimed to investigate the effects of G75 on wound healing in vivo and characterize associated molecular changes. G75 significantly increased proliferation and migration of keratinocytes and fibroblasts, and promoted wound closure in an excision wound mouse model compared with madecassoside (MA), which has been used to treat wounds. Additionally, RNA sequencing data revealed G75-mediated significant upregulation of connective tissue growth factor (CTGF), which is known to be produced via the glucocorticoid receptor (GR) pathway. Consistently, the increase in production of CTGF was confirmed by western blot and ELISA. In addition, GR-competitive binding assay and GR translocation assay results demonstrated that G75 can be bound to GR and translocated into the nucleus. These results demonstrated that G75 is a newly identified effective component in wound healing. Full article
(This article belongs to the Special Issue Saponins)
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Open AccessArticle An Efficient Synthesis of Aryl-Substituted Pyrroles by the Suzuki–Miyaura Coupling Reaction of SEM-Protected Pyrroles
Molecules 2019, 24(8), 1594; https://doi.org/10.3390/molecules24081594 (registering DOI)
Received: 19 March 2019 / Revised: 5 April 2019 / Accepted: 20 April 2019 / Published: 22 April 2019
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Abstract
An efficient arylation of SEM-protected pyrroles by the Suzuki–Miyaura coupling reaction has been developed. The reaction can be carried out under mild conditions to provide aryl-substituted pyrroles in moderate to excellent yields. The scope and limitations of the methodology were evaluated, and the [...] Read more.
An efficient arylation of SEM-protected pyrroles by the Suzuki–Miyaura coupling reaction has been developed. The reaction can be carried out under mild conditions to provide aryl-substituted pyrroles in moderate to excellent yields. The scope and limitations of the methodology were evaluated, and the reaction was tolerant of a wide range of functionalities. Compared to the reported methods, the protocol has some advantages, such as commercially available materials, no debrominated by-products being formed, and the amine-protecting group being stable under the reaction conditions. The synthetic utility of the product has also been demonstrated, with several common transformations of the aryl-substituted pyrrole product being conducted. This protocol will offer the opportunity to explore other metal-catalyzed cross-coupling reactions employing SEM-protected pyrroles. Full article
(This article belongs to the Section Organic Chemistry)
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Open AccessArticle High-Throughput Biochemical Fingerprinting of Oleaginous Aurantiochytrium sp. Strains by Fourier Transform Infrared Spectroscopy (FT-IR) for Lipid and Carbohydrate Productions
Molecules 2019, 24(8), 1593; https://doi.org/10.3390/molecules24081593 (registering DOI)
Received: 20 March 2019 / Revised: 19 April 2019 / Accepted: 19 April 2019 / Published: 22 April 2019
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Abstract
The traditional biochemical methods for analyzing cellular composition of oleaginous microorganisms are time-consuming, polluting, and expensive. In the present study, an FT-IR method was used to analyze the cellular composition of the marine oleaginous protist Aurantiochytrium sp. during various research processes, such as [...] Read more.
The traditional biochemical methods for analyzing cellular composition of oleaginous microorganisms are time-consuming, polluting, and expensive. In the present study, an FT-IR method was used to analyze the cellular composition of the marine oleaginous protist Aurantiochytrium sp. during various research processes, such as strains screening, medium optimization, and fermentation, and was evaluated as a green, low-cost, high throughput, and accurate method compared with the traditional methods. A total of 109 Aurantiochytrium sp. strains were screened for lipid and carbohydrate production and the best results were found for the strains No. 6 and No. 32. The yields and productivities could reach up to 47.2 g/L and 0.72 g/L/h for lipid, 21.6 g/L and 0.33 g/L/h for docosahexaenoic acid (DHA) in the strain No. 6, and 15.4 g/L and 0.18 g/L/h for carbohydrate in the strain No. 32, under the optimal conditions, respectively. These results confirmed potentials of the two Aurantiochytrium sp. strains for lipid, DHA, and carbohydrate productions at industrial scales. The FT-IR method in this study will facilitate research on the oleaginous Aurantiochytrium sp., and the obtained two strains for lipid and carbohydrate productions will provide the foundations for their applications in medical, food, and feed industries. Full article
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Open AccessFeature PaperArticle Detecting Zn(II) Ions in Live Cells with Near-Infrared Fluorescent Probes
Molecules 2019, 24(8), 1592; https://doi.org/10.3390/molecules24081592 (registering DOI)
Received: 25 March 2019 / Revised: 4 April 2019 / Accepted: 4 April 2019 / Published: 22 April 2019
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Abstract
Two near-infrared fluorescent probes (A and B) containing hemicyanine structures appended to dipicolylamine (DPA), and a dipicolylamine derivative where one pyridine was substituted with pyrazine, respectively, were synthesized and tested for the identification of Zn(II) ions in live cells. In both [...] Read more.
Two near-infrared fluorescent probes (A and B) containing hemicyanine structures appended to dipicolylamine (DPA), and a dipicolylamine derivative where one pyridine was substituted with pyrazine, respectively, were synthesized and tested for the identification of Zn(II) ions in live cells. In both probes, an acetyl group is attached to the phenolic oxygen atom of the hemicyanine platform to decrease the probe fluorescence background. Probe A displays sensitive fluorescence responses and binds preferentially to Zn(II) ions over other metal ions such as Cd2+ ions with a low detection limit of 0.45 nM. In contrast, the emission spectra of probe B is not significantly affected if Zn(II) ions are added. Probe A possesses excellent membrane permeability and low cytotoxicity, allowing for sensitive imaging of both exogenously supplemented Zn(II) ions in live cells, and endogenously releases Zn(II) ions in cells after treatment of 2,2-dithiodipyridine. Full article
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Open AccessArticle Synthesis of a Fluorous-Tagged Hexasaccharide and Interaction with Growth Factors Using Sugar-Coated Microplates
Molecules 2019, 24(8), 1591; https://doi.org/10.3390/molecules24081591
Received: 20 February 2019 / Revised: 17 April 2019 / Accepted: 18 April 2019 / Published: 22 April 2019
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Abstract
Here, we report the synthesis of a sulfated, fully protected hexasaccharide as a glycosaminoglycan mimetic and the study of its interactions with different growth factors: midkine, basic fibroblast growth factor (FGF-2) and nerve growth factor (NGF). Following a fluorous-assisted approach, monosaccharide building blocks [...] Read more.
Here, we report the synthesis of a sulfated, fully protected hexasaccharide as a glycosaminoglycan mimetic and the study of its interactions with different growth factors: midkine, basic fibroblast growth factor (FGF-2) and nerve growth factor (NGF). Following a fluorous-assisted approach, monosaccharide building blocks were successfully assembled and the target oligosaccharide was prepared in excellent yield. The use of more acid stable 4,6-O-silylidene protected glucosamine units was crucial for the efficiency of this strategy because harsh reaction conditions were needed in the glycosylations to avoid the formation of orthoester side products. Fluorescence polarization experiments demonstrated the strong interactions between the synthesized hexamer, and midkine and FGF-2. In addition, we have developed an alternative assay to analyse these molecular recognition events. The prepared oligosaccharide was non-covalently attached to a fluorous-functionalized microplate and the direct binding of the protein to the sugar-immobilized surface was measured, affording the corresponding KD,surf value. Full article
(This article belongs to the Special Issue Carbohydrates in Synthesis)
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Open AccessArticle Tuscan Varieties of Sweet Cherry Are Rich Sources of Ursolic and Oleanolic Acid: Protein Modeling Coupled to Targeted Gene Expression and Metabolite Analyses
Molecules 2019, 24(8), 1590; https://doi.org/10.3390/molecules24081590
Received: 11 March 2019 / Revised: 20 April 2019 / Accepted: 20 April 2019 / Published: 22 April 2019
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Abstract
The potential of six ancient Tuscan sweet cherry (Prunus avium L.) varieties as a source of health-promoting pentacyclic triterpenes is here evaluated by means of a targeted gene expression and metabolite analysis. By using a sequence homology criterion, we identify five oxidosqualene [...] Read more.
The potential of six ancient Tuscan sweet cherry (Prunus avium L.) varieties as a source of health-promoting pentacyclic triterpenes is here evaluated by means of a targeted gene expression and metabolite analysis. By using a sequence homology criterion, we identify five oxidosqualene cyclase genes (OSCs) and three cytochrome P450s (CYP85s) that are putatively involved in the triterpene production pathway in sweet cherries. We performed 3D structure prediction and induced-fit docking using cation intermediates and reaction products for some OSCs to predict their function. We show that the Tuscan varieties have different amounts of ursolic and oleanolic acids and that these variations are related to different gene expression profiles. This study stresses the interest of valorizing ancient fruits as alternative sources of functional molecules with nutraceutical value. It also provides information on sweet cherry triterpene biosynthetic genes, which could be the object of follow-up functional studies. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessReview Could Polyphenols Help in the Control of Rheumatoid Arthritis?
Molecules 2019, 24(8), 1589; https://doi.org/10.3390/molecules24081589
Received: 14 March 2019 / Revised: 16 April 2019 / Accepted: 20 April 2019 / Published: 22 April 2019
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Abstract
Rheumatoid arthritis (RA) is a chronic, systemic, joint-invading, autoimmune inflammatory disease, which causes joint cartilage breakdown and bone damage, resulting in functional impairment and deformation of the joints. The percentage of RA patients has been rising and RA represents a substantial burden for [...] Read more.
Rheumatoid arthritis (RA) is a chronic, systemic, joint-invading, autoimmune inflammatory disease, which causes joint cartilage breakdown and bone damage, resulting in functional impairment and deformation of the joints. The percentage of RA patients has been rising and RA represents a substantial burden for patients around the world. Despite the development of many RA therapies, because of the side effects and low effectiveness of conventional drugs, patients still need and researchers are seeking new therapeutic alternatives. Polyphenols extracted from natural products are effective on several inflammatory diseases, including RA. In this review polyphenols are classified into four types: flavonoids, phenolic acids, stilbenes and others, among which mainly flavonoids are discussed. Researchers have reported that anti-RA efficacies of polyphenols are based mainly on three mechanisms: their anti-inflammatory, antioxidant and apoptotic properties. The main RA factors modified by polyphenols are mitogen-activated protein kinase (MAPK), interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), nuclear factor κ light chain enhancer of activated B cells (NF-κB) and c-Jun N-terminal kinases (JNK). Polyphenols could be potent alternative RA therapies and sources for novel drugs for RA by affecting its key mechanisms. Full article
(This article belongs to the Special Issue Synthesis, Study and Utilization of Natural Products)
Open AccessFeature PaperArticle [1,2,5]Thiadiazolo[3,4-d]Pyridazine as an Internal Acceptor in the D-A-π-A Organic Sensitizers for Dye-Sensitized Solar Cells
Molecules 2019, 24(8), 1588; https://doi.org/10.3390/molecules24081588
Received: 4 April 2019 / Revised: 18 April 2019 / Accepted: 19 April 2019 / Published: 22 April 2019
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Abstract
Four new D-A-π-A metal-free organic sensitizers for dye-sensitized solar cells (DSSCs), with [1,2,5]thiadiazolo[3,4-d]pyridazine as internal acceptor, thiophene unit as π-spacer and cyanoacrylate as anchoring electron acceptor, have been synthesized. The donor moiety was introduced into [1,2,5]thiadiazolo[3,4-d]pyridazine by nucleophilic aromatic [...] Read more.
Four new D-A-π-A metal-free organic sensitizers for dye-sensitized solar cells (DSSCs), with [1,2,5]thiadiazolo[3,4-d]pyridazine as internal acceptor, thiophene unit as π-spacer and cyanoacrylate as anchoring electron acceptor, have been synthesized. The donor moiety was introduced into [1,2,5]thiadiazolo[3,4-d]pyridazine by nucleophilic aromatic substitution and Suzuki cross-coupling reactions, allowing design of D-A-π-A sensitizers with the donor attached to the internal heterocyclic acceptor not only by the carbon atom, as it is in a majority of DSSCs, but by the nitrogen atom also. Although low values of power conversion efficiency (PCE) were found, a few important consequences were identified: (i) poor PCE data can be attributed to high electron deficiency of the internal [1,2,5]thiadiazolo[3,4-d]pyridazine acceptor due to lower light harvesting by the dye; (ii) the manner in which the donor was attached to the internal acceptor (by carbon or nitrogen) did not play an essential role in the photovoltaic properties of the dyes; (iii) dyes based on the novel donor 2,3,4,4a,9,9a-hexahydro-1H-1,4-methanocarbazolyl and 9-(p-tolyl)-2,3,4,4a,9,9a-hexahydro-1H- carbazole moieties showed similar photovoltaic properties to dyes based on the well-known 4-(p-tolyl)-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indolyl building block, which opens the door for further optimization potential of new dye families. Full article
(This article belongs to the Special Issue Non-Natural Multi-Heteroatom Heterocycles: New Chemical Space)
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Open AccessArticle Anticandidal Potential of Stem Bark Extract from Schima superba and the Identification of Its Major Anticandidal Compound
Molecules 2019, 24(8), 1587; https://doi.org/10.3390/molecules24081587
Received: 2 March 2019 / Revised: 18 April 2019 / Accepted: 22 April 2019 / Published: 22 April 2019
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Abstract
Plant-derived extracts are a promising source of new drugs. Schima superba is traditionally used in China for heat clearing, detoxification, and treatment of furuncles. In this study, the anticandidal properties and mechanism of action of S. superba (SSE) were explored using a stem [...] Read more.
Plant-derived extracts are a promising source of new drugs. Schima superba is traditionally used in China for heat clearing, detoxification, and treatment of furuncles. In this study, the anticandidal properties and mechanism of action of S. superba (SSE) were explored using a stem bark extract. SSE possessed high polyphenol and saponin contents of 256.6 ± 5.1 and 357.8 ± 31.5 µg/mg, respectively. A clear inhibition zone was observed for C. albicans growth through the disc diffusion method and the 50% inhibition of C. albicans by SSE was 415.2 µg/mL. Transcriptomic analysis in C. albicans treated with different doses of SSE was conducted through RNA-seq. Average values of 6068 genes and 20,842,500 clean reads were identified from each sample. Among these samples, 1680 and 1956 genes were differentially expressed genes (DEGs) from the SSE treatments of 0.2 and 0.4 mg/mL, respectively. C. albicans growth was inhibited by the changes in gene expression associated with the cell wall and membrane composition including the regulation of chitin degradation and ergosterol biosynthesis. This result could be reflected in the irregularly wrinkled morphology of the ruptured cell as revealed through SEM analysis. ESI-MS and NMR analyses revealed that the major compound purified from SSE was sasanquasaponin III and the 50% inhibition of C. albicans was 93.1 µg/mL. In summary, the traditional Chinese medicine S. superba can be applied as an anticandidal agent in complementary and alternative medicine. Full article
(This article belongs to the Special Issue Antimicrobial Properties of Natural Products)
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Open AccessArticle Evaluation of Polyphenolic Compounds and Pharmacological Activities in Hairy Root Cultures of Ligularia fischeri Turcz. f. spiciformis (Nakai)
Molecules 2019, 24(8), 1586; https://doi.org/10.3390/molecules24081586
Received: 20 March 2019 / Revised: 17 April 2019 / Accepted: 17 April 2019 / Published: 22 April 2019
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Abstract
A considerable amount of bioactive compounds have been used for the biopharmaceutical engineering to help human health and nutrition. Hairy root culture (HRC) or transgenic root is a favourable alternative technique for phytochemical production. Ligularia fischeri is a significant source of pharmaceutically important [...] Read more.
A considerable amount of bioactive compounds have been used for the biopharmaceutical engineering to help human health and nutrition. Hairy root culture (HRC) or transgenic root is a favourable alternative technique for phytochemical production. Ligularia fischeri is a significant source of pharmaceutically important active compounds with an enormous range of health care applications. HRC of L. fischeri was developed using Agrobacterium rhizogenes for the production of polyphenolic compounds with antioxidant, antimicrobial, antidiabetic, anticancer and anti-inflammatory pharmaceutical activities. Hairy roots (HRs) were selected by morphological assessment, genetic and molecular analyses. The maximum accumulation of fresh mass (94.15 g/L) and dry mass (9.45 g/L) was recorded in MS liquid medium supplemented with 30 g/L sucrose at 28 days. Furthermore, HRs successfully produced numerous polyphenolic compounds, including six hydroxycinnamic acids, seven flavonols, seven hydroxybenzoic acids, vanillin, resveratrol, pyrogallol, homogentisic, and veratric acids, which were identified by UHPLC analysis. HRs produced higher total phenolic (185.65 mg/g), and flavonoid (5.25 mg/g) contents than non-transformed roots (125.55 mg/g and 3.75 mg/g). As a result of these metabolic changes, pharmaceutical activities were found higher in HRs than non-transformed roots (NTRs). The present study indicates that HRC has the potential to increase the content of beneficial polyphenolic compounds with higher potential pharmaceutical activities. To the best of our knowledge, the present study is the first report on enhancing the production of polyphenolic compounds with pharmaceutical activities from the HRCs of L. fischeri. Full article
(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)
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Open AccessArticle Comparative Study of the Chemical Constituents and Bioactivities of the Extracts from Fruits, Leaves and Root Barks of Lycium barbarum
Molecules 2019, 24(8), 1585; https://doi.org/10.3390/molecules24081585
Received: 1 April 2019 / Revised: 15 April 2019 / Accepted: 19 April 2019 / Published: 22 April 2019
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Abstract
The fruits, leaves and root barks of L. barbarum plant are widely used as functional foods and as ingredients in traditional Chinese prescriptions and patent medicines. They are considered to have different pharmacological activities and health benefits because of their diverse constituents. Here, [...] Read more.
The fruits, leaves and root barks of L. barbarum plant are widely used as functional foods and as ingredients in traditional Chinese prescriptions and patent medicines. They are considered to have different pharmacological activities and health benefits because of their diverse constituents. Here, the chemical constituents of the extracts from fruits, leaves and root barks of L. barbarum were compared by ultra-high performance liquid chromatography coupled with high resolution mass spectrometry (UPLC-HR-MS). A total of 131 compounds were identified and seven of them were quantified. Among them, 98, 28 and 35 constituents were detected in fruits, leaves and root barks respectively. Dicaffeoylspermidine/spermine derivatives were the most detected compounds (74/131); among them, dicaffeoylspermine isomers and propionyl-dicaffeoylspermidine were found in root barks in very large amounts (e.g., kukoamine B = 10.90 mg/g dry powder); dicaffeoyl-spermidine isomers were detected in fruits/leaves in a high amount, and many of their glycosylated derivatives were mainly detected in fruits. In addition, six saponins from L. barbarum fruits were reported for the first time, and 5,6-dihydrosolasonine was reported for the first time in plants. The activity assays showed that the root bark extract possessed the strongest antioxidative activity and cytotoxicity, which was presumed due to the large amount of dicaffeoylspermine/spermidines in root barks. Fourteen potential bioactive components from fruits were identified by a target cell-based screening method. These results will help to understand the different biological activities of these three parts of L. barbarum plant and will benefit the discovery of new functional components. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Brassinin Represses Invasive Potential of Lung Carcinoma Cells through Deactivation of PI3K/Akt/mTOR Signaling Cascade
Molecules 2019, 24(8), 1584; https://doi.org/10.3390/molecules24081584
Received: 15 April 2019 / Revised: 19 April 2019 / Accepted: 19 April 2019 / Published: 22 April 2019
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Abstract
The epithelial–mesenchymal transition (EMT) is a phenomenon that facilitates epithelial cells to acquire invasive potential to induce the initiation the metastatic spread of tumor cells. Here, we determined if brassinin (BSN) can affect the EMT process and deciphered its anti-cancer effects. BSN attenuated [...] Read more.
The epithelial–mesenchymal transition (EMT) is a phenomenon that facilitates epithelial cells to acquire invasive potential to induce the initiation the metastatic spread of tumor cells. Here, we determined if brassinin (BSN) can affect the EMT process and deciphered its anti-cancer effects. BSN attenuated the levels of EMT linked genes and suppressed transforming growth factor beta (TGF-β)-mediated regulation of diverse mesenchymal markers. Additionally, BSN did increase the expression of various epithelial marker proteins in lung cancer cells. TGF-β-induced morphological changes and induction of invasive ability of tumor cells was also found to be abrogated by BSN treatment. Finally, BSN not only suppressed constitutive, but also inducible phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) phosphorylation in tumor cells. Full article
(This article belongs to the Special Issue Discovery of Active Ingredients from Natural Products)
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Open AccessReview Oxidative Stress: A Key Modulator in Neurodegenerative Diseases
Molecules 2019, 24(8), 1583; https://doi.org/10.3390/molecules24081583
Received: 28 February 2019 / Revised: 2 April 2019 / Accepted: 16 April 2019 / Published: 22 April 2019
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Abstract
Oxidative stress is proposed as a regulatory element in ageing and various neurological disorders. The excess of oxidants causes a reduction of antioxidants, which in turn produce an oxidation–reduction imbalance in organisms. Paucity of the antioxidant system generates oxidative-stress, characterized by elevated levels [...] Read more.
Oxidative stress is proposed as a regulatory element in ageing and various neurological disorders. The excess of oxidants causes a reduction of antioxidants, which in turn produce an oxidation–reduction imbalance in organisms. Paucity of the antioxidant system generates oxidative-stress, characterized by elevated levels of reactive species (oxygen, hydroxyl free radical, and so on). Mitochondria play a key role in ATP supply to cells via oxidative phosphorylation, as well as synthesis of essential biological molecules. Various redox reactions catalyzed by enzymes take place in the oxidative phosphorylation process. An inefficient oxidative phosphorylation may generate reactive oxygen species (ROS), leading to mitochondrial dysfunction. Mitochondrial redox metabolism, phospholipid metabolism, and proteolytic pathways are found to be the major and potential source of free radicals. A lower concentration of ROS is essential for normal cellular signaling, whereas the higher concentration and long-time exposure of ROS cause damage to cellular macromolecules such as DNA, lipids and proteins, ultimately resulting in necrosis and apoptotic cell death. Normal and proper functioning of the central nervous system (CNS) is entirely dependent on the chemical integrity of brain. It is well established that the brain consumes a large amount of oxygen and is highly rich in lipid content, becoming prone to oxidative stress. A high consumption of oxygen leads to excessive production of ROS. Apart from this, the neuronal membranes are found to be rich in polyunsaturated fatty acids, which are highly susceptible to ROS. Various neurodegenerative diseases such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), among others, can be the result of biochemical alteration (due to oxidative stress) in bimolecular components. There is a need to understand the processes and role of oxidative stress in neurodegenerative diseases. This review is an effort towards improving our understanding of the pivotal role played by OS in neurodegenerative disorders. Full article
(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress 2018)
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Open AccessArticle Radioprotective Effect of Walnut Oligopeptides Against Gamma Radiation-Induced Splenocyte Apoptosis and Intestinal Injury in Mice
Molecules 2019, 24(8), 1582; https://doi.org/10.3390/molecules24081582
Received: 18 March 2019 / Revised: 18 April 2019 / Accepted: 20 April 2019 / Published: 22 April 2019
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Walnut oligopeptides (WOPs) intake is associated with the augment of the antioxidant defense system and immune system. The chief object of this study is to evaluate the radioprotective effect of walnut oligopeptides extracted from walnut seed protein against 60Coγ-irradiation induced damage in [...] Read more.
Walnut oligopeptides (WOPs) intake is associated with the augment of the antioxidant defense system and immune system. The chief object of this study is to evaluate the radioprotective effect of walnut oligopeptides extracted from walnut seed protein against 60Coγ-irradiation induced damage in mice. Female BALB/c mice were administered WOPs through drinking water for 14 days until a single dose of whole-body 60Coγ-irradiation. The 30-day survival test was carried out in the first group (8 Gy), and the other two groups (3.5 Gy) were sacrificed at 3 days and 14 days post-irradiation. Blood and organ samples of mice in the three groups were collected, the histopathological analysis and immunohistochemistry were conducted. The number of peripheral blood leukocytes, bone marrow DNA content, inflammatory cytokines, antioxidant capacity, and intestinal permeability were measured. We found that the administration of WOPs augmented antioxidant defense system, accelerated hematopoietic recovery and showed the significant trend toward higher survival rate and less weight loss compared with non-administrated control mice. In addition, WOPs administration appeared to be important to limit IR-induced splenocyte apoptosis and inflammatory cascade as well as reduce intestine epithelial barrier dysfunction and promote epithelial integrity. These results suggest that pre and post-treatment of WOPs may help to ameliorate acute damage, which is induced by ionizing radiation in mice and accelerate its recovery. Full article
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Open AccessArticle Field-Based Affinity Optimization of a Novel Azabicyclohexane Scaffold HIV-1 Entry Inhibitor
Molecules 2019, 24(8), 1581; https://doi.org/10.3390/molecules24081581
Received: 19 February 2019 / Revised: 19 April 2019 / Accepted: 20 April 2019 / Published: 22 April 2019
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Abstract
Small-molecule HIV-1 entry inhibitors are an extremely attractive therapeutic modality. We have previously demonstrated that the entry inhibitor class can be optimized by using computational means to identify and extend the chemotypes available. Here we demonstrate unique and differential effects of previously published [...] Read more.
Small-molecule HIV-1 entry inhibitors are an extremely attractive therapeutic modality. We have previously demonstrated that the entry inhibitor class can be optimized by using computational means to identify and extend the chemotypes available. Here we demonstrate unique and differential effects of previously published antiviral compounds on the gross structure of the HIV-1 Env complex, with an azabicyclohexane scaffolded inhibitor having a positive effect on glycoprotein thermostability. We demonstrate that modification of the methyltriazole-azaindole headgroup of these entry inhibitors directly effects the potency of the compounds, and substitution of the methyltriazole with an amine-oxadiazole increases the affinity of the compound 1000-fold over parental by improving the on-rate kinetic parameter. These findings support the continuing exploration of compounds that shift the conformational equilibrium of HIV-1 Env as a novel strategy to improve future inhibitor and vaccine design efforts. Full article
(This article belongs to the Special Issue Recent Advances in the Development of Antiviral Agents)
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Open AccessCommunication Enoxacin and Epigallocatechin Gallate (EGCG) Act Synergistically to Inhibit the Growth of Cervical Cancer Cells in Culture
Molecules 2019, 24(8), 1580; https://doi.org/10.3390/molecules24081580
Received: 8 February 2019 / Revised: 11 April 2019 / Accepted: 18 April 2019 / Published: 22 April 2019
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Abstract
Cervical cancer is a major cause of death in females worldwide. While survival rates have historically improved, there remains a continuous need to identify novel molecules that are effective against this disease. Here, we show that enoxacin, a drug most commonly used to [...] Read more.
Cervical cancer is a major cause of death in females worldwide. While survival rates have historically improved, there remains a continuous need to identify novel molecules that are effective against this disease. Here, we show that enoxacin, a drug most commonly used to treat a broad array of bacterial infections, is able to inhibit growth of the cervical cancer cells. Furthermore, our data show that epigallocatechin gallate (EGCG), a plant bioactive compound abundant in green tea, and known for its antioxidant effects, similarly functions as an antiproliferative agent. Most importantly, we provide evidence that EGCG functions synergistically against cancer cell proliferation in combined treatment with enoxacin. These data collectively suggest that enoxacin and EGCG may be useful treatment options for cases of cervical cancer. Full article
(This article belongs to the Special Issue Plant Bioactives in Preventing Chronic Diseases)
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