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Molecules, Volume 21, Issue 9 (September 2016)

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Open AccessArticle New Oral Formulation and in Vitro Evaluation of Docetaxel-Loaded Nanomicelles
Molecules 2016, 21(9), 1265; https://doi.org/10.3390/molecules21091265
Received: 23 August 2016 / Revised: 17 September 2016 / Accepted: 17 September 2016 / Published: 21 September 2016
Cited by 5 | PDF Full-text (1622 KB) | HTML Full-text | XML Full-text
Abstract
Intravenous administration of Taxotere® (a commercial form of docetaxel, DTX) leads to many problems such as hypersensitivity, hemolysis, cutaneous allergy, and patient refusal due to its prolonged injection. The oral absorption of DTX is very low due to its hydrophobic nature. The
[...] Read more.
Intravenous administration of Taxotere® (a commercial form of docetaxel, DTX) leads to many problems such as hypersensitivity, hemolysis, cutaneous allergy, and patient refusal due to its prolonged injection. The oral absorption of DTX is very low due to its hydrophobic nature. The purpose of this study was to prepare and carry out an in vitro evaluation of DTX-loaded nanomicelles for oral administration in order to increase the oral delivery of DTX. Studied formulations were prepared with the two surfactants Tween 20 and Tween 80 and were characterized for their particle size, zeta potential, stability, encapsulation efficiency, stability studies in gastric fluid and intestinal fluid, toxicity studies in C26 colon carcinoma cell line, and cellular uptake. The prepared nanomicelles with particle size of around 14 nm and encapsulation efficiency of 99% were stable in gastric fluid and intestinal fluid for at least 6 h and IC50 decreased significantly after 72 h exposure compared to that of Taxotere®. Nanomicelles increased the water solubility of DTX more than 1500 times (10 mg/mL in nanomicelles compared to 6 µg/mL in water). Results of this study reveal that the new formulation of DTX could be used for the oral delivery of DTX and merits further investigation. Full article
(This article belongs to the collection Nanomedicine)
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Open AccessReview Cyanidin-3-O-glucoside: Physical-Chemistry, Foodomics and Health Effects
Molecules 2016, 21(9), 1264; https://doi.org/10.3390/molecules21091264
Received: 15 August 2016 / Revised: 9 September 2016 / Accepted: 13 September 2016 / Published: 21 September 2016
Cited by 27 | PDF Full-text (2279 KB) | HTML Full-text | XML Full-text
Abstract
Anthocyanins (ACNs) are plant secondary metabolites from the flavonoid family. Red to blue fruits are major dietary sources of ACNs (up to 1 g/100 g FW), being cyanidin-3-O-glucoside (Cy3G) one of the most widely distributed. Cy3G confers a red hue to
[...] Read more.
Anthocyanins (ACNs) are plant secondary metabolites from the flavonoid family. Red to blue fruits are major dietary sources of ACNs (up to 1 g/100 g FW), being cyanidin-3-O-glucoside (Cy3G) one of the most widely distributed. Cy3G confers a red hue to fruits, but its content in raspberries and strawberries is low. It has a good radical scavenging capacity (RSC) against superoxide but not hydroxyl radicals, and its oxidative potential is pH-dependent (58 mV/pH unit). After intake, Cy3G can be metabolized (phases I, II) by oral epithelial cells, absorbed by the gastric epithelium (1%–10%) and it is gut-transformed (phase II & microbial metabolism), reaching the bloodstream (<1%) and urine (about 0.02%) in low amounts. In humans and Caco-2 cells, Cy3G’s major metabolites are protocatechuic acid and phloroglucinaldehyde which are also subjected to entero-hepatic recycling, although caffeic acid and peonidin-3-glucoside seem to be strictly produced in the large bowel and renal tissues. Solid evidence supports Cy3G’s bioactivity as DNA-RSC, gastro protective, anti-inflammatory, anti-thrombotic chemo-preventive and as an epigenetic factor, exerting protection against Helicobacter pylori infection, age-related diseases, type 2 diabetes, cardiovascular disease, metabolic syndrome and oral cancer. Most relevant mechanisms include RSC, epigenetic action, competitive protein-binding and enzyme inhibition. These and other novel aspects on Cy3G’s physical-chemistry, foodomics, and health effects are discussed. Full article
(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)
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Open AccessReview Promiscuous Effects of Some Phenolic Natural Products on Inflammation at Least in Part Arise from Their Ability to Modulate the Expression of Global Regulators, Namely microRNAs
Molecules 2016, 21(9), 1263; https://doi.org/10.3390/molecules21091263
Received: 15 July 2016 / Revised: 12 September 2016 / Accepted: 14 September 2016 / Published: 21 September 2016
Cited by 9 | PDF Full-text (1278 KB) | HTML Full-text | XML Full-text
Abstract
Recent years have seen the exploration of a puzzling number of compounds found in human diet that could be of interest for prevention or treatment of various pathologies. Although many of these natural products (NPs) have long been used as remedies, their molecular
[...] Read more.
Recent years have seen the exploration of a puzzling number of compounds found in human diet that could be of interest for prevention or treatment of various pathologies. Although many of these natural products (NPs) have long been used as remedies, their molecular effects still remain elusive. With the advent of biotechnology revolution, NP studies turned from chemistry and biochemistry toward global analysis of gene expression. Hope is to use genetics to identify groups of patient for whom certain NPs or their derivatives may offer new preventive or therapeutic treatments. Recently, microRNAs have gained the statute of global regulators controlling cell homeostasis by regulating gene expression through genetic and epigenetic regulatory loops. Realization that certain plant polyphenols can modify microRNA expression and thus impact gene expression globally, initiated new, mainly in vitro studies, in particular to determine phytochemicals effects on inflammatory response, whose exacerbation has been linked to several disorders including cancer, auto-immune, metabolic, cardiovascular and neuro-inflammatory diseases. However, very few mechanistic insights have been provided, given the complexity of genetic regulatory networks implicated. In this review, we will concentrate on data showing the potential interest of some plant polyphenols in manipulating the expression of pro- and anti-inflammatory microRNAs in pathological conditions. Full article
(This article belongs to the Special Issue Natural Products and Inflammation)
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Open AccessArticle The Anticonvulsant Activity of a Flavonoid-Rich Extract from Orange Juice Involves both NMDA and GABA-Benzodiazepine Receptor Complexes
Molecules 2016, 21(9), 1261; https://doi.org/10.3390/molecules21091261
Received: 30 July 2016 / Revised: 31 August 2016 / Accepted: 9 September 2016 / Published: 21 September 2016
Cited by 8 | PDF Full-text (1870 KB) | HTML Full-text | XML Full-text
Abstract
The usage of dietary supplements and other natural products to treat neurological diseases has been growing over time, and accumulating evidence suggests that flavonoids possess anticonvulsant properties. The aim of this study was to examine the effects of a flavonoid-rich extract from orange
[...] Read more.
The usage of dietary supplements and other natural products to treat neurological diseases has been growing over time, and accumulating evidence suggests that flavonoids possess anticonvulsant properties. The aim of this study was to examine the effects of a flavonoid-rich extract from orange juice (OJe) in some rodent models of epilepsy and to explore its possible mechanism of action. The genetically audiogenic seizures (AGS)-susceptible DBA/2 mouse, the pentylenetetrazole (PTZ)-induced seizures in ICR-CD1 mice and the WAG/Rij rat as a genetic model of absence epilepsy with comorbidity of depression were used. Our results demonstrate that OJe was able to exert anticonvulsant effects on AGS-sensible DBA/2 mice and to inhibit PTZ-induced tonic seizures, increasing their latency. Conversely, it did not have anti-absence effects on WAG/Rij rats. Our experimental findings suggest that the anti-convulsant effects of OJe are likely mediated by both an inhibition of NMDA receptors at the glycine-binding site and an agonistic activity on benzodiazepine-binding site at GABAA receptors. This study provides evidences for the antiepileptic activity of OJe, and its results could be used as scientific basis for further researches aimed to develop novel complementary therapy for the treatment of epilepsy in a context of a multitarget pharmacological strategy. Full article
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Open AccessArticle Effects of Dihydrophaseic Acid 3′-O-β-d-Glucopyranoside Isolated from Lycii radicis Cortex on Osteoblast Differentiation
Molecules 2016, 21(9), 1260; https://doi.org/10.3390/molecules21091260
Received: 14 August 2016 / Revised: 16 September 2016 / Accepted: 17 September 2016 / Published: 21 September 2016
PDF Full-text (1786 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Our previous study showed that ethanol extract of Lycii radicis cortex (LRC) prevented the loss of bone mineral density in ovariectomized mice by promoting the differentiation of osteoblast linage cells. Here, we performed fractionation and isolation of the bioactive compound(s) responsible for the
[...] Read more.
Our previous study showed that ethanol extract of Lycii radicis cortex (LRC) prevented the loss of bone mineral density in ovariectomized mice by promoting the differentiation of osteoblast linage cells. Here, we performed fractionation and isolation of the bioactive compound(s) responsible for the bone formation–enhancing effect of LRC extract. A known sesquiterpene glucoside, (1′R,3′S,5′R,8′S,2Z,4E)-dihydrophaseic acid 3′-O-β-d-glucopyranoside (abbreviated as DPA3G), was isolated from LRC extract and identified as a candidate constituent. We investigated the effects of DPA3G on osteoblast and osteoclast differentiation, which play fundamental roles in bone formation and bone resorption, respectively, during bone remodeling. The DPA3G fraction treatment in mesenchymal stem cell line C3H10T1/2 and preosteoblast cell line MC3T3-E1 significantly enhanced cell proliferation and alkaline phosphatase activity in both cell lines compared to the untreated control cells. Furthermore, DPA3G significantly increased mineralized nodule formation and the mRNA expression of osteoblastogenesis markers, Alpl, Runx2, and Bglap, in MC3T3-E1 cells. The DPA3G treatment, however, did not influence osteoclast differentiation in primary-cultured monocytes of mouse bone marrow. Because osteoblastic and osteoclastic precursor cells coexist in vivo, we tested the DPA3G effects under the co-culture condition of MC3T3-E1 cells and monocytes. Remarkably, DPA3G enhanced not only osteoblast differentiation of MC3T3-El cells but also osteoclast differentiation of monocytes, indicating that DPA3G plays a role in the maintenance of the normal bone remodeling balance. Our results suggest that DPA3G may be a good candidate for the treatment of osteoporosis. Full article
(This article belongs to the collection Herbal Medicine Research)
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Open AccessArticle Virtual Screening for Potential Allosteric Inhibitors of Cyclin-Dependent Kinase 2 from Traditional Chinese Medicine
Molecules 2016, 21(9), 1259; https://doi.org/10.3390/molecules21091259
Received: 19 July 2016 / Revised: 1 September 2016 / Accepted: 17 September 2016 / Published: 21 September 2016
Cited by 6 | PDF Full-text (4098 KB) | HTML Full-text | XML Full-text
Abstract
Cyclin-dependent kinase 2 (CDK2), a member of Cyclin-dependent kinases (CDKs), plays an important role in cell division and DNA replication. It is regarded as a desired target to treat cancer and tumor by interrupting aberrant cell proliferation. Compared to lower subtype selectivity of
[...] Read more.
Cyclin-dependent kinase 2 (CDK2), a member of Cyclin-dependent kinases (CDKs), plays an important role in cell division and DNA replication. It is regarded as a desired target to treat cancer and tumor by interrupting aberrant cell proliferation. Compared to lower subtype selectivity of CDK2 ATP-competitive inhibitors, CDK2 allosteric inhibitor with higher subtype selectivity has been used to treat CDK2-related diseases. Recently, the first crystal structure of CDK2 with allosteric inhibitor has been reported, which provides new opportunities to design pure allosteric inhibitors of CDK2. The binding site of the ATP-competition inhibitors and the allosteric inhibitors are partially overlapped in space position, so the same compound might interact with the two binding sites. Thus a novel screening strategy was essential for the discovery of pure CDK2 allosteric inhibitors. In this study, pharmacophore and molecular docking were used to screen potential CDK2 allosteric inhibitors and ATP-competition inhibitors from Traditional Chinese Medicine (TCM). In the docking result of the allosteric site, the compounds which can act with the CDK2 ATP site were discarded, and the remaining compounds were regarded as the potential pure allosteric inhibitors. Among the results, prostaglandin E1 and nordihydroguaiaretic acid (NDGA) were available and their growth inhibitory effect on human HepG2 cell lines was determined by MTT assay. The two compounds could substantially inhibit the growth of HepG2 cell lines with an estimated IC50 of 41.223 μmol/L and 45.646 μmol/L. This study provides virtual screening strategy of allosteric compounds and a reliable method to discover potential pure CDK2 allosteric inhibitors from TCM. Prostaglandin E1 and NDGA could be regarded as promising candidates for CDK2 allosteric inhibitors. Full article
(This article belongs to the Special Issue Computational Design: A New Approach to Drug and Molecular Discovery)
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Open AccessArticle Antiangiogenic Effects of VH02, a Novel Urea Derivative: In Vitro and in Vivo Studies
Molecules 2016, 21(9), 1258; https://doi.org/10.3390/molecules21091258
Received: 30 July 2016 / Revised: 14 September 2016 / Accepted: 17 September 2016 / Published: 21 September 2016
Cited by 1 | PDF Full-text (13176 KB) | HTML Full-text | XML Full-text
Abstract
Vascular endothelial growth factor receptor 2 (VEGFR2) is a vital target for therapeutic intervention in cancer. We have recently described a computer-based drug design for a small molecule VEGFR2 inhibitor named VH02 (1-((1-(1H-indazol-6-yl)-1H-1,2,3-triazol-4-yl)methyl)-3-(3-chloromethylphenyl)urea). This study aimed to further explore
[...] Read more.
Vascular endothelial growth factor receptor 2 (VEGFR2) is a vital target for therapeutic intervention in cancer. We have recently described a computer-based drug design for a small molecule VEGFR2 inhibitor named VH02 (1-((1-(1H-indazol-6-yl)-1H-1,2,3-triazol-4-yl)methyl)-3-(3-chloromethylphenyl)urea). This study aimed to further explore the anti-angiogenic activity of VH02 both in vitro and in vivo. The in vitro assays include cell viability, capillary-like tube formation, MMP activity, and western blot analyses of signaling through VEGFR2 while the in vivo anti-angiogenic response were performed to evaluate the effect on vascularization in Matrigel plug applied in C57BL/6L mice. VH02 reduced angiogenesis behavior of EA.hy926 including cell viability, migration, adhesion, capillary-like tube formation, and MMP-2 activity induced by VEGF. Furthermore, VH02 regulated angiogenesis by directly inhibiting VEGFR2 on Tyr1175 signaling pathway leading to the inhibition of Akt-mediated cell survival and migration. Disruption of phosphorylation at VEGFR2-Tyr1175 by VH02 abolished FAK-Tyr397 signaling but not phosphorylation of p38 MAPK. This suggests that blockade of FAK by VH02 apparently associated with reduction of endothelial cell motility. Actin cytoskeleton rearrangement was diminished by VH02 in human endothelial cells. The anti-angiogenic effect of VH02 was confirmed in the in vivo model, revealing the reduction of vascular density in Matrigel plug after VH02 treatment. Additionally, the pericyte-like cells surrounding blood vessels in the plugs were significantly reduced as well as vascular density and p-Akt intensity. Our findings indicate that VH02 successfully inhibits VEGF-induced angiogenesis both in vitro and in vivo models. The compound could be further developed as an antiangiogenesis agent for cancer therapy. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Optimized Conditions for Passerini-Smiles Reactions and Applications to Benzoxazinone Syntheses
Molecules 2016, 21(9), 1257; https://doi.org/10.3390/molecules21091257
Received: 27 July 2016 / Revised: 13 September 2016 / Accepted: 13 September 2016 / Published: 21 September 2016
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Abstract
Initial conditions disclosed for the Passerini-Smiles reaction are associated with a lack of efficiency that has prevented chemists from using it since its discovery. We wish to report herein our thorough study in the development of new experimental conditions for this coupling between
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Initial conditions disclosed for the Passerini-Smiles reaction are associated with a lack of efficiency that has prevented chemists from using it since its discovery. We wish to report herein our thorough study in the development of new experimental conditions for this coupling between electron-poor phenols, isocyanides, and carbonyl derivatives. These new conditions have been applied to several synthetic strategies towards benzoxazinones. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle Silver Nanocomposite Biosynthesis: Antibacterial Activity against Multidrug-Resistant Strains of Pseudomonas aeruginosa and Acinetobacter baumannii
Molecules 2016, 21(9), 1255; https://doi.org/10.3390/molecules21091255
Received: 17 August 2016 / Revised: 9 September 2016 / Accepted: 14 September 2016 / Published: 20 September 2016
Cited by 3 | PDF Full-text (935 KB) | HTML Full-text | XML Full-text
Abstract
Bacterial resistance is an emerging public health issue that is disseminated worldwide. Silver nanocomposite can be an alternative strategy to avoid Gram-positive and Gram-negative bacteria growth, including multidrug-resistant strains. In the present study a silver nanocomposite was synthesized, using a new green chemistry
[...] Read more.
Bacterial resistance is an emerging public health issue that is disseminated worldwide. Silver nanocomposite can be an alternative strategy to avoid Gram-positive and Gram-negative bacteria growth, including multidrug-resistant strains. In the present study a silver nanocomposite was synthesized, using a new green chemistry process, by the addition of silver nitrate (1.10−3 mol·L−1) into a fermentative medium of Xanthomonas spp. to produce a xanthan gum polymer. Transmission electron microscopy (TEM) was used to evaluate the shape and size of the silver nanoparticles obtained. The silver ions in the nanocomposite were quantified by flame atomic absorption spectrometry (FAAS). The antibacterial activity of the nanomaterial against Escherichia coli (ATCC 22652), Enterococcus faecalis (ATCC 29282), Pseudomonas aeruginosa (ATCC 27853) and Staphylococcus aureus (ATCC 25923) was carried out using 500 mg of silver nanocomposite. Pseudomonas aeruginosa and Acinetobacter baumannii multidrug-resistant strains, isolated from hospitalized patients were also included in the study. The biosynthesized silver nanocomposite showed spherical nanoparticles with sizes smaller than 10 nm; 1 g of nanocomposite contained 49.24 µg of silver. Multidrug-resistant strains of Pseudomonas aeruginosa and Acinetobacter baumannii, and the other Gram-positive and Gram-negative bacteria tested, were sensitive to the silver nanocomposite (10–12.9 mm of inhibition zone). The biosynthesized silver nanocomposite seems to be a promising antibacterial agent for different applications, namely biomedical devices or topical wound coatings. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Effect of Phyllanthus amarus Extract on 5-Fluorouracil-Induced Perturbations in Ribonucleotide and Deoxyribonucleotide Pools in HepG2 Cell Line
Molecules 2016, 21(9), 1254; https://doi.org/10.3390/molecules21091254
Received: 16 August 2016 / Revised: 14 September 2016 / Accepted: 14 September 2016 / Published: 20 September 2016
Cited by 2 | PDF Full-text (1950 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study was to investigate the antitumor activities of Phyllanthus amarus (PHA) and its potential of herb–drug interactions with 5-Fluorouracil (5-FU). Cell viability, ribonucleotides (RNs) and deoxyribonucleotides (dRNs) levels, cell cycle distribution, and expression of thymidylate synthase (TS) and ribonucleotide
[...] Read more.
The aim of this study was to investigate the antitumor activities of Phyllanthus amarus (PHA) and its potential of herb–drug interactions with 5-Fluorouracil (5-FU). Cell viability, ribonucleotides (RNs) and deoxyribonucleotides (dRNs) levels, cell cycle distribution, and expression of thymidylate synthase (TS) and ribonucleotide reductase (RR) proteins were measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, high performance liquid chromatography tandem mass spectrometry (HPLC/MS/MS) method, flow cytometry and Western blot analysis, respectively. Our standardized PHA extract showed toxicity to HepG2 cells at high concentrations after 72 h exposure and induced G2/M cell cycle arrest. Combined use of 5-FU with PHA resulted in significant decreases in ATP, CTP, GTP, UTP and dTTP levels, while AMP, CMP, GMP and dUMP levels increased significantly compared with use of 5-FU alone. Further, PHA could increase the role of cell cycle arrest at S phase induced by 5-FU. Although PHA alone had no direct impact on TS and RR, PHA could change the levels of RNs and dRNs when combined with 5-FU. This may be due to cell cycle arrest or regulation of key enzyme steps in intracellular RNs and dRNs metabolism. Full article
(This article belongs to the collection Herbal Medicine Research)
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Open AccessArticle The Suppressive Effects of Cinnamomi Cortex and Its Phytocompound Coumarin on Oxaliplatin-Induced Neuropathic Cold Allodynia in Rats
Molecules 2016, 21(9), 1253; https://doi.org/10.3390/molecules21091253
Received: 14 July 2016 / Revised: 10 September 2016 / Accepted: 12 September 2016 / Published: 20 September 2016
Cited by 6 | PDF Full-text (3348 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Oxaliplatin, a chemotherapy drug, induces acute peripheral neuropathy characterized by cold allodynia, spinal glial activation and increased levels of pro-inflammatory cytokines. Herein, we determined whether Cinnamomi Cortex (C. Cortex), a widely used medicinal herb in East Asia for cold-related diseases, could attenuate oxaliplatin-induced
[...] Read more.
Oxaliplatin, a chemotherapy drug, induces acute peripheral neuropathy characterized by cold allodynia, spinal glial activation and increased levels of pro-inflammatory cytokines. Herein, we determined whether Cinnamomi Cortex (C. Cortex), a widely used medicinal herb in East Asia for cold-related diseases, could attenuate oxaliplatin-induced cold allodynia in rats and the mechanisms involved. A single oxaliplatin injection (6 mg/kg, i.p.) induced significant cold allodynia signs based on tail immersion tests using cold water (4 °C). Daily oral administration of water extract of C. Cortex (WECC) (100, 200, and 400 mg/kg) for five consecutive days following an oxaliplatin injection dose-dependently alleviated cold allodynia with only a slight difference in efficacies between the middle dose at 200 mg/kg and the highest dose at 400 mg/kg. WECC at 200 mg/kg significantly suppressed the activation of astrocytes and microglia and decreased the expression levels of IL-1β and TNF in the spinal cord after injection with oxaliplatin. Furthermore, oral administration of coumarin (10 mg/kg), a major phytocompound of C. Cortex, markedly reduced cold allodynia. These results indicate that C. Cortex has a potent anti-allodynic effect in oxaliplatin-injected rats through inhibiting spinal glial cells and pro-inflammatory cytokines. We also suggest that coumarin might play a role in the anti-allodynic effect of C. Cortex. Full article
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Open AccessReview Therapeutic Effects of Phytochemicals and Medicinal Herbs on Chemotherapy-Induced Peripheral Neuropathy
Molecules 2016, 21(9), 1252; https://doi.org/10.3390/molecules21091252
Received: 11 July 2016 / Revised: 11 September 2016 / Accepted: 12 September 2016 / Published: 20 September 2016
Cited by 8 | PDF Full-text (1715 KB) | HTML Full-text | XML Full-text
Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent adverse effect of neurotoxic anticancer medicines. It leads to autonomic and somatic system dysfunction and decreases the patient’s quality of life. This side effect eventually causes chemotherapy non-compliance. Patients are prompted to seek alternative treatment options
[...] Read more.
Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent adverse effect of neurotoxic anticancer medicines. It leads to autonomic and somatic system dysfunction and decreases the patient’s quality of life. This side effect eventually causes chemotherapy non-compliance. Patients are prompted to seek alternative treatment options since there is no conventional remedy for CIPN. A range of medicinal herbs have multifarious effects, and they have shown some evidence of efficacy in various neurological and immunological diseases. While CIPN has multiple mechanisms of neurotoxicity, these phytomedicines might offer neuronal protection or regeneration with the multiple targets in CIPN. Thus far, researchers have investigated the therapeutic benefits of several herbs, herbal formulas, and phytochemicals in preventing the onset and progress of CIPN in animals and humans. Here, we summarize current knowledge regarding the role of phytochemicals, herb extracts, and herbal formulas in alleviating CIPN. Full article
Open AccessArticle Digital Gene Expression Profiling to Explore Differentially Expressed Genes Associated with Terpenoid Biosynthesis during Fruit Development in Litsea cubeba
Molecules 2016, 21(9), 1251; https://doi.org/10.3390/molecules21091251
Received: 28 July 2016 / Revised: 25 August 2016 / Accepted: 13 September 2016 / Published: 20 September 2016
PDF Full-text (1997 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Mountain pepper (Litsea cubeba (Lour.) Pers.) (Lauraceae) is an important industrial crop as an ingredient in cosmetics, pesticides, food additives and potential biofuels. These properties are attributed to monoterpenes and sesquiterpenes. However, there is still no integrated model describing differentially expressed genes
[...] Read more.
Mountain pepper (Litsea cubeba (Lour.) Pers.) (Lauraceae) is an important industrial crop as an ingredient in cosmetics, pesticides, food additives and potential biofuels. These properties are attributed to monoterpenes and sesquiterpenes. However, there is still no integrated model describing differentially expressed genes (DEGs) involved in terpenoid biosynthesis during the fruit development of L. cubeba. Here, we performed digital gene expression (DGE) using the Illumina NGS platform to evaluated changes in gene expression during fruit development in L. cubeba. DGE generated expression data for approximately 19354 genes. Fruit at 60 days after flowering (DAF) served as the control, and a total of 415, 1255, 449 and 811 up-regulated genes and 505, 1351, 1823 and 1850 down-regulated genes were identified at 75, 90, 105 and 135 DAF, respectively. Pathway analysis revealed 26 genes involved in terpenoid biosynthesis pathways. Three DEGs had continued increasing or declining trends during the fruit development. The quantitative real-time PCR (qRT-PCR) results of five differentially expressed genes were consistent with those obtained from Illumina sequencing. These results provide a comprehensive molecular biology background for research on fruit development, and information that should aid in metabolic engineering to increase the yields of L. cubeba essential oil. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessReview Delivery of RNAi Therapeutics to the Airways—From Bench to Bedside
Molecules 2016, 21(9), 1249; https://doi.org/10.3390/molecules21091249
Received: 16 August 2016 / Revised: 5 September 2016 / Accepted: 13 September 2016 / Published: 20 September 2016
Cited by 11 | PDF Full-text (1057 KB) | HTML Full-text | XML Full-text
Abstract
RNA interference (RNAi) is a potent and specific post-transcriptional gene silencing process. Since its discovery, tremendous efforts have been made to translate RNAi technology into therapeutic applications for the treatment of different human diseases including respiratory diseases, by manipulating the expression of disease-associated
[...] Read more.
RNA interference (RNAi) is a potent and specific post-transcriptional gene silencing process. Since its discovery, tremendous efforts have been made to translate RNAi technology into therapeutic applications for the treatment of different human diseases including respiratory diseases, by manipulating the expression of disease-associated gene(s). Similar to other nucleic acid-based therapeutics, the major hurdle of RNAi therapy is delivery. Pulmonary delivery is a promising approach of delivering RNAi therapeutics directly to the airways for treating local conditions and minimizing systemic side effects. It is a non-invasive route of administration that is generally well accepted by patients. However, pulmonary drug delivery is a challenge as the lungs pose a series of anatomical, physiological and immunological barriers to drug delivery. Understanding these barriers is essential for the development an effective RNA delivery system. In this review, the different barriers to pulmonary drug delivery are introduced. The potential of RNAi molecules as new class of therapeutics, and the latest preclinical and clinical studies of using RNAi therapeutics in different respiratory conditions are discussed in details. We hope this review can provide some useful insights for moving inhaled RNAi therapeutics from bench to bedside. Full article
(This article belongs to the Special Issue Nucleic Acid-based Drug)
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Open AccessCommunication Two New Clerodane Diterpenes from Tinospora sagittata
Molecules 2016, 21(9), 1250; https://doi.org/10.3390/molecules21091250
Received: 24 August 2016 / Revised: 16 September 2016 / Accepted: 16 September 2016 / Published: 19 September 2016
Cited by 2 | PDF Full-text (932 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new clerodane-type diterpenes, tinosporins C (1) and tinosporins D (2) were isolated from the stems of Tinospora sagittata (Oliv.), together with three known ones, columbin (3), tinophylloloside (4), and tinospinoside D (5).
[...] Read more.
Two new clerodane-type diterpenes, tinosporins C (1) and tinosporins D (2) were isolated from the stems of Tinospora sagittata (Oliv.), together with three known ones, columbin (3), tinophylloloside (4), and tinospinoside D (5). The structures of these compounds were determined on the basis of spectroscopic data interpretation, with that of the absolute configuration of compound 1 was assigned by experimental and calculated ECD spectra. The cytotoxicity and α-glucosidase inhibitory activities of isolated compounds were evaluated in vitro. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Asiatic Acid Attenuates Myocardial Ischemia/Reperfusion Injury via Akt/GSK-3β/HIF-1α Signaling in Rat H9c2 Cardiomyocytes
Molecules 2016, 21(9), 1248; https://doi.org/10.3390/molecules21091248
Received: 26 August 2016 / Revised: 13 September 2016 / Accepted: 16 September 2016 / Published: 19 September 2016
Cited by 16 | PDF Full-text (4297 KB) | HTML Full-text | XML Full-text
Abstract
Myocardial ischemic/reperfusion injury results from severe impairment of coronary blood supply and leads to irreversible cell death, with limited therapeutic possibilities. Asiatic acid is a pentacyclic triterpenoid derived from the tropical medicinal plant Centella asiatica and serves a variety of bioactivities. In this
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Myocardial ischemic/reperfusion injury results from severe impairment of coronary blood supply and leads to irreversible cell death, with limited therapeutic possibilities. Asiatic acid is a pentacyclic triterpenoid derived from the tropical medicinal plant Centella asiatica and serves a variety of bioactivities. In this study, we determined the effect of asiatic acid on myocardial ischemia/reperfusion injury and investigated the underlying mechanisms, using an in vitro rat H9c2 cardiomyocytes model of oxygen-glucose deprivation/reoxygenation (OGD/R) injury. Results showed that pre-treatment with asiatic acid significantly augmented cell viability and prevented lactate dehydrogenase (LDH) release in a concentration-dependent manner after OGD/R exposure. Asiatic acid at 10 μM effectively inhibited apoptotic cell death, suppressed the activities of caspase-3 and caspase-9, and reversed Bax/Bcl-2 ratio in hypoxic H9c2 cells. In addition, asiatic acid improved mitochondrial function, as evidenced by reduced reactive oxygen species (ROS) accumulation, enhanced mitochondrial membrane potential and decreased intracellular calcium concentration. Using Western blot assay, we found that asiatic acid promoted the phosphorylation of Akt and subsequent inactivation of glycogen synthase kinase-3β (GSK-3β), and induced the expression of hypoxia-inducible factor 1α (HIF-1α) after OGD/R. The cardioprotective effects of asiatic acid were attenuated by the Akt or HIF-1α inhibitor. Taken together, these data suggested that asiatic acid exerted protective effects against OGD/R-induced apoptosis in cardiomyocytes, at least partly via the Akt/GSK-3β/HIF-1α pathway. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Comparison of the Antioxidant Effects of Quercitrin and Isoquercitrin: Understanding the Role of the 6″-OH Group
Molecules 2016, 21(9), 1246; https://doi.org/10.3390/molecules21091246
Received: 6 July 2016 / Revised: 28 August 2016 / Accepted: 6 September 2016 / Published: 19 September 2016
Cited by 18 | PDF Full-text (3837 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The role of the 6″-OH (ω-OH) group in the antioxidant activity of flavonoid glycosides has been largely overlooked. Herein, we selected quercitrin (quercetin-3-O-rhamnoside) and isoquercitrin (quercetin-3-O-glucoside) as model compounds to investigate the role of the 6″-OH group in several
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The role of the 6″-OH (ω-OH) group in the antioxidant activity of flavonoid glycosides has been largely overlooked. Herein, we selected quercitrin (quercetin-3-O-rhamnoside) and isoquercitrin (quercetin-3-O-glucoside) as model compounds to investigate the role of the 6″-OH group in several antioxidant pathways, including Fe2+-binding, hydrogen-donating (H-donating), and electron-transfer (ET). The results revealed that quercitrin and isoquercitrin both exhibited dose-dependent antioxidant activities. However, isoquercitrin showed higher levels of activity than quercitrin in the Fe2+-binding, ET-based ferric ion reducing antioxidant power, and multi-pathways-based superoxide anion-scavenging assays. In contrast, quercitrin exhibited greater activity than isoquercitrin in an H-donating-based 1,1-diphenyl-2-picrylhydrazyl radical-scavenging assay. Finally, in a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl assay based on an oxidatively damaged mesenchymal stem cell (MSC) model, isoquercitrin performed more effectively as a cytoprotector than quercitrin. Based on these results, we concluded that (1) quercitrin and isoquercitrin can both indirectly (i.e., Fe2+-chelating or Fe2+-binding) and directly participate in the scavenging of reactive oxygen species (ROS) to protect MSCs against ROS-induced oxidative damage; (2) the 6″-OH group in isoquercitrin enhanced its ET and Fe2+-chelating abilities and lowered its H-donating abilities via steric hindrance or H-bonding compared with quercitrin; and (3) isoquercitrin exhibited higher ROS scavenging activity than quercitrin, allowing it to improve protect MSCs against ROS-induced oxidative damage. Full article
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Open AccessArticle On the Effect of Microwave Energy on Lipase-Catalyzed Polycondensation Reactions
Molecules 2016, 21(9), 1245; https://doi.org/10.3390/molecules21091245
Received: 27 July 2016 / Revised: 7 September 2016 / Accepted: 13 September 2016 / Published: 19 September 2016
Cited by 5 | PDF Full-text (1228 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Microwave energy (MWe) is, nowadays, widely used as a clean synthesis tool to improve several chemical reactions, such as drug molecule synthesis, carbohydrate conversion and biomass pyrolysis. On the other hand, its exploitation in enzymatic reactions has only been fleetingly investigated and, hence,
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Microwave energy (MWe) is, nowadays, widely used as a clean synthesis tool to improve several chemical reactions, such as drug molecule synthesis, carbohydrate conversion and biomass pyrolysis. On the other hand, its exploitation in enzymatic reactions has only been fleetingly investigated and, hence, further study of MWe is required to reach a precise understanding of its potential in this field. Starting from the authors’ experience in clean synthesis and biocatalyzed reactions, this study sheds light on the possibility of using MWe for enhancing enzyme-catalyzed polycondensation reactions and pre-polymer formation. Several systems and set ups were investigated involving bulk and organic media (solution phase) reactions, different enzymatic preparations and various starting bio-based monomers. Results show that MWe enables the biocatalyzed synthesis of polyesters and pre-polymers in a similar way to that reported using conventional heating with an oil bath, but in a few cases, notably bulk phase polycondensations under intense microwave irradiation, MWe leads to a rapid enzyme deactivation. Full article
(This article belongs to the Special Issue Chemicals from Biomass)
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Open AccessArticle The Use of Mass Spectrometric Techniques to Differentiate Isobaric and Isomeric Flavonoid Conjugates from Axyris amaranthoides
Molecules 2016, 21(9), 1229; https://doi.org/10.3390/molecules21091229
Received: 27 July 2016 / Revised: 1 September 2016 / Accepted: 8 September 2016 / Published: 19 September 2016
Cited by 3 | PDF Full-text (2026 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Flavonoids are a group of compounds that are commonly found in various plants, where they play important roles in many processes, including free radical scavenging and UV protection. These compounds can also act as chemical messengers, physiological regulators or protectants against pathogens in
[...] Read more.
Flavonoids are a group of compounds that are commonly found in various plants, where they play important roles in many processes, including free radical scavenging and UV protection. These compounds can also act as chemical messengers, physiological regulators or protectants against pathogens in the defense reactions of plants. Flavonoid activity is regulated by the addition of various substituents, usually mono- or oligosaccharides of common sugars, such as glucose, rhamnose or galactose. In some plants, glucuronic acid is attached, and this sugar is often acylated by phenylpropanoic acids. Identification of these compounds and their derivatives is of great importance to understanding their role in plant metabolism and defense mechanisms; this research is important because flavonoids are frequently a significant constituent of the human diet. In this study, we identify the flavonoid conjugates present in Axyris amaranthoides L. extracts and demonstrate the usefulness of high-resolution mass spectrometry (HRMS) analyzers for the differentiation of isobaric compounds and the utility of fragmentation spectra for the differentiation of isomeric structures. According to our knowledge, some of the structures, especially dehydrodiferulated conjugates of tricin, whose structures are proposed here have been found for the first time in plant material. Full article
(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)
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Open AccessArticle Molecular Modeling Studies of 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors through Receptor-Based 3D-QSAR and Molecular Dynamics Simulations
Molecules 2016, 21(9), 1222; https://doi.org/10.3390/molecules21091222
Received: 13 July 2016 / Revised: 21 August 2016 / Accepted: 9 September 2016 / Published: 19 September 2016
Cited by 4 | PDF Full-text (4438 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a potential target for the treatment of numerous human disorders, such as diabetes, obesity, and metabolic syndrome. In this work, molecular modeling studies combining molecular docking, 3D-QSAR, MESP, MD simulations and free energy calculations were performed on
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11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a potential target for the treatment of numerous human disorders, such as diabetes, obesity, and metabolic syndrome. In this work, molecular modeling studies combining molecular docking, 3D-QSAR, MESP, MD simulations and free energy calculations were performed on pyridine amides and 1,2,4-triazolopyridines as 11β-HSD1 inhibitors to explore structure-activity relationships and structural requirement for the inhibitory activity. 3D-QSAR models, including CoMFA and CoMSIA, were developed from the conformations obtained by docking strategy. The derived pharmacophoric features were further supported by MESP and Mulliken charge analyses using density functional theory. In addition, MD simulations and free energy calculations were employed to determine the detailed binding process and to compare the binding modes of inhibitors with different bioactivities. The binding free energies calculated by MM/PBSA showed a good correlation with the experimental biological activities. Free energy analyses and per-residue energy decomposition indicated the van der Waals interaction would be the major driving force for the interactions between an inhibitor and 11β-HSD1. These unified results may provide that hydrogen bond interactions with Ser170 and Tyr183 are favorable for enhancing activity. Thr124, Ser170, Tyr177, Tyr183, Val227, and Val231 are the key amino acid residues in the binding pocket. The obtained results are expected to be valuable for the rational design of novel potent 11β-HSD1 inhibitors. Full article
(This article belongs to the collection Molecular Docking)
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Open AccessEditorial Does a Graphical Abstract Bring More Visibility to Your Paper?
Molecules 2016, 21(9), 1247; https://doi.org/10.3390/molecules21091247
Received: 14 September 2016 / Accepted: 15 September 2016 / Published: 18 September 2016
Cited by 4 | PDF Full-text (164 KB) | HTML Full-text | XML Full-text
Abstract
A graphical abstract (GA) represents a piece of artwork that is intended to summarize the main findings of an article for readers at a single glance. Many publishers currently encourage authors to supplement their articles with GAs, in the hope that such a
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A graphical abstract (GA) represents a piece of artwork that is intended to summarize the main findings of an article for readers at a single glance. Many publishers currently encourage authors to supplement their articles with GAs, in the hope that such a convenient visual summary will facilitate readers with a clearer outline of papers that are of interest and will result in improved overall visibility of the respective publication. To test this assumption, we statistically compared publications with or without GA published in Molecules between March 2014 and March 2015 with regard to several output parameters reflecting visibility. Contrary to our expectations, manuscripts published without GA performed significantly better in terms of PDF downloads, abstract views, and total citations than manuscripts with GA. To the best of our knowledge, this is the first empirical study on the effectiveness of GA for attracting attention to scientific publications. Full article
(This article belongs to the Special Issue Effects of Natural Products in the Context of Cardiometabolic Disease)
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Open AccessArticle Chemical Composition and in Vitro Antimicrobial, Cytotoxic, and Central Nervous System Activities of the Essential Oils of Citrus medica L. cv. ‘Liscia’ and C. medica cv. ‘Rugosa’ Cultivated in Southern Italy
Molecules 2016, 21(9), 1244; https://doi.org/10.3390/molecules21091244
Received: 19 July 2016 / Revised: 6 September 2016 / Accepted: 12 September 2016 / Published: 18 September 2016
Cited by 5 | PDF Full-text (1754 KB) | HTML Full-text | XML Full-text
Abstract
Citrus medica cv. ‘liscia’ and C. medica cv. ‘rugosa’ are two taxa of citron, belonging to the biodiversity of South Italy, in particular of Amalfi Coast, in the Campania region. The chemical composition of the essential oils (EOs) from fruit peels of both
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Citrus medica cv. ‘liscia’ and C. medica cv. ‘rugosa’ are two taxa of citron, belonging to the biodiversity of South Italy, in particular of Amalfi Coast, in the Campania region. The chemical composition of the essential oils (EOs) from fruit peels of both C. medica cultivars was studied by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) analyses. In all, 100 compounds were identified, 82 for C. medica cv. ‘liscia’, accounting for 91.4% of the total oil, and 88 for C. medica cv. ‘rugosa’, accounting for 92.0% of the total oil. Monoterpene hydrocarbons are the main constituents in both oils of C. medica cv. ‘liscia’ (79.1%) and C. medica cv. ‘rugosa’ (80.2%). In both oils, limonene (67.2%–62.8%) and camphene (8.5%–10.9%) are the main constituents. The antimicrobial activity of the EOs was assayed against some bacterial strains: Bacillus cereus (DSM 4313), Bacillus cereus (DSM 4384), Staphylococcus aureus (DSM 25693), Pseudomonas aeruginosa (ATCC 50071), and Escherichia coli (DSM 8579). Low concentrations of C. medica cv. ‘rugosa’ EO showed an inhibitory effect on P. aeruginosa and higher concentrations inhibited more B. cereus (4384) and E. coli than S. aureus. The cytotoxicity of the EO was evaluated against SH-SY5Y cell line. The influence of the EO on the expression of adenylate cyclase 1 (ADCY1) was also studied. The antimicrobial activity registered confirm their traditional uses as food preserving agents and led us to hypothesize the possible use of these oils as antimicrobials. The alterations in ADCY1 expression suggested a role for limonene in effects on the central nervous system. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
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Open AccessReview Curcumin and Resveratrol in the Management of Cognitive Disorders: What is the Clinical Evidence?
Molecules 2016, 21(9), 1243; https://doi.org/10.3390/molecules21091243
Received: 26 July 2016 / Accepted: 12 September 2016 / Published: 17 September 2016
Cited by 20 | PDF Full-text (495 KB) | HTML Full-text | XML Full-text
Abstract
A growing body of in vitro and in vivo evidences shows a possible role of polyphenols in counteracting neurodegeneration: curcumin and resveratrol are attractive substances in this regard. In fact, epidemiological studies highlight a neuroprotective effect of turmeric (rhizome of Curcuma longa L.),
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A growing body of in vitro and in vivo evidences shows a possible role of polyphenols in counteracting neurodegeneration: curcumin and resveratrol are attractive substances in this regard. In fact, epidemiological studies highlight a neuroprotective effect of turmeric (rhizome of Curcuma longa L.), the main source of curcumin. Moreover, the consumption of red wine, the main source of resveratrol, has been related to a lower risk of developing dementia. In this review, we analyzed the published clinical trials investigating curcumin and resveratrol in the prevention or treatment of cognitive disorders. The ongoing studies were also described, in order to give an overview of the current search on this topic. The results of published trials (five for curcumin, six for resveratrol) are disappointing and do not allow to draw conclusions about the therapeutic or neuroprotective potential of curcumin and resveratrol. These compounds, being capable of interfering with several processes implicated in the early stages of dementia, could be useful in preventing or in slowing down the pathology. To this aim, an early diagnosis using peripheral biomarkers becomes necessary. Furthermore, the potential preventive activity of curcumin and resveratrol should be evaluated in long-term exposure clinical trials, using preparations with high bioavailability and that are well standardized. Full article
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Open AccessArticle Screening of Potential Xanthine Oxidase Inhibitors in Gnaphalium hypoleucum DC. by Immobilized Metal Affinity Chromatography and Ultrafiltration-Ultra Performance Liquid Chromatography-Mass Spectrometry
Molecules 2016, 21(9), 1242; https://doi.org/10.3390/molecules21091242
Received: 22 August 2016 / Accepted: 13 September 2016 / Published: 17 September 2016
Cited by 6 | PDF Full-text (3680 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this study, a new method based on immobilized metal affinity chromatography (IMAC) combined with ultrafiltration-ultra performance liquid chromatography-mass spectrometry (UF-UPLC-MS) was developed for discovering ligands for xanthine oxidase (XO) in Gnaphalium hypoleucum DC., a folk medicine used in China for the treatment
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In this study, a new method based on immobilized metal affinity chromatography (IMAC) combined with ultrafiltration-ultra performance liquid chromatography-mass spectrometry (UF-UPLC-MS) was developed for discovering ligands for xanthine oxidase (XO) in Gnaphalium hypoleucum DC., a folk medicine used in China for the treatment of gout. By IMAC, the high flavonoid content of G. hypoleucum could be determined rapidly and efficiently. UF-UPLC-MS was used to select the bound xanthine oxidase ligands in the mixture and identify them. Finally, two flavonoids, luteolin-4′-O-glucoside and luteolin, were successfully screened and identified as the candidate XO inhibitors of G. hypoleucum. They were evaluated in vitro for XO inhibitory activity and their interaction mechanism was studied coupled with molecular simulations. The results were in favor of the hypothesis that the flavonoids of G. hypoleucum might be the active content for gout treatment by inhibiting XO. Full article
(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)
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Open AccessArticle Xanthium strumarium as an Inhibitor of α-Glucosidase, Protein Tyrosine Phosphatase 1β, Protein Glycation and ABTS+ for Diabetic and Its Complication
Molecules 2016, 21(9), 1241; https://doi.org/10.3390/molecules21091241
Received: 27 July 2016 / Revised: 6 September 2016 / Accepted: 12 September 2016 / Published: 16 September 2016
Cited by 4 | PDF Full-text (1223 KB) | HTML Full-text | XML Full-text
Abstract
Phytochemical investigation of the natural products from Xanthium strumarium led to the isolation of fourteen compounds including seven caffeoylquinic acid (CQA) derivatives. The individual compounds were screened for inhibition of α-glucosidase, protein tyrosine phosphatase 1β (PTP1β), advanced glycation end products (AGEs), and ABTS
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Phytochemical investigation of the natural products from Xanthium strumarium led to the isolation of fourteen compounds including seven caffeoylquinic acid (CQA) derivatives. The individual compounds were screened for inhibition of α-glucosidase, protein tyrosine phosphatase 1β (PTP1β), advanced glycation end products (AGEs), and ABTS+ radical scavenging activity using in vitro assays. Among the isolated compounds, methyl-3,5-di-caffeoyquinic acid exhibited significant inhibitory activity against α-glucosidase (18.42 μM), PTP1β (1.88 μM), AGEs (82.79 μM), and ABTS+ (6.03 μM). This effect was marked compared to that of the positive controls (acarbose 584.79 μM, sumarin 5.51 μM, aminoguanidine 1410.00 μM, and trolox 29.72 μM respectively). In addition, 3,5-di-O-CQA (88.14 μM) and protocatechuic acid (32.93 μM) had a considerable inhibitory effect against α-glucosidase and ABTS+. Based on these findings, methyl-3,5-di-caffeoyquinic acid was assumed to be potentially responsible for the anti-diabetic actions of X. strumarium. Full article
(This article belongs to the Special Issue Natural Products and Chronic Diseases)
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Open AccessArticle A Prenylated Xanthone, Cudratricusxanthone A, Isolated from Cudrania tricuspidata Inhibits Lipopolysaccharide-Induced Neuroinflammation through Inhibition of NF-κB and p38 MAPK Pathways in BV2 Microglia
Molecules 2016, 21(9), 1240; https://doi.org/10.3390/molecules21091240
Received: 28 July 2016 / Revised: 30 August 2016 / Accepted: 11 September 2016 / Published: 16 September 2016
Cited by 6 | PDF Full-text (1866 KB) | HTML Full-text | XML Full-text
Abstract
Cudrania tricuspidata Bureau (Moraceae) is an important source of traditional Korean and Chinese medicines used to treat neuritis and inflammation. Cudratricusxanthone A (1), a prenylated xanthone, isolated from C. tricuspidata, has a variety of biological and therapeutic activities. The goal
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Cudrania tricuspidata Bureau (Moraceae) is an important source of traditional Korean and Chinese medicines used to treat neuritis and inflammation. Cudratricusxanthone A (1), a prenylated xanthone, isolated from C. tricuspidata, has a variety of biological and therapeutic activities. The goal of this study was to examine the effects of compound 1 on neuroinflammation and characterize its mechanism of action in lipopolysaccharide (LPS)-stimulated BV2 microglia. Cudratricusxanthone A (1) suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 enzymes and decreased the production of iNOS-derived nitric oxide and COX-2-derived prostaglandin E2 in LPS-stimulated mouse BV2 microglia. The compound also decreased tumor necrosis factor-α, interleukin (IL)-1β, and IL-12 production; inhibited the phosphorylation and degradation of IκB-α; and blocked the nuclear translocation of p50 and p65 in mouse BV2 microglia induced by LPS. Cudratricusxanthone A (1) had inhibitory effects on nuclear factor kappa B DNA-binding activity. Additionally, it inhibited the p38 mitogen-activated protein kinase signaling pathway. Our data suggests that cudratricusxanthone A (1) may be a useful therapeutic agent in the treatment of neurodegenerative diseases caused by neuroinflammation. Full article
(This article belongs to the Special Issue Natural Products and Inflammation)
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Open AccessArticle Chemical Constituents from Flueggea virosa and the Structural Revision of Dehydrochebulic Acid Trimethyl Ester
Molecules 2016, 21(9), 1239; https://doi.org/10.3390/molecules21091239
Received: 9 August 2016 / Revised: 5 September 2016 / Accepted: 12 September 2016 / Published: 16 September 2016
Cited by 1 | PDF Full-text (2057 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In an attempt to study the chemical constituents from the twigs and leaves of Flueggea virosa, a new terpenoid, 9(10→20)-abeo-ent-podocarpane, 3β,10α-dihydroxy-12-methoxy-13- methyl-9(10→20)-abeo-ent-podocarpa-6,8,11,13-tetraene (1), as well as five known compounds were characterized. Their
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In an attempt to study the chemical constituents from the twigs and leaves of Flueggea virosa, a new terpenoid, 9(10→20)-abeo-ent-podocarpane, 3β,10α-dihydroxy-12-methoxy-13- methyl-9(10→20)-abeo-ent-podocarpa-6,8,11,13-tetraene (1), as well as five known compounds were characterized. Their structures were elucidated on the basis of spectroscopic analysis. In addition, the structure of dehydrochebulic acid trimethyl ester was revised as (2S,3R)-4E-dehydrochebulic acid trimethyl ester based on a single-crystal X-ray diffraction study. The in vitro anti-hepatitis C virus (anti-HCV) activity and cytotoxicity against Huh7.5 cells for the isolated compounds were evaluated. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Chemical and Sensory Evaluation of Silicone and Polylactic Acid-Based Remedial Treatments for Elevated Methoxypyrazine Levels in Wine
Molecules 2016, 21(9), 1238; https://doi.org/10.3390/molecules21091238
Received: 3 May 2016 / Revised: 31 August 2016 / Accepted: 12 September 2016 / Published: 16 September 2016
Cited by 3 | PDF Full-text (993 KB) | HTML Full-text | XML Full-text
Abstract
Alkylmethoxypyrazines (MPs) are a class of compounds that can elicit undesirable aroma and flavor characteristics in wine, and resist remediation using traditional wine making approaches. MPs are grape-derived constituents as well as contaminants from Coccinellidae beetles present during wine processing; the latter eliciting
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Alkylmethoxypyrazines (MPs) are a class of compounds that can elicit undesirable aroma and flavor characteristics in wine, and resist remediation using traditional wine making approaches. MPs are grape-derived constituents as well as contaminants from Coccinellidae beetles present during wine processing; the latter eliciting an off-flavor referred to as ‘ladybug taint’. In this study we investigated the capacity of two plastic polymers—one silicone-based, the other polylactic acid-based—applied with varying surface areas to reduce concentrations of isopropylmethoxypyrazine (IPMP), sec-butylmethoxypyrazine (SBMP) and isobutylmethoxypyrazine (IBMP) in a Merlot wine using multi-dimensional gas chromatography coupled with mass spectrometry and headspace solid phase microextraction (SPME-MDGCMS). The impact of treatments on the sensory characteristics of the wine (descriptive analysis) and volatile aroma compounds (VOCs) (SPME-MDGCMS) was also investigated. Results showed substantial reductions for all of the target odorants: up to 38%, 44% and 39% for IPMP, SBMP and IBMP, respectively, for the silicone polymer, and up to 75%, 78% and 77% for IPMP, SBMP and IBMP, respectively, for the polylactic acid polymer. These polymers had no or minimal effect on VOCs at applications of 200 cm2/L for silicone or for all polylactic acid treatments. Sensory impacts were less clear, but generally showed minimal effect from the treatments. Taken overall, the data confirm the utility of both polylactic acid and silicone polymers in reducing elevated levels of grape-derived MPs, as well as potentially improving wine contaminated by ladybug taint. Full article
(This article belongs to the collection Wine Chemistry)
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Open AccessArticle Combinatorial Synthesis of Structurally Diverse Triazole-Bridged Flavonoid Dimers and Trimers
Molecules 2016, 21(9), 1230; https://doi.org/10.3390/molecules21091230
Received: 29 July 2016 / Revised: 26 August 2016 / Accepted: 8 September 2016 / Published: 16 September 2016
Cited by 5 | PDF Full-text (5121 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Flavonoids are a large family of compounds associated with a broad range of biologically useful properties. In recent years, synthetic compounds that contain two flavonoid units linked together have attracted attention in drug discovery and development projects. Numerous flavonoid dimer systems, incorporating a
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Flavonoids are a large family of compounds associated with a broad range of biologically useful properties. In recent years, synthetic compounds that contain two flavonoid units linked together have attracted attention in drug discovery and development projects. Numerous flavonoid dimer systems, incorporating a range of monomers attached via different linkers, have been reported to exhibit interesting bioactivities. From a medicinal chemistry perspective, the 1,2,3-triazole ring system has been identified as a particularly attractive linker moiety in dimeric derivatives (owing to several favourable attributes including proven biological relevance and metabolic stability) and triazole-bridged flavonoid dimers possessing anticancer and antimalarial activities have recently been reported. However, there are relatively few examples of libraries of triazole-bridged flavonoid dimers and the diversity of flavonoid subunits present within these is typically limited. Thus, this compound type arguably remains underexplored within drug discovery. Herein, we report a modular strategy for the synthesis of novel and biologically interesting triazole-bridged flavonoid heterodimers and also very rare heterotrimers from readily available starting materials. Application of this strategy has enabled step-efficient and systematic access to a library of structurally diverse compounds of this sort, with a variety of monomer units belonging to six different structural subclasses of flavonoid successfully incorporated. Full article
(This article belongs to the Special Issue Diversity Oriented Synthesis 2016)
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Open AccessArticle Long-Term Sodium Ferulate Supplementation Scavenges Oxygen Radicals and Reverses Liver Damage Induced by Iron Overloading
Molecules 2016, 21(9), 1219; https://doi.org/10.3390/molecules21091219
Received: 12 August 2016 / Revised: 3 September 2016 / Accepted: 8 September 2016 / Published: 16 September 2016
Cited by 3 | PDF Full-text (1945 KB) | HTML Full-text | XML Full-text
Abstract
Ferulic acid is a polyphenolic compound contained in various types of fruits and wheat bran. As a salt of the active ingredient, sodium ferulate (SF) has potent free radical scavenging activity and can effectively scavenge ROS. In this study, we examined the effect
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Ferulic acid is a polyphenolic compound contained in various types of fruits and wheat bran. As a salt of the active ingredient, sodium ferulate (SF) has potent free radical scavenging activity and can effectively scavenge ROS. In this study, we examined the effect of SF on iron-overloaded mice in comparison to a standard antioxidant, taurine (TAU). We determined the protective role of SF against liver injury by examining liver-to-body ratio (%), transaminase and hepatocyte apoptosis in rats supplied with 10% dextrose intraperitoneal injection. In addition, antioxidative enzymes activities, ROS formation, mitochondrial swelling, and mitochondrial membrane potential (MMP) were all evaluated to clarify the mechanism of protective effect of SF associated with oxidative stress. After 15 weeks of SF treatment, we found a significant reduction in liver-to-body weight radio and elevation in both transaminase and hepatocyte apoptosis associated with iron-injected to levels comparable to those achieved with TAU. Both SF and TAU significantly attenuated the impaired liver function associated with iron-overloaded in mice, whereas neither showed any significant effect on the iron uptake. Furthermore, treatment with either SF or TAU in iron-overloaded mice attenuated oxidative stress, associated with elevated oxidant enzymes activities, decreased ROS production, prevented mitochondrial swelling and dissipation of MMP and then inhibited hepatic apoptosis. Taken together, the current study shows that, SF alleviated oxidative stress and liver damage associated with iron-overload conditions compared to the standard ROS scavenger (TAU), and potentially could encourage higher consumption and utilization as healthy and sustainable ingredients by the food and drink. Full article
(This article belongs to the Section Natural Products Chemistry)
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