Molecules

13 pages, 537 KiB

Open AccessReview

Application of Molecular Methods in the Identification of Ingredients in Chinese Herbal Medicines

by Ke Han, Miao Wang, Lei Zhang and Chunyu Wang

Molecules 2018, 23(10), 2728; https://doi.org/10.3390/molecules23102728 - 22 Oct 2018

Cited by 28 | Viewed by 6627

There are several kinds of Chinese herbal medicines originating from diverse sources. However, the rapid taxonomic identification of large quantities of Chinese herbal medicines is difficult using traditional methods, and the process of identification itself is prone to error. Therefore, the traditional methods [...] Read more.

There are several kinds of Chinese herbal medicines originating from diverse sources. However, the rapid taxonomic identification of large quantities of Chinese herbal medicines is difficult using traditional methods, and the process of identification itself is prone to error. Therefore, the traditional methods of Chinese herbal medicine identification must meet higher standards of accuracy. With the rapid development of bioinformatics, methods relying on bioinformatics strategies offer advantages with respect to the speed and accuracy of the identification of Chinese herbal medicine ingredients. This article reviews the applicability and limitations of biochip and DNA barcoding technology in the identification of Chinese herbal medicines. Furthermore, the future development of the two technologies of interest is discussed. Full article

(This article belongs to the Special Issue Molecular Computing and Bioinformatics)

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16 pages, 1374 KiB

Open AccessArticle

Ag/Pyridine Co-Mediated Oxidative Arylthiocyanation of Activated Alkenes

by De-Long Kong, Jian-Xun Du, Wei-Ming Chu, Chun-Ying Ma, Jia-Yi Tao and Wen-Hua Feng

Molecules 2018, 23(10), 2727; https://doi.org/10.3390/molecules23102727 - 22 Oct 2018

Cited by 21 | Viewed by 5168

Abstract

An efficient Ag/pyridine co-mediated oxidative arylthiocyanation of activated alkenes via radical addition/cyclization cascade process was developed. This reaction could be carried out under mild conditions to provide biologically interesting 3-alkylthiocyanato-2-oxindoles in good to excellent yields. Mechanistic studies suggested a unique NCS• radical addition [...] Read more.

An efficient Ag/pyridine co-mediated oxidative arylthiocyanation of activated alkenes via radical addition/cyclization cascade process was developed. This reaction could be carried out under mild conditions to provide biologically interesting 3-alkylthiocyanato-2-oxindoles in good to excellent yields. Mechanistic studies suggested a unique NCS• radical addition path and clarified the dual roles of catalytic pyridine as base and crucial ligand to accelerate the oxidation of Ag(I) to Ag(II), which is likely oxidant responsible for the formation of NCS• radical. These mechanistic results may impact the design and refinement of other radical based reactions proceeding through catalytic oxidations mediated by Ag(I)-pyridine/persulfate. The chemical versatility of thiocyanate moiety was also highlighted via SCN-tailoring chemistry in post-synthetic transformation for new S-C(sp³/sp²/sp), S-P, and S-S bonds constructions. The protocol provides an easy access to many important bioisosteres in medicinal chemistry and an array of sulfur-containing 2-oxindoles that are difficult to prepare by other approaches. Full article

(This article belongs to the Section Organic Chemistry)

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12 pages, 3642 KiB

Open AccessArticle

Structural Basis for the Interaction between p53 Transactivation Domain and the Mediator Subunit MED25

by Min-Sung Lee, Kyungeun Lim, Mi-Kyung Lee and Seung-Wook Chi

Molecules 2018, 23(10), 2726; https://doi.org/10.3390/molecules23102726 - 22 Oct 2018

Cited by 10 | Viewed by 4790

Abstract

Eukaryotic transcription initiation is mediated by interactions between transcriptional activators and the mediator coactivator complex. Molecular interaction of p53 transcription factor with mediator complex subunit 25 (MED25) is essential for its target gene transcription. In this study, we characterized the molecular interaction between [...] Read more.

Eukaryotic transcription initiation is mediated by interactions between transcriptional activators and the mediator coactivator complex. Molecular interaction of p53 transcription factor with mediator complex subunit 25 (MED25) is essential for its target gene transcription. In this study, we characterized the molecular interaction between p53 transactivation domain (p53TAD) and activator interaction domain (ACID) of MED25 using nuclear magnetic resonance (NMR) spectroscopy. The NMR chemical shift perturbation and isothermal titration calorimetry (ITC) data showed that p53TAD interacted with MED25 ACID mainly through the p53TAD2 sequence motif. Taken together with the mutagenesis data, the refined structural model of MED25 ACID/p53TAD2 peptide complex showed that an amphipathic α-helix of p53TAD2 peptide bound an elongated hydrophobic groove of MED25 ACID. Furthermore, our results revealed the highly conserved mechanism of MED25 interaction with intrinsically unfolded acidic TADs from the transcriptional activators p53, ERM (Ets-related molecule), and herpes simplex virus protein 16 (VP16). Full article

(This article belongs to the Special Issue NMR as a Tool to Investigate Biomolecular Structure, Recognition and Dynamics)

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14 pages, 2749 KiB

Open AccessArticle

A Potent Tyrosinase Inhibitor, (E)-3-(2,4-Dihydroxyphenyl)-1-(thiophen-2-yl)prop-2-en-1-one, with Anti-Melanogenesis Properties in α-MSH and IBMX-Induced B16F10 Melanoma Cells

by Chang Seok Kim, Sang Gyun Noh, Yujin Park, Dongwan Kang, Pusoon Chun, Hae Young Chung, Hee Jin Jung and Hyung Ryong Moon

Molecules 2018, 23(10), 2725; https://doi.org/10.3390/molecules23102725 - 22 Oct 2018

Cited by 42 | Viewed by 5525

Abstract

In this study, we designed and synthesized eight thiophene chalcone derivatives (1a–h) as tyrosinase inhibitors and evaluated their mushroom tyrosinase inhibitory activities. Of these eight compounds, (E)-3-(2,4-dihydroxyphenyl)-1-(thiophen-2-yl)prop-2-en-1-one (1c) showed strong competitive inhibition activity against mushroom [...] Read more.

In this study, we designed and synthesized eight thiophene chalcone derivatives (1a–h) as tyrosinase inhibitors and evaluated their mushroom tyrosinase inhibitory activities. Of these eight compounds, (E)-3-(2,4-dihydroxyphenyl)-1-(thiophen-2-yl)prop-2-en-1-one (1c) showed strong competitive inhibition activity against mushroom tyrosinase with IC₅₀ values of 0.013 μM for tyrosine hydroxylase and 0.93 μM for dopa oxidase. In addition, we used enzyme kinetics study and docking program to further evaluate the inhibitory mechanism of 1c toward tyrosinase. As an underlying mechanism of 1c mediated anti-melanogenic effect, we investigated the inhibitory activity against melanin contents and cellular tyrosinase in B16F10 melanoma cells. As the results, the enzyme kinetics and docking results supports that 1c highly interacts with tyrosinase residues in the tyrosinase active site and it can directly inhibit tyrosinase as competitive inhibitor. In addition, 1c exhibited dose-dependent inhibitory effects in melanin contents and intracellular tyrosinase on α-MSH and IBMX-induced B16F10 cells. Overall, our results suggested that 1c might be considered potent tyrosinase inhibitor for use in the development of therapeutic agents for diseases associated with hyperpigment disorders. Full article

(This article belongs to the Section Chemical Biology)

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17 pages, 6267 KiB

Open AccessReview

Isoxazole Derivatives as Regulators of Immune Functions

by Michał Zimecki, Urszula Bąchor and Marcin Mączyński

Molecules 2018, 23(10), 2724; https://doi.org/10.3390/molecules23102724 - 22 Oct 2018

Cited by 83 | Viewed by 5550

Abstract

In this review, we present reports on the immunoregulatory properties of isoxazole derivatives classified into several categories, such as immunosuppressive, anti-inflammatory, immunoregulatory, and immunostimulatory compounds. The compounds were tested in various models using resident cells from rodents and humans, cell lines, and experimental [...] Read more.

In this review, we present reports on the immunoregulatory properties of isoxazole derivatives classified into several categories, such as immunosuppressive, anti-inflammatory, immunoregulatory, and immunostimulatory compounds. The compounds were tested in various models using resident cells from rodents and humans, cell lines, and experimental animal disease models corresponding to human clinical situations. Beneficial features of the described isoxazole derivatives include low toxicity and good bioactivity at low doses. In a majority of studies, the activities of investigated compounds were comparable or even higher than registered reference drugs. Whenever possible, a plausible mechanism of action of the investigated compounds and their potential therapeutic utility were proposed. Among the described compounds, particular attention was paid to the class of immune stimulators with a potential application in chemotherapy patients. Full article

(This article belongs to the Section Medicinal Chemistry)

11 pages, 2360 KiB

Open AccessArticle

Nuciferine Inhibits Proinflammatory Cytokines via the PPARs in LPS-Induced RAW264.7 Cells

by Chao Zhang, Jianjun Deng, Dan Liu, Xingxia Tuo, Yan Yu, Haixia Yang and Nanping Wang

Molecules 2018, 23(10), 2723; https://doi.org/10.3390/molecules23102723 - 22 Oct 2018

Cited by 35 | Viewed by 6123

Abstract

Inflammation is important and has been found to be an underlying cause in many acute and chronic human diseases. Nuciferine, a natural alkaloid containing an aromatic ring, is found in the nelumbo nucifera leaves. It has been shown to have potential anti-inflammatory activities, [...] Read more.

Inflammation is important and has been found to be an underlying cause in many acute and chronic human diseases. Nuciferine, a natural alkaloid containing an aromatic ring, is found in the nelumbo nucifera leaves. It has been shown to have potential anti-inflammatory activities, but the molecular mechanism has remained unclear. In this study, we found that nuciferine (10 μM) significantly inhibited the lipopolysaccharide (LPS)-induced inflammatory cytokine IL-6 and TNF-α production in RAW 264.7 cells. In addition, the luciferase reporter assay results of different subtypes of the peroxisome proliferator-activated receptor (PPAR) showed that nuciferine dose-dependently activated all the PPAR activities. Specific inhibitors of PPARα and PPARγ significantly abolished the production of inflammatory cytokines as well as IκBα degradation. However, PPARδ inhibitor did not show this effect. Our results suggested a potential molecular mechanism of the anti-inflammatory effects of nuciferine in LPS-induced inflammation, at least in part, by activating PPARα and PPARγ in RAW 264.7 cells. Full article

(This article belongs to the Special Issue Role of Natural Compounds in Inflammation and Inflammatory-Related Diseases)

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11 pages, 1455 KiB

Open AccessArticle

Design, Synthesis, and Evaluation of Amphiphilic Cyclic and Linear Peptides Composed of Hydrophobic and Positively-Charged Amino Acids as Antibacterial Agents

by Neda Riahifard, Saghar Mozaffari, Taibah Aldakhil, Francisco Nunez, Qamar Alshammari, Saud Alshammari, Jason Yamaki, Keykavous Parang and Rakesh Kumar Tiwari

Molecules 2018, 23(10), 2722; https://doi.org/10.3390/molecules23102722 - 22 Oct 2018

Cited by 29 | Viewed by 6420

Abstract

Antimicrobial peptides (AMPs) contain amphipathic structures and are derived from natural resources. AMPs have been found to be effective in treating the infections caused by antibiotic-resistant bacteria (ARB), and thus, are potential lead compounds against ARB. AMPs’ physicochemical properties, such as cationic nature, [...] Read more.

Antimicrobial peptides (AMPs) contain amphipathic structures and are derived from natural resources. AMPs have been found to be effective in treating the infections caused by antibiotic-resistant bacteria (ARB), and thus, are potential lead compounds against ARB. AMPs’ physicochemical properties, such as cationic nature, amphiphilicity, and their size, will provide the opportunity to interact with membrane bilayers leading to damage and death of microorganisms. Herein, AMP analogs of [R₄W₄] were designed and synthesized by changing the hydrophobicity and cationic nature of the lead compound with other amino acids to provide insights into a structure-activity relationship against selected model Gram-negative and Gram-positive pathogens. Clinical resistant strains of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) were used in the studies. Our results provided information about the structural requirements for optimal activity of the [R₄W₄] template. When tryptophan was replaced with other hydrophobic amino acids, such as phenylalanine, tyrosine, alanine, leucine, and isoleucine, the antibacterial activities were significantly reduced with MIC values of >128 µg/mL. Furthermore, a change in stereochemistry caused by d-arginine, and use of N-methyltryptophan, resulted in a two-fold reduction of antibacterial activity. It was found that the presence of tryptophan is critical for antibacterial activity, and could not be substituted with other hydrophobic residues. The study also confirmed that cyclic peptides generally showed higher antibacterial activities when compared with the corresponding linear counterparts. Furthermore, by changing tryptophan numbers in the compound while maintaining a constant number of arginine, we determined the optimal number of tryptophan residues to be four, as shown when the number of tryptophan residues increased, a decrease in activity was observed. Full article

(This article belongs to the Special Issue Peptides in Chemical Biology and Drug Discovery)

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17 pages, 761 KiB

Open AccessFeature PaperReview

Vipers of the Middle East: A Rich Source of Bioactive Molecules

by Mohamad Rima, Seyedeh Maryam Alavi Naini, Marc Karam, Riyad Sadek, Jean-Marc Sabatier and Ziad Fajloun

Molecules 2018, 23(10), 2721; https://doi.org/10.3390/molecules23102721 - 22 Oct 2018

Cited by 13 | Viewed by 6655

Abstract

Snake venom serves as a tool of defense against threat and helps in prey digestion. It consists of a mixture of enzymes, such as phospholipase A2, metalloproteases, and l-amino acid oxidase, and toxins, including neurotoxins and cytotoxins. Beside their toxicity, venom components [...] Read more.

Snake venom serves as a tool of defense against threat and helps in prey digestion. It consists of a mixture of enzymes, such as phospholipase A2, metalloproteases, and l-amino acid oxidase, and toxins, including neurotoxins and cytotoxins. Beside their toxicity, venom components possess many pharmacological effects and have been used to design drugs and as biomarkers of diseases. Viperidae is one family of venomous snakes that is found nearly worldwide. However, three main vipers exist in the Middle Eastern region: Montivipera bornmuelleri, Macrovipera lebetina, and Vipera (Daboia) palaestinae. The venoms of these vipers have been the subject of many studies and are considered as a promising source of bioactive molecules. In this review, we present an overview of these three vipers, with a special focus on their venom composition as well as their biological activities, and we discuss further frameworks for the exploration of each venom. Full article

(This article belongs to the Special Issue Natural Toxins/Molecules (and Derivatives) from Animal Venoms: From Basic Research to Therapeutic Applications)

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11 pages, 4823 KiB

Open AccessReview

Oxysterols and Retinal Degeneration in a Rat Model of Smith-Lemli-Opitz Syndrome: Implications for an Improved Therapeutic Intervention

by Steven J. Fliesler and Libin Xu

Molecules 2018, 23(10), 2720; https://doi.org/10.3390/molecules23102720 - 22 Oct 2018

Cited by 12 | Viewed by 5189

Abstract

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive human disease caused by mutations in the gene encoding 7-dehydrocholesterol (7DHC) reductase (DHCR7), resulting in abnormal accumulation of 7DHC and reduced levels of cholesterol in bodily tissues and fluids. A rat model of the disease has [...] Read more.

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive human disease caused by mutations in the gene encoding 7-dehydrocholesterol (7DHC) reductase (DHCR7), resulting in abnormal accumulation of 7DHC and reduced levels of cholesterol in bodily tissues and fluids. A rat model of the disease has been created by treating normal rats with the DHCR7 inhibitor, AY9944, which causes progressive, irreversible retinal degeneration. Herein, we review the features of this disease model and the evidence linking 7DHC-derived oxysterols to the pathobiology of the disease, with particular emphasis on the associated retinal degeneration. A recent study has shown that treating the rat model with cholesterol plus suitable antioxidants completely prevents the retinal degeneration. These findings are discussed with regard to their translational implications for developing an improved therapeutic intervention for SLOS over the current standard of care. Full article

(This article belongs to the Special Issue Chemical Biology of Sterols, Triterpenoids and Other Natural Products: A Themed Issue in Honor of Professor W. David Nes on the Occasion of His 65th Birthday)

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12 pages, 2575 KiB

Open AccessArticle

Isolation of Tricin as a Xanthine Oxidase Inhibitor from Sweet White Clover (Melilotus albus) and Its Distribution in Selected Gramineae Species

by Xiao-Xiao Liu, Shi-Wei Sun, Wen-Jing Yuan, Hua Gao, Yue-Yue Si, Kun Liu, Shuang Zhang, Yang Liu and Wei Wang

Molecules 2018, 23(10), 2719; https://doi.org/10.3390/molecules23102719 - 22 Oct 2018

Cited by 11 | Viewed by 4555

Abstract

Xanthine oxidase, an enzyme present in significant levels in the intestine and liver, metabolizes hypoxanthine to xanthine and xanthine to uric acid in the purine catabolic pathway. An inhibitory compound acting against xanthine oxidase was isolated from sweet white clover (Melilotus albus [...] Read more.

Xanthine oxidase, an enzyme present in significant levels in the intestine and liver, metabolizes hypoxanthine to xanthine and xanthine to uric acid in the purine catabolic pathway. An inhibitory compound acting against xanthine oxidase was isolated from sweet white clover (Melilotus albus) by bioassay and high-performance liquid chromatography guided separation. It was identified as tricin by spectroscopic analysis. Tricin possessed a potent xanthine oxidase inhibitory activity with an IC₅₀ value of 4.13 μM. Further inhibition kinetics data indicated it to be a mixed-type inhibitor and K_i and K_I values were determined to be 0.47 μM and 4.41 μM. To find a rich source of tricin, the distribution of tricin in seven different tissues from four Gramineae species was investigated by high-performance liquid chromatography analysis. The highest amount (1925.05 mg/kg dry materials) was found in the straw of wheat, which is considered as a potentially valuable source of natural tricin. Full article

(This article belongs to the Special Issue Natural Product Isolation, Identification and Biological Activity)

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15 pages, 1835 KiB

Open AccessArticle

The Pro-Tumoral Activity of Heparan Sulfate 3-O-Sulfotransferase 3B (HS3ST3B) in Breast Cancer MDA-MB-231 Cells Is Dependent on the Expression of Neuropilin-1

by Charles Hellec, Mariama Diawara, Mathieu Carpentier, Agnès Denys and Fabrice Allain

Molecules 2018, 23(10), 2718; https://doi.org/10.3390/molecules23102718 - 22 Oct 2018

Cited by 8 | Viewed by 3811

Abstract

Heparan sulfate 3-O-sulfotransferases (HS3STs) catalyze the maturation step of heparan sulfate (HS) 3-O-sulfation. This modification is relatively rare. Moreover, only a few biological processes have been described to be influenced by 3-O-sulfated HS, and few ligands have [...] Read more.

Heparan sulfate 3-O-sulfotransferases (HS3STs) catalyze the maturation step of heparan sulfate (HS) 3-O-sulfation. This modification is relatively rare. Moreover, only a few biological processes have been described to be influenced by 3-O-sulfated HS, and few ligands have been identified so far. Among them, neuropilin-1 (Nrp1) was reported to exhibit tumor-promoting properties by enhancing the action of various growth factors. We recently demonstrated that transient overexpression of HS3ST2, 3B or 4 enhanced the proliferation of breast cancer MDA-MB-231 cells and promote efficient protection against pro-apoptotic stimuli. Hence, we hypothesized that the pro-tumoral activity of these HS3STs could depend on the expression of Nrp1. To test this, MDA-MB-231 cells were stably transfected with a construct encoding HS3ST3B and the expression of Nrp1 was down-regulated by RNA interference. First, we confirmed that stable expression of HS3ST3B effectively increased cell proliferation and viability. Silencing the expression of Nrp1 markedly attenuated the promoting effects of HS3ST3B, while the same treatment had only a moderate effect on the behavior of the parental cells. Altogether, our findings support the idea that the tumor-promoting effects of HS3ST3B could be dependent on the expression of Nrp1 in cancer cells. Full article

(This article belongs to the Special Issue Heparan Sulfate and Heparin: Challenges and Controversies)

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8 pages, 1104 KiB

Open AccessArticle

Effects of Water Content and Particle Size on Yield and Reactivity of Lignite Chars Derived from Pyrolysis and Gasification

by Yong Huang, Yonggang Wang, Hao Zhou, Yaxuan Gao, Deliang Xu, Lei Bai and Shu Zhang

Molecules 2018, 23(10), 2717; https://doi.org/10.3390/molecules23102717 - 22 Oct 2018

Cited by 8 | Viewed by 3695

Abstract

Water inside coal particles could potentially enhance the interior char–steam reactions during pyrolysis and gasification. This study aims to examine the effects of water contents on the char conversion during the pyrolysis and gasification of Shengli lignite. The ex-situ reactivities of chars were [...] Read more.

Water inside coal particles could potentially enhance the interior char–steam reactions during pyrolysis and gasification. This study aims to examine the effects of water contents on the char conversion during the pyrolysis and gasification of Shengli lignite. The ex-situ reactivities of chars were further analyzed by a thermo gravimetric analyzer (TGA). Under the pyrolysis condition, the increase in water contents has monotonically decreased the char yields only when the coal particles were small (<75 µm). In contrast, the water in only large coal particles (0.9–2.0 mm) has clearly favored the increase in char conversion during the gasification condition where 50% steam in argon was used as external reaction atmosphere. The waved reactivity curves for the subsequent char–air reactions were resulted from the nature of heterogeneity of char structure. Compared to the large particles, the less interior char–steam reactions for the small particles have created more differential char structure which showed two different stages when reacting with air at the low temperature in TGA. Full article

(This article belongs to the Special Issue Biorefinery and Biomass Conversion and Utilization)

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15 pages, 1743 KiB

Open AccessArticle

Preclinical Pharmacokinetics of Scoparone, Geniposide and Rhein in an Herbal Medicine Using a Validated LC-MS/MS Method

by Tun-Pin Hsueh and Tung-Hu Tsai

Molecules 2018, 23(10), 2716; https://doi.org/10.3390/molecules23102716 - 22 Oct 2018

Cited by 21 | Viewed by 5305

Abstract

The herbal formula Yin-Chen-Hao-Tang has been reported to have anti-fibrosis properties. The aim of this study was to reveal the pharmacokinetic characteristics of bioactive compounds in this herbal formula. A new high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous [...] Read more.

The herbal formula Yin-Chen-Hao-Tang has been reported to have anti-fibrosis properties. The aim of this study was to reveal the pharmacokinetic characteristics of bioactive compounds in this herbal formula. A new high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous determination of scoparone, geniposide and rhein in rat plasma. A pharmaceutical herbal powder was administered to rats at doses of 1 g/kg and 3 g/kg orally. The method showed excellent linearity (r² > 0.999) and validation was successfully conducted for the pharmacokinetic study. The results show that the C_max values and areas under the curve of scoparone, geniposide and rhein were higher and not proportional to the dose in rat plasma, while the T_max and half-life values were consistent in the group that received 1 g/kg. The clearance of the higher dose (3 g/kg) did not decrease proportionally to that of the low dose. The results showed the nonlinear pharmacokinetic properties of scoparone, geniposide and rhein in Yin-Chen-Hao-Tang that suggested possible accumulation of bioactive compounds through oral administration. This pharmacokinetic study reveals that an increased dose of this herbal formula would largely increase the maximum concentration and bioavailability of scoparone, geniposide and rhein. Full article

(This article belongs to the Collection Advances in Liquid Separation Techniques for Food and Pharmaceutical Analysis)

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12 pages, 1847 KiB

Open AccessArticle

NMR Structure of μ-Conotoxin GIIIC: Leucine 18 Induces Local Repacking of the N-Terminus Resulting in Reduced Na_V Channel Potency

by Peta J. Harvey, Nyoman D. Kurniawan, Rocio K. Finol-Urdaneta, Jeffrey R. McArthur, Dorien Van Lysebetten, Thomas S. Dash, Justine M. Hill, David J. Adams, Thomas Durek and David J. Craik

Molecules 2018, 23(10), 2715; https://doi.org/10.3390/molecules23102715 - 22 Oct 2018

Cited by 4 | Viewed by 4037

Abstract

μ-Conotoxins are potent and highly specific peptide blockers of voltage-gated sodium channels. In this study, the solution structure of μ-conotoxin GIIIC was determined using 2D NMR spectroscopy and simulated annealing calculations. Despite high sequence similarity, GIIIC adopts a three-dimensional structure that differs from [...] Read more.

μ-Conotoxins are potent and highly specific peptide blockers of voltage-gated sodium channels. In this study, the solution structure of μ-conotoxin GIIIC was determined using 2D NMR spectroscopy and simulated annealing calculations. Despite high sequence similarity, GIIIC adopts a three-dimensional structure that differs from the previously observed conformation of μ-conotoxins GIIIA and GIIIB due to the presence of a bulky, non-polar leucine residue at position 18. The side chain of L18 is oriented towards the core of the molecule and consequently the N-terminus is re-modeled and located closer to L18. The functional characterization of GIIIC defines it as a canonical μ-conotoxin that displays substantial selectivity towards skeletal muscle sodium channels (Na_V), albeit with ~2.5-fold lower potency than GIIIA. GIIIC exhibited a lower potency of inhibition of Na_V1.4 channels, but the same Na_V selectivity profile when compared to GIIIA. These observations suggest that single amino acid differences that significantly affect the structure of the peptide do in fact alter its functional properties. Our work highlights the importance of structural factors, beyond the disulfide pattern and electrostatic interactions, in the understanding of the functional properties of bioactive peptides. The latter thus needs to be considered when designing analogues for further applications. Full article

(This article belongs to the Special Issue Natural Toxins/Molecules (and Derivatives) from Animal Venoms: From Basic Research to Therapeutic Applications)

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17 pages, 2848 KiB

Open AccessArticle

Sialic Acid-Binding Lectin from Bullfrog Eggs Exhibits an Anti-Tumor Effect Against Breast Cancer Cells Including Triple-Negative Phenotype Cells

by Takeo Tatsuta, Shoko Sato, Toshiyuki Sato, Shigeki Sugawara, Tsuneyoshi Suzuki, Akiyoshi Hara and Masahiro Hosono

Molecules 2018, 23(10), 2714; https://doi.org/10.3390/molecules23102714 - 21 Oct 2018

Cited by 9 | Viewed by 4558

Abstract

Sialic acid-binding lectin from Rana catesbeiana eggs (cSBL) is a multifunctional protein that has lectin and ribonuclease activity. In this study, the anti-tumor activities of cSBL were assessed using a panel of breast cancer cell lines. cSBL suppressed the cell growth of all [...] Read more.

Sialic acid-binding lectin from Rana catesbeiana eggs (cSBL) is a multifunctional protein that has lectin and ribonuclease activity. In this study, the anti-tumor activities of cSBL were assessed using a panel of breast cancer cell lines. cSBL suppressed the cell growth of all cancer cell lines tested here at a concentration that is less toxic, or not toxic at all, to normal cells. The growth suppressive effect was attributed to the cancer-selective induction of apoptosis. We assessed the expressions of several key molecules associated with the breast cancer phenotype after cSBL treatment by western blotting. cSBL decreased the expression level of estrogen receptor (ER) α, while it increased the phosphorylation level of p38 mitogen-activated protein kinase (MAPK). cSBL also suppressed the expression of the progesterone receptor (PgR) and human epidermal growth factor receptor type 2 (HER2). Furthermore, it was revealed that cSBL decreases the expression of the epidermal growth factor receptor (EGFR/HER1) in triple-negative breast cancer cells. These results indicate that cSBL induces apoptosis with decreasing ErbB family proteins and may have great potential for breast cancer chemotherapy, particularly in triple-negative phenotype cells. Full article

(This article belongs to the Special Issue Lectins: From Basic Science to Application for Glycobiology, Cell Biology, and Medicine)

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11 pages, 871 KiB

Open AccessArticle

Changes in Soybean (Glycine max L.) Flour Fatty-Acid Content Based on Storage Temperature and Duration

by Mayakrishnan Prabakaran, Kyoung-Jin Lee, Yeonju An, Chang Kwon, Soyeon Kim, Yujin Yang, Ateeque Ahmad, Seung-Hyun Kim and Ill-Min Chung

Molecules 2018, 23(10), 2713; https://doi.org/10.3390/molecules23102713 - 21 Oct 2018

Cited by 39 | Viewed by 4830

Abstract

Soybeans are low in saturated fat and a rich source of protein, dietary fiber, and isoflavone; however, their nutritional shelf life is yet to be established. This study evaluated the change in the stability and quality of fatty acids in raw and roasted [...] Read more.

Soybeans are low in saturated fat and a rich source of protein, dietary fiber, and isoflavone; however, their nutritional shelf life is yet to be established. This study evaluated the change in the stability and quality of fatty acids in raw and roasted soybean flour under different storage temperatures and durations. In both types of soybean flour, the fatty-acid content was the highest in the order of linoleic acid (18-carbon chain with two double bonds; C18:2), oleic acid (C18:1), palmitic acid (C16:0), linolenic acid (18:3), and stearic acid (C18:0), which represented 47%, 26%, 12%, 9%, and 4% of the total fatty-acid content, respectively. The major unsaturated fatty acids of raw soybean flour—oleic acid, linoleic acid, and linolenic acid—decreased by 30.0%, 94.4%, and 97.7%, and 38.0%, 94.8%, and 98.0% when stored in polyethylene and polypropylene film, respectively, after 48 weeks of storage under high-temperature conditions. These values were later increased due to hydrolysis. This study presents the changes in composition and content of two soybean flour types and the changes in quality and stability of fatty acids in response to storage temperature and duration. This study shows the influence of storage conditions and temperature on the nutritional quality which is least affected by packing material. Full article

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12 pages, 5818 KiB

Open AccessArticle

XPS Analysis of 2- and 3-Aminothiophenol Grafted on Silicon (111) Hydride Surfaces

by Chieh-Hua Lee, Wan-Cian Chen and Yit Lung Khung

Molecules 2018, 23(10), 2712; https://doi.org/10.3390/molecules23102712 - 21 Oct 2018

Cited by 13 | Viewed by 6470

Abstract

Following on from our previous study on the resonance/inductive structures of ethynylaniline, this report examines similar effects arising from resonance structures with aromatic aminothiophenol with dual electron-donating substituents. In brief, 2- and 3-aminothiophenol were thermally grafted on silicon (111) hydride substrate at 130 [...] Read more.

Following on from our previous study on the resonance/inductive structures of ethynylaniline, this report examines similar effects arising from resonance structures with aromatic aminothiophenol with dual electron-donating substituents. In brief, 2- and 3-aminothiophenol were thermally grafted on silicon (111) hydride substrate at 130 °C under nonpolar aprotic mesitylene. From the examination of high resolution XPS Si2p, N1s, and S2p spectrum, it was noticed that there was a strong preference of NH₂ over SH to form Si–N linkage on the silicon hydride surface for 2-aminothiophenol. However, for 3-aminothiophenol, there was a switch in reactivity of the silicon hydride toward SH group. This was attributed to the antagonistic and cooperative resonance effects for 2- and 3-aminothiophenol, respectively. The data strongly suggested that the net resonance of the benzylic-based compound could have played an important role in the net distribution of negative charge along the benzylic framework and subsequently influenced the outcome of the surface reaction. To the best of the authors’ knowledge, this correlation between dual electron-donating substituents and the outcome of the nucleophilic addition toward silicon hydride surfaces has not been described before in literature. Full article

(This article belongs to the Special Issue Chemical Surface Functionalization)

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11 pages, 2059 KiB

Open AccessArticle

Astragalus Polysaccharide Improves Insulin Sensitivity via AMPK Activation in 3T3-L1 Adipocytes

by Ruixin Zhang, Xuze Qin, Ting Zhang, Qian Li, Jianxin Zhang and Junxing Zhao

Molecules 2018, 23(10), 2711; https://doi.org/10.3390/molecules23102711 - 21 Oct 2018

Cited by 64 | Viewed by 5818

Abstract

Astragalus polysaccharide (APS) is an important bioactive component of Astragalus membranaceus which is used as an anti-diabetes herb in traditional Chinese medicine. The objective of this study was to investigate the effects and mechanisms of APS on insulin-sensitizing of adipocytes. Mouse 3T3-L1 preadipocytes [...] Read more.

Astragalus polysaccharide (APS) is an important bioactive component of Astragalus membranaceus which is used as an anti-diabetes herb in traditional Chinese medicine. The objective of this study was to investigate the effects and mechanisms of APS on insulin-sensitizing of adipocytes. Mouse 3T3-L1 preadipocytes were used as a model. The results showed that APS increased preadipocytes proliferation in a dose dependent manner, and 0.1 μg/mL APS sufficiently increased Proliferating Cell Nuclear Antigen (PCNA) content (p < 0.01). Moreover, APS enhanced intracellular lipid accumulation and mRNA expression of proliferator-activated receptor γ (PPARγ, p < 0.01), CCAAT/enhancer binding protein α (C/EBPα, p < 0.01) and fatty acid binding protein (aP2, p < 0.01). As expected, corresponding protein contents were elevated. Importantly, APS increased 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-Deoxyglucose (2-NBDG) uptake (p < 0.01). Meanwhile, both mRNA and protein content of glucose transporter 4 (Glut4) were elevated by APS (p < 0.01). The APS treatment enhanced tyrosine phosphorylation of insulin receptor substrate 1 (IRS1, p < 0.05) and phosphor-Akt content (p < 0.01). Besides, phosphorylated AMP-activated protein kinase (AMPK) content was increased in the APS treated cells (p < 0.01). Taken together, APS improved insulin sensitivity by enhancing glucose uptake, possibly through AMPK activation. These results suggested that APS might be a therapeutic candidate for insulin resistance. Full article

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12 pages, 2811 KiB

Open AccessFeature PaperArticle

Immobilizing Polyether Imidazole Ionic Liquids on ZSM-5 Zeolite for the Catalytic Synthesis of Propylene Carbonate from Carbon Dioxide

by Liying Guo, Xianchao Jin, Xin Wang, Longzhu Yin, Yirong Wang and Ying-Wei Yang

Molecules 2018, 23(10), 2710; https://doi.org/10.3390/molecules23102710 - 21 Oct 2018

Cited by 17 | Viewed by 5606

Abstract

Traditional ionic liquids (ILs) catalysts suffer from the difficulty of product purification and can only be used in homogeneous catalytic systems. In this work, by reacting ILs with co-catalyst (ZnBr₂), we successfully converted three polyether imidazole ionic liquids (PIILs), i.e., HO-[Poly-epichlorohydrin-methimidazole]Cl [...] Read more.

Traditional ionic liquids (ILs) catalysts suffer from the difficulty of product purification and can only be used in homogeneous catalytic systems. In this work, by reacting ILs with co-catalyst (ZnBr₂), we successfully converted three polyether imidazole ionic liquids (PIILs), i.e., HO-[Poly-epichlorohydrin-methimidazole]Cl (HO-[PECH-MIM]Cl), HOOC-[Poly-epichlorohydrin-methimidazole]Cl (HOOC-[PECH-MIM]Cl), and H₂N-[Poly-epichlorohydrin-methimidazole]Cl (H₂N-[PECH-MIM]Cl), to three composite PIIL materials, which were further immobilized on ZSM-5 zeolite by chemical bonding to result in three immobilized catalysts, namely ZSM-5-HO-[PECH-MIM]Cl/[ZnBr₂], ZSM-5-HOOC-[PECH-MIM]Cl/[ZnBr₂], and ZSM-5-H₂N-[PECH-MIM]Cl/[ZnBr₂]. Their structures, thermal stabilities, and morphologies were fully characterized by Fourier-transform infrared spectroscopy (FT-IR), X-ray diffractometry (XRD), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). The amount of composite PIIL immobilized on ZSM-5 was determined by elemental analysis. Catalytic performance of the immobilized catalysts was evaluated through the catalytic synthesis of propylene carbonate (PC) from CO₂ and propylene oxide (PO). Influences of reaction temperature, time, and pressure on catalytic performance were investigated through the orthogonal test, and the effect of catalyst circulation was also studied. Under an optimal reaction condition (130 °C, 2.5 MPa, 0.75 h), the composite catalyst, ZSM-5-HOOC- [PECH-MIM]Cl/[ZnBr₂], exhibited the best catalytic activity with a conversion rate of 98.3% and selectivity of 97.4%. Significantly, the immobilized catalyst could still maintain high heterogeneous catalytic activity even after being reused for eight cycles. Full article

(This article belongs to the Special Issue Smart and Functional Polymers)

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12 pages, 2610 KiB

Open AccessFeature PaperArticle

The Way to Ultrafast, High-Throughput Enantioseparations of Bioactive Compounds in Liquid and Supercritical Fluid Chromatography

by Omar H. Ismail, Simona Felletti, Chiara De Luca, Luisa Pasti, Nicola Marchetti, Valentina Costa, Francesco Gasparrini, Alberto Cavazzini and Martina Catani

Molecules 2018, 23(10), 2709; https://doi.org/10.3390/molecules23102709 - 20 Oct 2018

Cited by 33 | Viewed by 4021

Abstract

Until less than 10 years ago, chiral separations were carried out with columns packed with 5 or 3

μ

m fully porous particles (FPPs). Times to resolve enantiomeric mixtures were easily larger than 30 min, or so. Pushed especially by stringent requirements from [...] Read more.

Until less than 10 years ago, chiral separations were carried out with columns packed with 5 or 3

μ

m fully porous particles (FPPs). Times to resolve enantiomeric mixtures were easily larger than 30 min, or so. Pushed especially by stringent requirements from medicinal and pharmaceutical industries, during the last years the field of chiral separations by liquid chromatography has undergone what can be defined a “true revolution”. With the purpose of developing ever faster and efficient method of separations, indeed, very efficient particle formats, such as superficially porous particles (SPPs) or Full article

(This article belongs to the Collection Advances in Liquid Separation Techniques for Food and Pharmaceutical Analysis)

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22 pages, 7639 KiB

Open AccessReview

Phytochemical Constituents and Biological Activities of Melicope lunu-ankenda

by Enas Mohamed Eliaser, Jun Hui Ho, Najihah Mohd. Hashim, Yaya Rukayadi, Gwendoline Cheng Lian Ee and Ahmad Faizal Abdull Razis

Molecules 2018, 23(10), 2708; https://doi.org/10.3390/molecules23102708 - 20 Oct 2018

Cited by 17 | Viewed by 7168

Abstract

Natural products, either pure compounds or standardized plant extracts, have provided opportunities for the discovery of new drugs. Nowadays, most of the world’s population still relies on traditional medicines for healthcare purposes. Plants, in particular, are always used as traditional medicine, as they [...] Read more.

Natural products, either pure compounds or standardized plant extracts, have provided opportunities for the discovery of new drugs. Nowadays, most of the world’s population still relies on traditional medicines for healthcare purposes. Plants, in particular, are always used as traditional medicine, as they contain a diverse number of phytochemicals that can be used for the treatment of diseases. The multicomponent feature in the plants is considered a positive phytotherapeutic hallmark. Hence, ethnopharmacognosy has been the focus for finding alternative treatments for diseases. Melicope lunu-ankenda, also known as Euodia lunu-ankenda, is widely distributed in tropical regions of Asia. Different parts of M. lunu-ankenda have been used for treatment of hypertension, menstrual disorder, diabetes, and fever, and as an emmenagogue and tonic. It has also been consumed as salad and as a condiment for food flavorings. The justification of use of M. lunu-ankenda in folk medicines is supported by its reported biological activities, including its cytotoxic, antibacterial, antioxidant, analgesic, antidiabetic, and anti-inflammatory activities. This review summarizes the phytochemical compounds isolated from various parts of M. lunu-ankenda, such as root and leaves, and also its biological activities, which could make the species a new therapeutic agent for some diseases, including diabetes, in the future. Full article

(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)

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19 pages, 1856 KiB

Open AccessArticle

Assessing Nutritional Traits and Phytochemical Composition of Artisan Jams Produced in Comoros Islands: Using Indigenous Fruits with High Health-Impact as an Example of Biodiversity Integration and Food Security in Rural Development

by Dario Donno, Maria Gabriella Mellano, Saandia Hassani, Marta De Biaggi, Isidoro Riondato, Giovanni Gamba, Cristina Giacoma and Gabriele Loris Beccaro

Molecules 2018, 23(10), 2707; https://doi.org/10.3390/molecules23102707 - 20 Oct 2018

Cited by 8 | Viewed by 4673

Abstract

In the Comoros Islands, as in other developing countries, malnutrition and food insecurity affect a very large percentage of the population. Developing fruit-based products in order to make profit, reduce poverty and improve indigenous people diet could be very important for local population [...] Read more.

In the Comoros Islands, as in other developing countries, malnutrition and food insecurity affect a very large percentage of the population. Developing fruit-based products in order to make profit, reduce poverty and improve indigenous people diet could be very important for local population of countries as Comoros Islands. The aim of the present work was to study the chemical composition of jams and jellies produced from seven fruit species harvested in Grand Comore Island. The following parameters were studied sugars and organic acids, total phenolics, total anthocyanins and high-performance liquid chromatography (HPLC) fingerprint of the main phytochemicals. Antioxidant activity was also measured. A multivariate approach (Principal Component Analysis) was performed in order to better characterize the products and to set a potential analytical tool for jam characterisation. Results showed that the analysed products are a good source of polyphenolic constituents, as caffeic and gallic acids, catechin and quercetin and volatile compounds, as limonene and γ-terpinene: these molecules may be considered as suitable markers for these fruit-derived products as characterizing the chromatographic patterns. The characterisation of these products and their nutritional and nutraceutical traits is important as valorisation of local food production for poverty reduction and rural development. Further benefits of this approach include the maintenance of local agro-biodiversity as raw material for fruit-based products and the strengthening of food security practices. Full article

(This article belongs to the Collection Advances in Food Analysis)

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15 pages, 4534 KiB

Open AccessFeature PaperArticle

Long-Term Effect on Bioactive Components and Antioxidant Activity of Thermal and High-Pressure Pasteurization of Orange Juice

by Fabiana N. Vieira, Sónia Lourenço, Liliana G. Fidalgo, Sónia A. O. Santos, Armando J. D. Silvestre, Eliana Jerónimo and Jorge A. Saraiva

Molecules 2018, 23(10), 2706; https://doi.org/10.3390/molecules23102706 - 20 Oct 2018

Cited by 34 | Viewed by 6756

Abstract

The long-term effect of thermal pasteurization (TP) and high-pressure processing (HPP) of orange juices stored under refrigeration, on the bioactive components and antioxidant activity, was compared. Total phenolic content (TPC), flavonoid, anthocyanin, and carotenoid contents, the individual content of major phenolic components, and [...] Read more.

The long-term effect of thermal pasteurization (TP) and high-pressure processing (HPP) of orange juices stored under refrigeration, on the bioactive components and antioxidant activity, was compared. Total phenolic content (TPC), flavonoid, anthocyanin, and carotenoid contents, the individual content of major phenolic components, and the antioxidant activity, were evaluated in TP- and HPP-treated juices over a 36-day period. At day 0, no significant differences in TPC, and a decrease in carotenoid content after both treatments, were observed. TP caused a decrease of flavonoid and anthocyanin contents, while HPP increased flavonoid content. Three major phenolic components were identified: apigenin-6,8-di-C-glucoside, naringenin-7-O-rutinoside, and hesperetin-7-O-rutinoside, the latter increasing ca. 45% immediately after HPP. During storage, a decrease in TPC, and in the anthocyanin and carotenoid contents of both treated juices was observed, with higher anthocyanin and phenolic contents in HPP juices. A significant increase of hesperetin-7-O-rutinoside content was observed in HPP juice. Both treatments caused a decrease (26% and 13%, respectively) of antioxidant activity. Most of the kinetic profiles followed zero-order patterns, with HPP juices showing a considerably higher half-life than TP ones. These results clearly demonstrate the advantages of HPP for orange juice preservation allowing, also, their nutritional benefits to be enhanced by increasing the content of some bioactive components. Full article

(This article belongs to the Special Issue The Antioxidant Capacities of Natural Products)

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7 pages, 789 KiB

Open AccessArticle

Validation of UPLC-MS/MS Method for Determination of Urinary Lactulose/Mannitol

by Jacopo Gervasoni, Aniello Primiano, Cristina Graziani, Franco Scaldaferri, Antonio Gasbarrini, Andrea Urbani and Silvia Persichilli

Molecules 2018, 23(10), 2705; https://doi.org/10.3390/molecules23102705 - 20 Oct 2018

Cited by 15 | Viewed by 5717

Abstract

Determination of urinary lactulose/mannitol is one of the most used tests to evaluate intestinal barrier function. High-performance liquid chromatography (HPLC) separation with electrospray ionization tandem mass spectrometry guarantees high levels of selectivity and reproducibility. In this paper we report an upgrade of the [...] Read more.

Determination of urinary lactulose/mannitol is one of the most used tests to evaluate intestinal barrier function. High-performance liquid chromatography (HPLC) separation with electrospray ionization tandem mass spectrometry guarantees high levels of selectivity and reproducibility. In this paper we report an upgrade of the previous published liquid chromatography tandem mass spectrometry method, introducing more reliable internal standards and ultra-performance liquid chromatography with ethylene bridged hybrid amide columns. The ultra-performance liquid chromatography provided an efficient chromatographic separation of the two sugars in 5 min, compared to 15 min using the previous method. The limit of quantification was 10 µg/mL for mannitol and 2.5 µg/mL for lactulose, and the assay was linear up to 1000 µg/mL for mannitol and 1000 µg/mL for lactulose. The within-run precision and accuracy ranged from 0.7 to 2.9% and 97.2 to 101.2%, respectively. The between-run precision and accuracy ranged from 1.9 to 4.7% and 94.8 to 97.5%, respectively. Recovery was higher than 90.2% for both lactulose and mannitol, and the matrix effect for both lactulose and mannitol was lower than 15%. With this new method we have a real improvement in terms of accuracy and reproducibility, ensuring results in shorter time. The changes to the previous protocol make this method excellent for routine purposes. Full article

(This article belongs to the Collection Advances in Liquid Separation Techniques for Food and Pharmaceutical Analysis)

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1 pages, 151 KiB

Open AccessCorrection

Correction: Meng, X., et al. Neuroprotective Effects of Radix Scrophulariae on Cerebral Ischemia and Reperfusion Injury via MAPK Pathways. Molecules 2018, 23, 2401

by Xiangbao Meng, Weijie Xie, Quanfu Xu, Tian Liang, Xudong Xu, Guibo Sun and Xiaobo Sun

Molecules 2018, 23(10), 2704; https://doi.org/10.3390/molecules23102704 - 19 Oct 2018

Cited by 4 | Viewed by 2846

Abstract

The authors wish to make the following correction to their paper [...] Full article

20 pages, 5777 KiB

Open AccessArticle

Cationic Cyclopentadienyliron Complex as a Novel and Successful Nucleating Agent on the Crystallization Behavior of the Biodegradable PHB Polymer

by Safaa H. El-Taweel, Arwa O. Al-Ahmadi, Omaima Alhaddad and Rawda M. Okasha

Molecules 2018, 23(10), 2703; https://doi.org/10.3390/molecules23102703 - 19 Oct 2018

Cited by 8 | Viewed by 3867

Abstract

Cationic cyclopentadienyliron (CpFe⁺) is one of the most fruitful organometallic moieties that has been utilized to mediate the facile synthesis of a massive number of macromolecules. However, the ability of this compound to function as a nucleating agent to improve other [...] Read more.

Cationic cyclopentadienyliron (CpFe⁺) is one of the most fruitful organometallic moieties that has been utilized to mediate the facile synthesis of a massive number of macromolecules. However, the ability of this compound to function as a nucleating agent to improve other macromolecule properties has not been explored. This report scrutinizes the influence of the cationic complex as a novel nucleating agent on the spherulitic morphology, crystal structure, and isothermal and non-isothermal crystallization behavior of the Poly(3-hydroxybutyrate) (PHB) bacterial origin. The incorporation of the CpFe⁺ into the PHB materials caused a significant increase in its spherulitic numbers with a remarkable reduction in the spherulitic sizes. Unlike other nucleating agents, the SEM imageries exhibited a good dispersion without forming agglomerates of the CpFe⁺ moieties in the PHB matrix. Moreover, according to the FTIR analysis, the cationic organoiron complex has a strong interaction with the PHB polymeric chains via the coordination with its ester carbonyl. Yet, the XRD results revealed that this incorporation had no significant effect on the PHB crystalline structure. Though the CpFe⁺ had no effect on the polymer’s crystal structure, it accelerated outstandingly the melt crystallization of the PHB. Meanwhile, the crystallization half-times (t_0.5) of the PHB decreased dramatically with the addition of the CpFe⁺. The isothermal and non-isothermal crystallization processes were successfully described using the Avrami model and a modified Avrami model, as well as a combination of the Avrami and Ozawa methods. Finally, the effective activation energy of the PHB/CpFe⁺ nanocomposites was much lower than those of their pure counterparts, which supported the heterogeneous nucleation mechanism with the organometallic moieties, indicating that the CpFe⁺ is a superior nucleating agent for this class of polymer. Full article

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14 pages, 1575 KiB

Open AccessArticle

Investigation of the In Vivo Metabolism of Sibirioside A and Angoroside C in Rats by HPLC-ESI-IT-TOF-MSⁿ

by Yi-Fan Zhang, Li-Jia Liu, Feng Xu, Ming-Ying Shang, Guang-Xue Liu and Shao-Qing Cai

Molecules 2018, 23(10), 2702; https://doi.org/10.3390/molecules23102702 - 19 Oct 2018

Cited by 9 | Viewed by 3890

Abstract

Sibirioside A and angoroside C are two important phenylpropanoid glycosides of the traditional Chinese medicine Scrophulariae Radix. High performance liquid chromatography, coupled with an ion trap time-of-flight multistage mass spectrometry equipped with electrospray ionization source (HPLC-ESI-IT-TOF-MSⁿ), was applied to the profile [...] Read more.

Sibirioside A and angoroside C are two important phenylpropanoid glycosides of the traditional Chinese medicine Scrophulariae Radix. High performance liquid chromatography, coupled with an ion trap time-of-flight multistage mass spectrometry equipped with electrospray ionization source (HPLC-ESI-IT-TOF-MSⁿ), was applied to the profile and we identified the metabolites of sibirioside A and angoroside C in vivo in rats. A total of four metabolites of sibirioside A were identified: SM1, SM2 and SM3 which were known as new compounds. A total of 25 metabolites were detected for angoroside C: AM4, AM5, AM6, AM7, AM16, AM17, AM20, AM21, AM22, AM23 and AM25 which were identified to be new compounds. The main metabolic reactions were hydrolysis, reduction, hydroxylation, methylation, sulfation, and gluconylation. The prototype of sibirioside A was widely distributed in tissues found in the heart, liver, spleen, lung, kidney, stomach and small intestine of rats, and mainly distributed in the stomach, small intestine, kidney and liver. But for angoroside C, nothing was found in the viscera except the stomach and small intestine. The metabolites of sibirioside A were mainly eliminated from feces, while it was urine for the metabolites of angoroside C. Furthermore, 19 metabolites were likely to have bioactivities based on the ‘PharmMapper’ analysis, which roughly matched the known pharmacological activities of Scrophulariae Radix (SR) and the prototypes. One of the main pharmacological activities of SR in traditional Chinese medicine is anti-diabetes, and the predicted results showed that SM1, SM2, SM3, AM2, AM4, AM5, AM6, AM9, AM10, AM11, AM12, AM13, AM15, AM18, AM19, AM24, and AM25 might be used to cure diabetes. These findings provide a reference for studying the metabolism, distribution and pharmacological actions of phenylpropanoid glycosides in vivo. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

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17 pages, 2158 KiB

Open AccessArticle

Purified Phlorizin from DocynIa Indica (Wall.) Decne by HSCCC, Compared with Whole Extract, Phlorizin and Non-Phlorizin Fragment Ameliorate Obesity, Insulin Resistance, and Improves Intestinal Barrier Function in High-Fat-Diet-Fed Mice

by Xiao-yu Zhang, Kang Yi, Jiang Chen, Rui-ping Li, Jie Xie, Yan Jin, Xue-ran Mei, Yao-jun Li, Gang Liu and Zhan-guo Wang

Molecules 2018, 23(10), 2701; https://doi.org/10.3390/molecules23102701 - 19 Oct 2018

Cited by 16 | Viewed by 5028

Abstract

Natural products generally contain complex and multiple bioactive compounds that are responsible for the effects on health through complicated synergistic and/or suppressive actions. As an important raw material of local ethnic minority tea, ethnomedicines and food supplements in southwestern areas of China, Docynia [...] Read more.

Natural products generally contain complex and multiple bioactive compounds that are responsible for the effects on health through complicated synergistic and/or suppressive actions. As an important raw material of local ethnic minority tea, ethnomedicines and food supplements in southwestern areas of China, Docynia indica (Wall.) Decne (DID) mainly consists of phlorizin (PHZ), which is the main active component. In this study, the holistic activities and the interactions of components of PHZ, non-phlorizin (NP) in the DID extract (DIDE) were evaluated. A rapid and effective high-speed counter-current chromatography (HSCCC) was performed to knock out PHZ from DIDE and the purity of PHZ was 96.01% determined by HPLC, with a recovery rate of 96.76%. After 13 weeks of treatment course in a high-fat diet (HFD)-induced obese mice model, the results revealed that the DIDE and PHZ significantly decreased weight gain, blood lipid levels, hyperplasia of adipocytes and alleviated inflammation (p < 0.05). Both DIDE and PHZ improves insulin resistance (p < 0.001). Meanwhile, the intestinal barrier function was improved compared to HFD group, through the determination of serum lipopolysaccharides (LPS), glucagon-likepeptide-2 (GLP-2) and hematoxylin-eosin staining of jejunum. Interestingly, after NP treatment, the metabolic syndrome of the HFD-induced obesity appeared to have a similar improvement. All the experiments showed that there is a synergistic weakening phenomenon when PHZ and NP interact with each other in the mixed state. In conclusion, for the PHZ and NP showing a good effect on anti-obesity, anti-inflammation, and intestinal barrier function, DIDE could be a good source of functional food to prevent obesity. Full article

(This article belongs to the Special Issue Natural Bioactives in Anti-Obesity Therapy)

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11 pages, 4192 KiB

Open AccessArticle

Ultrasensitive and Multifunction Plasmonic Temperature Sensor with Ethanol-Sealed Asymmetric Ellipse Resonators

by Jun Zhu and Jian Lou

Molecules 2018, 23(10), 2700; https://doi.org/10.3390/molecules23102700 - 19 Oct 2018

Cited by 17 | Viewed by 3394

Abstract

In order to improve the low temperature sensitivity of conventional sensors, a plasmonic multifunction temperature sensor with high sensitivity is proposed and investigated systematically in this paper. The sensor consists of two metal layers and two ethanol-sealed elliptical resonators connected to a straight [...] Read more.

In order to improve the low temperature sensitivity of conventional sensors, a plasmonic multifunction temperature sensor with high sensitivity is proposed and investigated systematically in this paper. The sensor consists of two metal layers and two ethanol-sealed elliptical resonators connected to a straight waveguide by two rectangular tubes. We numerically analyzed the transmission characteristics of the Nano-device to assess its performance with the finite element method and achieved great optical properties. The results show that an obvious blue shift of the transmission spectrum appears by varying temperatures, exhibiting a great sensing effect. Sensitivity of the sensor reaches −3.64 nm/°C, far greater than conventional temperature sensors. Our research also demonstrates that the transmission spectrum could be modulated efficiently by the ratio of semi-short axis to semi-major axis of the ellipse resonators and the width of two same rectangular tubes. Furthermore, the Nano-device has a filtering characteristic. The transmittances of pass-band and stop-band are 96.1% and 0.1%, respectively. The results of this study can pave the way for low-cost sensing application in high-density photonic circuits and biosensors. Full article

(This article belongs to the Special Issue Graphene Nanocomposites)

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18 pages, 2574 KiB

Open AccessArticle

Peroxidative Oxidation of Alkanes and Alcohols under Mild Conditions by Di- and Tetranuclear Copper (II) Complexes of Bis (2-Hydroxybenzylidene) Isophthalohydrazide

by Manas Sutradhar, Elisabete C.B.A. Alegria, M. Fátima C. Guedes da Silva, Cai-Ming Liu and Armando J. L. Pombeiro

Molecules 2018, 23(10), 2699; https://doi.org/10.3390/molecules23102699 - 19 Oct 2018

Cited by 20 | Viewed by 3960

Abstract

Bis(2-hydroxybenzylidene)isophthalohydrazide (H₄L) has been used to synthesize the dinuclear [Cu₂(1κNO²:2κN′O′²-H₂L)(NO₃)₂(H₂O)₂] (1) and the tetranuclear [Cu₄(μ-1κNO²:2κN [...] Read more.

Bis(2-hydroxybenzylidene)isophthalohydrazide (H₄L) has been used to synthesize the dinuclear [Cu₂(1κNO²:2κN′O′²-H₂L)(NO₃)₂(H₂O)₂] (1) and the tetranuclear [Cu₄(μ-1κNO²:2κN′O²-H₂L)₂(μ-NO₃)₂(H₂O)₄]·2C₂H₅OH (2) complexes. The solvent plays an important role in determining the ligand behaviour in the syntheses of the complexes. An ethanol-acetonitrile mixture of solvents favours partials enolization in the case of 2. Both complexes have been characterized by elemental analysis, infrared radiation (IR), single crystal X-ray crystallography and electrochemical methods. The variable temperature magnetic susceptibility measurements of 2 show strong antiferromagnetic coupling between the central nitrato-bridged Cu (II) ions. The catalytic activity of both 1 and 2 has been screened toward the solvent-free microwave-assisted oxidation of alcohols and the peroxidative oxidation of alkanes under mild conditions. Complex 1 exhibits the highest activity for both oxidation reactions, leading selectively to a maximum product yield of 99% (for the 1-phenylethanol oxidation after 1 h without any additive) and 13% (for the cyclohexane oxidation to cyclohexyl hydroperoxide, cyclohexanol and cyclohexanone after 3 h). Full article

(This article belongs to the Special Issue Metal Complexes of Biological Ligands)

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