Molecules

22 pages, 619 KiB

Open AccessFeature PaperReview

Instrumentation for Vibrational Circular Dichroism Spectroscopy: Method Comparison and Newer Developments

by Timothy A. Keiderling

Department of Chemistry, University of Illinois at Chicago, Chicago, IL 60607-7061, USA

Molecules 2018, 23(9), 2404; https://doi.org/10.3390/molecules23092404 - 19 Sep 2018

Cited by 25 | Viewed by 10535

Vibrational circular dichroism (VCD) is a widely used standard method for determination of absolute stereochemistry, and somewhat less so for biomolecule characterization and following dynamic processes. Over the last few decades, different VCD instrument designs have developed for various purposes, and reliable commercial [...] Read more.

Vibrational circular dichroism (VCD) is a widely used standard method for determination of absolute stereochemistry, and somewhat less so for biomolecule characterization and following dynamic processes. Over the last few decades, different VCD instrument designs have developed for various purposes, and reliable commercial instrumentation is now available. This review will briefly survey historical and currently used instrument designs and describe some aspects of more recently reported developments. An important factor in applying VCD to conformational studies is theoretical modeling of spectra for various structures, techniques for which are briefly surveyed. Full article

(This article belongs to the Special Issue Recent Advances in Chiroptical Spectroscopy)

▼ Show Figures

Figure 1

16 pages, 4263 KiB

Open AccessArticle

Optimization of Transesterification Reactions with CLEA-Immobilized Feruloyl Esterases from Thermothelomyces thermophila and Talaromyces wortmannii

by Anastasia Zerva¹

, Io Antonopoulou¹

, Josefine Enman¹

, Laura Iancu², Peter Jütten³, Ulrika Rova¹

and Paul Christakopoulos^1,*

¹ Division of Chemical Engineering, Department of Civil, Environmental and Natural Resources Engineering, Luleå University of Technology, 97187 Luleå, Sweden

² DuPont Industrial Biosciences, Nieuwe Kanaal 7-S, 6709 PA Wageningen, The Netherlands

³ Taros Chemicals GmbH & Co. KG, Emil Figge Str 76a, 44227 Dortmund, Germany

Molecules 2018, 23(9), 2403; https://doi.org/10.3390/molecules23092403 - 19 Sep 2018

Cited by 14 | Viewed by 4573

Abstract

Feruloyl esterases (FAEs, E.C. 3.1.1.73) are biotechnologically important enzymes with several applications in ferulic acid production from biomass, but also in synthesis of hydroxycinnamic acid derivatives. The use of such biocatalysts in commercial processes can become feasible by their immobilization, providing the advantages [...] Read more.

Feruloyl esterases (FAEs, E.C. 3.1.1.73) are biotechnologically important enzymes with several applications in ferulic acid production from biomass, but also in synthesis of hydroxycinnamic acid derivatives. The use of such biocatalysts in commercial processes can become feasible by their immobilization, providing the advantages of isolation and recycling. In this work, eight feruloyl esterases, immobilized in cross-linked enzyme aggregates (CLEAs) were tested in regard to their transesterification performance, towards the production of prenyl ferulate (PFA) and arabinose ferulate (AFA). After solvent screening, comparison with the activity of respective soluble enzymes, and operational stability tests, FAE125 was selected as the most promising biocatalyst. A central composite design revealed the optimum conditions for each transesterification product, in terms of water content, time, and substrate ratio for both products, and temperature and enzyme load additionally for prenyl ferulate. The optimum product yields obtained were 83.7% for PFA and 58.1% for AFA. FAE125 CLEAs are stable in the optimum conditions of transesterification reactions, maintaining 70% residual activity after five consecutive reactions. Overall, FAE125 CLEAs seem to be able to perform as a robust biocatalyst, offering satisfactory yields and stability, and thus showing significant potential for industrial applications. Full article

(This article belongs to the Special Issue Natural Product Enzymes in Biosynthesis and Biocatalysis)

▼ Show Figures

Graphical abstract

21 pages, 2885 KiB

Open AccessArticle

Characterization of α-Glucosidase Inhibitors from Clinacanthus nutans Lindau Leaves by Gas Chromatography-Mass Spectrometry-Based Metabolomics and Molecular Docking Simulation

by Suganya Murugesu¹, Zalikha Ibrahim¹

, Qamar-Uddin Ahmed¹, Nik-Idris Nik Yusoff¹, Bisha-Fathamah Uzir¹, Vikneswari Perumal², Faridah Abas³

, Khozirah Saari³, Hesham El-Seedi^4,5 and Alfi Khatib^1,3,*

¹ Department of Pharmaceutical Chemistry, Kulliyyah of Pharmacy, International Islamic University Malaysia, Kuantan 25200, Pahang Darul Makmur, Malaysia

² Faculty Pharmacy & Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh 30450, Perak Darul Ridzuan, Malaysia

³ Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43300, Selangor Darul Ehsan, Malaysia

⁴ Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden

⁵ H.E.J. Research Institute of Chemistry, International Centre for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan

Molecules 2018, 23(9), 2402; https://doi.org/10.3390/molecules23092402 - 19 Sep 2018

Cited by 69 | Viewed by 9165

Abstract

Background: Clinacanthus nutans (C. nutans) is an Acanthaceae herbal shrub traditionally consumed to treat various diseases including diabetes in Malaysia. This study was designed to evaluate the α-glucosidase inhibitory activity of C. nutans leaves extracts, and to identify the metabolites responsible [...] Read more.

Background: Clinacanthus nutans (C. nutans) is an Acanthaceae herbal shrub traditionally consumed to treat various diseases including diabetes in Malaysia. This study was designed to evaluate the α-glucosidase inhibitory activity of C. nutans leaves extracts, and to identify the metabolites responsible for the bioactivity. Methods: Crude extract obtained from the dried leaves using 80% methanolic solution was further partitioned using different polarity solvents. The resultant extracts were investigated for their α-glucosidase inhibitory potential followed by metabolites profiling using the gas chromatography tandem with mass spectrometry (GC-MS). Results: Multivariate data analysis was developed by correlating the bioactivity, and GC-MS data generated a suitable partial least square (PLS) model resulting in 11 bioactive compounds, namely, palmitic acid, phytol, hexadecanoic acid (methyl ester), 1-monopalmitin, stigmast-5-ene, pentadecanoic acid, heptadecanoic acid, 1-linolenoylglycerol, glycerol monostearate, alpha-tocospiro B, and stigmasterol. In-silico study via molecular docking was carried out using the crystal structure Saccharomyces cerevisiae isomaltase (PDB code: 3A4A). Interactions between the inhibitors and the protein were predicted involving residues, namely LYS156, THR310, PRO312, LEU313, GLU411, and ASN415 with hydrogen bond, while PHE314 and ARG315 with hydrophobic bonding. Conclusion: The study provides informative data on the potential α-glucosidase inhibitors identified in C. nutans leaves, indicating the plant’s therapeutic effect to manage hyperglycemia. Full article

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

▼ Show Figures

Graphical abstract

19 pages, 5674 KiB

Open AccessArticle

Neuroprotective Effects of Radix Scrophulariae on Cerebral Ischemia and Reperfusion Injury via MAPK Pathways

by Xiangbao Meng^1,2,3,4,†, Weijie Xie^1,2,3,4,†

, Quanfu Xu^1,2,3,4,†, Tian Liang^1,2,3,4, Xudong Xu^1,2,3,4,*, Guibo Sun^1,2,3,4,* and Xiaobo Sun^1,2,3,4,*

¹ Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China

² Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China

³ Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China

⁴ Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing 100193, China

^† These authors contributed equally to this paper.

Molecules 2018, 23(9), 2401; https://doi.org/10.3390/molecules23092401 - 19 Sep 2018

Cited by 70 | Viewed by 6896 | Correction

Abstract

Ischemic stroke is a clinically common cerebrovascular disease whose main risks include necrosis, apoptosis and cerebral infarction, all caused by cerebral ischemia and reperfusion (I/R). Ischemia and reperfusion-induced injury or apoptosis inhibition in human brain tissue may exert an irreplaceable protective effect on [...] Read more.

Ischemic stroke is a clinically common cerebrovascular disease whose main risks include necrosis, apoptosis and cerebral infarction, all caused by cerebral ischemia and reperfusion (I/R). Ischemia and reperfusion-induced injury or apoptosis inhibition in human brain tissue may exert an irreplaceable protective effect on ischemic nerves. This process has particular significance for the treatment of stroke patients. However, the development of neuroprotective drugs remains challenging. Radix Scrophulariae, traditionally considered a valuable medicine, has been discovered to have neuroprotective effects. To explore the neuroprotective effects of an aqueous extract of Radix Scrophulariae (RSAE) on cerebral ischemia/reperfusion and their underlying mechanisms, oxygen-glucose deprivation and reperfusion (OGD/R)-induced PC12 cells were used, and a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model was established. In vitro results showed that 12.5 μg/mL RSAE markedly improved cell viability; inhibited LDH leakage; increased SOD, GSH-Px and CAT enzyme activity; stabilized the mitochondrial membrane potential; and reduced OGD-induced cell injury and apoptosis. Additionally, in vivo results preliminarily suggested that in MCAO/R model mice, RSAE treatments attenuated infarct volume; reduced brain water content and nitric oxide (NO) and malondialdehyde (MDA) concentrations; inhibited I/R-induced neurological deficits; reduced the levels of lactate dehydrogenase (LDH) leakage release; improved antioxidant capacity by upregulating SOD, GSH-Px and CAT enzyme activity; and reduced neuronal apoptosis, necrosis and loss of neurons. Moreover, it was found that RSAE upregulated the expression of Bcl-2 and downregulated the expression of Bax. In addition, the phosphorylation levels of MAPK signal pathways were elucidated via western blot analysis and immunohistochemical evaluation. In summary, this study investigated the neuroprotective effects and potential mechanisms of RSAE on focal cerebral I/R injury in mice. Radix Scrophulariae has been previously identified as a potential neuroprotective natural plant. Hence, our results may offer insight into discovering new active compounds or drugs for the treatment of ischemic stroke. Many new natural active chemicals in this extract may be discovered by chemical separation and identification and may provide new insights into therapeutic targets in stroke patients. Full article

(This article belongs to the Collection Herbal Medicine Research)

▼ Show Figures

Figure 1

8 pages, 551 KiB

Open AccessCommunication

Isolation and Identification of Benzochroman and Acylglycerols from Massa Medicata Fermentata and Their Inhibitory Effects on LPS-Stimulated Cytokine Production in Bone Marrow-Derived Dendritic Cells

by Ya Nan Sun^1,†, Seo Young Yang^1,†, Young-Sang Koh², Young Ho Kim^1,* and Wei Li^3,*

¹ College of Pharmacy, Chungnam National University, Daejeon 34134, Korea

² School of Medicine and Brain Korea 21 Program, and Institute of Medical Science, Jeju National University, Jeju 690-756, Korea

³ Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Korea

^† These authors contributed equally to this work.

Molecules 2018, 23(9), 2400; https://doi.org/10.3390/molecules23092400 - 19 Sep 2018

Cited by 7 | Viewed by 4556

Abstract

Massa Medicata Fermentata (MMF), known as Shenqu, is an important traditional Chinese medicine widely used to treat indigestion, vomiting, and diarrhea. In this study, a new benzochroman, 3(S)-3,4-dihydro-5,10-di-β-d-glucopyranoside-2,2-dimethyl-2H-naphtho(2,3-b)pyran-3-ol (1), and five [...] Read more.

Massa Medicata Fermentata (MMF), known as Shenqu, is an important traditional Chinese medicine widely used to treat indigestion, vomiting, and diarrhea. In this study, a new benzochroman, 3(S)-3,4-dihydro-5,10-di-β-d-glucopyranoside-2,2-dimethyl-2H-naphtho(2,3-b)pyran-3-ol (1), and five known galactosyl acylglycerols (2–6) were isolated from a methanol extract from MMF. In addition, their chemical structures were determined by chemical and spectroscopic methods, which were compared with the previously reported data. Furthermore, the effects of isolated compounds on lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells were investigated. Compounds 1–3 exhibited significant inhibitory effects on the LPS-induced production of IL-6 and IL-12 p40, with IC₅₀ values ranging from 1.6 to 10.2 μM. Compounds 2 and 3 also exhibited strong inhibitory effects on the LPS-stimulated production of TNF-α with IC₅₀ values of 12.0 and 11.2 μM, respectively. The results might provide a scientific basis for the development of the active components in MMF, as well as for novel anti-inflammatory agents. Full article

(This article belongs to the Section Natural Products Chemistry)

▼ Show Figures

Graphical abstract

16 pages, 2544 KiB

Open AccessArticle

Hydrogen Peroxide Generation of Copper/Ascorbate Formulations on Cotton: Effect on Antibacterial and Fibroblast Activity for Wound Healing Application

by J. Vincent Edwards^1,*, Nicolette T. Prevost¹, Michael Santiago¹, Terri Von Hoven¹, Brian D. Condon¹, Huzaifah Qureshi² and Dorne R. Yager²

¹ Southern Regional Research Center, USDA-ARS, New Orleans, LA 70120, USA

² Plastic and Reconstructive Surgery, Virginia Commonwealth University, Richmond, VA 23111, USA

Molecules 2018, 23(9), 2399; https://doi.org/10.3390/molecules23092399 - 19 Sep 2018

Cited by 13 | Viewed by 5435

Abstract

Greige cotton (unbleached cotton) is an intact plant fiber that retains much of the outer cotton fiber layers. These layers contain pectin, peroxidases, and trace metals that are associated with hydrogen peroxide (H₂O₂) generation during cotton fiber development. When [...] Read more.

Greige cotton (unbleached cotton) is an intact plant fiber that retains much of the outer cotton fiber layers. These layers contain pectin, peroxidases, and trace metals that are associated with hydrogen peroxide (H₂O₂) generation during cotton fiber development. When greige cotton is subjected to a nonwoven hydroentanglement process, components of the outer cotton fiber layers are retained. When hydrated, this fabric can generate H₂O₂ (5–50 micromolar). This range has been characterized as inducing accelerated wound healing associated with enhanced cell signaling and the proliferation of cells vital to wound restoration. On the other hand, H₂O₂ levels above 50 micromolar have been associated with bacteriostatic activity. Here, we report the preparation and hydrogen peroxide activity of copper/ascorbate formulations, both as adsorbed and in situ synthesized analogs on cotton. The cooper/ascorbate-cotton formulations were designed with the goal of modulating hydrogen peroxide levels within functional ranges beneficial to wound healing. The cotton/copper formulation analogs were prepared on nonwoven unbleached cotton and characterized with cotton impregnation titers of 3–14 mg copper per gram of cotton. The copper/ascorbate cotton analog formulations were characterized spectroscopically, and the copper titer was quantified with ICP analysis and probed for peroxide production through assessment with Amplex Red. All analogs demonstrated antibacterial activity. Notably, the treatment of unbleached cotton with low levels of ascorbate (~2 mg/g cotton) resulted in a 99 percent reduction in Klebsiella pneumoniae and Staphylococcus aureus. In situ synthesized copper/ascorbate nanoparticles retained activity and did not leach out upon prolonged suspension in an aqueous environment. An assessment of H₂O₂ effects on fibroblast proliferation are discussed in light of the copper/cotton analogs and wound healing. Full article

(This article belongs to the Special Issue Recent Advances in Antimicrobial Biomaterials)

▼ Show Figures

Figure 1

14 pages, 3629 KiB

Open AccessArticle

Salidroside Improves Bone Histomorphology and Prevents Bone Loss in Ovariectomized Diabetic Rats by Upregulating the OPG/RANKL Ratio

by Hongxing Zheng¹, Shanshan Qi^2,* and Chen Chen^1,*

¹ Chinese-German Joint Laboratory for Natural Product Research, College of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong 723000, Shaanxi, China

² Vitamin D Research Institute, Qinling-Bashan Mountains Bioresources Comprehensive Department C.I.C, Shaanxi University of Technology, Hanzhong 723000, Shaanxi, China

Molecules 2018, 23(9), 2398; https://doi.org/10.3390/molecules23092398 - 19 Sep 2018

Cited by 52 | Viewed by 5258

Abstract

Postmenopausal diabetic women have a high risk of fractures. Salidroside has preventive effects on estrogen deficiency-induced osteoporosis and has hypoglycemic effects on diabetes in rats. However, whether salidroside inhibits bone loss in postmenopausal diabetic patients is still unknown. Here, we established a rat [...] Read more.

Postmenopausal diabetic women have a high risk of fractures. Salidroside has preventive effects on estrogen deficiency-induced osteoporosis and has hypoglycemic effects on diabetes in rats. However, whether salidroside inhibits bone loss in postmenopausal diabetic patients is still unknown. Here, we established a rat model of osteoporosis to investigate the protective effects of salidroside on bone loss induced by ovariectomy combined with diabetes, also investigating the underlying mechanisms. Two-month-old female Sprague-Dawley rats were divided into three equal groups (10 rats in each group): control group (with sham operation, treated with drug vehicle); OVX/T1DM group (ovariectomized diabetic rats); OVX/T1DM-SAL group, comprising ovariectomized diabetic rats treated with salidroside (20 mg/kg body weight) by gavage. The results showed that after 60 consecutive days of treatment, the bone mineral density (BMD) of OVX/T1DM-SAL increased significantly compared with the OVX/T1DM group (p < 0.01). The level of serum bone turnover markers, including alkaline phosphatase (ALP), cross linked c-telopeptide of type I collagen (CTX-1), osteocalcin, N-terminal propeptide of type I procollagen (PINP), and tartrate-resistant acid phosphatase 5b (TRACP 5b) were all increased in the OVX/T1DM group compared with the control (p < 0.01), and those were decreased by salidroside treatment. Meanwhile, the bone histopathological changes were also attenuated, and the bone marrow adipogenesis was inhibited in salidroside treated rats. Moreover, protein and mRNA ratio of bone osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) was upregulated in ovariectomized diabetic rats by salidroside treatment. The results above indicated that the protective effect of salidroside on bone loss induced by ovariectomy and diabetes was mainly due to its ability to suppress bone turnover, inhibit bone marrow adipogenesis, and up-regulate the OPG/RANKL ratio. Full article

(This article belongs to the Special Issue Medicinal Plants and Diabetes)

▼ Show Figures

Figure 1

11 pages, 2174 KiB

Open AccessArticle

A New Strategy for Rapidly Screening Natural Inhibitors Targeting the PCSK9/LDLR Interaction In Vitro

by Li Li¹

, Chen Shen¹

, Ya-Xuan Huang¹, Ya-Nan Li¹, Xiu-Feng Liu¹, Xu-Ming Liu^2,* and Ji-Hua Liu^1,3,*

¹ Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China

² School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China

³ State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China

Molecules 2018, 23(9), 2397; https://doi.org/10.3390/molecules23092397 - 19 Sep 2018

Cited by 11 | Viewed by 6172

Abstract

The interaction between proprotein convertase subtilisin/kexin type 9 (PCSK9) and the low-density lipoprotein receptor (LDLR) is a promising target for the treatment of hyperc-holesterolemia. In this study, a new method based on competitive affinity and tag detection was developed, which aimed to evaluate [...] Read more.

The interaction between proprotein convertase subtilisin/kexin type 9 (PCSK9) and the low-density lipoprotein receptor (LDLR) is a promising target for the treatment of hyperc-holesterolemia. In this study, a new method based on competitive affinity and tag detection was developed, which aimed to evaluate potent natural inhibitors preventing the interaction of PCSK9/LDLR directly. Herein, natural compounds with efficacy in the treatment of hypercholesterolemia were chosen to investigate their inhibitory activities on the PCSK9/LDLR interaction. Two of them, polydatin (1) and tetrahydroxydiphenylethylene-2-O-glucoside (2), were identified as potential inhibitors for the PCSK9/LDLR interaction and were proven to prevent PCSK9-mediated LDLR degradation in HepG2 cells. The results suggested that this strategy could be applied for evaluating potential bioactive compounds inhibiting the interaction of PCSK9/LDLR and this strategy could accelerate the discovery of new drug candidates for the treatment of PCSK9-mediated hypercholesterolemia. Full article

(This article belongs to the Special Issue Natural Products in Prevention and Treatment of Metabolic Syndrome)

▼ Show Figures

Figure 1

12 pages, 1755 KiB

Open AccessArticle

Quality Analysis of American Ginseng Cultivated in Heilongjiang Using UPLC-ESI⁻-MRM-MS with Chemometric Methods

by Yong-Gang Xia, Yan Song, Jun Liang, Xin-Dong Guo, Bing-You Yang and Hai-Xue Kuang^*

Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, China

Molecules 2018, 23(9), 2396; https://doi.org/10.3390/molecules23092396 - 19 Sep 2018

Cited by 24 | Viewed by 4969

Abstract

American ginseng (Panax quinquefolium) has long been cultivated in China for the function food and medicine. Here, ultra-high performance liquid chromatography was coupled with electrospray ionization and triple quadrupole mass spectrometry (UPLC-ESI⁻-TQ-MS) for simultaneous detection of 22 ginsenosides in [...] Read more.

American ginseng (Panax quinquefolium) has long been cultivated in China for the function food and medicine. Here, ultra-high performance liquid chromatography was coupled with electrospray ionization and triple quadrupole mass spectrometry (UPLC-ESI⁻-TQ-MS) for simultaneous detection of 22 ginsenosides in American ginseng cultivated in Mudanjiang district of Heilongjiang. The extraction conditions also were optimized by a Box Behnken design experiment. The optimized result was 31.8 mL/g as ratio of liquid to raw materials, 20.3 min of extraction time, and 235.0 W of extraction powers. The quantitative MS parameters for these 22 compounds were rapidly optimized by single factor experiments employing UPLC-ESI⁻-multiple reaction monitoring or multiple ion monitoring (MRM/MIM) scans. Furthermore, the established UPLC-ESI⁻-MRM-MS method showed good linear relationships (R² > 0.99), repeatability (RSD < 3.86%), precision (RSD < 2.74%), and recovery (94–104%). This method determined 22 bioactive ginsenosides in different parts of the plant (main roots, hairy roots, rhizomes, leaves, and stems) and growth years (one year to four years) of P. quinquefolium. The highest total content of the 22 analytes was in the hairy roots (1.3 × 10⁵ µg/g) followed by rhizomes (7.1 × 10⁴ µg/g), main roots (6.5 × 10⁴ µg/g), leaves (4.2 × 10⁴ µg/g), and stems (2.4 × 10⁴ µg/g). Finally, chemometric methods, hierarchical clustering analysis (HCA) and partial least squares discrimination analysis (PLS-DA), were successfully used to classify and differentiate American ginseng attributed to different growth years. The proposed UPLC-ESI⁻-MRM-MS coupled with HCA and PLS-DA methods was elucidated to be a simple and reliable method for quality evaluation of American ginseng. Full article

▼ Show Figures

Figure 1

13 pages, 1765 KiB

Open AccessArticle

Determination of Total Polysaccharides and Total Flavonoids in Chrysanthemum morifolium Using Near-Infrared Hyperspectral Imaging and Multivariate Analysis

by Juan He¹, Lidan Chen², Bingquan Chu^3,* and Chu Zhang^4,5,*

¹ Key Laboratory of Research and Development of Chinese Medicine of Zhejiang Province, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310007, China

² College of Automobile Technology, Zhejiang Technical Institute of Economics, Hangzhou 310018, China

³ School of Biological and Chemical Engineering, Zhejiang University of Science and Technology, Hangzhou 310023, China

⁴ College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, China

⁵ Key Laboratory of Spectroscopy Sensing, Ministry of Agriculture, Hangzhou 310058, China

Molecules 2018, 23(9), 2395; https://doi.org/10.3390/molecules23092395 - 19 Sep 2018

Cited by 66 | Viewed by 6826

Abstract

The rapid and nondestructive determination of active compositions in Chrysanthemum morifolium (Hangbaiju) is of great value for producers and consumers. Hyperspectral imaging as a rapid and nondestructive technique was used to determine total polysaccharides and total flavonoids content in Chrysanthemum morifolium. Hyperspectral [...] Read more.

The rapid and nondestructive determination of active compositions in Chrysanthemum morifolium (Hangbaiju) is of great value for producers and consumers. Hyperspectral imaging as a rapid and nondestructive technique was used to determine total polysaccharides and total flavonoids content in Chrysanthemum morifolium. Hyperspectral images of different sizes of Chrysanthemum morifolium flowers were acquired. Pixel-wise spectra within all samples were preprocessed by wavelet transform (WT) followed by standard normal variate (SNV). Partial least squares (PLS) and least squares-support vector machine (LS-SVM) were used to build prediction models using sample average spectra calculated by preprocessed pixel-wise spectra. The LS-SVM model performed better than the PLS models, with the determination of the coefficient of calibration (R²c) and prediction (R²p) being over 0.90 and the residual predictive deviation (RPD) being over 3 for total polysaccharides and total flavonoids content prediction. Prediction maps of total polysaccharides and total flavonoids content in Chrysanthemum morifolium flowers were successfully obtained by LS-SVM models, which exhibited the best performances. The overall results showed that hyperspectral imaging was a promising technique for the rapid and accurate determination of active ingredients in Chrysanthemum morifolium, indicating the great potential to develop an online system for the quality determination of Chrysanthemum morifolium. Full article

(This article belongs to the Special Issue Application of Spectroscopic Sensors in Life Science and Analytical Chemistry)

▼ Show Figures

Figure 1

13 pages, 704 KiB

Open AccessArticle

The Effect of Ultrasound, Oxygen and Sunlight on the Stability of (−)-Epigallocatechin Gallate

by Jiajun Zeng^1,†, Huanhua Xu^2,3,†, Yu Cai¹, Yan Xuan¹, Jia Liu¹, Yue Gao^2,* and Qingxian Luan^1,*

¹ Department of Periodontology, Peking University School of Stomatology, Beijing 100081, China

² Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China

³ College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China

^† These authors contributed equally to this work.

Molecules 2018, 23(9), 2394; https://doi.org/10.3390/molecules23092394 - 18 Sep 2018

Cited by 14 | Viewed by 4494

Abstract

(−)-Epigallocatechin gallate (EGCG), is the main catechin found in green tea, and has several beneficial effects. This study investigated the stability of EGCG aqueous solution under different stored and ultrasonic conditions to determine whether it can be used with an ultrasonic dental scaler [...] Read more.

(−)-Epigallocatechin gallate (EGCG), is the main catechin found in green tea, and has several beneficial effects. This study investigated the stability of EGCG aqueous solution under different stored and ultrasonic conditions to determine whether it can be used with an ultrasonic dental scaler to treat periodontal infection. Four concentrations (0.05, 0.1, 0.15, 2 mg/mL) of EGCG aqueous solution were prepared and stored under four different conditions (A: Exposed to neither sunlight nor air, B: Exposed to sunlight, but not air, C: Not exposed to sunlight, but air, D: Exposed to sunlight and air) for two days. The degradation rate of EGCG was measured by high performance liquid chromatography (HPLC). On the other hand, an ultrasonic dental scaler was used to atomize the EGCG solution under four different conditions (a: Exposed to neither air nor sunlight, b: Not exposed to air, but sunlight, c: Not exposed to sunlight, but air, d: Exposed to air and sunlight), the degradation of EGCG was measured by HPLC. We found that the stability of EGCG was concentration-dependent in water at room temperature. Both sunlight and oxygen influenced the stability of EGCG, and oxygen had a more pronounced effect on stability of EGCG than sunlight. The most important conclusion was that the ultrasound may accelerate the degradation of EGCG due to the presence of oxygen and sunlight, but not because of the ultrasonic vibration. Thus, EGCG aqueous solution has the potential to be used through an ultrasonic dental scaler to treat periodontal infection in the future. Full article

▼ Show Figures

Figure 1

14 pages, 2246 KiB

Open AccessArticle

Actinofuranones D-I from a Lichen-Associated Actinomycetes, Streptomyces gramineus, and Their Anti-Inflammatory Effects

by Jian Ma¹, Bixuan Cao¹, Chengbin Liu², Peipei Guan¹, Yu Mu¹, Yi Jiang^2,*, Li Han^1,* and Xueshi Huang¹

¹ Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China

² Yunnan Institute of Microbiology, School of Life Science, Yunnan University, Kunming 650091, China

Molecules 2018, 23(9), 2393; https://doi.org/10.3390/molecules23092393 - 18 Sep 2018

Cited by 16 | Viewed by 4617

Abstract

Six new metabolites, actinofuranones D-I (compounds 1–6), were isolated together with three known compounds—JBIR-108 (7), E-975 (8), and E-492 (9)—from a fermentation broth of Streptomyces gramineus derived from the lichen Leptogium trichophorum. The [...] Read more.

Six new metabolites, actinofuranones D-I (compounds 1–6), were isolated together with three known compounds—JBIR-108 (7), E-975 (8), and E-492 (9)—from a fermentation broth of Streptomyces gramineus derived from the lichen Leptogium trichophorum. The structures of the new compounds 1–6 were established using comprehensive NMR spectroscopic data analysis, as well as UV, IR, and MS data. The anti-inflammatory activity of these isolated compounds were evaluated by examining their ability to inhibit nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophage cells. Compounds 4, 5, 8, and 9 attenuated the production of NO due to the suppression of the expression of nitric oxide synthase (iNOS) in LPS-induced RAW 264.7 cells. Moreover, 4, 5, 8, and 9 also inhibited LPS-induced release of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). Full article

▼ Show Figures

Graphical abstract

23 pages, 1564 KiB

Open AccessReview

Treatment Strategies for Infected Wounds

by Irina Negut^1,2

, Valentina Grumezescu^1,3 and Alexandru Mihai Grumezescu^3,4,*

¹ National Institute for Lasers, Plasma and Radiation Physics, Magurele RO-77125, Romania

² Faculty of Physics, University of Bucharest, Magurele 077125, Romania

³ Faculty of Applied Chemistry and Materials Science, Politehnica University of Bucharest, Bucharest 011061, Romania

⁴ Research Institute of University of Bucharest, ICUB, Bucharest 050107, Romania

Molecules 2018, 23(9), 2392; https://doi.org/10.3390/molecules23092392 - 18 Sep 2018

Cited by 545 | Viewed by 33281

Abstract

The treatment of skin wounds is a key research domain owing to the important functional and aesthetic role of this tissue. When the skin is impaired, bacteria can soon infiltrate into underlying tissues which can lead to life-threatening infections. Consequently, effective treatments are [...] Read more.

The treatment of skin wounds is a key research domain owing to the important functional and aesthetic role of this tissue. When the skin is impaired, bacteria can soon infiltrate into underlying tissues which can lead to life-threatening infections. Consequently, effective treatments are necessary to deal with such pathological conditions. Recently, wound dressings loaded with antimicrobial agents have emerged as viable options to reduce wound bacterial colonization and infection, in order to improve the healing process. In this paper, we present an overview of the most prominent antibiotic-embedded wound dressings, as well as the limitations of their use. A promising, but still an underrated group of potential antibacterial agents that can be integrated into wound dressings are natural products, especially essential oils. Some of the most commonly used essential oils against multidrug-resistant microorganisms, such as tea tree, St. John’s Wort, lavender and oregano, together with their incorporation into wound dressings are presented. In addition, another natural product that exhibits encouraging antibacterial activity is honey. We highlight recent results of several studies carried out by researchers from different regions of the world on wound dressings impregnated with honey, with a special emphasis on Manuka honey. Finally, we highlight recent advances in using nanoparticles as platforms to increase the effect of pharmaceutical formulations aimed at wound healing. Silver, gold, and zinc nanoparticles alone or functionalized with diverse antimicrobial compounds have been integrated into wound dressings and demonstrated therapeutic effects on wounds. Full article

▼ Show Figures

Figure 1

3 pages, 151 KiB

Open AccessEditorial

Innovative Extraction Techniques and Hyphenated Instrument Configuration for Complex Matrices Analysis

by Marcello Locatelli^1,*

, Simone Carradori^1,*

and Andrei Mocan^2,*

¹ Department of Pharmacy, University “G. d’Annunzio” of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy

² Department of Pharmaceutical Botany, Faculty of Pharmacy, “Iuliu Haţieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania

Molecules 2018, 23(9), 2391; https://doi.org/10.3390/molecules23092391 - 18 Sep 2018

Cited by 1 | Viewed by 3131

Abstract

n/a Full article

(This article belongs to the Special Issue Innovative Extraction Techniques and Hyphenated Instrument Configuration for Complex Matrices Analysis)

17 pages, 2161 KiB

Open AccessArticle

Design, Synthesis and Evaluation of N-pyrazinylbenzamides as Potential Antimycobacterial Agents

by Jan Zitko^1,*

, Alžběta Mindlová¹, Ondřej Valášek¹, Ondřej Jand’ourek¹

, Pavla Paterová², Jiří Janoušek¹

, Klára Konečná¹

and Martin Doležal¹

¹ Faculty of Pharmacy in Hradec Králové, Charles University, Heyrovského 1203, Hradec Králové 500 05, Czech Republic

² Department of Clinical Microbiology, University Hospital, Sokolská 581, Hradec Králové 500 05, Czech Republic

Molecules 2018, 23(9), 2390; https://doi.org/10.3390/molecules23092390 - 18 Sep 2018

Cited by 9 | Viewed by 4515

Abstract

Three series of N-(pyrazin-2-yl)benzamides were designed as retro-amide analogues of previously published N-phenylpyrazine-2-carboxamides with in vitro antimycobacterial activity. The synthesized retro-amides were evaluated for in vitro growth inhibiting activity against Mycobacterium tuberculosis H37Rv (Mtb), three non-tuberculous mycobacterial strains ( [...] Read more.

Three series of N-(pyrazin-2-yl)benzamides were designed as retro-amide analogues of previously published N-phenylpyrazine-2-carboxamides with in vitro antimycobacterial activity. The synthesized retro-amides were evaluated for in vitro growth inhibiting activity against Mycobacterium tuberculosis H37Rv (Mtb), three non-tuberculous mycobacterial strains (M. avium, M. kansasii, M. smegmatis) and selected bacterial and fungal strains of clinical importance. Regarding activity against Mtb, most N-pyrazinylbenzamides (retro-amides) possessed lower or no activity compared to the corresponding N-phenylpyrazine-2-carboxamides with the same substitution pattern. However, the active retro-amides tended to have lower HepG2 cytotoxicity and better selectivity. Derivatives with 5-chloro substitution on the pyrazine ring were generally more active compared to their 6-cloro positional isomers or non-chlorinated analogues. The best antimycobacterial activity against Mtb was found in N-(5-chloropyrazin-2-yl)benzamides with short alkyl (2h: R² = Me; 2i: R² = Et) in position 4 of the benzene ring (MIC = 6.25 and 3.13 µg/mL, respectively, with SI > 10). N-(5-Chloropyrazin-2-yl)benzamides with hydroxy substitution (2b: R² = 2-OH; 2d: R² = 4-OH) on the benzene ring or their acetylated synthetic precursors possessed the broadest spectrum of activity, being active in all three groups of mycobacterial, bacterial and fungal strains. The substantial differences in in silico calculated properties (hydrogen-bond pattern analysis, molecular electrostatic potential, HOMO and LUMO) can justify the differences in biological activities between N-pyrazinylbenzamides and N-phenylpyrazine-2-carboxamides. Full article

▼ Show Figures

Graphical abstract

15 pages, 1940 KiB

Open AccessArticle

Binding Performance of Human Intravenous Immunoglobulin and 20(S)-7-Ethylcamptothecin

by Yong-Chun Liu^1,2,*, Ying-Ying Li^1,2, Xiao-Jun Yao³, Hui-Li Qi^1,2, Xiao-Xia Wei^1,2 and Jian-Ning Liu^1,2

¹ College of Chemistry and Chemical Engineering, Longdong University, Qingyang 745000, China

² Longdong University & FLUOBON Collaborative Innovation Center, Longdong University, Qingyang 745000, China

³ College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China

Molecules 2018, 23(9), 2389; https://doi.org/10.3390/molecules23092389 - 18 Sep 2018

Viewed by 4089

Abstract

A previous study showed that intravenous immunoglobulin (IVIG) could preserve higher levels of biologically active lactone moieties of topotecan, 7-ethyl-10-hydroxycamptothecin (SN-38) and 10-hydroxycamptothecin at physiological pH 7.40. As one of camptothecin analogues (CPTs), the interaction of 7-ethylcamptothecin and IVIG was studied in vitro [...] Read more.

A previous study showed that intravenous immunoglobulin (IVIG) could preserve higher levels of biologically active lactone moieties of topotecan, 7-ethyl-10-hydroxycamptothecin (SN-38) and 10-hydroxycamptothecin at physiological pH 7.40. As one of camptothecin analogues (CPTs), the interaction of 7-ethylcamptothecin and IVIG was studied in vitro in this study. It was shown that the main binding mode of IVIG to 7-ethylcamptothecin was hydrophobic interaction and hydrogen bonding, which is a non-specific and spontaneous interaction. The hydrophobic antigen-binding cavity of IgG would enwrap the drug into a host-guest inclusion complex and prevent hydrolysis of the encapsulated drug, while the drug is adjacent to the chromophores of IgG and may exchange energy with chromophores and quench the fluorescence of the protein. Also, the typical β-sheet structure of IVIG unfolded partially after binding to 7-ethylcamptothecin. Additionally, the binding properties of IVIG and six CPTs with different substituents at A-ring and/or B-ring including camptothecin, topotecan, irinotecan, 10-hydroxycamptothecin, 7-ethylcamptothecin and SN-38 were collected together and compared each other. Synergizing with anti-cancer drugs, IVIG could be used as a transporter protein for 7-ethylcamptothecin and other CPTs, allowing clinicians to devise new treatment protocols for patients. Full article

▼ Show Figures

Figure 1

13 pages, 2093 KiB

Open AccessArticle

Physico-Chemical and Antifungal Properties of a Trypsin Inhibitor from the Roots of Pseudostellaria heterophylla

by Xixi Cai^1,2, Xiaoli Xie², Nanyan Fu¹ and Shaoyun Wang^2,*

¹ The Key Lab of Analysis and Detection Technology for Food Safety of the MOE, College of Chemistry, Fuzhou University, Fuzhou 350108, China

² Institute of Food and Marine Bio-Resources, College of Biological Science and Technology, Fuzhou University, Fuzhou 350108, China

Molecules 2018, 23(9), 2388; https://doi.org/10.3390/molecules23092388 - 18 Sep 2018

Cited by 16 | Viewed by 5184

Abstract

Plant peptidase inhibitors play essential roles in the defense systems of plants. A trypsin inhibitor (PHTI) with a molecular mass of 20.5 kDa was isolated from the fresh roots of the medicinal herb, Pseudostellaria heterophylla. The purification process involved ammonium sulfate precipitation, [...] Read more.

Plant peptidase inhibitors play essential roles in the defense systems of plants. A trypsin inhibitor (PHTI) with a molecular mass of 20.5 kDa was isolated from the fresh roots of the medicinal herb, Pseudostellaria heterophylla. The purification process involved ammonium sulfate precipitation, gel filtration chromatography on Sephadex G50, and ion-exchange chromatography on DEAE 650M. The PHTI contained 3.7% α-helix, 42.1% β-sheets, 21.2% β-turns, and 33% disordered structures, which showed similarity with several Kunitz-type trypsin inhibitors. Inhibition kinetic studies indicated that PHTI was a competitive inhibitor, with a Ki value of 3.01 × 10⁻⁹ M, indicating a high affinity to trypsin. The PHTI exhibited considerable stability over a broad range of pH (2–10) and temperatures (20–70 °C); however, metal ions, including Fe³⁺, Ba²⁺, Mn²⁺, and Al³⁺, could inactivate PHTI to different degrees. Results of fluorescence spectroscopy and circular dichroism showed that Fe³⁺ could bind to TI with an association constant of 2.75 × 10⁵ M⁻¹ to form a 1:1 complex, inducing conformation changes and inactivation of PHTI. In addition, PHTI could inhibit the growth of the phytopathogens, Colletotrichum gloeosporioides and Fusarium oxysporum, through disruption of the cell membrane integrity. The present study extended research on Pseudostellaria heterophylla proteins and makes PHTI an exploitable candidate as an antifungal protein for further investigation. Full article

▼ Show Figures

Figure 1

23 pages, 6873 KiB

Open AccessFeature PaperArticle

d-Amino Acid Pseudopeptides as Potential Amyloid-Beta Aggregation Inhibitors

by Banafsheh Mehrazma, Stanley Opare, Anahit Petoyan and Arvi Rauk^*

Department of Chemistry, University of Calgary; Calgary, AB T2N 1N4, Canada

Molecules 2018, 23(9), 2387; https://doi.org/10.3390/molecules23092387 - 18 Sep 2018

Cited by 11 | Viewed by 4935

Abstract

A causative factor for neurotoxicity associated with Alzheimer’s disease is the aggregation of the amyloid-β (Aβ) peptide into soluble oligomers. Two all d-amino acid pseudo-peptides, SGB1 and SGD1, were designed to stop the aggregation. Molecular dynamics (MD) simulations have been carried out [...] Read more.

A causative factor for neurotoxicity associated with Alzheimer’s disease is the aggregation of the amyloid-β (Aβ) peptide into soluble oligomers. Two all d-amino acid pseudo-peptides, SGB1 and SGD1, were designed to stop the aggregation. Molecular dynamics (MD) simulations have been carried out to study the interaction of the pseudo-peptides with both Aβ_13–23 (the core recognition site of Aβ) and full-length Aβ_1–42. Umbrella sampling MD calculations have been used to estimate the free energy of binding, ∆G, of these peptides to Aβ_13–23. The highest ∆G_binding is found for SGB1. Each of the pseudo-peptides was also docked to Aβ_1–42 and subjected up to seven microseconds of all atom molecular dynamics simulations. The resulting structures lend insight into how the dynamics of Aβ_1–42 are altered by complexation with the pseudo-peptides and confirmed that SGB1 may be a better candidate for developing into a drug to prevent Alzheimer’s disease. Full article

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

▼ Show Figures

Graphical abstract

21 pages, 6179 KiB

Open AccessArticle

Phenolic Compounds in Organic and Aqueous Extracts from Acacia farnesiana Pods Analyzed by ULPS-ESI-Q-oa/TOF-MS. In Vitro Antioxidant Activity and Anti-Inflammatory Response in CD-1 Mice

by Delgadillo Puga Claudia^1,*

, Cuchillo-Hilario Mario¹

, Navarro Ocaña Arturo², Medina-Campos Omar Noel³

, Nieto Camacho Antonio⁴, Ramírez Apan Teresa⁴, López-Tecpoyotl Zenón Gerardo⁵, Díaz Martínez Margarita¹

, Álvarez-Izazaga Marsela Alejandra⁶, Cruz Martínez Yessica Rosalina⁷, Sánchez-Quezada Vanessa⁸, Gómez Francisco Enrique⁹

, Iván Torre-Villalvazo⁹

, Furuzawa Carballeda Janette¹⁰, Camacho-Corona María del Rayo¹¹ and Pedraza-Chaverri José³

¹ Departamento de Nutrición Animal Dr. Fernando Pérez-Gil Romo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), CDMX 14080, Mexico

² Departamento de Alimentos y Biotecnología, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), CDMX 04510, Mexico

³ Facultad de Química, Departamento de Biología, Universidad Nacional Autónoma de México (UNAM), CDMX 04510, Mexico

⁴ Instituto de Química, Universidad Nacional Autónoma de México (UNAM), CDMX 04510, Mexico

⁵ Colegio de Posgraduados en Ciencias Agrícolas, Puebla 72760, Mexico

⁶ Departamento de Nutrición Aplicada y Educación Nutricional, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), CDMX 14080, Mexico

⁷ Facultad de Química, Universidad Nacional Autónoma de México (UNAM), CDMX 04510, Mexico

⁸ Facultad de Química, Universidad Autónoma de Zacatecas, Zacatecas 98500, Mexico

⁹ Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), CDMX 14080, Mexico

¹⁰ Departamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), CDMX 14080, Mexico

¹¹ Facultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, Monterrey 64570, Mexico

Show full affiliation list Hide full affiliation list

Molecules 2018, 23(9), 2386; https://doi.org/10.3390/molecules23092386 - 18 Sep 2018

Cited by 25 | Viewed by 7576

Abstract

Background: Acacia farnesiana (AF) pods have been traditionally used to treat dyspepsia, diarrhea and topically for dermal inflammation. Main objectives: (1) investigate the antioxidant activity and protection against oxidative-induced damage of six extracts from AF pods and (2) their capacity to curb the [...] Read more.

Background: Acacia farnesiana (AF) pods have been traditionally used to treat dyspepsia, diarrhea and topically for dermal inflammation. Main objectives: (1) investigate the antioxidant activity and protection against oxidative-induced damage of six extracts from AF pods and (2) their capacity to curb the inflammation process as well as to down-regulate the pro-inflammatory mediators. Methods: Five organic extracts (chloroformic, hexanic, ketonic, methanolic, methanolic:aqueous and one aqueous extract) were obtained and analyzed by UPLC-ESI-Q-oa/TOF-MS. Antioxidant activity (DPPH•, ORAC and FRAP assays) and lipid peroxidation (TBARS assay) were performed. Assessment of anti-inflammatory properties was made by the ear edema induced model in CD-1 mice and MPO activity assay. Likewise, histological analysis, IL-1β, IL-6, IL-10, TNF-α, COX measurements plus nitrite and immunohistochemistry analysis were carried out. Results: Methyl gallate, gallic acid, galloyl glucose isomer 1, galloyl glucose isomer 2, galloyl glucose isomer 3, digalloyl glucose isomer 1, digalloyl glucose isomer 2, digalloyl glucose isomer 3, digalloyl glucose isomer 4, hydroxytyrosol acetate, quinic acid, and caffeoylmalic acid were identified. Both organic and aqueous extracts displayed antioxidant activity. All extracts exhibited a positive effect on the interleukins, COX and immunohistochemistry assays. Conclusion: All AF pod extracts can be effective as antioxidant and topical anti-inflammatory agents. Full article

(This article belongs to the Section Natural Products Chemistry)

▼ Show Figures

Graphical abstract

22 pages, 5955 KiB

Open AccessArticle

A Comprehensive In Silico Method to Study the QSTR of the Aconitine Alkaloids for Designing Novel Drugs

by Ming-Yang Wang, Jing-Wei Liang, Kamara Mohamed Olounfeh

, Qi Sun, Nan Zhao and Fan-Hao Meng^*

School of Pharmacy, China Medical University, Shenyang 110122, Liaoning, China

Molecules 2018, 23(9), 2385; https://doi.org/10.3390/molecules23092385 - 18 Sep 2018

Cited by 17 | Viewed by 5919

Abstract

A combined in silico method was developed to predict potential protein targets that are involved in cardiotoxicity induced by aconitine alkaloids and to study the quantitative structure–toxicity relationship (QSTR) of these compounds. For the prediction research, a Protein-Protein Interaction (PPI) network was built [...] Read more.

A combined in silico method was developed to predict potential protein targets that are involved in cardiotoxicity induced by aconitine alkaloids and to study the quantitative structure–toxicity relationship (QSTR) of these compounds. For the prediction research, a Protein-Protein Interaction (PPI) network was built from the extraction of useful information about protein interactions connected with aconitine cardiotoxicity, based on nearly a decade of literature and the STRING database. The software Cytoscape and the PharmMapper server were utilized to screen for essential proteins in the constructed network. The Calcium-Calmodulin-Dependent Protein Kinase II alpha (CAMK2A) and gamma (CAMK2G) were identified as potential targets. To obtain a deeper insight on the relationship between the toxicity and the structure of aconitine alkaloids, the present study utilized QSAR models built in Sybyl software that possess internal robustness and external high predictions. The molecular dynamics simulation carried out here have demonstrated that aconitine alkaloids possess binding stability for the receptor CAMK2G. In conclusion, this comprehensive method will serve as a tool for following a structural modification of the aconitine alkaloids and lead to a better insight into the cardiotoxicity induced by the compounds that have similar structures to its derivatives. Full article

(This article belongs to the Special Issue Computational Approaches for Drug Discovery)

▼ Show Figures

Figure 1

15 pages, 1690 KiB

Open AccessReview

Deep Learning in Drug Discovery and Medicine; Scratching the Surface

by Dibyendu Dana^1,†, Satishkumar V. Gadhiya^1,†, Luce G. St. Surin^1,†, David Li¹, Farha Naaz¹, Quaisar Ali¹, Latha Paka¹, Michael A. Yamin¹, Mahesh Narayan², Itzhak D. Goldberg¹ and Prakash Narayan^1,*

¹ Department of Preclinical Research, Angion Biomedica Corporation, Nassau, NY 11553, USA

² Department of Chemistry and Biochemistry, The University of Texas, El Paso, TX 79968, USA

^† These authors contributed equally to this work.

Molecules 2018, 23(9), 2384; https://doi.org/10.3390/molecules23092384 - 18 Sep 2018

Cited by 85 | Viewed by 13654

Abstract

The practice of medicine is ever evolving. Diagnosing disease, which is often the first step in a cure, has seen a sea change from the discerning hands of the neighborhood physician to the use of sophisticated machines to use of information gleaned from [...] Read more.

The practice of medicine is ever evolving. Diagnosing disease, which is often the first step in a cure, has seen a sea change from the discerning hands of the neighborhood physician to the use of sophisticated machines to use of information gleaned from biomarkers obtained by the most minimally invasive of means. The last 100 or so years have borne witness to the enormous success story of allopathy, a practice that found favor over earlier practices of medical purgatory and homeopathy. Nevertheless, failures of this approach coupled with the omics and bioinformatics revolution spurred precision medicine, a platform wherein the molecular profile of an individual patient drives the selection of therapy. Indeed, precision medicine-based therapies that first found their place in oncology are rapidly finding uses in autoimmune, renal and other diseases. More recently a new renaissance that is shaping everyday life is making its way into healthcare. Drug discovery and medicine that started with Ayurveda in India are now benefiting from an altogether different artificial intelligence (AI)—one which is automating the invention of new chemical entities and the mining of large databases in health-privacy-protected vaults. Indeed, disciplines as diverse as language, neurophysiology, chemistry, toxicology, biostatistics, medicine and computing have come together to harness algorithms based on transfer learning and recurrent neural networks to design novel drug candidates, a priori inform on their safety, metabolism and clearance, and engineer their delivery but only on demand, all the while cataloging and comparing omics signatures across traditionally classified diseases to enable basket treatment strategies. This review highlights inroads made and being made in directed-drug design and molecular therapy. Full article

(This article belongs to the Special Issue Directed Drug Design and Molecular Therapy)

▼ Show Figures

Graphical abstract

11 pages, 1342 KiB

Open AccessArticle

Surface Hydrophobicity and Functional Properties of Citric Acid Cross-Linked Whey Protein Isolate: The Impact of pH and Concentration of Citric Acid

by Tong Li, Chunyan Wang, Tianqi Li, Ling Ma, Dongxue Sun, Juncai Hou^* and Zhanmei Jiang^*

Key Laboratory of Dairy Science (Northeast Agricultural University), Ministry of Education, Harbin 150030, China

Molecules 2018, 23(9), 2383; https://doi.org/10.3390/molecules23092383 - 18 Sep 2018

Cited by 70 | Viewed by 10144

Abstract

The effects of citric acid-mediated cross-linking under non-acidic conditions on the surface hydrophobicity, solubility, emulsifying, and foaming properties of whey protein isolate (WPI) were investigated. In this research, citric acid-mediated cross-linking could not only increase the surface hydrophobicity of whey proteins at pH [...] Read more.

The effects of citric acid-mediated cross-linking under non-acidic conditions on the surface hydrophobicity, solubility, emulsifying, and foaming properties of whey protein isolate (WPI) were investigated. In this research, citric acid-mediated cross-linking could not only increase the surface hydrophobicity of whey proteins at pH 7.0 and 8.0, but it also improved its emulsifying and foaming properties. The emulsifying activity and foaming ability of WPI reached a maximum under the condition of 1% citric acid and pH 7.0. However, the solubility of WPI-CA gradually decreased with pH and the content of citric acid increased. Therefore, the cross-linking mediated by citric acid under non-acidic aqueous conditions, markedly altered the surface hydrophobicity and enhanced emulsifying and foaming properties of WPI. Full article

▼ Show Figures

Graphical abstract

17 pages, 5877 KiB

Open AccessReview

Direct Transamidation Reactions: Mechanism and Recent Advances

by Paola Acosta-Guzmán, Alejandra Mateus-Gómez and Diego Gamba-Sánchez^*

Laboratory of Organic Synthesis Bio- and Organocatalysis, Chemistry Department, Universidad de los Andes, Cra. 1 No 18A-12 Q:305, Bogotá 111711, Colombia

Molecules 2018, 23(9), 2382; https://doi.org/10.3390/molecules23092382 - 18 Sep 2018

Cited by 70 | Viewed by 12475

Abstract

Amides are undeniably some of the most important compounds in Nature and the chemical industry, being present in biomolecules, materials, pharmaceuticals and many other substances. Unfortunately, the traditional synthesis of amides suffers from some important drawbacks, principally the use of stoichiometric activators or [...] Read more.

Amides are undeniably some of the most important compounds in Nature and the chemical industry, being present in biomolecules, materials, pharmaceuticals and many other substances. Unfortunately, the traditional synthesis of amides suffers from some important drawbacks, principally the use of stoichiometric activators or the need to use highly reactive carboxylic acid derivatives. In recent years, the transamidation reaction has emerged as a valuable alternative to prepare amides. The reactivity of amides makes their direct reaction with nitrogen nucleophiles difficult; thus, the direct transamidation reaction needs a catalyst in order to activate the amide moiety and to promote the completion of the reaction because equilibrium is established. In this review, we present research on direct transamidation reactions ranging from studies of the mechanism to the recent developments of more applicable and versatile methodologies, emphasizing those reactions involving activation with metal catalysts. Full article

(This article belongs to the Special Issue Amide Bond Activation)

▼ Show Figures

Graphical abstract

7 pages, 359 KiB

Open AccessArticle

Antimycobacterial Activity of Cinnamaldehyde in a Mycobacterium tuberculosis(H37Ra) Model

by Rafal Sawicki^1,*

, Joanna Golus¹, Agata Przekora¹

, Agnieszka Ludwiczuk²

, Elwira Sieniawska²

and Grazyna Ginalska¹

¹ Chair and Department of Biochemistry and Biotechnology, Medical University of Lublin, Chodzki 1, PL-20093 Lublin, Poland

² Medical Plant Unit, Chair and Department of Pharmacognosy, Medical University of Lublin, Chodzki 1, PL-20093 Lublin, Poland

Molecules 2018, 23(9), 2381; https://doi.org/10.3390/molecules23092381 - 18 Sep 2018

Cited by 37 | Viewed by 5652

Abstract

The purpose of the study was to evaluate the antimycobacterial activity and the possible action mode of cinnamon bark essential oil and its main constituent—cinnamaldehyde—against the Mycobacterium tuberculosis ATCC 25177 strain. Cinnamaldehyde was proved to be the main bioactive compound responsible for mycobacterial [...] Read more.

The purpose of the study was to evaluate the antimycobacterial activity and the possible action mode of cinnamon bark essential oil and its main constituent—cinnamaldehyde—against the Mycobacterium tuberculosis ATCC 25177 strain. Cinnamaldehyde was proved to be the main bioactive compound responsible for mycobacterial growth inhibition and bactericidal effects. The antimycobacterial activity of cinnamaldehyde was found to be comparable with that of ethambutol, one of the first-line anti-TB antibiotics. The selectivity index determined using cell culture studies in vitro showed a high biological potential of cinnamaldehyde. In M. tuberculosis cells exposed to cinnamaldehyde the cell membrane stress sensing and envelope preserving system are activated. Overexpression of clgR gene indicates a threat to the stability of the cell membrane and suggests a possible mechanism of action. No synergism was detected with the basic set of antibiotics used in tuberculosis treatment: ethambutol, isoniazid, streptomycin, rifampicin, and ciprofloxacin. Full article

(This article belongs to the Special Issue Natural Active Agents Against Bacteria, Fungi and Parasites)

▼ Show Figures

Figure 1

20 pages, 4514 KiB

Open AccessFeature PaperReview

Affinity Ionic Liquids for Chemoselective Gas Sensing

by Albert Chang¹, Hsin-Yi Li¹, I-Nan Chang² and Yen-Ho Chu^1,*

¹ Department of Chemistry and Biochemistry, National Chung Cheng University, 168 University Road, Minghsiung, Chiayi 62102, Taiwan

² ANT Technology Co., Ltd., 137, Section 1, Fushing South Road, Taipei 10666, Taiwan

Molecules 2018, 23(9), 2380; https://doi.org/10.3390/molecules23092380 - 18 Sep 2018

Cited by 10 | Viewed by 6647

Abstract

Selective gas sensing is of great importance for applications in health, safety, military, industry and environment. Many man-made and naturally occurring volatile organic compounds (VOCs) can harmfully affect human health or cause impairment to the environment. Gas analysis based on different principles has [...] Read more.

Selective gas sensing is of great importance for applications in health, safety, military, industry and environment. Many man-made and naturally occurring volatile organic compounds (VOCs) can harmfully affect human health or cause impairment to the environment. Gas analysis based on different principles has been developed to convert gaseous analytes into readable output signals. However, gas sensors such as metal-oxide semiconductors suffer from high operating temperatures that are impractical and therefore have limited its applications. The cost-effective quartz crystal microbalance (QCM) device represents an excellent platform if sensitive, selective and versatile sensing materials were available. Recent advances in affinity ionic liquids (AILs) have led them to incorporation with QCM to be highly sensitive for real-time detection of target gases at ambient temperature. The tailorable functional groups in AIL structures allow for chemoselective reaction with target analytes for single digit parts-per-billion detection on mass-sensitive QCM. This structural diversity makes AILs promising for the creation of a library of chemical sensor arrays that could be designed to efficiently detect gas mixtures simultaneously as a potential electronic in future. This review first provides brief introduction to some conventional gas sensing technologies and then delivers the latest results on our development of chemoselective AIL-on-QCM methods. Full article

(This article belongs to the Special Issue Ionic Liquids for Chemical and Biochemical Applications)

▼ Show Figures

Graphical abstract

9 pages, 818 KiB

Open AccessArticle

Bioactive Novel Indole Alkaloids and Steroids from Deep Sea-Derived Fungus Aspergillus fumigatus SCSIO 41012

by Salendra Limbadri^1,2, Xiaowei Luo^1,2

, Xiuping Lin¹, Shengrong Liao¹, Junfeng Wang¹

, Xuefeng Zhou¹

, Bin Yang^1,* and Yonghong Liu^1,*

¹ Key Laboratory of Tropical Marine Bio-resources and Ecology/Guangdong Key Laboratory of Marine Materia Medica/Research Center for Marine Microbes, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China

² University of Chinese Academy of Sciences, Beijing 100049, China

Molecules 2018, 23(9), 2379; https://doi.org/10.3390/molecules23092379 - 18 Sep 2018

Cited by 50 | Viewed by 5114

Abstract

Two new alkaloids, fumigatosides E (1) and F (2), and a new natural product, 3, 7-diketo-cephalosporin P₁ (6) along with five known compounds (3–5, 7, 8) were isolated from deep-sea [...] Read more.

Two new alkaloids, fumigatosides E (1) and F (2), and a new natural product, 3, 7-diketo-cephalosporin P₁ (6) along with five known compounds (3–5, 7, 8) were isolated from deep-sea derived fungal Aspergillus fumigatus SCSIO 41012. Their structures were determined by extensive spectroscopic data analysis, including 1D, 2D nuclear magnetic resonance (NMR) and mass spectrometry (MS), and comparison between the calculated and experimental electronic circular dichroism (ECD) spectra. In addition, all compounds were tested for antibacterial and antifungal inhibitory activities. Compound 1 showed significant antifungal activity against Fusarium oxysporum f. sp. momordicae with MIC at 1.56 µg/mL. Compound 4 exhibited significant higher activity against S. aureus (16,339 and 29,213) with MIC values of 1.56 and 0.78 µg/mL, respectively, and compound 2 exhibited significant activity against A. baumanii ATCC 19606 with a MIC value of 6.25 µg/mL. Full article

▼ Show Figures

Figure 1

12 pages, 3478 KiB

Open AccessArticle

Compound Ammonium Glycyrrhizin Protects Hepatocytes from Injury Induced by Lipopolysaccharide/Florfenicol through a Mitochondrial Pathway

by Wenyang Li, Ying Li, Xiangyuan Jiang, Xiaohui Li and Zugong Yu^*

Laboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China

Molecules 2018, 23(9), 2378; https://doi.org/10.3390/molecules23092378 - 17 Sep 2018

Cited by 17 | Viewed by 4159

Abstract

Florfenicol (FFC), a widely used drug for chicken diseases, can aggravate lipopolysaccharide (LPS) damage to the liver. For this condition, natural or synthetic products displaying strong antioxidant capacity are expected to prevent LPS/FFC from inducing liver injury, so in our study, the compound [...] Read more.

Florfenicol (FFC), a widely used drug for chicken diseases, can aggravate lipopolysaccharide (LPS) damage to the liver. For this condition, natural or synthetic products displaying strong antioxidant capacity are expected to prevent LPS/FFC from inducing liver injury, so in our study, the compound ammonium glycyrrhizin (CAG) is used as the protective drug to decrease the injury to liver. The research aims to illustrate the underlying mechanism of combining LPS with FFC-induced liver injury and the protective role of CAG by using primary chicken hepatocytes as an in vitro model. The results show that LPS/FFC induced cell apoptosis and CAG protected hepatocytes from injury. The permeability of the cell membrane is elevated by LPS/FFC, leading to the efflux of enzymes (ALT, AST). Flow cytometry analysis indicates that LPS/FFC treatment increased the apoptosis rate significantly. Furthermore, with the up-regulation of apoptosis genes bax, cytochrome c and the down-regulation of bcl-2, caspase-3 and caspase-9 are activated at the gene level. LPS/FFC-induced mitochondrial damage is accompanied by a significant decrease in mitochondrial membrane potential (MMP) and severe mitochondrial damage. However, CAG improves the situation for the purpose of protecting the liver. In conclusion, it is speculated that LPS/FFC induces severe liver injury through apoptosis and the CAG protects hepatocytes from injury via the mitochondria-mediated apoptosis pathway. Full article

▼ Show Figures

Figure 1

11 pages, 1515 KiB

Open AccessArticle

Crinipellins A and I, Two Diterpenoids from the Basidiomycete Fungus Crinipellis rhizomaticola, as Potential Natural Fungicides

by Jae Woo Han^1,†, Mira Oh^1,2,†, Yu Jeong Lee^1,2, Jaehyuk Choi³

, Gyung Ja Choi^1,2 and Hun Kim^1,2,*

¹ Center for Eco-friendly New Materials, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea

² Department of Green Chemistry and Environmental Biotechnology, University of Science and Technology, Daejeon 34113, Korea

³ Division of Life Sciences, Incheon National University, Incheon 22012, Korea

^† These authors contributed equally to this work.

Molecules 2018, 23(9), 2377; https://doi.org/10.3390/molecules23092377 - 17 Sep 2018

Cited by 26 | Viewed by 5079

Abstract

In the course of screening for microbes with antifungal activity, we found that the culture filtrate of the IUM00035 isolate exhibited strong antifungal activity against Magnaporthe oryzae and Colletotrichum coccodes in planta. Based on the phylogenetic analysis with the ITS region, the [...] Read more.

In the course of screening for microbes with antifungal activity, we found that the culture filtrate of the IUM00035 isolate exhibited strong antifungal activity against Magnaporthe oryzae and Colletotrichum coccodes in planta. Based on the phylogenetic analysis with the ITS region, the IUM00035 isolate was identified as Crinipellis rhizomaticola. To identify antifungal compounds from the C. rhizomaticola IUM00035 isolate, the culture filtrate of the isolate was partitioned with ethyl acetate and n-butanol and, consequently, two active compounds were isolated from the ethyl acetate extract. The chemical structures of the isolated compounds were determined as crinipellin A (1) and a new crinipellin derivative, crinipellin I (2), by NMR spectral analyses and a comparison of their NMR and MS data with those reported in the literature. Crinipellin A (1) exhibited a wide range of antifungal activity in vitro against C. coccodes, M. oryzae, Botrytis cinerea, and Phytophthora infestans (MICs = 1, 8, 31, and 31 µg/mL, respectively). Furthermore, when plants were treated with crinipellin A (1) (500 µg/mL) prior to inoculation with fungal pathogens, crinipellin A (1) exhibited disease control values of 88%, 65%, and 60% compared with non-treatment control against tomato late blight, pepper anthracnose, and wheat leaf rust, respectively. In contrast to crinipellin A (1), crinipellin I (2) showed weak or no activity (MICs > 250 µg/mL). Taken together, our results show that the C. rhizomaticola IUM00035 isolate suppresses the development of plant fungal diseases, in part through the production of crinipellin A (1). Full article

(This article belongs to the Section Natural Products Chemistry)

▼ Show Figures

Figure 1

18 pages, 1665 KiB

Open AccessArticle

Characterization of Cultivar Differences of Blueberry Wines Using GC-QTOF-MS and Metabolic Profiling Methods

by Fang Yuan^1,2,*

, Ke Cheng¹, Jihui Gao¹ and Siyi Pan^1,2

¹ College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China

² Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, China

Molecules 2018, 23(9), 2376; https://doi.org/10.3390/molecules23092376 - 17 Sep 2018

Cited by 27 | Viewed by 5832

Abstract

A non-targeted volatile metabolomic approach based on the gas chromatography-quadrupole time of fight-mass spectrometry (GC-QTOF-MS) coupled with two different sample extraction techniques (solid phase extraction and solid phase microextraction) was developed. Combined mass spectra of blueberry wine samples, which originated from two different [...] Read more.

A non-targeted volatile metabolomic approach based on the gas chromatography-quadrupole time of fight-mass spectrometry (GC-QTOF-MS) coupled with two different sample extraction techniques (solid phase extraction and solid phase microextraction) was developed. Combined mass spectra of blueberry wine samples, which originated from two different cultivars, were subjected to orthogonal partial least squares-discriminant analysis (OPLS-DA). Principal component analysis (PCA) reveals an excellent separation and OPLS-DA highlight metabolic features responsible for the separation. Metabolic features responsible for the observed separation were tentatively assigned to phenylethyl alcohol, cinnamyl alcohol, benzenepropanol, 3-hydroxy-benzenethanol, methyl eugenol, methyl isoeugenol, (E)-asarone, (Z)-asarone, and terpenes. Several of the selected markers enabled a distinction in secondary metabolism to be drawn between two blueberry cultivars. It highlights the metabolomic approaches to find out the influence of blueberry cultivar on a volatile composition in a complex blueberry wine matrix. The distinction in secondary metabolism indicated a possible O-methyltransferases activity difference among the two cultivars. Full article

(This article belongs to the Special Issue Technology for Natural Products Research)

▼ Show Figures

Figure 1

14 pages, 968 KiB

Open AccessArticle

Targeted Neurotransmitters Profiling Identifies Metabolic Signatures in Rat Brain by LC-MS/MS: Application in Insomnia, Depression and Alzheimer’s Disease

by Huarong Xu¹

, Zhenru Wang¹, Lin Zhu¹, Zhenyu Sui^1,2, Wenchuan Bi³, Ran Liu¹, Kaishun Bi¹ and Qing Li^1,*

¹ School of Pharmacy, National and Local Joint Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, Shenyang Pharmaceutical University, 103 Wenhua Rd, Shenyang 110016, China

² China Food and Drug Administration Institute of Executive Development, 16 Xi Zhan Nan Rd, Beijing 100073, China

³ Health Science Center Department of Pharmacy, Shenzhen University, 3688 Nanhai Ave, Shenzhen 518060, China

Molecules 2018, 23(9), 2375; https://doi.org/10.3390/molecules23092375 - 17 Sep 2018

Cited by 50 | Viewed by 9443

Abstract

Epidemiological, cross-sectional, and prospective studies have suggested that insomnia, Alzheimer’s disease (AD) and depression are mutually interacting conditions and frequently co-occur. The monoamine and amino acid neurotransmitter systems in central nervous system were involved in the examination of neurobiological processes of this symptom [...] Read more.

Epidemiological, cross-sectional, and prospective studies have suggested that insomnia, Alzheimer’s disease (AD) and depression are mutually interacting conditions and frequently co-occur. The monoamine and amino acid neurotransmitter systems in central nervous system were involved in the examination of neurobiological processes of this symptom complex. However, few studies have reported systematic and contrastive discussion of different neurotransmitters (NTs) changing in these neurological diseases. Thus, it is necessary to establish a reliable analytical method to monitoring NTs and their metabolite levels in rat brain tissues for elucidating the differences in pathophysiology of these neurological diseases. A rapid, sensitive and reliable LC-MS/MS method was established for simultaneous determination of the NTs and their metabolites, including tryptophan (Trp), tyrosine (Tyr), serotonin (5-HT), 5-hydroxyindolacetic acid (5-HIAA), dopamine (DA), acetylcholine (ACh), norepinephrine (NE), glutamic acid (Glu), and γ-aminobutyric acid (GABA) in rat brain tissues. The mobile phase consisting of methanol and 0.01% formic acid in water was performed on an Inertsil EP C18 column, and the developed method was validated well. Results demonstrated that there were significant differences for 5-HT, DA, NE, Trp, Tyr and ACh between model and control group in all three models, and a Bayes linear discriminant function was established to distinguish these three kinds of nervous system diseases by DA, Tyr and ACh for their significant differences among control and three model groups. It could be an excellent strategy to provide perceptions into the similarity and differentia of mechanisms from the point of NTs’ changing in brain directly and a new method to distinguish insomnia, depression and AD from view of essence. Full article

(This article belongs to the Section Analytical Chemistry)

▼ Show Figures

Figure 1

Journal Menu

Journal Browser

Molecules, Volume 23, Issue 9 (September 2018) – 317 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI