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Applications of Metabolomics within Natural Products Chemistry

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Metabolites".

Deadline for manuscript submissions: closed (30 July 2015) | Viewed by 63149

Special Issue Editor

1. CCB-Center for Chemistry and Biomedicine, Institute of Pharmacy/Pharmacognosy, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria
2. Department of Pharmacognosy and Natural Product Chemistry, Faculty of Pharmacy, University of Athens, Panepistimioupoli-Zografou, 15771 Athens, Greece
Interests: pharmacognosy; natural products chemistry; natural extracts characterization; dereplication; profiling; metabolomics

Special Issue Information

Dear Colleagues,

Natural products (NPs), low molecular weight compounds originated from nature, possess a predominant position among prevailing chemical entities. NPs are characterized by an unmet and untapped structural diversity and uniqueness; they are more complex in respect to decoration patterns and dispersal of functionalities while they cover an extended chemical space compared to other chemical agents. This particular nature is the positive consequence of the evolutionary process, which furnished NPs with competitive advantages, enabling them to interact with biological targets for the benefit of every living organism. The NPs privileged features have led to their broad utilization in medicine, pharmacology, and biology, where NPs still comprise a considerable driving force in drug discovery and inspiration for chemists. Additionally, NPs find several applications in many other fields and areas of research and development, such as in nutrition, agriculture, cosmetics, biotechnology, food chemistry, environmental chemistry, and botany, to name just a few.

Despite the proven track record of NPs, a declined interest of both the scientific community and private sector, such as big pharma, is evident. Some factors are strongly related to the endogenous problems of NP’s discovery process, which is traditionally laborious, costly, and time consuming, while the emergence of other concepts and approaches, such as combinatorial chemistry and high throughput screening (HTS) also guided toward this direction. Nevertheless, in the last few years, NP’s discovery and, generally, natural products chemistry and pharmacognosy are experiencing a breakthrough. The entire process is gradually becoming technology-driven. New techniques and approaches have been introduced and incorporated, especially in the areas of natural product’s isolation, identification, and analytics, altering traditional concepts and perceptions. One of these approaches, which was rapidly embraced by scientists, and generally the experts in the fiend of NPs, is metabolomics.

Metabolomics, taking advantage of technological advances and state-of-the-art analytical techniques, as well as the power of bioinformatics, comprise a new approach promising a holistic view of the metabolome of every biological system, aiming to a more comprehensive and multifaceted view in Systems Biology. Metabolomics, have been rapidly employed for the analysis of natural materials in a more holistic way, finding multiple applications and uses. According to the scope of the study, metabolic fingerprinting and metabolic profiling are applied in a targeted or non-targeted manner seeking to respond to a, usually, given biological or chemical question. Such approaches or NPs metabolomics, have been incorporated for chemotaxonomic studies, quality, safety and toxicity assessment, quality control, as well as for the exploration of physiological and biochemical effects in different environmental and stress conditions. Additionally, metabolomics have been employed for the investigation of the physiological development of different organisms and drug discovery. It is, indeed, worth mention that the number of metabolomics and metabolomics-related studies is gradually elevated in the area of NPs and new applications constantly appear. The integration and harmonization of metabolomics with traditional and contemporary methods and approaches could effectively facilitate the discovery and chemistry of NPs, which is expected to be seen.

Dr. Maria Halabalaki
Guest Editor

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Keywords

  • NPs metabolomics and
  • plants, marine organisms and microorganisms
  • study design and workflows
  • sample preparation protocols and related issues
  • targeted and non-targeted approaches
  • data processing and data interpretation
  • identification of biomarkers and databases
  • chemotaxonomy, abiotic stress and fluxomics
  • quality assurance and quality control
  • dereplication

Published Papers (8 papers)

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Research

2089 KiB  
Article
The Application of Vibrational Spectroscopy Techniques in the Qualitative Assessment of Material Traded as Ginseng
by Maxleene Sandasi, Ilze Vermaak, Weiyang Chen and Alvaro Viljoen
Molecules 2016, 21(4), 472; https://doi.org/10.3390/molecules21040472 - 12 Apr 2016
Cited by 12 | Viewed by 5786
Abstract
The name “ginseng” is collectively used to describe several plant species, including Panax ginseng (Asian/Oriental ginseng), P. quinquefolius (American ginseng), P. pseudoginseng (Pseudoginseng) and Eleutherococcus senticosus (Siberian ginseng), each with different applications in traditional medicine practices. The use of a generic name may [...] Read more.
The name “ginseng” is collectively used to describe several plant species, including Panax ginseng (Asian/Oriental ginseng), P. quinquefolius (American ginseng), P. pseudoginseng (Pseudoginseng) and Eleutherococcus senticosus (Siberian ginseng), each with different applications in traditional medicine practices. The use of a generic name may lead to the interchangeable use or substitution of raw materials which poses quality control challenges. Quality control methods such as vibrational spectroscopy-based techniques are here proposed as fast, non-destructive methods for the distinction of four ginseng species and the identification of raw materials in commercial ginseng products. Certified ginseng reference material and commercial products were analysed using hyperspectral imaging (HSI), mid-infrared (MIR) and near-infrared (NIR) spectroscopy. Principal component analysis (PCA) and (orthogonal) partial least squares discriminant analysis models (OPLS-DA) were developed using multivariate analysis software. UHPLC-MS was used to analyse methanol extracts of the reference raw materials and commercial products. The holistic analysis of ginseng raw materials revealed distinct chemical differences using HSI, MIR and NIR. For all methods, Eleutherococcus senticosus displayed the greatest variation from the three Panax species that displayed closer chemical similarity. Good discrimination models with high R2X and Q2 cum vales were developed. These models predicted that the majority of products contained either /P. ginseng or P. quinquefolius. Vibrational spectroscopy and HSI techniques in tandem with multivariate data analysis tools provide useful alternative methods in the authentication of ginseng raw materials and commercial products in a fast, easy, cost-effective and non-destructive manner. Full article
(This article belongs to the Special Issue Applications of Metabolomics within Natural Products Chemistry)
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1991 KiB  
Article
Production of Fusaric Acid by Fusarium spp. in Pure Culture and in Solid Medium Co-Cultures
by Nadine Bohni, Valérie Hofstetter, Katia Gindro, Bart Buyck, Olivier Schumpp, Samuel Bertrand, Michel Monod and Jean-Luc Wolfender
Molecules 2016, 21(3), 370; https://doi.org/10.3390/molecules21030370 - 18 Mar 2016
Cited by 22 | Viewed by 9295
Abstract
The ability of fungi isolated from nails of patients suffering from onychomycosis to induce de novo production of bioactive compounds in co-culture was examined. Comparison between the metabolite profiles produced by Sarocladium strictum, by Fusarium oxysporum, and by these two species [...] Read more.
The ability of fungi isolated from nails of patients suffering from onychomycosis to induce de novo production of bioactive compounds in co-culture was examined. Comparison between the metabolite profiles produced by Sarocladium strictum, by Fusarium oxysporum, and by these two species in co-culture revealed de novo induction of fusaric acid based on HRMS. Structure confirmation of this toxin, using sensitive microflow NMR, required only three 9-cm Petri dishes of fungal culture. A targeted metabolomics study based on UHPLC-HRMS confirmed that the production of fusaric acid was strain-dependent. Furthermore, the detected toxin levels suggested that onychomycosis-associated fungal strains of the F. oxysporum and F. fujikuroi species complexes are much more frequently producing fusaric acid, and in higher amount, than strains of the F. solani species complex. Fusarium strains producing no significant amounts of this compound in pure culture, were shown to de novo produce that compound when grown in co-culture. The role of fusaric acid in fungal virulence and defense is discussed. Full article
(This article belongs to the Special Issue Applications of Metabolomics within Natural Products Chemistry)
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1540 KiB  
Article
Statistical Correlations between HPLC Activity-Based Profiling Results and NMR/MS Microfraction Data to Deconvolute Bioactive Compounds in Mixtures
by Samuel Bertrand, Antonio Azzollini, Andreas Nievergelt, Julien Boccard, Serge Rudaz, Muriel Cuendet and Jean-Luc Wolfender
Molecules 2016, 21(3), 259; https://doi.org/10.3390/molecules21030259 - 24 Feb 2016
Cited by 12 | Viewed by 6546
Abstract
Recent approaches in natural product (NP) research are leading toward the discovery of bioactive chemical entities at the microgram level. In comparison to classical large scale bioassay-guided fractionation, the use of LC-MS metabolite profiling in combination with microfractionation for both bioactivity profiling and [...] Read more.
Recent approaches in natural product (NP) research are leading toward the discovery of bioactive chemical entities at the microgram level. In comparison to classical large scale bioassay-guided fractionation, the use of LC-MS metabolite profiling in combination with microfractionation for both bioactivity profiling and NMR analysis, allows the identification of bioactive compounds at a very early stage. In that context, this study aims to assess the potential of statistic correlation analysis to enable unambiguous identification of features related to bioactive compounds in mixtures, without the need for complete isolation. For that purpose, a mixture of NPs was microfractionated by rapid small-scale semi-preparative HPLC for proof-of-concept. UHPLC-ESI-TOFMS profiles, micro-flow CapNMR spectra and a cancer chemopreventive assay carried out on every microfraction were analysed by statistical correlations. Full article
(This article belongs to the Special Issue Applications of Metabolomics within Natural Products Chemistry)
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3847 KiB  
Article
Multicomponent Analysis of the Differential Induction of Secondary Metabolite Profiles in Fungal Endophytes
by Víctor González-Menéndez, Mercedes Pérez-Bonilla, Ignacio Pérez-Victoria, Jesús Martín, Francisca Muñoz, Fernando Reyes, José R. Tormo and Olga Genilloud
Molecules 2016, 21(2), 234; https://doi.org/10.3390/molecules21020234 - 18 Feb 2016
Cited by 44 | Viewed by 9354
Abstract
Small molecule histone deacetylase (HDAC) and DNA methyltransferase (DNMT) inhibitors are commonly used to perturb the production of fungal metabolites leading to the induction of the expression of silent biosynthetic pathways. Several reports have described the variable effects observed in natural product profiles [...] Read more.
Small molecule histone deacetylase (HDAC) and DNA methyltransferase (DNMT) inhibitors are commonly used to perturb the production of fungal metabolites leading to the induction of the expression of silent biosynthetic pathways. Several reports have described the variable effects observed in natural product profiles in fungi treated with HDAC and DNMT inhibitors, such as enhanced chemical diversity and/or the induction of new molecules previously unknown to be produced by the strain. Fungal endophytes are known to produce a wide variety of secondary metabolites (SMs) involved in their adaptation and survival within higher plants. The plant-microbe interaction may influence the expression of some biosynthetic pathways, otherwise cryptic in these fungi when grown in vitro. The aim of this study was to setup a systematic approach to evaluate and identify the possible effects of HDAC and DNMT inhibitors on the metabolic profiles of wild type fungal endophytes, including the chemical identification and characterization of the most significant SMs induced by these epigenetic modifiers. Full article
(This article belongs to the Special Issue Applications of Metabolomics within Natural Products Chemistry)
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2153 KiB  
Article
Antiproliferative and Apoptotic Activity of Chamaecyparis obtusa Leaf Extract against the HCT116 Human Colorectal Cancer Cell Line and Investigation of the Bioactive Compound by Gas Chromatography-Mass Spectrometry-Based Metabolomics
by Hye-Youn Kim, Seul-Gi Lee, Taek-Joo Oh, Sa Rang Lim, So-Hyun Kim, Hong Jin Lee, Young-Suk Kim and Hyung-Kyoon Choi
Molecules 2015, 20(10), 18066-18082; https://doi.org/10.3390/molecules201018066 - 02 Oct 2015
Cited by 17 | Viewed by 7190
Abstract
Chamaecyparis obtusa (CO) belongs to the Cupressaceae family, and it is found widely distributed in Japan and Korea. In this study, the anti-proliferative activities of the methanol and water extracts of CO leaves against a human colorectal cancer cell line (HCT116) were investigated. [...] Read more.
Chamaecyparis obtusa (CO) belongs to the Cupressaceae family, and it is found widely distributed in Japan and Korea. In this study, the anti-proliferative activities of the methanol and water extracts of CO leaves against a human colorectal cancer cell line (HCT116) were investigated. The methanol extract of CO leaves, at a concentration of 1.25 µg/mL, exhibited anti-proliferative activity against HCT116 cells, while displaying no cytotoxicity against Chang liver cells. Comparative global metabolite profiling was performed using gas chromatography-mass spectrometry coupled with multivariate statistical analysis, and it was revealed that anthricin was the major compound contributing to the anti-proliferative activity. The activation of c-Jun N-terminal kinases played a key role in the apoptotic effect of the methanol extract of CO leaves in HCT116 human colon cancer cells. These results suggest that the methanol extract and anthricin derived from CO leaves might be useful in the development of medicines with anti-colorectal cancer activity. Full article
(This article belongs to the Special Issue Applications of Metabolomics within Natural Products Chemistry)
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1224 KiB  
Article
Fast Identification of Radical Scavengers from Securigera varia by Combining 13C-NMR-Based Dereplication to Bioactivity-Guided Fractionation
by Pacôme Sientzoff, Jane Hubert, Coralie Janin, Laurence Voutquenne-Nazabadioko, Jean-Hugues Renault, Jean-Marc Nuzillard, Dominique Harakat and Abdulmagid Alabdul Magid
Molecules 2015, 20(8), 14970-14984; https://doi.org/10.3390/molecules200814970 - 14 Aug 2015
Cited by 17 | Viewed by 7037
Abstract
Securigera varia (Fabaceae) is a common herbaceous perennial plant widely growing in Europe and Asia and purposely established for erosion control, roadside planting, and soil rehabilitation. The aim of this study was to determine the radical scavenging activity of a crude methanol extract [...] Read more.
Securigera varia (Fabaceae) is a common herbaceous perennial plant widely growing in Europe and Asia and purposely established for erosion control, roadside planting, and soil rehabilitation. The aim of this study was to determine the radical scavenging activity of a crude methanol extract of S. varia aerial parts by using the free radical DPPH (1,1-diphenyl-2-picrylhydrazyl) and to rapidly identify the compounds involved in this activity. The crude extract was initially separated in five fractions on Diaion HP20 resin and the most active part was fractionated by Centrifugal Partition Extraction (CPE). Known compounds were directly identified by a 13C-NMR-based dereplication method. Semi-preparative high performance liquid chromatography purification experiments were further performed to identify unknown or minor active compounds. As a result, one new (13) and twelve known flavonoid glycosides together with three nitropropanoylglucopyranoses were isolated, including astragalin (1), kaempferol-3-O-(6-O-acetyl)-β-D-glucopyranoside (2), kaempferol-3,4′-di-O-β-D-glucopyranoside (3), trifolin (4), isoquercitrin (5), hyperoside (6), isovitexin (7), isoorientin (8), isovitexin 4′-O-β-D-glucopyranoside (9), apigenin 7-O-β-D-glucuronopyranoside (10), luteolin 7-O-β-D-glucuronopyranoside (11), apigenin 7-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucuronopyranoside (12), apigenin 7-O-β-D-glucopyranosyl-(1→2)-β-D-glucuronopyranoside (13), 6-O-(3-nitropropanoyl)-β-D-glucopyranoside (14), coronillin (16) and coronarian (15). 120 mg of the most active compound isoorientin against the free radical DPPH was recovered by CPE with an HPLC purity of 99%. Full article
(This article belongs to the Special Issue Applications of Metabolomics within Natural Products Chemistry)
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2260 KiB  
Article
Comparison of Fruits of Forsythia suspensa at Two Different Maturation Stages by NMR-Based Metabolomics
by Jinping Jia, Fusheng Zhang, Zhenyu Li, Xuemei Qin and Liwei Zhang
Molecules 2015, 20(6), 10065-10081; https://doi.org/10.3390/molecules200610065 - 29 May 2015
Cited by 38 | Viewed by 8025
Abstract
Forsythiae Fructus (FF), the dried fruit of Forsythia suspensa, has been widely used as a heat-clearing and detoxifying herbal medicine in China. Green FF (GF) and ripe FF (RF) are fruits of Forsythia suspensa at different maturity stages collected about a month [...] Read more.
Forsythiae Fructus (FF), the dried fruit of Forsythia suspensa, has been widely used as a heat-clearing and detoxifying herbal medicine in China. Green FF (GF) and ripe FF (RF) are fruits of Forsythia suspensa at different maturity stages collected about a month apart. FF undergoes a complex series of physical and biochemical changes during fruit ripening. However, the clinical uses of GF and RF have not been distinguished to date. In order to comprehensively compare the chemical compositions of GF and RF, NMR-based metabolomics coupled with HPLC and UV spectrophotometry methods were adopted in this study. Furthermore, the in vitro antioxidant and antibacterial activities of 50% methanol extracts of GF and RF were also evaluated. A total of 27 metabolites were identified based on NMR data, and eight of them were found to be different between the GF and RF groups. The GF group contained higher levels of forsythoside A, forsythoside C, cornoside, rutin, phillyrin and gallic acid and lower levels of rengyol and β-glucose compared with the RF group. The antioxidant activity of GF was higher than that of RF, but no significant difference was observed between the antibacterial activities of GF and RF. Given our results showing their distinct chemical compositions, we propose that NMR-based metabolic profiling can be used to discriminate between GF and RF. Differences in the chemical and biological activities of GF and RF, as well as their clinical efficacies in traditional Chinese medicine should be systematically investigated in future studies. Full article
(This article belongs to the Special Issue Applications of Metabolomics within Natural Products Chemistry)
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1628 KiB  
Article
A 1H-NMR-Based Metabonomic Study on the Anti-Depressive Effect of the Total Alkaloid of Corydalis Rhizoma
by Hongwei Wu, Peng Wang, Mengting Liu, Liying Tang, Jing Fang, Ye Zhao, Yi Zhang, Defeng Li, Haiyu Xu and Hongjun Yang
Molecules 2015, 20(6), 10047-10064; https://doi.org/10.3390/molecules200610047 - 29 May 2015
Cited by 45 | Viewed by 8789
Abstract
Corydalis Rhizoma, named YuanHu in China, is the dried tuber of Corydalis yanhusuo W.T. Wang which is used in Traditional Chinese Medicine for pain relief and blood activation. Previous pharmacological studies showed that apart from analgesics, the alkaloids from YuanHu may be useful [...] Read more.
Corydalis Rhizoma, named YuanHu in China, is the dried tuber of Corydalis yanhusuo W.T. Wang which is used in Traditional Chinese Medicine for pain relief and blood activation. Previous pharmacological studies showed that apart from analgesics, the alkaloids from YuanHu may be useful in the therapy of depression by acting on the GABA, dopamine and benzodiazepine receptors. In this study, the antidepressive effect of the total alkaloid of YuanHu (YHTA) was investigated in a chronic unpredictable mild stress (CUMS) rat model using 1H-NMR-based metabonomics. Plasma metabolic profiles were analyzed and multivariate data analysis was applied to discover the metabolic biomarkers in CUMS rats. Thirteen biomarkers of CUMS-introduced depression were identified, which are myo-inositol, glycerol, glycine, creatine, glutamine, glutamate, β-glucose, α-glucose, acetoacetate, 3-hydroxybutyrate, leucine and unsaturated lipids (L7, L9). Moreover, a metabolic network of the potential biomarkers in plasma perturbed by CUMS was detected. After YHTA treatment, clear separation between the model group and YHTA-treated group was achieved. The levels of all the abnormal metabolites mentioned above showed a tendency of restoration to normal levels. The results demonstrated the therapeutic efficacy of YHTA against depression and suggested that NMR-based metabolomics can provide a simple and easy tool for the evaluation of herbal therapeutics. Full article
(This article belongs to the Special Issue Applications of Metabolomics within Natural Products Chemistry)
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