The development of new drugs will certainly benefit from an ever improving knowledge of the living beings chemistry. However, identification of drugable molecules within the immense biodiversity of ...forests, soils or oceans still requires considerable investments in technical equipments, time and human resources. An important part of this process is the quick identification of known substances in order to concentrate the efforts on the discovery of new ones. A range of “dereplication” procedures are currently emerging to meet this challenge as key strategies to improve the performance of natural product screening programs. Initially defined in 1990 as “a process of quickly identifying known chemotypes”, dereplication is today a not so univocal concept and has evolved over the last years in different ways. The present review covers all dereplication-related sudies in natural product research from 1990 to 2014. Its writing brought to light five distinct dereplication workflows that can be characterized by the nature of starting materials, by the selected analytical technique, and above all by the final objective. Dereplication can be used as an untargeted workflow for the rapid identification of the major compounds whatever their chemical class in a single sample or for the acceleration of bioactivity-guided fractionation procedures. In other cases dereplication is fully integrated in metabolomic studies for the untargeted chemical profiling of natural extract collections or for the targeted identification of a predetermined class of metabolites. Finally a quite distinct dereplication approach mainly based on gene-sequence analyses is frequently used for the taxonomic identification of microbial strains.
A large variety of phytochemicals commonly consumed with the human diet, influence health and may contribute to the prevention of diseases. However, it is still difficult to make nutritional ...recommendations for these bioactive compounds. Current studies of phytochemicals are generally focused on specific compounds and their effects on a limited number of markers. New approaches are needed to take into account both the diversity of phytochemicals found in the diet and the complexity of their biological effects. Recent progress in high-throughput analytical technologies and in bioinformatics now allows the simultaneous analysis of the hundreds or more metabolites constituting the metabolome in urine or plasma. These analyses give complex metabolic fingerprints characteristic of a given phenotype. The exploitation of the wealth of information it contains, in randomized controlled trials and cohort studies, should lead to the discovery of new markers of intake for phytochemicals and new markers of effects. In this paper, we briefly review the current methods used to evaluate intake of phytochemicals and their effects on health. We then describe the applications of metabolomics in this field. Recent metabolomics studies illustrate the potential of such a global approach to explore the complex relationships linking phytochemical intake and metabolism and health.
is a cosmopolitan protozoan parasite which affects approximately 30% of the population worldwide. The drugs currently used against toxoplasmosis are few in number and show several limitations, such ...as drug intolerance, poor bioavailability, or drug resistance mechanism developed by the parasite. Thus, it is important to find new compounds able to inhibit parasite invasion or proliferation. In this study, the 400 compounds of the open-access Pathogen Box, provided by the Medicines for Malaria Venture (MMV) foundation, were screened for their anti-
activity. A preliminary
screening performed over 72 h by an enzyme-linked immunosorbent assay (ELISA) revealed 15 interesting compounds that were effective against
at 1 μM. Their cytotoxicity was estimated on Vero cells, and their 50% inhibitory concentrations (IC
) were further calculated. As a result, eight anti-
compounds with an IC
of less than 2 μM and a selectivity index (SI) value of greater than 4 were identified. The most active was MMV675968, showing an IC
of 0.02 μM and a selectivity index value equal to 275. Two other compounds, MMV689480 and MMV687807, also showed a good activity against
, with IC
s of 0.10 μM (SI of 86.6) and 0.15 μM (SI of 11.3), respectively. Structure-activity relationships for the eight selected compounds also were discussed on the basis of fingerprinting similarity measurements using the Tanimoto method. The anti-
compounds highlighted here represent potential candidates for the development of new drugs that could be used against toxoplasmosis.
Because of their highly complex metabolite profile, the chemical characterization of bioactive natural extracts usually requires time-consuming multistep purification procedures to achieve the ...structural elucidation of pure individual metabolites. The aim of the present work was to develop a dereplication strategy for the identification of natural metabolites directly within mixtures. Exploiting the polarity range of metabolites, the principle was to rapidly fractionate a multigram quantity of a crude extract by centrifugal partition extraction (CPE). The obtained fractions of simplified chemical composition were subsequently analyzed by 13C NMR. After automatic collection and alignment of 13C signals across spectra, hierarchical clustering analysis (HCA) was performed for pattern recognition. As a result, strong correlations between 13C signals of a single structure within the mixtures of the fraction series were visualized as chemical shift clusters. Each cluster was finally assigned to a molecular structure with the help of a locally built 13C NMR chemical shift database. The proof of principle of this strategy was achieved on a simple model mixture of commercially available plant secondary metabolites and then applied to a bark extract of the African tree Anogeissus leiocarpus Guill. & Perr. (Combretaceae). Starting from 5 g of this genuine extract, the fraction series was generated by CPE in only 95 min. 13C NMR analyses of all fractions followed by pattern recognition of 13C chemical shifts resulted in the unambiguous identification of seven major compounds, namely, sericoside, trachelosperogenin E, ellagic acid, an epimer mixture of (+)-gallocatechin and (−)-epigallocatechin, 3,3′-di-O-methylellagic acid 4′-O-xylopyranoside, and 3,4,3′-tri-O-methylflavellagic acid 4′-O-glucopyranoside.
Coffee silverskin (CS) is the thin epidermis covering and protecting the coffee bean and it represents the main by-product of the coffee roasting process. CS has recently gained attention due to its ...high content in bioactive molecules and the growing interest in valuable reutilization of waste products. Drawing inspiration from its biological function, here its potential in cosmetic applications was investigated. CS was recovered from one of the largest coffee roasters located in Switzerland and processed through supercritical CO
extraction, thereby generating coffee silverskin extract. Chemical profiling of this extract revealed the presence of potent molecules, among which cafestol and kahweol fatty acid esters, as well as acylglycerols, β-sitosterol and caffeine. The CS extract was then dissolved in organic shea butter, yielding the cosmetic active ingredient SLVR'Coffee™. In vitro gene expression studies performed on keratinocytes showed an upregulation of genes involved in oxidative stress responses and skin-barrier functionality upon treatment with the coffee silverskin extract. In vivo, our active protected the skin against Sodium Lauryl Sulfate (SLS)-induced irritation and accelerated its recovery. Furthermore, this active extract improved measured as well as perceived skin hydration in female volunteers, making it an innovative, bioinspired ingredient that comforts the skin and benefits the environment.
Elucidation of the relationships between genotype, diet, and health requires accurate dietary assessment. In intervention and epidemiological studies, dietary assessment usually relies on ...questionnaires, which are susceptible to recall bias. An alternative approach is to quantify biomarkers of intake in biofluids, but few such markers have been validated so far. Here we describe the use of metabolomics for the discovery of nutritional biomarkers, using citrus fruits as a case study. Three study designs were compared. Urinary metabolomes were profiled for volunteers that had (a) consumed an acute dose of orange or grapefruit juice, (b) consumed orange juice regularly for one month, and (c) reported high or low consumption of citrus products for a large cohort study. Some signals were found to reflect citrus consumption in all three studies. Proline betaine and flavanone glucuronides were identified as known biomarkers, but various other biomarkers were revealed. Further, many signals that increased after citrus intake in the acute study were not sensitive enough to discriminate high and low citrus consumers in the cohort study. We propose that urine profiling of cohort subjects stratified by consumption is an effective strategy for discovery of sensitive biomarkers of consumption for a wide range of foods.
In the present study, resveratrol and various oligomeric derivatives were obtained from a 14 L bioreactor culture of elicited grapevine cell suspensions (Vitis labrusca L.). The crude ethyl acetate ...stilbene extract obtained from the culture medium was fractionated by centrifugal partition chromatography (CPC) using a gradient elution method and the major stilbenes contained in the fractions were subsequently identified by using a
C-NMR-based dereplication procedure and further 2D NMR analyses including HSQC, HMBC, and COSY. Beside δ-viniferin (2), leachianol F (4) and G (4'), four stilbenes (resveratrol (1), ε-viniferin (5), pallidol (3) and a newly characterized dimer (6)) were recovered as pure compounds in sufficient amounts to allow assessment of their biological activity on the cell growth of three different cell lines, including two human skin malignant melanoma cancer cell lines (HT-144 and SKMEL-28) and a healthy human dermal fibroblast HDF line. Among the dimers obtained in this study, the newly characterized resveratrol dimer (6) has never been described in nature and its biological potential was evaluated here for the first time. ε-viniferin as well as dimer (6) showed IC
values on the three tested cell lines lower than the ones exerted by resveratrol and pallidol. However, activities of the first two compounds were significantly decreased in the presence of fetal bovine serum although that of resveratrol and pallidol was not. The differential tumor activity exerted by resveratrol on healthy and cancer lines was also discussed.
Filipendula ulmaria, commonly known as meadowsweet, is a wild herbaceous flowering plant that is widely distributed in Europe. A range of salicylic acid derivatives and flavonol glycosides have been ...previously associated with the antirheumatic and diuretic properties of F. ulmaria. In the present work, a hydroalcoholic extract from F. ulmaria aerial parts was extensively profiled using an efficient NMR-based dereplication strategy. The approach involves the fractionation of the crude extract by centrifugal partition chromatography (CPC), 13C NMR analysis of the fractions, 2D-cluster mapping of the entire NMR dataset, and, finally, structure elucidation using a natural metabolite database, validated by 2D NMR data interpretation and liquid chromatography coupled with mass spectrometry. The chemodiversity of the aerial parts was extensive, with 28 compounds unambiguously identified, spanning various biosynthetic classes. The F. ulmaria extract and CPC fractions were screened for their potential to enhance skin epidermal barrier function and skin renewal properties using in vitro assays performed on Normal Human Epidermal Keratinocytes. Fractions containing quercetin, kaempferol glycosides, ursolic acid, pomolic acid, naringenin, β-sitosterol, and Tellimagrandins I and II were found to upregulate genes related to skin barrier function, epidermal renewal, and stress responses. This research is significant as it could provide a natural solution for improving hydration and skin renewal properties.
The fungus growing termite species
(
) is used in nutrition and traditional medicine in the Republic of Benin for the treatment of infectious and inflammatory diseases. Previous findings demonstrated ...evidence of anti-inflammatory and spasmolytic properties of
. The aim of the present study was to evaluate the antimicrobial potential of different extracts of
samples and determine the chemical profile of an ethanolic
extract. Chemical profiling was conducted using centrifugal partition chromatography and
C-NMR, followed by MALDI-TOF MS. Major identified compounds include hydroquinone (HQ), methylhydroquinone (MHQ), 3,4-dihydroxyphenethyl glycol (DHPG),
-acetyldopamine (NADA) and niacinamide. The fatty acid mixture of the extract was mainly composed of linoleic and oleic acid and highlights the nutritional purpose of
. Using the Kirby-Bauer disc diffusion and broth microdilution assay, an antibacterial activity of
samples was observed against various clinical strains with a highest growth inhibition of
. In addition, HQ and MHQ as well as fractions containing DHPG, niacinamide and NADA inhibited
growth. The reported antimicrobial activity of
and identified active substances provide a rationale for the traditional medicinal use of
.
Soy germ is a remarkable source of bioactive phytochemicals offering an interesting alternative as starting ingredient for fermented food. This work aimed to determine whether lactic acid bacteria ...fermentation of soy germ induces changes on its phytochemical composition. The antioxidant properties of fermented soy germ samples periodically taken during the fermentation process were evaluated and correlated with the concentration and structural modifications of isoflavones, saponins, phytosterols and tocopherols. Fermented soy germ extracts exhibited a higher inhibition effect against the superoxide anion radical, and lesser but significant ferric-reducing and DPPH radical scavenging effects compared with raw soy germ. By comparison to the traditional whole seed-based products, soy germ exhibits higher levels of isoflavones, saponins, phytosterols and tocopherols. All these phytochemicals contributed to the antioxidant capacity of soy germ and were conserved under lactic acid bacteria fermentation.
PDF
