It has long been known that coumarins (γ-pyrones) and xanthones (α-pyrones) together form a large class of naturally occurring compounds exhibiting a wide range of biological activities....
Systemic vitamin E metabolites have been proposed as signaling molecules, but their physiological role is unknown. Here we show, by library screening of potential human vitamin E metabolites, that ...long-chain ω-carboxylates are potent allosteric inhibitors of 5-lipoxygenase, a key enzyme in the biosynthesis of chemoattractant and vasoactive leukotrienes. 13-((2R)-6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)-2,6,10-trimethyltridecanoic acid (α-T-13'-COOH) can be synthesized from α-tocopherol in a human liver-on-chip, and is detected in human and mouse plasma at concentrations (8-49 nM) that inhibit 5-lipoxygenase in human leukocytes. α-T-13'-COOH accumulates in immune cells and inflamed murine exudates, selectively inhibits the biosynthesis of 5-lipoxygenase-derived lipid mediators in vitro and in vivo, and efficiently suppresses inflammation and bronchial hyper-reactivity in mouse models of peritonitis and asthma. Together, our data suggest that the immune regulatory and anti-inflammatory functions of α-tocopherol depend on its endogenous metabolite α-T-13'-COOH, potentially through inhibiting 5-lipoxygenase in immune cells.
Whether chemists or biologists, researchers dealing with metabolomics require tools to decipher complex mixtures. As a part of metabolomics and initially dedicated to identifying bioactive natural ...products, dereplication aims at reducing the usual time-consuming process of known compounds isolation. Mass spectrometry and nuclear magnetic resonance are the most commonly reported analytical tools during dereplication analysis. Though it has low sensitivity, 13C NMR has many advantages for such a study. Notably, it is nonspecific allowing simultaneous high-resolution analysis of any organic compounds including stereoisomers. Since NMR spectrometers nowadays provide useful data sets in a reasonable time frame, we have embarked upon writing software dedicated to 13C NMR dereplication. The present study describes the development of a freely distributed algorithm, namely MixONat and its ability to help researchers decipher complex mixtures. Based on Python 3.5, MixONat analyses a {1H}-13C NMR spectrum optionally combined with DEPT-135 and 90 datato distinguish carbon types (i.e., CH3, CH2, CH, and C)as well as a MW filtering. The software requires predicted or experimental carbon chemical shifts (δc) databases and displays results that can be refined based on user interactions. As a proof of concept, this 13C NMR dereplication strategy was evaluated on mixtures of increasing complexity and exhibiting pharmaceutical (poppy alkaloids), nutritional (rosemary extracts) or cosmetics (mangosteen peel extract) applications. Associated results were compared with other methods commonly used for dereplication. MixONat gave coherent results that rapidly oriented the user toward the correct structural types of secondary metabolites, allowing the user to distinguish between structurally close natural products, including stereoisomers.
is the causal agent of
leaf blight (ALB) in carrot (
) crops around the world. However, to date,
has received limited attention in its production of phytotoxic metabolites. In this investigation, the ...bioassay-guided isolation of the extract from liquid cultures of
resulted in the isolation of two metabolites identified as
-acetylorcinol (
) and
-hydroxybenzoic acid (
), based on their spectroscopic data and results from chemical correlation reactions. Testing of both metabolites in different assays showed an important phytotoxic activity for
-hydroxybenzoic acid (
) when tested in the leaf-spot assay on parsley (
), in the leaf infiltration assay on tobacco (
) and marigold (
), and in the immersion assay on parsley and parsnip (
) leaves. Quantification of the two metabolites in the crude extract of
kept at different times showed that
-hydroxybenzoic acid (
) is one of the first metabolites to be synthesized by the pathogen, suggesting that this salicylic acid derivative could play an important role in the pathogenicity of the fungus.
Alkaloids represent a major group of natural products (NPs), derived from highly diverse organisms. These structurally varied specialized metabolites are widely used for medicinal purposes and also ...known as toxic contaminants in agriculture and dietary supplements. While the detection of alkaloids is generally facilitated by GC- or LC-MS, these techniques do require considerable efforts in sample preparation and method optimization. Bypassing these limitations and also reducing experimental time, matrix-free laser desorption ionization (LDI) and related methods may provide an interesting alternative. As many alkaloids show close structural similarities to matrices used in matrix-assisted laser desorption ionization (MALDI), they should ionize upon simple laser irradiation without matrix support. With this in mind, the current work presents a systematic evaluation of LDI properties of a wide range of structurally diverse alkaloids. Facilitating a direct comparison between LDI and ESI-MS fragmentation, all tested compounds were further studied by electrospray ionization (ESI). Moreover, crude plant extracts of
Atropa belladonna
,
Cinchona succirubra
, and
Colchicum autumnale
were analyzed by LDI in order to evaluate direct alkaloid detection and dereplication from complex mixtures. Finally, dose-dependent evaluation of MALDI and LDI detection using an extract of
Rosmarinus officinalis
spiked with atropine, colchicine, or quinine was conducted. Overall, present results suggest that LDI provides a versatile analytical tool for analyzing structurally diverse alkaloids as single compounds and from complex mixtures. It may further serve various potential applications ranging from quality control to the screening for toxic compounds as well as the build up of MS databases.
Graphical abstract
Mycosporine-like amino acids (MAAs) are water-soluble metabolites, reported to exhibit strong UV-absorbing properties. They have been found in a wide range of marine organisms, especially those that ...are exposed to extreme levels of sunlight, to protect them against solar radiation. In the present study, the absolute configuration of 14 mycosporine-like-amino acids was determined by combining the results of electronic circular dichroism (ECD) experiments and that of advanced Marfey's method using LC-MS. The crystal structure of a shinorine hydrate was determined from single crystal X-ray diffraction data and its absolute configuration was established from anomalous-dispersion effects. Furthermore, the anti-aging and wound-healing properties of these metabolites were evaluated in three different assays namely the inhibition of collagenase, inhibition of advanced glycation end products (AGEs) and wound healing assay (scratch assay).
Advanced glycation end-products (AGEs) are involved in the pathogenesis of numerous diseases. Among them, cellular accumulation of AGEs contributes to vascular complications in diabetes. Besides ...using drugs to lower blood sugar, a balanced diet and the intake of herbal products potentially limiting AGE formation could be considered beneficial for patients' health. The current paper presents a simple and cheap high-throughput screening (HTS) assay based on AGE fluorescence and suitable for plant extract screening. We have already implemented an HTS assay based on vesperlysines-like fluorescing AGEs quickly (24 h) formed from BSA and ribose under physiological conditions. However, interference was noted when fluorescent compounds and/or complex mixtures were tested. To overcome these problems and apply this HTS assay to plant extracts, we developed a technique for systematic quantification of both vesperlysines (λ(exc) 370 nm; λ(em) 440 nm) and pentosidine-like (λ(exc) 335 nm; λ(em) 385 nm) AGEs. In a batch of medicinal and food plant extracts, hits were selected as soon as fluorescence decreased under a fixed threshold for at least one wavelength. Hits revealed during this study appeared to contain well-known and powerful anti-AGE substances, thus demonstrating the suitability of this assay for screening crude extracts (0.1 mg/mL). Finally, quercetin was found to be a more powerful reference compound than aminoguanidine in such assay.
Summary
This study aimed to compare the protective effect of two geographically distinct propolis against the formation of advanced glycation end products (AGEs). The polyphenol content of propolis ...extracts (EEPs) was analysed using HPLC‐DAD‐MS profiling and evaluated for their protective effects against pentosidine‐like AGEs. Dicarbonyl trapping capacities of major EEP compounds were determined using a methylglyoxal scavenging in vitro assay. Both propolis samples were characterised with high levels of pinobanksin derivatives exhibiting strong anti‐AGE properties. EEPs reduced AGE formation more effectively than well‐known natural AGE inhibitors such as quercetin or chlorogenic acid. Individual evaluations of the five major compounds in EEPs showed that flavonoids strongly inhibit the formation of AGEs by trapping dicarbonyl intermediates, whereas compounds such as caffeic acid derivatives only act as antioxidant agents. Propolis is thus a promising candidate for the prevention and control of AGE‐related chronic diseases.
Propolis collected from two distinct areas of Iran were evaluated for their effects on pentosidine‐like AGEs and free radicals. Major propolis phenolic components were screened for their ability to trap reactive dicarbonyl species such as methylglyoxal, an intermediate component in AGEs formation. HPLC‐DAD followed by MS analyses revealed that the majority of components showing strong anti‐AGEs properties used the anti‐dicarbonyl pathway through the formation of MGO adducts, while prenyl caffeate would rather use the antioxidant pathway.
Essential oils of aromatic plants represent an alternative to classical pest control with synthetic chemicals. They are especially promising for the alternative control of stored product pest ...insects. Here, we tested behavioral and electrophysiological responses of the stored product pest Tribolium confusum, to the essential oil of a Brazilian indigenous plant, Varronia globosa, collected in the Caatinga ecosystem. We analyzed the essential oil by GC-MS, tested the effects of the entire oil and its major components on the behavior of individual beetles in a four-way olfactometer, and investigated responses to these stimuli in electroantennogram recordings (EAG). We could identify 25 constituents in the essential oil of V. globosa, with anethole, caryophyllene and spathulenole as main components. The oil and its main component anethole had repellent effects already at low doses, whereas caryophyllene had only a repellent effect at a high dose. In addition, the essential oil abolished the attractive effect of the T. confusum aggregation pheromone. EAG recordings revealed dose-dependent responses to the individual components and increasing responses to the blend and even more to the entire oil. Our study reveals the potential of anethole and the essential oil of V. globosa in the management of stored product pests.
Introduction
Xanthones are metabolites with a variety of biological properties. The Clusiaceae family, which until recently included the genus Calophyllum, is recognised for its production of ...monohydroxylated and polyhydroxylated xanthones. Presently, C. brasiliense is the only Calophyllum spp. known to occur in the Yucatan peninsula.
Objective
To use a combination of traditional phytochemical methods and carbon‐13 nuclear magnetic resonance (13C‐NMR) dereplication analysis to identify xanthones in the stem bark of C. brasiliense.
Material and methods
Initial fractionation and purification of the stem bark extract of C. brasiliense produced macluraxanthone (1). Additional xanthones, together with chromanones and terpenoids, were identified using 13C‐NMR dereplication analysis in different semipurified fractions obtained from the low and medium polarity fractions of the stem bark extract of C. brasiliense.
Results
Initial identification of macluraxanthone (1) was confirmed by 13C‐NMR dereplication analysis; additionally, 13C‐NMR dereplication analysis allowed the identification of a number of monohydroxylated and polyhydroxylated xanthones, together with chromanones and terpenoids.
Conclusion
This study confirms C. brasiliense as a rich source of xanthones and the 13C‐NMR dereplication analysis as a suitable method to quickly identify the presence of different families of secondary metabolites in semipurified fractions.
Calophyllum brasiliense is recognised for its production of xanthones having different biological activities. In this investigation, a combination of phytochemical methods and carbon‐13 nuclear magnetic resonance (13C‐NMR) dereplication analysis allowed the identification of a number of monohydroxylated and polyhydroxylated xanthones, together with chromanones and terpenoids, from the stem bark extract of the plant.
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