Open and reusable annotated mass spectrometry dataset of a chemodiverse collection of 1,600 plant extracts.

As privileged structures, natural products often display potent biological activities. However, the discovery of novel bioactive scaffolds is often hampered by the chemical complexity of the biological matrices they are found in. Large natural extract collections are thus extremely valuable for their chemical novelty potential but also complicated to exploit in the frame of drug-discovery projects. In the end, it is the pure chemical substances that are desired for structural determination purposes and bioactivity evaluation. Researchers interested in the exploration of large and chemodiverse extract collections should thus establish strategies aiming to efficiently tackle such chemical complexity and access these structures. Establishing carefully crafted digital layers documenting the spectral and chemical complexity as well as bioactivity results of natural extracts collections can help prioritize time-consuming but mandatory isolation efforts. In this note, we report the results of our initial exploration of a collection of 1,600 plant extracts in the frame of a drug-discovery effort. After describing the taxonomic coverage of this collection, we present the results of its liquid chromatography high-resolution mass spectrometric profiling and the exploitation of these profiles using computational solutions. The resulting annotated mass spectral dataset and associated chemical and taxonomic metadata are made available to the community, and data reuse cases are proposed. We are currently continuing our exploration of this plant extract collection for drug-discovery purposes (notably looking for novel antitrypanosomatids, anti-infective and prometabolic compounds) and ecometabolomics insights. We believe that such a dataset can be exploited and reused by researchers interested in computational natural products exploration.

Comparison of the Phytochemical Composition of Serenoa repens Extracts by a Multiplexed Metabolomic Approach.

Phytochemical extracts are highly complex chemical mixtures. In the context of an increasing demand for phytopharmaceuticals, assessment of the phytochemical equivalence of extraction procedures is of utmost importance. Compared to routine analytical methods, comprehensive metabolite profiling has pushed forward the concept of phytochemical equivalence. In this study, an untargeted metabolomic approach was used to cross-compare four marketed extracts from Serenoa repens obtained with three different extraction processes: ethanolic, hexanic and sCO2 (supercritical carbon dioxide). Our approach involved a biphasic extraction of native compounds followed by liquid chromatography coupled to a high-resolution mass spectrometry based metabolomic workflow. Our results showed significant differences in the contents of major and minor compounds according to the extraction solvent used. The analyses showed that ethanolic extracts were supplemented in phosphoglycerides and polyphenols, hexanic extracts had higher amounts of free fatty acids and minor compounds, and sCO2 samples contained more glycerides. The discriminant model in this study could predict the extraction solvent used in commercial samples and highlighted the specific biomarkers of each process. This metabolomic survey allowed the authors to assess the phytochemical content of extracts and finished products of S. repens and unequivocally established that sCO2, hexanic and ethanolic extracts are not chemically equivalent and are therefore unlikely to be pharmacologically equivalent.

Trends and patterns of marijuana use in men and women seeking drug treatment / Tendencias y patrones de consumo de mariguana en hombres y mujeres solicitantes de tratamiento

Abstract Introduction Marijuana is the world's most widely used illegal drug. In Mexico, it is the drug of choice for both male and female users of all ages, and there has been a recent increase in its use. Objective To describe drug use trends in people seeking treatment by sex and age range, and to explore different patterns. Method To provide a description of trends and rates of increase for the population attended between 2005 and 2016 and to make a comparative analysis of patterns of use in a sample of 11 595 marijuana users who received treatment in 2016. Results In general, there has been a greater increase in use in the group ages twelve to seventeen. The greatest increase in lifetime use was reported among women in this age range. The greatest increase in marijuana use in the past month was found among women aged eighteen to thirty-five. Women use a greater variety of substances, and a higher number of younger women report using cocaine, methamphetamines, benzodiazepines and hallucinogens than men. Discussion and conclusion Significant increases in marijuana use have been registered among girls under 18 and women in recent years. The differences in trends and patterns of use for men and women are being reduced and reconfigured.

Resumen Introducción La mariguana es la droga de mayor consumo en el mundo. En México, es la droga preferida por ambos sexos y en todos los grupos de edad, y en su consumo ha habido un incremento desde hace varios años. Objetivo Describir las tendencias del uso de mariguana en solicitantes de tratamiento, por sexo y rango de edad, y explorar diferencias en el patrón de consumo, según sexo. Método Se describieron tendencias y tasas de crecimiento en población atendida entre 2005 y 2016 y se realizó un análisis comparativo del patrón de consumo con una muestra de 11 595 usuarios de mariguana recibidos para tratamiento en 2016. Resultados En general, se registran mayores tasas de crecimiento en el grupo de 12 a 17 años. El mayor incremento del uso alguna vez en la vida corresponde a las mujeres de este rango; el del uso en el último mes y como droga de mayor impacto, a las de 18 a 35 años. Las mujeres consumen un mayor número de sustancias. Las de menor edad refieren el uso de cocaína, metanfetaminas, éxtasis, benzodiacepinas y alucinógenos en mayor proporción que los hombres. Discusión y conclusión Los menores de edad y las mujeres tienen un mayor peso en el aumento del uso de mariguana registrado en los últimos años. Las diferencias en las tendencias y el patrón de consumo entre sexos se están reduciendo y reconfigurando.

Constituents of Vigna angularis and their in vitro anti-inflammatory activity.

Nine non-phenolic compounds, including four furanylmethyl glycosides, angularides A-D, one ent-kaurane diterpene glycoside, angularin A, and four triterpenoid saponins, angulasaponins A-D, were isolated from seeds of Vigna angularis, together with eight known compounds. Their structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic analysis as well as chemical methods. Angularin A, angulasaponins A-C, and azukisaponins III and VI showed inhibition of nitric oxide production in LPS-activated RAW264.7 macrophages, with IC50 values ranging from 13µM to 24µM.

Quality assessment of commercial Magnoliae officinalis Cortex by ¹H-NMR-based metabolomics and HPLC methods.

INTRODUCTION: The quality control of Magnoliae officinalis Cortex, a commonly used traditional Chinese medicine, is currently based on the assay of the two active compounds, honokiol and magnolol, by TLC or HPLC. OBJECTIVE: To compare ¹H-NMR-based metabolomics with the HPLC method for controlling the quality of Magnoliae officinalis Cortex. To identify the metabolites contributing to the differences between the samples and to discriminate different medicinal parts and geographic origins of these samples by ¹H-NMR-based metabolomics. METHODOLOGY: ¹H-NMR and several multivariate analysis techniques were applied to analyse the extracts of 18 batches of Magnoliae officinalis Cortex commercial samples, and the contents of honokiol and magnolol in these samples were determined by HPLC. The correlation analysis between the data from ¹H-NMR and HPLC was performed with the mixOmics software based on an unsupervised method. RESULTS: Honokiol and magnolol were the main compounds responsible for the discrimination of samples from different batches, thus proving that the choice of these two compounds as markers for quality assessment by HPLC is relevant. The two sources of Magnoliae officinalis Cortex recorded in the Chinese Pharmacopoeia, Magnolia officinalis and Magnolia officinalis var. biloba, could be differentiated from ¹H-NMR data, but the pattern recognition analysis by PLS-DA was unsuccessful in discriminating samples from various geographical origins. CONCLUSION: The combination of ¹H-NMR that gives a comprehensive profile of the metabolites and HPLC that targets two biomarkers is an efficient means for a better quality control of Magnoliae officinalis Cortex.

Recent analytical approaches in quality control of traditional Chinese medicines--a review.

Traditional Chinese medicines (TCMs) are gaining more and more attention all over the world, due to their specific theory and long historical clinical practice. But the uncontrollable quality is a bottleneck for its modernization and globalization. This paper reviewed the recent analytical methods in the quality control of TCMs, including screening strategies of bioactive markers from TCMs through biochromatographic methods, the traditional chromatographic methods, DNA methods, as well as the spectroscopic methods, including FT-IR, NIR and NMR. The comprehensive methods, such as fingerprint and multi-component quantification are emphasized; hyphenated techniques, like HPLC-MS, GC-MS, CE-MS, LC-NMR, chemometric methods, and combination of chemical and biological methods, such as biofingerprint, metabolic fingerprint are now more and more widely used in TCMs. In a few word, the analysis and quality control of TCMs are moving towards an integrative and comprehensive direction, in order to better address the inherent holistic nature of TCMs.

Meroterpenes from Dichrostachys cinerea inhibit protein farnesyl transferase activity.

Eighteen new meroterpene derivatives, dichrostachines A-R (1-18), have been isolated from the root and stem barks of Dichrostachys cinerea, and their structures determined by spectroscopic means and molecular modeling. From a biosynthetic standpoint these compounds arise from a Diels-Alder reaction between a labdane diene of the raimonol type and a flavonoid B-ring-derived quinone. The hypothesis was tested by the partial synthesis of similar compounds by simply mixing methyl communate and a synthetic flavonoid quinone. The hemisynthetic compounds were shown by NMR to have configurations different from those of the natural products, thus allowing a refinement of the biosynthesis hypothesis. Most of the compounds were assayed for their ability to inhibit the enzyme protein farnesyl transferase. The most active compounds exhibited IC50 and cytotoxicity values in the 1 microM range.

N-caffeoylphenalkylamide derivatives as bacterial efflux pump inhibitors.

As part of an ongoing project to identify plant natural products as efflux pump inhibitors (EPIs), bioassay-guided fractionation of the methanolic extract of Mirabilis jalapa Linn. (Nyctaginaceae) led to the isolation of an active polyphenolic amide: N-trans-feruloyl 4'-O-methyldopamine. This compound showed moderate activity as an EPI against multidrug-resistant (MDR) Staphylococcus aureus overexpressing the multidrug efflux transporter NorA, causing an 8-fold reduction of norfloxacin MIC at 292 microM (100 microg/mL). This prompted us to synthesize derivatives in order to provide structure-activity relationships and to access more potent inhibitors. Among the synthetic compounds, some were more active than the natural compound and N-trans-3,4-O-dimethylcaffeoyl tryptamine showed potentiation of norfloxacin in MDR S. aureus comparable to that of the standard reserpine.

Acylphloroglucinol derivatives from Mahurea palustris.

Five new acylphloroglucinol derivatives, mahureones A-E (1, 3-6), have been isolated from the leaves of Mahurea palustris, and their structures determined by spectroscopic means. During the isolation process, several byproducts (7-9) were formed by reaction of one of the isoprenyl side chains with TFA, water, and acetonitrile. All the compounds were assayed for their ability to inhibit human DNA polymerase beta. The most active compounds, mahureones A (1) and D (5), exhibited IC50 values in the 10 microM range.

Bioactive flavonoids of Tanacetum parthenium revisited.

Bio-guided fractionation of an extract from Tanacetum parthenium showing activity as mitotic blocker allowed the isolation and identification of santin 3, jaceidin 2 and centaureidin 1. The latter two closely related flavonols, which, to the best of our knowledge, are isolated here together for the first time, form a mixture difficult to resolve and which is probably the reason for the confusion in the literature regarding their occurrence. Centaureidin 1 had an IC50 of 1 microM while jaceidin 2 and santin 3 were 200 times less active.

Antioxidant flavonoids and phenolic acids from leaves of Leea guineense G Don (Leeaceae).

From leaves of Leea guineense (Leeaceae) three hydrophilic flavonoids were isolated and identified as quercetin-3'-sulphate-3-O-alpha-L-rhamnopyranoside, quercetin-3,3'-disulphate and a new flavonoid sulphate, quercetin-3,3',4'-trisulphate, together with kaempferol, quercetin, quercitrin, mearnsitrin, gallic acid and ethyl gallate. The structures were established by spectroscopic analysis (UV, MS, (1)H-NMR, (13)C-NMR and 2D-NMR). Their antioxidant effect on free radical scavenging was evaluated in the DPPH assay.