Genkwanin glycosides are major active compounds in Phaleria nisidai extract mediating improved glucose homeostasis by stimulating glucose uptake into adipose tissues.

Natural remedies are used as standalone treatments or complementary to modern medicine to control type 2 diabetes. In Palau, the traditional leaf decoction of Phaleria nisidai (PNe) is selected to treat hyperglycemia and its efficacy has been supported by a small clinical trial. As part of a reverse pharmacology approach, we here investigated the anti-diabetic potential of PNe and its bioactive compounds to alleviate insulin resistance in diet-induced obese, male mice.

Degradation of extracellular polymeric substances shapes microbial community diversity.

Metabolic cross-feeding networks are central to shaping microbial community dynamics in environments ranging from the rhizosphere, gut, and marine carbon cycling. Yet cross-feeding has predominantly been viewed by examining exchanged small metabolites. In contrast, the role of extracellular polymeric substance (EPS)-a complex mixture of proteins, polysaccharides, DNA, and humic-like compounds-in cross-feeding remains poorly understood, mainly due to technical challenges in measuring their secretion relative to small metabolites.

: A trategy to nalyze lant Extracts Taste n epth. Application to the complex taste of (Roxb.) H.Karst.

Analyzing bitterness is challenging because of the diverse range of bitter compounds, the variability in sensory perception, and its complex interaction with other tastes. To address this, we developed an untargeted approach to deconvolute the taste and molecular composition of complex plant extracts. We applied our methodology to an ethanolic extract of (Roxb.

Translating community-wide spectral library into actionable chemical knowledge: a proof of concept with monoterpene indole alkaloids.

With over 3000 representatives, the monoterpene indole alkaloids (MIAs) class is among the most diverse families of plant natural products. The MS/MS spectral space exploration of these complex compounds using chemoinformatic and computational mass spectrometry tools offers a valuable opportunity to extract and share chemical insights from this emblematic family of natural products (NPs). In this work, we first present a substantially updated version of the MIADB, a database now containing 422 MS/MS spectra of MIAs that has been uploaded to the GNPS library versus 172 initial entries.

MIBiG 4.0: advancing biosynthetic gene cluster curation through global collaboration.

Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015.

Untargeted metabolomics analyses to identify a new sweet compound released during post-fermentation maceration of wine.

The sensory quality of a wine is mainly based on its aroma and flavor. Sweetness contributes in the gustatory balance of red wines. The investigation of compounds involved in this flavor was based on empirical observations, such as the increase in wine sweetness during yeast autolysis, concomitant to post-fermentation maceration in red winemaking.

A Sample-Centric and Knowledge-Driven Computational Framework for Natural Products Drug Discovery.

The ENPKG framework organizes large heterogeneous metabolomics data sets as a knowledge graph, offering exciting opportunities for drug discovery and chemodiversity characterization.

microbeMASST: a taxonomically informed mass spectrometry search tool for microbial metabolomics data.

microbeMASST, a taxonomically informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of >60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbe-derived metabolites and relative producers without a priori knowledge will vastly enhance the understanding of microorganisms' role in ecology and human health.

Comparative metabolomic study of fungal foliar endophytes and their long-lived host : a model for exploring the chemodiversity of host-microbe interactions.

Introduction: In contrast to the dynamics observed in plant/pathogen interactions, endophytic fungi have the capacity to establish enduring associations within their hosts, leading to the development of a mutually beneficial relationship that relies on specialized chemical interactions. Research indicates that the presence of endophytic fungi has the ability to significantly modify the chemical makeup of the host organism. Our hypothesis proposes the existence of a reciprocal exchange of chemical signals between plants and fungi, facilitated by specialized chemical processes that could potentially manifest within the tissues of the host.

Metabolomics in Ecology and Bioactive Natural Products Discovery: Challenges and Prospects for a Comprehensive Study of the Specialised Metabolome.

Metabolomics is playing an increasingly prominent role in chemical ecology and in the discovery of bioactive natural products (NPs). The identification of metabolites is a common/central objective in both research fields. NPs have significant biological properties and play roles in multiple chemical-ecological interactions.

Automated Composition Assessment of Natural Extracts: Untargeted Mass Spectrometry-Based Metabolite Profiling Integrating Semiquantitative Detection.

Recent developments in mass spectrometry-based metabolite profiling allow unprecedented qualitative coverage of complex biological extract composition. However, the electrospray ionization used in metabolite profiling generates multiple artifactual signals for a single analyte. This leads to thousands of signals per analysis without satisfactory means of filtering those corresponding to abundant constituents.

A Taxonomically-informed Mass Spectrometry Search Tool for Microbial Metabolomics Data.

MicrobeMASST, a taxonomically-informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of >60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbial-derived metabolites and relative producers, without knowledge, will vastly enhance the understanding of microorganisms' role in ecology and human health.

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.

: A computational tool to discover structural novelty in natural extracts libraries.

Collections of natural extracts hold potential for the discovery of novel natural products with original modes of action. The prioritization of extracts from collections remains challenging due to the lack of a workflow that combines multiple-source information to facilitate the data interpretation. Results from different analytical techniques and literature reports need to be organized, processed, and interpreted to enable optimal decision-making for extracts prioritization.

Unifying the identification of biomedical entities with the Bioregistry.

The standardized identification of biomedical entities is a cornerstone of interoperability, reuse, and data integration in the life sciences. Several registries have been developed to catalog resources maintaining identifiers for biomedical entities such as small molecules, proteins, cell lines, and clinical trials. However, existing registries have struggled to provide sufficient coverage and metadata standards that meet the evolving needs of modern life sciences researchers.

Combining Activity Profiling with Advanced Annotation to Accelerate the Discovery of Natural Products Targeting Oncogenic Signaling in Melanoma.

The discovery of bioactive natural products remains a time-consuming and challenging task. The ability to link high-confidence metabolite annotations in crude extracts with activity would be highly beneficial to the drug discovery process. To address this challenge, HPLC-based activity profiling and advanced UHPLC-HRMS/MS metabolite profiling for annotation were combined to leverage the information obtained from both approaches on a crude extract scaled down to the submilligram level.

The LOTUS initiative for open knowledge management in natural products research.

Contemporary bioinformatic and chemoinformatic capabilities hold promise to reshape knowledge management, analysis and interpretation of data in natural products research. Currently, reliance on a disparate set of non-standardized, insular, and specialized databases presents a series of challenges for data access, both within the discipline and for integration and interoperability between related fields. The fundamental elements of exchange are referenced structure-organism pairs that establish relationships between distinct molecular structures and the living organisms from which they were identified.

Targeted isolation of photoactive pigments from mushrooms yielded a highly potent new photosensitizer: 7,7'-biphyscion.

Pigments of fungi are a fertile ground of inspiration: they spread across various chemical backbones, absorption ranges, and bioactivities. However, basidiomycetes with strikingly colored fruiting bodies have never been explored as agents for photodynamic therapy (PDT), even though known photoactive compound classes (e.g.

Drug Repurposing to Identify a Synergistic High-Order Drug Combination to Treat Sunitinib-Resistant Renal Cell Carcinoma.

Repurposed drugs have been evaluated for the management of clear cell renal cell carcinoma (ccRCC), but only a few have influenced the overall survival of patients with advanced disease. To combine repurposed non-oncology with oncological drugs, we applied our validated phenotypic method, which consisted of a reduced experimental part and data modeling. A synergistic optimized multidrug combination (ODC) was identified to significantly reduce the energy levels in cancer remaining inactive in non-cancerous cells.

Molecular and Functional Analysis of Sunitinib-Resistance Induction in Human Renal Cell Carcinoma Cells.

Resistance in clear cell renal cell carcinoma (ccRCC) against sunitinib is a multifaceted process encompassing numerous molecular aberrations. This induces clinical complications, reducing the treatment success. Understanding these aberrations helps us to select an adapted treatment strategy that surpasses resistance mechanisms, reverting the treatment insensitivity.

Insights on the Structural and Metabolic Resistance of Potato () Cultivars to Tuber Black Dot ().

Black dot is a blemish disease of potato tubers caused by the phytopathogenic fungus . Qualitative resistance (monogenic) that leads to the hypersensitive response has not been reported against black dot, but commercial potato cultivars show different susceptibility levels to the disease, indicating that quantitative resistance (polygenic) mechanisms against this pathogen exist. Cytological studies are essential to decipher pathogen colonization of the plant tissue, and untargeted metabolomics has been shown effective in highlighting resistance-related metabolites in quantitative resistance.

Antiseizure potential of the ancient Greek medicinal plant Helleborus odorus subsp. cyclophyllus and identification of its main active principles.

Ethnopharmacological Relevance: Ethnopharmacological data and ancient texts support the use of black hellebore (Helleborus odorus subsp. cyclophyllus, Ranunculaceae) for the management and treatment of epilepsy in ancient Greece.

Aim Of The Study: A pharmacological investigation of the root methanolic extract (RME) was conducted using the zebrafish epilepsy model to isolate and identify the compounds responsible for a potential antiseizure activity and to provide evidence of its historical use.