Adding value to botanical resources: Metabolic network analysis along with high-resolution bioassays screening and UHPLC-qToF-high-resolution MS/MS profiling detail the pharmacological potential of underexplored Latin-American plants

Healthcare services are challenged by an increased incidence of diseases and a decline in new drugs being brought to market. Thus, there is renewed interest in drug discovery from plants. This paper focused on enhancing the value of a small but diverse botanical resource of 45 Latin-American plant species, mostly from Mexican origin, through untargeted metabolomics, metabolic network analysis and parallel-in-vitro-bioactivity screening. The plant-extract collection was tested for inhibitory activity of human neutrophil elastase (HNE), α-glucosidase and PTP-1B as well as reviewing in detail antifungal and CB₂-agonist activities previously reported for this collection. Through these approaches it was found that only 30 % of plants mentioned in traditional medicine to treat diabetes, had greater than 60 % inhibitory activity against PTP-1B or α-glucosidase and this could be part of their modes of action, while six plant species previously undescribed for antidiabetic use could inhibit these enzymes, with three of these plant species being ornamentals (Cosmos bipinnatus, Cuphea ignea and Clarkia amoena). Biochromatograms from active extracts show that the bioactivity is due to specific fractions/compounds. The results, indicate that parallel-in-vitro-bioactivity screening of plants is a valuable approach that could lead to the expansion of the natural-product chemical space for new therapeutics, even if no previous evidence of their use in traditional medicine exists. Results for HNE, CB₂-agonist and antifungal assays were similar. This study delivers a valuable UHPLC-qToF-HRMS/MS dataset along with bioactivity screens that can serve the natural-products community for future endeavors in exploring the valuable chemical space of Latin-American plants.