Editorial: Plant metabolites in drug discovery: the prism perspective between plant phylogeny, chemical composition, and medicinal efficacy, volume IV

the sustainable discovery of pharmaceutical resources amidst global biodiversity threats. The emergence of pharmacophylomics-integrating phylogenomics, transcriptomics, and metabolomics-has empowered researchers to decode biosynthetic pathways, predict therapeutic utilities, and accelerate natural product R&D (Hao et al., 2023(Hao et al., , 2024a;;Singh et al., 2022). This editorial synthesizes key insights from Volume IV and outlines future trajectories for the field, emphasizing how pharmacophylogeny and pharmacophylomics bridge ethnomedicine, conservation, and modern drug development.The eight studies in this volume span phylogenomics, metabolomics, and network pharmacology across diverse taxa, reinforcing pharmacophylogeny's predictive power and exemplifying the power of pharmacophylomics to resolve the triad of phylogeny-chemistry-efficacy. For example, the metabolic diversity in Paris spp. (Melanthiaceae) is astonishing (Sun et al., 2025); utilizing UHPLC-Q-TOF MS, researchers mapped metabolomic divergence across five newly identified Paris species.Terpenoids and steroidal saponins dominated chemoprofiles, with novel metabolitecompounds linked to anticancer and anti-inflammatory activities. This work underscores how phylogeny-guided metabolomics identifies taxon-specific bioactives and expands medicinal resources for phylogenetically related species. Similarly, palmatine's multi-target ethnopharmacology is also prominent (Shi et al., 2025). A comprehensive review highlighted palmatine-an isoquinoline alkaloid abundant in Berberis and Coptis-as a multi-target agent against inflammation, infection, Phylogenomic-guided resource substitution (e.g., palmatine-rich alternatives) mitigates overharvesting threats (Hao et al., 2023;Alum, 2025). Pharmacophylomics also refines ethnopharmacology, e.g., Fabaceae "aphrodisiac-fertility hot nodes" with neurological applications (e.g., Mimosa pudica L., Fabaceae) showed 62% incidence of estrogenic flavonoids-validating cross-therapeutic targeting for neuro-selective phytoestrogens (Thaweepanyaporn et al., 2025).As a cross-cutting imperative, AI-driven predictive modeling can be highlighted; neural networks can be trained on LOTUS database (Thaweepanyaporn et al., 2025) and phylogenomicchemotaxonomic matrices to forecast novel bioactive lineages (e.g., neuroprotective phytoestrogens in Fabaceae). Policy integration is also imperative; Nagoya Protocol compliance can be aligned with phytochemical resource mapping, ensuring equitable benefit-sharing for indigenous knowledge holders (e.g., Thai ethnomedicines; Thongyim et al., 2025).Future work must prioritize three synergistic dimensions to advance pharmacophylogeny and pharmacophylomics. First, horizontal expansion into uncharted taxonomic and metabolic spaces, e.g., including neglected lineages (e.g., algae, lichens) and fermentation-modified phytometabolites (Luo et al., 2024), can be a priority. For instance, the microbial-phytochemical interactions of algae and via synthetic biology and multi-omics convergence, phylogenomics can be coupled with synthetic biology to engineer high-yield metabolitecompounds (e.g., terpenoids, alkaloids). In pathway engineering, phylogenomics-predicted biosynthetic routes (e.g., palmatine in Ranunculales; Hao et al., 2022;Shi et al., 2025) can be leveraged to optimize high-value compoundmetabolites (e.g., CYP19A1-activated astragaloside IV in Kunxinning Granules; Wang et al., 2025). In nanophytocomplex delivery, targeted carriers (Kumar et al. 2025) can be developed for venomneutralizing phytoconstituents (e.g., terpenoid-flavonoid complexes in snakebite plants), enhancing bioavailability and reducing ecological harvest pressure. Last, in light of climate resilience through metabolic plasticity engineering, metabolomic plasticity in crops under environmental stress would be explored in depth (Hao et al., 2024b). In stress-induced chemodiversity, metabolomic shifts under abiotic stress can be characterized using proteomics and sphingolipidomics (Chi et al., 2025). For example, Saussurea's cold-adaptation mechanisms could be harnessed to engineer drought-tolerant medicinal crops. In order to improve ecophylogenetic conservation, IUCN Red List assessments can be combined with pharmacophylogenetic hot spots (e.g., Tetrastigma DNA-barcoded populations; Li et al., 2025) to establish in situ "pharmaco-sanctuaries" for critically endangered medicinal taxa (Alum, 2025).As anthropogenic pressures threaten medicinal biodiversity, pharmacophylogeny /pharmacophylomics offers a robust scaffold for ethical drug discovery. Volume IV exemplifies how phylogeny and omics converge to validate ethnomedicinal knowledge-from Kunxinning's steroid biosynthesis modulation to Fabaceae phytoestrogen prediction. We thank all contributors and encourage continued collaboration across phylogenetics, chemistry, and pharmacology. Let us harness pharmacophylomics to conserve nature's pharmacy while advancing sustainable therapeutics.Volume IV reaffirms that the simplest truths-evolutionary kinship begets chemical kinship-remain profound guides for science.