Da-Cheng Hao

Conservation tillage (CT) practices, including no-tillage and stover mulching, are increasingly recognized for their capacity to enhance soil health, sequester carbon, and mitigate greenhouse gas emissions in conventional agricultural systems. However, their application and mechanistic implications in medicinal crop cultivation—where soil quality directly influences not only yield but also the accumulation of pharmaceutically active secondary metabolites—remain underexplored. This review synthesizes recent advances in understanding how CT modulates soil microbial communities, with particular emphasis on nosZ II-type denitrifiers, to reduce nitrous oxide (N₂O) emissions and improve nitrogen use efficiency. The mechanistic pathways through which CT-induced changes in soil structure, moisture regimes, and organic matter dynamics influence the abundance, community composition, and activity of nitrogen-cycling microorganisms were examined. Based on evidence from black soil ecosystems and other agricultural systems, it is demonstrated that no-tillage with full stover mulching (NT100) selectively enriches specific nosZ II subclades (IIB, IIE, IIG) through deterministic community assembly processes, effectively decoupling N₂O emissions from nitrification activity. The implications of these soil improvements for medicinal plant growth, root development, nutrient acquisition, and stress tolerance were further explored, and case studies linking organic amendments, mycorrhizal associations, and microbial inoculants to enhanced accumulation of alkaloids, flavonoids, terpenoids, and saponins were synthesized. Importantly, findings from spatial phylogenetics and biocultural diversity research were integrated to examine how CT can support in situ conservation of medicinal flora and associated microbial communities in ethnomedicinally significant hotspots such as the Hengduan Mountains, southeastern Tibet, and subtropical refugia. Policy and community-based approaches for integrating CT into biocultural conservation strategies are discussed. By bridging agronomy, microbial ecology, phytochemistry, and ethnobotany, a framework for “eco-pharmacological” management is proposed, aligning sustainable soil practices with medicinal crop quality, climate mitigation, and the preservation of both biological and cultural heritage.

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.

The xeno-fungusphere, a novel microbial ecosystem formed by integrating exogenous fungi, indigenous soil microbiota, and electroactive microorganisms within microbial fuel cells (MFCs), offers a transformative approach for agricultural remediation and medicinal plant conservation. By leveraging fungal enzymatic versatility (e.g., laccases, cytochrome P450s) and conductive hyphae, this system achieves dual benefits. First, it enables efficient degradation of recalcitrant agrochemicals, such as haloxyfop-P, with a removal efficiency of 97.9% (vs. 72.4% by fungi alone) and a 27.6% reduction in activation energy. This is driven by a bioelectric field (0.2–0.5 V/cm), which enhances enzymatic activity and accelerates electron transfer. Second, it generates bioelectricity, up to 9.3 μW/cm², demonstrating real-world applicability. In medicinal plant soils, xeno-fungusphere MFCs restore soil health by stabilizing the pH, enriching dehydrogenase activity, and promoting nutrient cycling, thereby mitigating agrochemical-induced inhibition of secondary metabolite synthesis (e.g., ginsenosides, taxol). Field trials show 97.9% herbicide removal in 60 days, outperforming conventional methods. Innovations, such as adaptive electrodes, engineered strains, and phytoremediation-integrated systems, have been used to address soil and fungal limitations. This technology bridges sustainable agriculture and bioenergy recovery, offering the dual benefits of soil detoxification and enhanced crop quality. Future IoT-enabled monitoring and circular economy integration promise scalable, precision-based applications for global agroecological resilience.

There is a Chinese saying that goes, "The most profound takes the simpliest form". The phylogenetically close taxa usually have similar phytometabolite profiles, and taxa that are closely related in chemotaxonomy often have analogous ethnopharmacological uses and display similar bioactivities. This is the simple core idea of "Pharmacophylogeny", and consequent the proposed term "Pharmacophylomics" aims to disentangle the intricate relationships and connectivity between medicinal plant phylogeny, phytochemical constituents and bioactivities/therapeutic utilities based on emerging omics data (Fig. 1) (Hao and Xiao, 2023);, such as those of genomics, transcriptomics and metabolomics data are very useful, so as to promote pharmaceutical resource discovery and plantbased drug R&D. In recent years, more phytomedicine researchers become familiar with the theory and methods of pharmacophylogeny (Moutouama and Gaoue, 2024), but the research on the simultaneous examination of phylogeny/phylogenomics, phytochemical constituentsstry, and bioactivity is still limited. Based on the 21 papers published in Volume I and II of this Research Topic (Hao et al., 2023a), the volume III furtherhas contributed eight brilliant enlightening papers on the phylogenomics, metabolomics, network pharmacology, ethnopharmacology and bioactivity of various medicinal species, covering algae (Su et al., 2024), monocot (Bencheikh et al., 2024;Luo et al., 2024), basal eudicot (Bencheikh et al., 2024;Pan et al., 2024), core eudicot (Ding et al., 2024), Lamiids (Liu et al., 2024) and Campanulids (Luo et al., 2024), etc. These research findingworks provide rich phytometabolite and bioactivity information for deeper exploration on 设置了格式: 非突出显示 pharmacophylogeny, facilitating the analysis of distribution patterns of various medicinal compounds and pharmacological activities on the phylogenetic tree (Hao et al., 2024a), the inference of biosynthetic pathways and therapeutic mechanisms of phytometabolites, and the search for alternative/complementary medicine sources.Fermentation is an important concoction processing technique for botanical drugphytomedicines, which transforms and enhances the active ingredients of herbal medicine via specific microbial processes (Luo et al., 2024), therefore shifting their pharmacological effects. FermentationThis TCM processing method may contribute additional dimension for expanding theory and application of pharmacophylogeny, as similar fermentation strains and conditions could be used in species with similar phytometabolites, and overlapping but not completely consistent chemical profiles could be generated after microbial transformation, which provide more chemical space for the use of fermented botanical drugs in areas such as anti-cancer, hypolipidemic, antioxidant, antimicrobial, cosmetologycosmetics, and intestinalgut microflora regulation. The fermentation technology reduces toxic side effects of some crude drugs, enhances drug efficacy, and creates new active ingredients, which could be especially important to the species rich and alkaloid abundant genera (Pan et al., 2024).The puzzling interaction between microbial strains and crude drugs is another intriguing topic.Managing factors affecting the microbial activities and fermentation process is vital for the successful transformation and enhancement efficacy improvement of herbal drugs. In this regard, the pharmacophylogeny approach also has its place. For example, we can assume that bacteria or fungi with close genetic relationships interact with specific plant compounds in a similar way, and thus predict the similarities and differences in the spectrum of transformation products based on the composition of the microbial community. There is too much work to be done in this area, and it is not limited to TCM species. Fermentation microbial research can be conducted on ethnomedicine species around the world, e.g., those of Africa (Bencheikh et al., 2024) and Asia (Liu et al., 2024). The molecular phylogeny and metabolomic information are essential to understand the medicinal value of each microbial/plant genus and to develop alternative medicinal resources. They are also applicable in food medicine continuum (FMC) plants, which are extensively distributed in worldwide ethnomedicine. Pharmacophylogeny is very useful in expanding FMC and medicinal plant resources (Hao and Xiao, 2023), authentication/quality control of herbal medicines, predicting the chemicals or bioactive constituents of herbals and identification/quantification of chemicals. Reports on 设置了格式: 非突出显示 phytometabolites and pharmacological properties of algae (Su et al., 2024), regarded as lower plants, are relatively few, despite the presence of many types of vascular plant metabolites therein, e.g., coumarins and diterpenes. In the coming years, pharmacophylogeny and pharmacophylomics could be more powerful in mining natural products from taxa of various evolutionary levels (Lu and Tang, 2020), refining ethnopharmacology understandings, therefore advancing the sustainable conservation and consumption of natural pharmaceutical resources.The global medicinal plant diversity is threated by the increasingly intense anthropogenic activities, while phrmacophylogeny and pharmacophylomics help sustainable conservation and utilization of precious phytomedicine resources. Based on the harvest of first two volumes, the volume III (https://www.frontiersin.org/research-topics/62190/plant-metabolites-in-drug-discovery-the-prismperspective-between-plant-phylogeny-chemical-composition-and-medicinal-efficacy-volume-iii) strives to gain a deeper understanding of phylogeny/evolution, phytometabolites and polypharmacology of genera/families of interest. We always advocate to conduct such investigations within the context of pharmacophylogeny and pharmacophylomics, and we are happy to publish such comprehensive work...