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Plant-derived natural compounds in drug discovery: The prism

已有 464 次阅读 2022-9-28 23:11 |系统分类:博客资讯

Frontiers | Editorial: Plant-derived natural compounds in drug discovery: The prism perspective between plant phylogeny, chemical composition, and medicinal efficacy (frontiersin.org)

Plant based natural medicine research has evolved from a long history going back to the beginning of human civilization to the present in building on innovative research method systems of pharmacophylogeny and pharmacophylogenomics (Hao and Xiao, 2020). "Pharmacophylogeny" was conceived by Professor Xiao Pei-Gen four decades ago as a result of long-term studies of Chinese researchers, especially since the 1950s. The objective is to disentangle the intricate relationships and connectivity between medicinal plant phylogeny, phytochemical profiles and bioactivities/therapeutic utilities (Fig. 1), so as to benefit pioneering plant-based drug research and development (R&D). The historical research in this field while continuing with the status quo, pharmacophylogeny, has become increasingly familiar to more and more researchers. "Pharmacophylogenomics" is proposed to reflect the mounting range of applications of omics based pharmacophylogeny in phytomedicine research.Pharmacophylogeny/pharmacophylogenomics is a multidisciplinary integration, involving molecular phylogeny/phylogenomics, plant morphology, chemotaxonomy, phytochemistry, molecular biology and omics, ethnopharmacology/pharmacology, and the like; for example, Spjut (1985) had recognized the genus as the lowest chemotaxonomic level of diversity to suggest a phytogeographical approach in searching novel antitumor compounds. In the advent of phylogeny, this could become a phylogeographic approach. Pharmacophylogeny suggests that healing plants of the related taxonomic groups are more likely to possess the analogous chemical profiles/efficacies (Fig. 1), which is a law explored from long-term herbal medicine practice, and is used in practice after being confirmed and perfected by scientific research. It played an active role in bioprospecting domestic resources to replace imported medicines. Currently, it is very useful to expand medicinal plant resources (Cui et al.https://www.frontiersin.org/articles/10.3389/fpls.2022.949743/full), along with authentication/quality regulation of herbal medicines, and predicting the chemicals or bioactive constituents of herbals and identification/quantification of chemicals (Fig. 1). In the coming years, pharmacophylogeny and pharmacophylogenomics could be more powerful in mining original natural medicines, refining ethnopharmacology understandings, therefore advancing the workable protection and application of old/natural remedial resources.The goal of this issue (https://www.frontiersin.org/research-topics/31324/plant-derived-natural-compounds-indrug-discovery-the-prism-perspective-between-plant-phylogeny-chem) is to gain novel mechanism insights into the phylogeny/evolution, phytometabolites and pharmacological effects of selected medicinal genera/families. Where possible, we propose that such explorations should be conducted within the context of pharmacophylogeny and/or pharmacophylogenomics. To this end, this Research Topic presents three original articles that reconstructed the Polygonatum, an important TCM genus, and also suggests that Heteropolygonatum may be its sister group, except that Disporopsis, Maianthemum and Disporum may have diverged earlier. On the contrary, the phyllotaxy of Polygonatum is not stable at the intraspecies level, which cannot be taxonomically used as the unique morphology marker.Arnebiae Radix is an old oriental medication with diverse activities. The genome skimming methods were utilized to obtain cp genomes of five Arnebia species (Sun et al.), by which the phylogenetic relationship of five Arnebia species was completely resolved. The origin plants of Arnebiae Radix A. guttata and A. euchroma were of high genetic diversity, and had three and two subclades respectively. The cp genome is an useful genetic resource for phylogeny and evolution studies at both species and subspecies/population levels. The genetic resources provided in these studies will aid the conservation and exploitation of various medicinal taxonomic groups. Notwithstanding, hybridization has led to incomplete lineage sorting and polyploidy during long-term evolution of taxonomic groups; cp phylogeny does not equal to the exact species one (Lu et al., 2022). In RNA-Seq based phylotranscriptomics, nuclear orthologous genes are concatenated to reconstruct the phylogenetic tree (Hao et al., 2021), which, along with genome skimming (Sun et al.) and Hyb-Seq (Lu et al., 2022), represents the promising complementary approach in pharmacophylogenomics.According to pharmacophylogeny, taxa in sister phylogeny groups have closer genetic features (Hao and Xiao, 2020). Thus, they are more likely to possess analogous biosynthesis pathways and their chemical arsenals could be more similar (Liu et al., 2021 (Zhang et al., 2020). In Broussonetia papyrifera leaves, flavonoids accumulate gradually in leaf its development to its maturity (Jiao et al.), and female plants have greater flavonoid leaf content than in male plant, despite their analogous composition. The 192 identified flavonoids include flavonols, flavones, flavan-3-ols, flavonoid carbonoside, anthocyanins, among others, and their biosynthesis follows the well-known flavonoid biosynthetic pathways. Some differentially expressed genes and metabolites along the flavonoid biosynthetic pathway were quantified by transcriptome sequencing and metabolomic analyses respectively.The phenolic acids are distributed in 167 families of seed plant (Zhang et al., 2020). Natural phenolic compounds are commonly distributed in food and TCM (Hao et al.). In a suspension culture of Bletilla striata (Liu et al.), the content of Dactylorhin A peaked at the earliest, followed by p-hydroxybenzylalcohol (HBA), Militarine and Coelonin. Based on full-length transcriptome data, multiple unigenes involved in the biosynthesis of HBA, militarine, dactylorhin A and coelonin were identified. In the transcriptome analysis of Verbena officinalis, 206, 229 and 115 unigenes were identified in the biosynthetic pathways of iridoid glycoside, phenylethanol glycoside and flavonoid respectively (Peng et al.). The contents of these phytometabolites were highest in leaves, followed by stem and root, which is consistent with inter-tissue variations of biosynthetic gene expression levels.The above studies not only contribute a large number of unigenes for the ortholog extraction and phylotranscriptomic inference, but also greatly enrich the phytometabolite database at the genus/species level. In light of the expanding knowledge of plant chemodiversity, it is possible to study the phylogenetic distribution of diverse types of compounds, e.g., less studied pyrone glycoside (Shen et al.), at the subfamily, tribe, genus or subgenus levels, so as to bioprospecting medicinal taxa more precisely.A triple helix systems perspective, i.e., essentially holistic view, would be established if we qualitatively and quantitatively investigate the association between molecular phylogeny and phytochemical data (Zhang et al., 2020), between phylogeny and bioactivity/efficacy (Hao et al., 2022a, b), and between phytometabolite and bioactivity Of note, species relationships may be cryptic due to genetic and/or epigenetic factors, or species of the same taxonomic group may be morphologically and biochemically distinct, making it possible for closely related taxa to have diametrically opposite clinical effects. During long-term evolution, the phytochemical diversification parallels the expansion of biological complexity. Biologically active compounds are generally specialized metabolites, and the distribution of these compounds on phylogenetic trees of different levels is very worthy of deeper study. Many medicinally important phytometabolites, e.g., alkaloids, terpenoids and phenylpropanoids, can be further subdivided structurally, and the phylogenetic signals of different subtypes/subclasses could be distinct. For compounds with similar structures, not only the resemblances and variances of their bioactivities should be explored, but also those of their pharmacokinetic and pharmacodynamic properties should be clarified one by one (Hao et al., 2022c).Therefore, there is a great deal of work to be conducted on various topics of pharmacophylogeny. During the past two decades, various omics techniques have continued to evolve towards elucidating the cryptic connections between plant phylogeny, phytometabolites and their biosynthesis, as well as their bioactivities, which promisingly provide lead entities to develop novel plant-derived drugs.
Fig. 1 An illustrated overview of pharmacophylogeny, taking the order Ranunculales as an example.Keywords: Pharmacophylogeny, 药用亲缘学,植物系统发育/系统基因组学,化学成分,生物活性,多组学plant phylogeny/phylogenomics, Chemical composition, Biological activity, multiomics



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