Predicted ADMET properties of compounds abamectin ABM and R-carvone R-CNE. After more than 30 years of intensive use of MLs, the development of resistance is a seriously increasing problem in ruminants 31 , Plant-derived products may contribute to the improvement of parasite control by enhancing the effect of existing anthelmintic drugs.

However, after a combined treatment, it is necessary to evaluate the potential drug—drug interactions between the administered compounds. As many bioactive phytochemicals may interact with P-gp 13 , the R-CNE modulation of the intestinal accumulation of a known P-gp substrate was studied in the current work.

Ileum explants are an integrated system that offers diverse applications 33 , such as evaluation of intestinal drug accumulation and in vitro modulation of efflux proteins.

Increased extracellular LDH activity is expected after enterocyte plasma membrane damage, mainly when the intestinal tissue is exposed to potentially toxic drugs Thus, LDH is a stable intracellular enzyme that can be readily detected when cell membranes are no longer intact 35 , Both extracellular and intracellular LDH activities were measured in the current work.

Different pharmacological strategies have been evaluated to modify the pharmacokinetic behavior of the MLs and to improve their clinical efficacy. The involvement of P-gp in the excretion of ABM has been thoroughly investigated 10 , 38 , In vitro methodologies using intestinal tissue or enterocytes demonstrated the influence of ABC transporters on the absorption and excretion of MLs 18 , In the current trial, the influence of R-CNE on the intestinal accumulation of Rho, as specific P-gp substrate, was evaluated in ileum explants.

The presence of R-CNE significantly increased Rho intestinal accumulation at all incubation times Figure 1. As a forward step, R-CNE modulation of ABM intestinal accumulation was studied.

R-CNE significantly increased ABM accumulation in ileum only at 15 and 30 min of incubation Figure 2A. However, when the modulation was assessed with the known P-gp inhibitor, IVM, intestinal concentrations of ABM increased at all the analyzed times Figure 2B.

IVM has shown high potency as P-gp inhibitor, equivalent to most potent inhibitors such as valspodar 10 , 17 ; therefore, it was used as positive control in the intestinal explants assay. Although the interaction of MLs with other ABC transporters, such as MRP 16 , 41 and BCRP 42 , may confuse the interpretation of these results, it is clear that MLs are potent P-gp and rather weak MRP and BCRP inhibitors.

In a different in vitro model, the concentrations of ABM necessary to inhibit P-gp transport were 3-fold lower than the necessary one to inhibit MRPs-mediated transport In fact, using transfected canine kidney cells, no significant MRP1 and MRP2 avermectin transport was found in the presence of functional P-gp Although the P-gp—mediated transport of MLs is well-known, the potential interaction of R-CNE and ABM with P-gp should be thoroughly evaluated.

Determining the crystal structure of Cel-Pgp-1 28 is relevant to evaluate drug binding using molecular docking. Molecular docking studies have played a crucial role in computer-aided drug design The interaction of both molecules with P-gp was evaluated through in silico studies in the current work.

Although the use of C. elegans P-gp can be considered an experimental limitation if we intend to compare it with the transport in the host, it allows us to study drug—drug interactions at the parasite level.

Additionally, as P-gp is a very conserved and ubiquitous protein and the conformation described for Cel-Pgp-1 is similar to that found for mammalian P-gp 29 , the results of substrate recognition could be applied to the different animal models used in the current trial.

ADMET predictions showed that ABM would be a P-gp inhibitor, whereas R-CNE would not. The ADMET prediction also implies that ABM will have difficulty to cross the blood—brain barrier, whereas R-CNE may easily pass through it.

The molecular docking results of this work indicated different interactions of ABM and R-CNE with Cel-Pgp The binding affinity of drugs and drug candidates varies; however, in general, a design goal is engineering a compound with a binding affinity on the order of 0.

ABM showed a lower energy-binding value than R-CNE; this result is consistent with the specific binding of ABM to P-gp, as previously demonstrated The binding site and binding energy of R-CNE in the current work were similar to those of the anthelmintic drug thiabendazole These authors suggested that the transmembrane translocation of thiabendazole is unlikely.

Accordingly, the R-CNE translocation would be also unlikely, and R-CNE would not be a P-gp modulator at the parasite level. Thus, the influence of R-CNE on drug absorption and accumulation may be explained with other mechanisms.

Different bioactive phytochemicals may increase intestinal absorption by enhancing enterocyte membrane permeability or by opening paracellular tight junctions In fact, R-CNE was used as penetration enhancer that allows drug permeation through the skin and enhanced the effect of a vasodilator drug after topical administration Thus, the increased intestinal accumulation of Rho and ABM observed in the current trial may be supported by the effect of R-CNE on the membrane of intestinal cells.

Currently, numerous marketed pharmaceutical formulations contain the combination of two or three synthetic anthelmintics. However, there is scarce information of the combination of bioactive phytochemicals and antiparasitic drugs.

The concomitant administration of sainfoin and IVM to sheep by the oral route decreased the absorption of the synthetic anthelmintic In a recent study, the in vivo coadministration of the natural terpene thymol with albendazole also led to a negative pharmacokinetic interaction by significantly reducing the ruminal sulforeduction of the metabolite albendazole sulfoxide to the parent drug albendazole The information obtained with the in vitro and in silico studies was complemented with the in vivo trial.

The ABM T max tended to be delayed in the presence of R-CNE. Although P-gp modulation may enhance ML absorption, for example, after IVM oral coadministration with itraconazole in sheep 49 , the in silico simulations demonstrated that a drug—drug interaction between R-CNE and ABM at the P-gp level is unlikely.

Therefore, the beneficial effect of R-CNE on the pharmacokinetics of ABM may be based on the effect of the natural products on the enterocyte membrane permeability R-CNE is metabolized by phase I and phase II metabolism, which favors its rapid excretion In vitro efficacy tests on Haemonchus spp.

Given the low in vivo exposure of parasites to R-CNE, the compound would not be able to achieve a high anthelmintic efficacy if it were administered alone. The coadministration of R-CNE and ABM increased the anthelmintic efficacy from This enhanced efficacy may be based on the pharmacokinetic interaction between R-CNE and ABM within the host and on a pharmacodynamic interaction related to the in vivo effect of R-CNE on the nematodes.

The low level of resistance observed for the ABM alone treatment may be a limitation and may underestimate the impact of the treatment combined with R-CNE. The current trial was carried out on an experimental farm with a history of resistance to MLs and benzimidazoles.

However, at the time of the in vivo trial, the low proportion of Haemonchus spp. within the initial parasite population could explain the increase in the FECRT. Further studies are needed to test this pharmacological tool under different resistance scenarios.

Another important issue is to establish the additive or synergistic feature of this type of combination.

The in vitro evaluation of the binary combination of R-CNE with other bioactive phytochemicals, such as anethole, showed synergistic activity in the egg hatch assay with H. contortus eggs 7. contortus , but there was no effect on total worm count 9.

Proper dosing regimen and formulation are essential to ensure the best performance after the administration of a bioactive phytochemical to ruminants.

From a practical point of view, the dosing schedule used for R-CNE in the current trial is a limitation and needs to be improved by the pharmaceutical technology. The challenge for the future use of monoterpenes as antiparasitic compounds is conditioned to suitable pharmaceutical formulations that provide sustained concentrations in the tissues of parasite location.

In conclusion, this study has demonstrated a pharmacokinetic and pharmacodynamic interaction between the synthetic anthelmintic ABM and R-CNE. Despite the limitations described, the integration of in vitro assays, in silico analysis, and in vivo pharmacoparasitological studies is relevant for the knowledge of the combinations of bioactive natural products and synthetic anthelmintics.

Considering the increasing resistance of gastrointestinal nematodes to the different drug families, the development of new pharmacological tools is critical for the design of future successful strategies for parasite control.

MM: Acquisition of data, analysis, and interpretation of data, drafting the manuscript. SL: Acquisition of data on the field. PC and ML: Acquisition of data on the field. DS and AS: In silico evaluation.

LC-J: Contribution to conception and design, critically revising the manuscript. GV: Contribution to conception, design, and acquisition of data, critically revising the manuscript.

AL: Contribution to conception, design and acquisition of data, analysis and interpretation of data, drafting and critically revising the manuscript. All authors have read and approved the final manuscript. This research was supported by Consejo Nacional de Investigaciones Científicas y Técnicas CONICET, Agencia Nacional de Promoción Científica y Tecnológica PICT both from Argentina and FAPEMA Maranhão State Research Foundation, Brazil and FINEP Funding Authority for Studies and Projects for supporting the IECT Science and Technology Institute of Maranhão.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. English style was revised by the Specialist in Scientific and Technical Translation, Transl. Jorgelina Brasca. Supplementary Figure S1.

Docking analysis visualization of A Cel-Pgp-1 binding with ABA yellow surface and RCV green surface. Binding site visualization of Cel-Pgp-1 in complex with B ABA yellow sticks and C R-CNE red sticks. Cel-Pgp-1 is represented in blue ribbons. The key residues predicted for Cel-Pgp-1 interaction with ligands were highlighted in red.

Images were generated using pymol. Besier RB, Kahn LP, Sargison ND, Van Wyk JA. Diagnosis, treatment and management of haemonchus contortus in small ruminants. doi: PubMed Abstract CrossRef Full Text Google Scholar. André WPP, Cavalcante GS, Ribeiro WLC, Dos Santos JML, Macedo ITF, De Paula HCB, et al.

Anthelmintic effect of thymol and thymol acetate on sheep gastrointestinal nematodes and their toxicity in mice. Rev Bras. Lanusse C, Canton C, Virkel G, Alvarez L, Costa-Junior L, Lifschitz A. Strategies to optimize the efficacy of anthelmintic drugs in ruminants.

Trends Parasitol. Kotze AC, Prichard RK. Anthelmintic resistance in haemonchus contortus: history, mechanisms and diagnosis. Lespine A, Alvinerie M, Vercruysse J, Prichard RK, Eldhof P. ABC transporter modulation: a strategy to enhance the activity of macrocyclic lactone anthelmintics Trends Parasitol.

Hoste H, Torres-Acosta JFJ. Non chemical control of helminths in ruminants: adapting solutions for changing worms in a changing world. Katiki LM, Barbieri AME, Araujo RC, Veríssimo CJ, Louvandini H, Ferreira JFS.

Synergistic interaction of ten essential oils against Haemonchus contortus in vitro. European Food Safety Authority Scientific opinion on the safety assessment of carvone, considering all sources of exposure. EFSA J. CrossRef Full Text Google Scholar.

Katiki LM, Araujo RC, Ziegelmeyer L, Gomes ACP, Gutmanis G, Rodrigues L, et al. Evaluation of encapsulated anethole and carvone in lambs artificially- and naturally-infected with Haemonchus contortus.

Lespine A, Martin S. Interaction of macrocyclic lactones with P-glycoprotein: structure-affinity relationship. Lifschitz A, Entrocasso C, Alvarez L, Lloberas M, Ballent M, Manazza G, et al. Interference with P-glycoprotein improves ivermectin activity against adult resistant nematodes in sheep.

Virkel G, Ballent M, Lanusse C, Lifschitz A. Role of ABC transporters in veterinary medicine: pharmaco- toxicological implications. Dewanjee S, Dua TK, Bhattacharjee N, Das A, Gangopadhyay M, Khanra R, et al. Natural products as alternative choices for P-Glycoprotein P-gp Inhibition.

Zhao Q, Luan X, Zheng M, Tian XH, Zhao J, Zhang WD, et al. Synergistic mechanisms of constituents in herbal extracts during intestinal absorption: focus on natural occurring nanoparticles.

American Veterinary Medical Association. AVMA Guidelines for the Euthanasia of Animals. Schaumburg, IL Google Scholar.

S2CID IUPHAR Database. International Union of Basic and Clinical Pharmacology. August Arnason; Rachel Mata; John T. Romeo Phytochemistry of Medicinal Plants.

United States Department of Agriculture. Retrieved 18 February Cardiac Glycoside". The man credited with the introduction of digitalis into the practice of medicine was William Withering. Micronutrient Information Center, Linus Pauling Institute, Oregon State University.

Retrieved 11 October American Scientist. Research Triangle Park, NC: Sigma Xi, The Scientific Research Society. New Phytologist.

New York: Wiley. THYMOL is a phenol obtained from thyme oil or other volatile oils used as a stabilizer in pharmaceutical preparations, and as an antiseptic antibacterial or antifungal agent. It was formerly used as a vermifuge. Functional Foods in Health and Disease.

ISSN Annual Review of Cell and Developmental Biology. Annual Reviews. History Outline. Archaeobotany Astrobotany Bryology Dendrology Ethnobotany Paleobotany Phycology Phytochemistry Phytogeography Geobotany Plant anatomy Plant ecology Plant pathology.

Algae Archaeplastida Bryophyte Non-vascular plants Vascular plants Fern Lycophyte Spermatophytes Gymnosperm Angiosperm. Plant morphology glossary. Cell wall Phragmoplast Plastid Plasmodesma Vacuole. Cork Ground tissue Mesophyll Meristem Storage organs Vascular tissue Vascular bundle Wood.

Bulb Root Rhizoid Rhizome Shoot Bud Leaf Cataphyll Petiole Sessility Stem. Archegonium Antheridium Androecium Pollen Stamen Staminode Tapetum Flower Aestivation Flower development Floral diagram Floral formula Floral symmetry Whorl Fruit Anatomy Berry Capsule Nut Pyrena Seed Dispersal Endosperm Gametophyte Gynandrium Gynoecium Ovary Locule Ovule Stigma Hypanthium Floral cup Inflorescence Bract Pedicellate Raceme Umbel Perianth Tepal Petal Sepal Plant embryo Receptacle Sporophyll Sporophyte.

Cuticle Epicuticular wax Epidermis Nectar Stoma Thorns, spines, and prickles Trichome. Aleurone Apical dominance Bulk flow Cellulose Nutrition Photosynthesis Chlorophyll Phytomelanin Plant hormones Respiration Gas Exchange Cellular Respiration Sap Starch Sugar Transpiration Turgor pressure.

Habit Cushion plants Rosettes Shrubs Prostrate shrubs Subshrubs Succulent plants Trees Vines Lianas Herbaceous plants Secondary growth Woody plants. Evolution Ecology. Alternation of generations Double fertilization Evolutionary development Evolutionary history timeline Flora Germination Pollination Artificial Pollinators Pollen tube Self Sporangium Microsporangia Microspore Megasporangium Megaspore Spore.

Biological classification Botanical nomenclature Botanical name Correct name Author citation International Code of Nomenclature ICN ICN for Cultivated Plants ICNCP Cultivated plant taxonomy Citrus taxonomy Cultigen Cultivar Group Grex History of plant systematics Herbarium International Association for Plant Taxonomy IAPT Plant taxonomy systems Taxonomic rank.

Agronomy Floriculture Forestry Horticulture. Botanical terms Botanists by author abbreviation Botanical expedition Individual trees. WikiProject Category Commons. Branches of chemistry. Glossary of chemical formulae List of biomolecules List of inorganic compounds Periodic table.

Instrumental chemistry Electroanalytical methods Spectroscopy IR Raman UV-Vis NMR Mass spectrometry EI ICP MALDI Separation process Chromatography GC HPLC Crystallography Characterization Titration Wet chemistry Calorimetry Elemental analysis.

Quantum chemistry Computational chemistry Mathematical chemistry Molecular modelling Molecular mechanics Molecular dynamics Molecular geometry VSEPR theory. Electrochemistry Spectroelectrochemistry Photoelectrochemistry Thermochemistry Chemical thermodynamics Surface science Interface and colloid science Micromeritics Cryochemistry Sonochemistry Structural chemistry Chemical physics Molecular physics Femtochemistry Chemical kinetics Spectroscopy Photochemistry Spin chemistry Microwave chemistry Equilibrium chemistry Mechanochemistry.

Coordination chemistry Magnetochemistry Organometallic chemistry Organolanthanide chemistry Cluster chemistry Solid-state chemistry Ceramic chemistry.

Biochemistry Molecular biology Cell biology Chemical biology Bioorthogonal chemistry Medicinal chemistry Pharmacology Clinical chemistry Neurochemistry Bioorganic chemistry Bioorganometallic chemistry Bioinorganic chemistry Biophysical chemistry.

History of chemistry Nobel Prize in Chemistry Timeline of chemistry of element discoveries " The central science " Chemical reaction Catalysis Chemical element Chemical compound Atom Molecule Ion Chemical substance Chemical bond Alchemy Quantum mechanics.

Category Commons Portal WikiProject. The authors are grateful to the Journal for presenting this Editorial article. D-CH is supported by China Scholarship Council This work is also funded by the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine ZYYCXTDD and CAMS Innovation Fund for Medical Sciences CIFMS; I2M-1— The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Hao, D. Dissection of full-length transcriptome and metabolome of dichocarpum Ranunculaceae : implications in evolution of specialized metabolism of ranunculales medicinal plants.

PeerJ 9, e doi: PubMed Abstract CrossRef Full Text Google Scholar. Evaluating potentials of species rich taxonomic groups in cosmetics and dermatology: Clustering and dispersion of skin efficacy of asteraceae and ranunculales plants on the species phylogenetic tree.

CrossRef Full Text Google Scholar. Drug Metab. Pharmaceutical resource discovery from traditional medicinal plants: Pharmacophylogeny and pharmacophylogenomics.

Distribution of therapeutic efficacy of ranunculales plants used by ethnic minorities on the phylogenetic tree of Chinese species.

Based Comple. Liu, H. Informatics and big data: A new stage of pharmacophylogeny in medicinal plants. Lu, W. Hyb-seq provides new insights into the phylogeny and evolution of the chrysanthemum zawadskii species complex in China.

Souza, E. Which plants used in ethnomedicine are characterized? phylogenetic patterns in traditional use related to research effort. Plant Sci. Spjut, R. Limitations of a random screen: Search for new anticancer drugs in higher plants.

Zhang, Y. Citation: Hao D-C, He C-N, Spjut RW and Xiao P-G Editorial: Plant-derived natural compounds in drug discovery: The prism perspective between plant phylogeny, chemical composition, and medicinal efficacy.

Received: 12 September ; Accepted: 27 September ; Published: 07 October Copyright © Hao, He, Spjut and Xiao. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY. The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.

No use, distribution or reproduction is permitted which does not comply with these terms. cn ; Da-Cheng Hao, hao djtu. Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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In a suspension culture of Bletilla striata Liu et al. 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 , , and 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. In light of the expanding knowledge of plant chemodiversity, it is possible to study the phylogenetic distribution of diverse types of compounds, e.

A triple helix systems perspective, i. Based on extensive ethnomedicinal uses, the thorough phytochemistry and bioactivity characterizations contribute to the safe administration of herbals and discovery of lead compounds Souza et al.

In total, compounds were identified from essential oils EOs of six Lamiaceae herbs by GC-MS analysis Sun et al. All EOs had promising anti-inflammatory activity in rats with adjuvant arthritis, and Perilla frutescens EO was the best.

They alleviated the joint swelling in the rat models; the lymphocyte infiltration and cartilage damage were significantly inhibited. The TNF-α, IL-1, and IL-6 were reduced in rat articular tissues by EOs. Six EOs had substantial toxicity on tumor cell lines; they also had the significant antioxidant activity, and Salvia japonica EO was the strongest.

Berberine, baicalin and saponin from Coptis chinensis , Scutellaria baicalensis and Vincetoxicum atratum respectively were combined to produce the formula BBS Song et al. Although these bottom-up and intermediate approaches cannot replace the top-down approach, i.

The bioactivity studies provide more reference data for pharmacophylogeny research and drug discovery from ethnomedicinal plants. The deeper investigations of genomics of curative plants, metabolomics, and ethnopharmacology-based bioactivity will enable the workable protection and consumption of botanical possessions.

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.

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. 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.

D-CH and C-NH prepared the draft and finalized the manuscript. P-GX and RS edited and corrected the draft. All authors contributed to the article and approved the submitted version. The authors are grateful to the Journal for presenting this Editorial article.

D-CH is supported by China Scholarship Council This work is also funded by the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine ZYYCXTDD and CAMS Innovation Fund for Medical Sciences CIFMS; I2M-1— The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Hao, D. Dissection of full-length transcriptome and metabolome of dichocarpum Ranunculaceae : implications in evolution of specialized metabolism of ranunculales medicinal plants.

PeerJ 9, e doi: PubMed Abstract CrossRef Full Text Google Scholar. Evaluating potentials of species rich taxonomic groups in cosmetics and dermatology: Clustering and dispersion of skin efficacy of asteraceae and ranunculales plants on the species phylogenetic tree.

CrossRef Full Text Google Scholar. Drug Metab. Pharmaceutical resource discovery from traditional medicinal plants: Pharmacophylogeny and pharmacophylogenomics.

Distribution of therapeutic efficacy of ranunculales plants used by ethnic minorities on the phylogenetic tree of Chinese species. Based Comple. Liu, H. Informatics and big data: A new stage of pharmacophylogeny in medicinal plants.

Lu, W. Hyb-seq provides new insights into the phylogeny and evolution of the chrysanthemum zawadskii species complex in China. Souza, E. Which plants used in ethnomedicine are characterized? phylogenetic patterns in traditional use related to research effort. Plant Sci. Spjut, R. Limitations of a random screen: Search for new anticancer drugs in higher plants.

Zhang, Y. Citation: Hao D-C, He C-N, Spjut RW and Xiao P-G Editorial: Plant-derived natural compounds in drug discovery: The prism perspective between plant phylogeny, chemical composition, and medicinal efficacy.

Received: 12 September ; Accepted: 27 September ; Published: 07 October Copyright © Hao, He, Spjut and Xiao. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY. The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.

No use, distribution or reproduction is permitted which does not comply with these terms. cn ; Da-Cheng Hao, hao djtu. Digoxin is used to treat atrial fibrillation , atrial flutter and sometimes heart failure.

Further information: Polyphenol. Angelica , containing phytoestrogens. Polyphenols include phytoestrogens top and middle.

Anthocyanins are a class of polyphenol that contributes to the color of many plants. Tannic acids are one example of many complex polyphenolic structures produced by plants.

Further information: Terpenes. The essential oil of common thyme Thymus vulgaris , contains the monoterpene thymol , an antiseptic and antifungal. Thymol is one of many terpenes found in plants. Terpenes are polymer of isoprene. Encyclopædia Britannica volume 13, 15th edition.

Phytochemicals in Nutrition and Health. CRC Press. ISBN In Lanzotti, Virginia ed. Plant-Derived Natural Products: Synthesis, Function, and Application. Bibcode : Natur. doi : PMID Future Medicinal Chemistry. PMC The European Agency for the Evaluation of Medicinal Products.

Retrieved 26 February Plant and Soil. Heidelberg: Springer. JSTOR S2CID IUPHAR Database. International Union of Basic and Clinical Pharmacology. August Arnason; Rachel Mata; John T. Romeo Phytochemistry of Medicinal Plants. United States Department of Agriculture. Retrieved 18 February Cardiac Glycoside".

The man credited with the introduction of digitalis into the practice of medicine was William Withering. Micronutrient Information Center, Linus Pauling Institute, Oregon State University.

Retrieved 11 October American Scientist. Research Triangle Park, NC: Sigma Xi, The Scientific Research Society. New Phytologist. New York: Wiley. THYMOL is a phenol obtained from thyme oil or other volatile oils used as a stabilizer in pharmaceutical preparations, and as an antiseptic antibacterial or antifungal agent.

It was formerly used as a vermifuge. Functional Foods in Health and Disease. ISSN Annual Review of Cell and Developmental Biology. Annual Reviews. History Outline. Archaeobotany Astrobotany Bryology Dendrology Ethnobotany Paleobotany Phycology Phytochemistry Phytogeography Geobotany Plant anatomy Plant ecology Plant pathology.

Algae Archaeplastida Bryophyte Non-vascular plants Vascular plants Fern Lycophyte Spermatophytes Gymnosperm Angiosperm. Plant morphology glossary. Cell wall Phragmoplast Plastid Plasmodesma Vacuole. Cork Ground tissue Mesophyll Meristem Storage organs Vascular tissue Vascular bundle Wood.

Bulb Root Rhizoid Rhizome Shoot Bud Leaf Cataphyll Petiole Sessility Stem. Archegonium Antheridium Androecium Pollen Stamen Staminode Tapetum Flower Aestivation Flower development Floral diagram Floral formula Floral symmetry Whorl Fruit Anatomy Berry Capsule Nut Pyrena Seed Dispersal Endosperm Gametophyte Gynandrium Gynoecium Ovary Locule Ovule Stigma Hypanthium Floral cup Inflorescence Bract Pedicellate Raceme Umbel Perianth Tepal Petal Sepal Plant embryo Receptacle Sporophyll Sporophyte.

Cuticle Epicuticular wax Epidermis Nectar Stoma Thorns, spines, and prickles Trichome. Aleurone Apical dominance Bulk flow Cellulose Nutrition Photosynthesis Chlorophyll Phytomelanin Plant hormones Respiration Gas Exchange Cellular Respiration Sap Starch Sugar Transpiration Turgor pressure.

Habit Cushion plants Rosettes Shrubs Prostrate shrubs Subshrubs Succulent plants Trees Vines Lianas Herbaceous plants Secondary growth Woody plants.

Evolution Ecology. Alternation of generations Double fertilization Evolutionary development Evolutionary history timeline Flora Germination Pollination Artificial Pollinators Pollen tube Self Sporangium Microsporangia Microspore Megasporangium Megaspore Spore.

Biological classification Botanical nomenclature Botanical name Correct name Author citation International Code of Nomenclature ICN ICN for Cultivated Plants ICNCP Cultivated plant taxonomy Citrus taxonomy Cultigen Cultivar Group Grex History of plant systematics Herbarium International Association for Plant Taxonomy IAPT Plant taxonomy systems Taxonomic rank.

Agronomy Floriculture Forestry Horticulture. Botanical terms Botanists by author abbreviation Botanical expedition Individual trees. WikiProject Category Commons. Branches of chemistry. Glossary of chemical formulae List of biomolecules List of inorganic compounds Periodic table.

Instrumental chemistry Electroanalytical methods Spectroscopy IR Raman UV-Vis NMR Mass spectrometry EI ICP MALDI Separation process Chromatography GC HPLC Crystallography Characterization Titration Wet chemistry Calorimetry Elemental analysis.

Quantum chemistry Computational chemistry Mathematical chemistry Molecular modelling Molecular mechanics Molecular dynamics Molecular geometry VSEPR theory. Electrochemistry Spectroelectrochemistry Photoelectrochemistry Thermochemistry Chemical thermodynamics Surface science Interface and colloid science Micromeritics Cryochemistry Sonochemistry Structural chemistry Chemical physics Molecular physics Femtochemistry Chemical kinetics Spectroscopy Photochemistry Spin chemistry Microwave chemistry Equilibrium chemistry Mechanochemistry.

Coordination chemistry Magnetochemistry Organometallic chemistry Organolanthanide chemistry Cluster chemistry Solid-state chemistry Ceramic chemistry. Biochemistry Molecular biology Cell biology Chemical biology Bioorthogonal chemistry Medicinal chemistry Pharmacology Clinical chemistry Neurochemistry Bioorganic chemistry Bioorganometallic chemistry Bioinorganic chemistry Biophysical chemistry.

History of chemistry Nobel Prize in Chemistry Timeline of chemistry of element discoveries " The central science " Chemical reaction Catalysis Chemical element Chemical compound Atom Molecule Ion Chemical substance Chemical bond Alchemy Quantum mechanics.

A set of cp genome sequences of Asparagaceae tribe Polygonateae Wang et al. is essential for unearthing the links between phylogenomics and chemotaxonomy of medicinal taxa therein. The complete cp genomes of 26 Polygonateae species were de novo assembled and characterized; the cp genome-based phylogeny suggests the monophyly of 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.

The origin plants of Arnebiae Radix A. guttata and A. euchroma were of high genetic diversity, and had three and two subclades respectively. 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.

In RNA-Seq based phylotranscriptomics, nuclear orthologous genes are concatenated to reconstruct the phylogenetic tree Hao et al. and Hyb-Seq Lu et al.

According to pharmacophylogeny, taxa in sister phylogeny groups have closely related genetic features Hao and Xiao, Thus, they are more likely to possess analogous biosynthesis pathways and their chemical arsenals could be more similar Liu et al. The various tiers of chemical similarity result in the global resemblance of bioactivity or pharmacological efficacy Hao et al.

Pharmacophylogeny successfully guides the development of novel curative taxa Hao and Xiao, , while circumventing the limitations of old-style approaches and enabling the targeted studies.

In contrast, the random discovery accidental discovery relies too much on luck; new molecular entities obtained by combinatorial chemistry, high throughput screening or computer aided drug design very often fail due to improper pharmacokinetic and pharmacodynamic properties Hao et al.

This Research Topic presents a few original articles that carefully investigate the specialized metabolism and chemodiversity of Chrysanthemum Hao et al.

and Verbena Peng et al. More than 9, flavonoids are distributed in families of seed plant Zhang et al. In Broussonetia papyrifera leaves, flavonoids accumulate gradually in leaf development to until its maturity Jiao et al. The identified flavonoids include flavonols, flavones, flavanols, 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 families of seed plant Zhang et al. Natural phenolic compounds are commonly distributed in food and TCM Hao et al.

In a suspension culture of Bletilla striata Liu et al. 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 , , and 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. In light of the expanding knowledge of plant chemodiversity, it is possible to study the phylogenetic distribution of diverse types of compounds, e.

A triple helix systems perspective, i. Based on extensive ethnomedicinal uses, the thorough phytochemistry and bioactivity characterizations contribute to the safe administration of herbals and discovery of lead compounds Souza et al.

In total, compounds were identified from essential oils EOs of six Lamiaceae herbs by GC-MS analysis Sun et al. All EOs had promising anti-inflammatory activity in rats with adjuvant arthritis, and Perilla frutescens EO was the best.

They alleviated the joint swelling in the rat models; the lymphocyte infiltration and cartilage damage were significantly inhibited. The TNF-α, IL-1, and IL-6 were reduced in rat articular tissues by EOs. Six EOs had substantial toxicity on tumor cell lines; they also had the significant antioxidant activity, and Salvia japonica EO was the strongest.

Berberine, baicalin and saponin from Coptis chinensis , Scutellaria baicalensis and Vincetoxicum atratum respectively were combined to produce the formula BBS Song et al. Although these bottom-up and intermediate approaches cannot replace the top-down approach, i. Article CAS PubMed PubMed Central Google Scholar.

Badawy AA, El-Magd MA, AlSadrah SA Therapeutic effect of camel milk and its exosomes on MCF7 cells in vitro and in vivo. Integr Cancer Ther 17 4 — Baskar R et al Cancer and radiation therapy: current advances and future directions. Int J Med Sci 9 3 — Article PubMed PubMed Central Google Scholar.

Block K et al A broad-spectrum integrative prevention design for cancer prevention and therapy. Semin Cancer Biol 35 Suppl :S—S Choudhari AS et al Phytochemicals in cancer treatment: from preclinical studies to clinical practice. Front Pharmacol Cicerale S, Lucas L, Keast R Biological activities of phenolic compounds present in virgin olive oil.

Int J Mol Sci 11 2 — De Silva SF, Alcorn J Flaxseed lignans as important dietary polyphenols for cancer prevention and treatment: chemistry, pharmacokinetics, and molecular targets.

Pharmaceuticals 12 2 Article CAS PubMed Central Google Scholar. Demain AL, Vaishnav P Natural products for cancer chemotherapy. Microb Biotechnol 4 6 — Farooq A et al Natural products against cancer: review on phytochemicals from marine sources in preventing cancer.

Saudi Pharm J 27 6 — Feitelson MA et al Sustained proliferation in cancer: therapeutic targets. Semin Cancer Biol — Article Google Scholar.

Harsha Raj M et al Suppression of VEGF-induced angiogenesis and tumor growth by Eugenia jambolana, Musa paradisiaca, and Coccinia indica extracts. Pharm Biol 55 1 — Jiang T, Zhou C The past, present and future of immunotherapy against tumor. Trans Lung Cancer Res 4 3 — Khan T et al Anticancer plants: a review of the active phytochemicals, applications in animal models, and regulatory aspects.

Biomol Ther 10 1 Lichota A, Gwozdzinski K Anticancer activity of natural compounds from plant and marine environment. Int J Mol Sci 19 11 Luo KW et al Green tea Camellia sinensis extract inhibits both the metastasis and osteolytic components of mammary cancer 4T1 lesions in mice.

J Nutr Biochem 25 4 — Article CAS PubMed Google Scholar. Madka V, Rao CV Anti-inflammatory phytochemicals for chemoprevention of colon cancer. Curr Cancer Drug Targets 13 5 — Omara T, Kiprop AK, Ramkat RC, Cherutoi J, Kagoya S, Nyangena DM, Tebo TA, Nteziyaremye P, Karanja LN, Jepchirchir A, Maiyo A, Kiptui BJ, Mbabazi I, Nakiguli CK, Nakabuye BV, Koske MC Medicinal plants used in traditional management of cancer in Uganda: a review of ethnobotanical surveys phytochemistry and anticancer studies.

Evid Based Complement Alternat Med Oyeyinka BO, Afolayan AJ Comparative evaluation of the nutritive, mineral, and antinutritive composition of Musa sinensis L. Banana and Musa paradisiaca L. Plantain fruit compartments. Plan Theory 8 12 Pouchieu C, Galan P, Ducros V, Latino-Martel P, Hercberg S, Touvier M Plasma carotenoids and retinol and overall and breast cancer risk: a nested case-control study.

Herein, we will focus majorly on bioactive compounds as therapeutic agents for cancer treatment with emphasis on their other possible beneficiary roles. Keywords: Anticancer Mechanism , Apoptosis , Cancer , Chemotherapy , Flavonoids , Medicinal Plants , Phytochemicals , Plant Extracts , Polyphenols , Saponins , Secondary Metabolites , Therapeutic Agents , Terpenes , Vinca Alkaloids.

Plant Based Bioactive Compounds as an Alternative for Cancer Therapy, Herbal Medicine: Back to the Future Cancer Therapy 3: The Anatomical Foundations of Regional Anesthesia and Acute Pain Medicine Macroanatomy Microanatomy Sonoanatomy Functional anatomy.

Herbal Medicine: Back to the Future Volume: 3. Back Cancer Therapy DOI: Plant Based Bioactive Compounds as an Alternative for Cancer Therapy Author s : Nikita Sharma, R.

Cite as. About this chapter ×. Cite this chapter as: Nikita Sharma, R. Mankamna Kumari, Nidhi Gupta, Surendra Nimesh ; Plant Based Bioactive Compounds as an Alternative for Cancer Therapy, Herbal Medicine: Back to the Future Cancer Therapy 3: Close About this chapter.

Medicinal Plants have been known to be one of the oldest and most consistent sources for the production of novel drugs. Utilization of plant extracts as drugs can be attributed to their chemical and structural diversity along with their ability to interact with different biological targets in the cell.

Moreover, they act as huge reservoirs for the phytochemicals which provide defense against a number of diseases. Cost effectiveness along with lesser adverse effects, allowed natural plants to be used as an alternative to conventional strategies for cancer treatment.

Extracts from different natural plants have also been explored in the treatment of infectious diseases. The present chapter emphasizes on the use of plant extracts and their purified compound as cancer therapeutics.

Cancer is one of the major causes of mortality worldwide. Owing to several limitations of current treatment regimens of cancer, the attention of researchers has been drawn towards exploration of natural sources.

Herein, we will focus majorly on bioactive compounds as therapeutic agents for cancer treatment with emphasis on their other possible beneficiary roles. Keywords: Anticancer Mechanism , Apoptosis , Cancer , Chemotherapy , Flavonoids , Medicinal Plants , Phytochemicals , Plant Extracts , Polyphenols , Saponins , Secondary Metabolites , Therapeutic Agents , Terpenes , Vinca Alkaloids.

Plant Based Bioactive Compounds as an Alternative for Cancer Therapy, Herbal Medicine: Back to the Future Cancer Therapy 3: The Anatomical Foundations of Regional Anesthesia and Acute Pain Medicine Macroanatomy Microanatomy Sonoanatomy Functional anatomy.

Cicerale S, Lucas L, Keast R Biological activities of phenolic compounds present in virgin olive oil. Int J Mol Sci 11 2 — De Silva SF, Alcorn J Flaxseed lignans as important dietary polyphenols for cancer prevention and treatment: chemistry, pharmacokinetics, and molecular targets.

Pharmaceuticals 12 2 Article CAS PubMed Central Google Scholar. Demain AL, Vaishnav P Natural products for cancer chemotherapy. Microb Biotechnol 4 6 — Farooq A et al Natural products against cancer: review on phytochemicals from marine sources in preventing cancer.

Saudi Pharm J 27 6 — Feitelson MA et al Sustained proliferation in cancer: therapeutic targets. Semin Cancer Biol — Article Google Scholar.

Harsha Raj M et al Suppression of VEGF-induced angiogenesis and tumor growth by Eugenia jambolana, Musa paradisiaca, and Coccinia indica extracts. Pharm Biol 55 1 — Jiang T, Zhou C The past, present and future of immunotherapy against tumor. Trans Lung Cancer Res 4 3 — Khan T et al Anticancer plants: a review of the active phytochemicals, applications in animal models, and regulatory aspects.

Biomol Ther 10 1 Lichota A, Gwozdzinski K Anticancer activity of natural compounds from plant and marine environment. Int J Mol Sci 19 11 Luo KW et al Green tea Camellia sinensis extract inhibits both the metastasis and osteolytic components of mammary cancer 4T1 lesions in mice.

J Nutr Biochem 25 4 — Article CAS PubMed Google Scholar. Madka V, Rao CV Anti-inflammatory phytochemicals for chemoprevention of colon cancer. Curr Cancer Drug Targets 13 5 — Omara T, Kiprop AK, Ramkat RC, Cherutoi J, Kagoya S, Nyangena DM, Tebo TA, Nteziyaremye P, Karanja LN, Jepchirchir A, Maiyo A, Kiptui BJ, Mbabazi I, Nakiguli CK, Nakabuye BV, Koske MC Medicinal plants used in traditional management of cancer in Uganda: a review of ethnobotanical surveys phytochemistry and anticancer studies.

Evid Based Complement Alternat Med Oyeyinka BO, Afolayan AJ Comparative evaluation of the nutritive, mineral, and antinutritive composition of Musa sinensis L. Banana and Musa paradisiaca L. Plantain fruit compartments. Plan Theory 8 12 Pouchieu C, Galan P, Ducros V, Latino-Martel P, Hercberg S, Touvier M Plasma carotenoids and retinol and overall and breast cancer risk: a nested case-control study.

Nutr Cancer 66 6 — Prakash O et al Anticancer potential of plants and natural products: a review. Am J Pharm Sci — Rajesh E, Sankari LS, Malathi L, Krupaa JR Naturally occurring products in cancer therapy. J Phar Bioallied Sci 7 5 Samadi AK et al A multi-targeted approach to suppress tumor-promoting inflammation.

Semin Cancer Biol S—S Seca A, Pinto D Plant secondary metabolites as anticancer agents: successes in clinical trials and therapeutic application. Int J Mol Sci 19 1 Sharifi-Rad J et al Natural products and synthetic analogs as a source of antitumor drugs.

Thus, they are more likely to possess analogous biosynthesis pathways and their chemical arsenals could be more similar Liu et al. The various tiers of chemical similarity result in the global resemblance of bioactivity or pharmacological efficacy Hao et al. Pharmacophylogeny successfully guides the development of novel curative taxa Hao and Xiao, , while circumventing the limitations of old-style approaches and enabling the targeted studies.

In contrast, the random discovery accidental discovery relies too much on luck; new molecular entities obtained by combinatorial chemistry, high throughput screening or computer aided drug design very often fail due to improper pharmacokinetic and pharmacodynamic properties Hao et al.

This Research Topic presents a few original articles that carefully investigate the specialized metabolism and chemodiversity of Chrysanthemum Hao et al. and Verbena Peng et al. More than 9, flavonoids are distributed in families of seed plant Zhang et al.

In Broussonetia papyrifera leaves, flavonoids accumulate gradually in leaf development to until its maturity Jiao et al.

The identified flavonoids include flavonols, flavones, flavanols, 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 families of seed plant Zhang et al. Natural phenolic compounds are commonly distributed in food and TCM Hao et al.

In a suspension culture of Bletilla striata Liu et al. 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 , , and 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. In light of the expanding knowledge of plant chemodiversity, it is possible to study the phylogenetic distribution of diverse types of compounds, e.

A triple helix systems perspective, i. Based on extensive ethnomedicinal uses, the thorough phytochemistry and bioactivity characterizations contribute to the safe administration of herbals and discovery of lead compounds Souza et al. In total, compounds were identified from essential oils EOs of six Lamiaceae herbs by GC-MS analysis Sun et al.

All EOs had promising anti-inflammatory activity in rats with adjuvant arthritis, and Perilla frutescens EO was the best. They alleviated the joint swelling in the rat models; the lymphocyte infiltration and cartilage damage were significantly inhibited.

The TNF-α, IL-1, and IL-6 were reduced in rat articular tissues by EOs. Six EOs had substantial toxicity on tumor cell lines; they also had the significant antioxidant activity, and Salvia japonica EO was the strongest. Berberine, baicalin and saponin from Coptis chinensis , Scutellaria baicalensis and Vincetoxicum atratum respectively were combined to produce the formula BBS Song et al.

Although these bottom-up and intermediate approaches cannot replace the top-down approach, i. The bioactivity studies provide more reference data for pharmacophylogeny research and drug discovery from ethnomedicinal plants.

The deeper investigations of genomics of curative plants, metabolomics, and ethnopharmacology-based bioactivity will enable the workable protection and consumption of botanical possessions.

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. 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.

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.

D-CH and C-NH prepared the draft and finalized the manuscript. P-GX and RS edited and corrected the draft. All authors contributed to the article and approved the submitted version. The authors are grateful to the Journal for presenting this Editorial article.

D-CH is supported by China Scholarship Council This work is also funded by the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine ZYYCXTDD and CAMS Innovation Fund for Medical Sciences CIFMS; I2M-1—