Ethnopharmacology, chemodiversity, and bioactivity of Cephalotaxus medicinal plants / 中国天然药物

Cephalotaxus is the only genus of Cephalotaxaceae family, and its natural resources are declining due to habitat fragmentation, excessive exploitation and destruction. In many areas of China, folk herbal doctors traditionally use Cephalotaxus plants to treat innominate swollen poison, many of which are cancer. Not only among Han people, but also among minority ethnic groups, Cephalotaxus is used to treat various diseases, e.g., cough, internal bleeding and cancer in Miao medicine, bruises, rheumatism and pain in Yao medicine, and ascariasis, hookworm disease, scrofula in She medicine, etc. Medicinal values of some Cephalotaxus species and compounds are acknowledged officially. However, there is a lack of comprehensive review summarizing the ethnomedicinal knowledge of Cephalotaxus, relevant medicinal phytometabolites and their bioactivities. The research progresses in ethnopharmacology, chemodiversity, and bioactivities of Cephalotaxus medicinal plants are reviewed and commented here. Knowledge gaps are pinpointed and future research directions are suggested. Classic medicinal books, folk medicine books, herbal manuals and ethnomedicinal publications were reviewed for the genus Cephalotaxus (Sanjianshan in Chinese). The relevant data about ethnobotany, phytochemistry, and pharmacology were collected as comprehensively as possible from online databases including Scopus, NCBI PubMed, Bing Scholar, and China National Knowledge Infrastructure (CNKI). "Cephalotaxus", and the respective species name were used as keywords in database search. The obtained articles of the past six decades were collated and analyzed. Four Cephalotaxus species are listed in the official medicinal book in China. They are used as ethnomedicines by many ethnic groups such as Miao, Yao, Dong, She and Han. Inspirations are obtained from traditional applications, and Cephalotaxus phytometabolites are developed into anticancer reagents. Cephalotaxine-type alkaloids, homoerythrina-type alkaloids and homoharringtonine (HHT) are abundant in Cephalotaxus, e.g., C. lanceolata, C. fortunei var. alpina, C. griffithii, and C. hainanensis, etc. New methods of alkaloid analysis and purification are continuously developed and applied. Diterpenoids, sesquiterpenoids, flavonoids, lignans, phenolics, and other components are also identified and isolated in various Cephalotaxus species. Alkaloids such as HHT, terpenoids and other compounds have anticancer activities against multiple types of human cancer. Cephalotaxus extracts and compounds showed anti-inflammatory and antioxidant activities, immunomodulatory activity, antimicrobial activity and nematotoxicity, antihyperglycemic effect, and bone effect, etc. Drug metabolism and pharmacokinetic studies of Cephalotaxus are increasing. We should continue to collect and sort out folk medicinal knowledge of Cephalotaxus and associated organisms, so as to obtain new enlightenment to translate traditional tips into great therapeutic drugs. Transcriptomics, genomics, metabolomics and proteomics studies can contribute massive information for bioactivity and phytochemistry of Cephalotaxus medicinal plants. We should continue to strengthen the application of state-of-the-art technologies in more Cephalotaxus species and for more useful compounds and pharmacological activities.

Pharmaceutical resource discovery from traditional medicinal plants: Pharmacophylogeny and pharmacophylogenomics / 中草药·英文版

The worldwide botanical and medicinal culture diversity are astonishing and constitute a Pierian spring for innovative drug R&D. Here, the latest awareness and the perspectives of pharmacophylogeny and pharmacophylogenomics, as well as their expanding utility in botanical drug R&D, are systematically summarized and highlighted. Chemotaxonomy is based on the fact that closely related plants contain the same or similar chemical profiles. Correspondingly, it is better to combine morphological characters, DNA markers and chemical markers in the inference of medicinal plant phylogeny. Medicinal plants within the same phylogenetic groups may have the same or similar therapeutic effects, thus forming the core of pharmacophylogeny. Here we systematically review and comment on the versatile applications of pharmacophylogeny in (1) looking for domestic resources of imported drugs, (2) expanding medicinal plant resources, (3) quality control, identification and expansion of herbal medicines, (4) predicting the chemical constituents or active ingredients of herbal medicine and assisting in the identification and determination of chemical constituents, (5) the search for new drugs sorting out, and (6) summarizing and improving herbal medicine experiences, etc. Such studies should be enhanced within the context of deeper investigations of molecular biology and genomics of traditional medicinal plants, phytometabolites and metabolomics, and ethnomedicine-based pharmacological activity, thus enabling the sustainable conservation and utilization of traditional medicinal resources.

Deep in shadows: Epigenetic and epigenomic regulations of medicinal plants / 中草药·英文版

Around 60% of the extant plants have medicinal and health-promoting values. Genuine medicinal material (geoherb) is produced in particular geographic regions, that is defined ecological environment and cultivation pipeline. The clinical efficacy of a geoherb is superior to that of the same medicinal plant growing in other regions. The special medicinal features of a plant are determined by its genome, while the proper ecological conditions have major effects on the formation of a geoherb, which is at least partially mediated by the epigenetics. By epigenetics/epigenomics, researchers uncover the complexities of the influence of the environment on the expression of genes that control medicinal plant growth, development, stress responses, and medicinal phytometabolite yield, and put the other “omics layers” in a meaningful biological context. The unique phenotypes of geoherb are closely related to the growth, development, and stress responses of medicinal plants. In addition to the commonly known genetic control, epigenetic machineries, active at the population level, play an essential role in the formation of geoherbs. This contribution gives a comprehensive overview of the epigenetic regulation of medicinal plants, and the associated microbes, and the role of DNA methylation, small non-coding RNA, transposable elements, and histone modifications in the gene expression regulation of geoherbs and relevant microbiota. The epigenetic and epigenomic mechanisms should be highlighted in the study of specific phenotype and indigenousness of geoherbalism. Revealing the correlation between epigenetics and geoherbs could shed light on the quality assessment, authentication, molecular breeding, and sustainable utilization of medicinal plants and the associated microbes.

Rhizosphere Microbiota and Microbiome of Medicinal Plants: From Molecular Biology to Omics Approaches / 中草药·英文版

The rhizosphere is a narrow region of soil that is directly influenced by roots and associated soil microorganisms. Research on rhizosphere microbes of various medicinal plants is essential for microbial ecology, applied microbiology and industrial biotechnology with regard to the sustainable utilization of Chinese medicinal resources. However, the inability of culturing most rhizosphere microorganisms (around 99%) in the laboratory obviates the research progress. In recent years, there is enormous advances in applying non-culturing techniques based on molecular biology and omics to the study of rhizosphere microbial diversity and plant-microbe interactions. DGGE, T-RFLP, ARDRA, DNA cloning and Sanger sequencing are still useful in the rhizosphere studies, while various omics tools, such as FISH, SIP, microarray, next generation sequencing (NGS), etc., evolve quickly to provide more comprehensive understanding of the rhizosphere microbiota and microbiome. Flexible applications of NGS technologies are here exemplified, e.g., amplicon sequencing, metagenomic sequencing, whole genome sequencing, and transcriptome sequencing, which address the biology and biotechnology potentials of the rhizosphere microbiome of medicinal plants. This review discusses recent findings and future challenges in the study of rhizosphere microbes, highlighting medicinal plant rhizosphere study, evolution of research methods, and innovative combinations of novel high-throughput techniques. The top-down approaches such as metagenomics and bottom-up approaches targeting individual species or strains should be integrated and combined with modeling approaches to afford a wide-ranging understanding of the microbial community as a whole.

medicinal plants: ethnopharmacology, phytochemistry and biology

The Ranunculaceae genus(order Ranunculales), comprising more than 150 species, mostly herbs, has long been used in folk medicine and worldwide ethnomedicine. Various medicinal compounds have been found inplants, especially triterpenoid saponins, some of which have shown anti-cancer activities. Somecompounds and extracts display immunomodulatory, anti-inflammatory, antioxidant, and antimicrobial activities. More than 50 species have ethnopharmacological uses, which provide clues for modern drug discovery.compounds exert anticancer and other bioactivitiesmultiple pathways. However, a comprehensive review of themedicinal resources is lacking. We here summarize the ethnomedical knowledge and recent progress on the chemical and pharmacological diversity ofmedicinal plants, as well as the emerging molecular mechanisms and functions of these medicinal compounds. The phylogenetic relationships ofspecies were reconstructed based on nuclear ITS and chloroplast markers. The molecular phylogeny is largely congruent with the morphology-based classification. Commonly used medicinal herbs are distributed in each subgenus and section, and chemical and biological studies of more unexplored taxa are warranted. Gene expression profiling and relevant "omics" platforms could reveal differential effects of phytometabolites. Genomics, transcriptomics, proteomics, and metabolomics should be highlighted in deciphering novel therapeutic mechanisms and utilities ofphytometabolites.

Research progress of human cytochrome P450 2J2 and its ligands / 药学学报

Cytochrome P4502J2 (CYP2J2) is widely distributed in various human tissues and takes a part in the metabolism of endogenous compounds and drugs. CYP2J2 can convert arachidonic acid (AA) to expoxyeicosatrienoic acids (EETs), which have various biological effects, implying the important role of CYP2J2 in the regulation of cardiovascular system and promotion of tumor progression and metastasis. Additionally, CYP2J2 plays an indispensable role in the intestinal metabolism of various drugs, such as astemizole, terfenadine and ebastine. In this review, the metabolic function, characteristic of catalysis and tissue distribution of CYP2J2 are discussed with the latest literatures both in China and abroad. The state-of-the-art methods for characterization of CYP2J2 and current trend of substrate discovery as well as its relationship with disease are highlighted. This review gives in-depth understanding of the function of CYP2J2 and its role in disease advance. The information of ligand (substrate and inhibitor) will provide the theoretical guidance and reference to the development of novel drugs for CYP2J2.

Research and analysis of globally ecological suitability for Taxus plants / 药学学报

At present, taxol is an internationally acknowledged drug with a unique anticancer activity in the world and mainly come from Taxus plants, these plants have 12 species, all of which have been listed as endangered tree species and protected by the countries concerned. But available wild Taxus plants resources are rather rare, so it is very urgent to strengthen introduction and cultivation of Taxus plants to meet people's demand for taxol. According to the ecological similarity of growth of Taxus plants predict suitable areas in the whole world, which could put forward rational suggestions for introduction and planning production layout of plants. A geographic information system for global medicinal plants(GMPGIS)was developed by Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences independently, and using GMPGIS analyzed in detail the potential ecological suitable areas of Taxus plants. Ecological range of Taxus wallichiana var. chinensis, Taxus wallichiana var. mairei, Taxus baccata, Taxus brevifolia and Taxus wallichiana covered a wide field, and had larger suitable area in the northern and southern hemispheres; Taxus cuspidate mainly distributed in the northern hemisphere, and only scattered in the southern hemisphere; Taxus canadensis, Taxus floridana and Taxus cuspidata var. nana only distributed in the northern hemisphere, and the latter two prediction areas are relatively less areas; Taxus fauna, Taxus globosa and Taxus sumatrana grew up in relatively strict environment, belong to the niche species, scattered distribution and the distribution of the areas are rare. This research would exert an important promoting effect on the cultivation of Taxus plants and the escalation of abundance to guarantee the sufficient supply of raw materials for taxol production. Finally, this paper summarized the research on the ecological quality and resource conservation of Taxus plants, to provide the reference for scientific introduction and cultivation of Taxus plants.

Recent advances in phytochemistry and pharmacology of C21 steroid constituents from Cynanchum plants / 中国天然药物

Cynanchum is one of the most important genera in Asclepiadaceae family, which has long been known for its therapeutic effects. In this genus, 16 species are of high medicinal value. The extracts of the root and/or rhizome parts have been applied in traditional Chinese medicines (TCM) for the prevention and treatment of various illnesses for centuries. C21 steroids, as the typical constituents of Cynanchum species, possess a variety of structures and pharmacological activities. This review summarizes the comprehensive information on phytochemistry and pharmacology of C21 steroid constituents from Cynanchum plants, based on reports published between 2007 and 2015. Our aim is to provide a rationale for their therapeutic application, and to discuss the future trends in research and development of these compounds. A total of 172 newly identified compounds are reviewed according to their structural classifications. Their in vitro and in vivo pharmacological studies are also reviewed and discussed, focusing on antitumor, antidepressant, antifungal, antitaging, Na(+)/K(+)-ATPase inhibitory, appetite suppressing and antiviral activities. Future research efforts should concentrate on in vitro and in vivo biological studies and structure activity relationship of various C21 steroid constituents.

Essentials of pharmacophylogeny: knowledge pedigree, epistemology and paradigm shift / 中国中药杂志

Chinese materia medica resource (CMM resource) is the foundation of the development of traditional Chinese medicine. In the study of sustainable utilization of CMM resource, adopting innovative theory and method to find new CMM resource is one of hotspots and always highlighted. Pharmacophylogeny interrogates the phylogenetic relationship of medicinal organisms (especially medicinal plants), as well as the intrinsic correlation of morphological taxonomy, molecular phylogeny, chemical constituents, and therapeutic efficacy (ethnopharmacology and pharmacological activity). This new discipline may have the power to change the way we utilize medicinal plant resources and develop plant-based drugs. Phylogenomics is the crossing of evolutionary biology and genomics, in which genome data are utilized for evolutionary reconstructions. Phylogenomics can be integrated into the flow chart of drug discovery and development, and extends the field of pharmacophylogeny at the omic level, thus the concept of pharmacophylogenomics could be redefined in the context of plant pharmaceutical resources. This contribution gives a brief discourse of knowledge pedigree of pharmacophylogeny, epistemology and paradigm shift, highlighting the theoretical and practical values of pharmacophylogenomics. Many medicinally important tribes and genera, such as Clematis, Pulsatilla, Anemone, Cimicifugeae, Nigella, Delphinieae, Adonideae, Aquilegia, Thalictrum, and Coptis, belong to Ranunculaceae family. Compared to other plant families, Ranunculaceae has the most species that are recorded in China Pharmacopoeia (CP) 2010. However, many Ranunculaceae species, e. g., those that are closely related to CP species, as well as those endemic to China, have not been investigated in depth, and their phylogenetic relationship and potential in medicinal use remain elusive. As such, it is proposed to select Ranunculaceae to exemplify the utility of pharmacophylogenomics and to elaborate the new concept empirically. It is argued that phylogenetic and evolutionary relationship of medicinally important tribes and genera within Ranunculaceae could be elucidated at the genomic, transcriptomic, and metabolomic levels, from which the intrinsic correlation between medicinal plant genotype and metabolic phenotype, and between genetic diversity and chemodivesity of closely related taxa, could be revealed. This proof-of-concept study regards pharmacophylogenomics as the updated version of pharmacophylogeny and would enrich the intension and spread the extension of pharmacophylogeny. The interdisciplinary knowledge and techniques will be integrated in the proposed study to promote development of CMM resource discipline and to boost sustainable development of Chinese medicinal plant resources.

Mining chemodiversity from biodiversity: pharmacophylogeny of medicinal plants of Ranunculaceae / 中国天然药物

This paper reports a pharmacophylogenetic study of a medicinal plant family, Ranunculaceae, investigating the correlations between their phylogeny, chemical constituents, and pharmaceutical properties. Phytochemical, ethnopharmacological, and pharmacological data were integrated in the context of the systematics and molecular phylogeny of the Ranunculaceae. The chemical components of this family included several representative metabolic groups: benzylisoquinoline alkaloids, ranunculin, triterpenoid saponin, and diterpene alkaloids, among others. Ranunculin and magnoflorine were found to coexist in some genera. The pharmacophylogenetic analysis, integrated with therapeutic information, agreed with the taxonomy proposed previously, in which the family Ranunculaceae was divided into five sub-families: Ranunculoideae, Thalictroideae, Coptidoideae, Hydrastidoideae, and Glaucidioideae. It was plausible to organize the sub-family Ranunculoideae into ten tribes. The chemical constituents and therapeutic efficacy of each taxonomic group were reviewed, revealing the underlying connections between phylogeny, chemical diversity, and clinical use, which should facilitate the conservation and sustainable utilization of the pharmaceutical resources derived from the Ranunculaceae.

Recent advance in chemical and biological studies on cimicifugeae pharmaceutical resources / 中草药·英文版

Cimicifugeae is one of the rich sources for various active components and the health promoting and therapeutic values of the components have been corroborated by long-term use in folk medicine and traditional Chinese medicine. Increasing interest in Cimicifugeae pharmaceutical resources has led to the further discoveries of triterpenoid saponins, phenolic compounds, chromones, and many other compounds in various species of Cimicifugeae, and to the investigations on their chemotaxonomy, molecular phylogeny, and bioactivities. Based on our pharmacophylogenetic studies, the progress in phytochemistry, chemotaxonomy, molecular biology, and phylogeny of Cimicifugeae had been summarized since 2007, especially Cimicifuga L. ex Wernisch. and Actaea L., and their relevance to therapeutic efficacy. An exhaustive literature survey is used to characterize the global scientific effort in the phytochemical and biological studies of Cimicifugeae. More triterpenoid saponins have been found in various species, among which the cimigenol type (type A) is predominant. The versatile bioactivities of saponins and extracts, as well as those of phenolics and other ingredients, were summarized and discussed. The morphology-based five-genus classification of Cimicifugeae is not supported by molecular phylogeny. Molecular phylogeny based on nuclear and chloroplast DNA sequences tends to merge Cimicifuga Wernisch., Souliea Franch., and Actaea L. into a single genus. It is indispensable to integrate the emerging technologies into Cimicifugeae research for both the sustainable utilization of Cimicifugeae pharmaceutical resources and finding novel compounds with potential clinical utility and less adverse effects. Systems biology and omics technologies would play an increasingly important role in booming pharmaceutical research involving bioactive compounds of Cimicifugeae. © 2013 Tianjin Press of Chinese Herbal Medicines.

Pharmaphylogeny vs. pharmacophylogenomics: molecular phylogeny, evolution and drug discovery / 药学学报

With the surge of high-throughput sequencing technology, it is becoming popular to perform the phylogenetic study based on genomic data. A bundle of new terms is emerging, such as phylogenomics, pharmacophylogenomics and phylotranscriptomics, which are somewhat overlapping with pharmaphylogeny. Phylogenomics is the crossing of evolutionary biology and genomics, in which genome data are utilized for evolutionary reconstructions. Pharmaphylogeny, advocated by Prof. Pei-gen Xiao since 1980s, focuses on the phylogenetic relationship of medicinal plants and is thus nurtured by molecular phylogeny, chemotaxonomy and bioactivity studies. Phylogenomics can be integrated into the flow chart of drug discovery and development, and extend the field of pharmaphylogeny at the omic level, thus the concept of pharmacophylogenomics could be redefined. This review gives a brief analysis of the association and the distinguished feature of the pharmaphylogeny related terms, in the context of plant-based drug discovery and sustainable utilization of pharmaceutical resource.

Phytochemical and biological research of Fritillaria medicine resources / 中国天然药物

The genus Fritillaria is a botanical source for various pharmaceutically active components, which have been commonly used in traditional Chinese medicine for thousands of years. Increasing interest in Fritillaria medicinal resources has led to additional discoveries of steroidal alkaloids, saponins, terpenoids, glycosides and many other compounds in various Fritillaria species, and to investigations on their chemotaxonomy, molecular phylogeny and pharmacology. In continuation of studies on Fritillaria pharmacophylogeny, the phytochemistry, chemotaxonomy, molecular biology and phylogeny of Fritillaria and their relevance to drug efficacy is reviewed. Literature searching is used to characterize the global scientific effort in the flexible technologies being applied. The interrelationship within Chinese Bei Mu species and between Chinese species, and species distributed outside of China, is clarified by the molecular phylogenetic inferences based on nuclear and chloroplast DNA sequences. The incongruence between chemotaxonomy and molecular phylogeny is revealed and discussed. It is essential to study more species for both the sustainable utilization of Fritillaria medicinal resources and for finding novel compounds with potential clinical utility. Systems biology and omics technologies will play an increasingly important role in future pharmaceutical research involving the bioactive compounds of Fritillaria.

Research progress and trend analysis of biology and chemistry of Taxus medicinal resources / 药学学报

Taxus is the source plant of anti-cancer drug paclitaxel and its biosynthetic precursor, analogs and derivatives, which has been studying for decades. There are many endemic Taxus species in China, which have been studied in the field of multiple disciplines. Based on the recent studies of the researchers, this review comments on the study of Taxus biology and chemistry. The bibliometric method is used to quantify the global scientific production of Taxus-related research, and identify patterns and tendencies of Taxus-related articles. Gaps are present in knowledge about the genomics, epigenomics, transcriptomics, proteomics, metabolomics and bioinformatics of Taxus and their endophytic fungi. Systems biology and various omics technologies will play an increasingly important role in the coming decades.