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.

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.
China ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Knowledge ; Medicine, Chinese Traditional ; Phylogeny ; Plants, Medicinal ; chemistry ; classification ; genetics

Objective To investigate the correlation between virtual touch tissue quantification (VTQ) and the pathological grading of liver fibrosis in chronic hepatitis B.Methods 64 chronic hepatitis B patients (the chronic hepatitis group) and 40 healthy volunteers (the controlled group) were collected.The patients in the chronic hepatitis group were underwent liver biopsy.According to the hepatic fibrosis degree,the patients in the test group were classified into stage 0,1,2,3 and 4.The liver shear wave velocities (SWV) of all the participant were measured by VTQ.The cut-off values were determined by an analysis of receiver operating characteristic (ROC) curve.Results The mean SWV was (1.04± 0.13)m/s in the controlled group.The SWV in stages 0,1,2,3,and 4 were (1.17 ± 0.08)m/s,(1.33 ± 0.32)m/s,(1.53 ±0.32) m/s,(2.09 ± 0.54) m/s,(2.18 ± 0.70) m/s,respectively.There was a significantly difference in SWV between the controlled group and the chronic hepatitis group (F =34.97,P =0.00).The SWV were significantly different not only between stages 0-2,and 3,but also between 0-2 and 4 (F =8.87,P =0.00).A positive correlation was observed between the liver fibrosis and the SWV in the chronic hepatitis group (r =0.67,P =0.00).When a cut off value was set at 1.43 m/s,area under ROC curve was 0.875.The sensitivity and specificity were 100 ％ and 62.5 ％.Conclusions SWV has a better correlation with liver fibrosis.VTQ can make an accurate assessment for stage 3 and stage 4 of the chronic hepatitis B.Therefore,VTQ can be used as a noninvasive and reliable diagnostic indicator for chronic hepatitis B.

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.

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.

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.

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.
Drug Discovery ; Pharmacogenetics ; Phylogeny ; Plants, Medicinal ; chemistry ; genetics

OBJECTIVETo observe the efficacy of Chinese herbs for supplementing qi and activating blood circulation (CHSQABC) on patients with acute coronary syndrome (ACS) and type 2 diabetes mellitus (DM) after successful percutaneous coronary intervention (PCI).

METHODSIn this ChiCTR-TRC-00000021, a total of 281 ACS patients complicated with type 2 DM after successful PCI were randomly assigned to the Western medicine treatment group (the control group, treated by routine Western medicine treatment) and the combined treatment group (the treatment group, treated by CHSQABC + routine Western medicine treatment). Patients in the combined treatment group took Xinyue Capsule (2 pills each time, 3 times per day) and Compound Chuanxiong Capsule (2 pills each time, 3 times per day for half a year and 1-year follow-ups). Primary endpoints covered incidence of death, nonfatal myocardial infarction (MI), ischemia-driven revascularization, and secondary endpoints included stroke, heart failure, and rehospitalization for ACS. At the same time scores for blood stasis syndrome (BSS) and the incidence of angina pectoris were evaluated before treatment, at month 1, 3, 6, 9, and 12 after treatment.

RESULTSThe incidence of ischemia-driven revascularization was obviously less in the treatment group than in the control group (P < 0.05). No patient had nonfatal MI in the treatment group, while 5 patients in the control group had it. The incidence of non-fatal MI showed an obvious lowering tendency in the treatment group, but with no statistical difference when compared with that in the control group (P > 0.05). Four patients readmitted to hospital in the treatment group, while 12 patients readmitted. There existed obvious tendency in the treatment group, but with no statistical difference when compared with that in the control group (P > 0.05). The incidence of angina was significantly lower in the treatment group at month 6, 9, and 12 than that at month 1 , but it was lower in the control group at 9 months (P < 0.05). The incidence of angina was 15. 4% in the treatment group, obviously lower than that in the control group (26.2%, P < 0.05). Compared with before treatment, scores for BSS were obviously lowered in the treatment group at 1, 3, 6, 9, and 12 months of treatment and in the control group at 3, 6, 9, and 12 months of treatment (P < 0.05). It was obviously lower in the treatment group than in the control group at 3, 6, 9, and 12 months of treatment (P < 0.01).

CONCLUSIONAdministration of CHSQABC combined routine Western medicine treatment could reduce the event of revascularization and post-PCI recurrent angina, and improve scores for BSS of ACS patients complicated with DM after PCI.

Acute Coronary Syndrome ; complications ; surgery ; therapy ; Angina Pectoris ; Combined Modality Therapy ; Diabetes Mellitus, Type 2 ; complications ; therapy ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Incidence ; Medicine, Chinese Traditional ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Qi

Nucleos(t)ide analogues (NA) are widely used to treat hepatitis B virus (HBV) infection, but they cannot eradicate the virus and treatment duration can be lifelong if the endpoint is set at seroclearance of the hepatitis B surface antigen (HBsAg). As an alternative strategy, finite NA therapy without the prerequisite of HBsAg seroclearance has been proposed to allow treatment cessation in patients with sustained undetectable HBV viremia for two to three years. However, reactivation of viral replication almost always follows NA withdrawal. Whereas HBV reactivation might facilitate HBsAg seroclearance in some, it could lead to serious acute flare-ups in a certain proportion of patients. Occurrence and consequences of NA withdrawal flares are complicated with various factors involving the virus, host, and treatment. Accurate risk prediction for severe flares following NA cessation is essential to ensure patient safety. The risks of life-threatening flares in patients who discontinued NA according to the stopping rules of current guidelines or local reimbursement policies have recently been quantitatively estimated in large-scale studies, which also provided empirical evidence to help identify vulnerable patients at risk of devastating outcomes. Moreover, risk predictors were further explored and validated to hopefully aid in patient selection and management. In this narrative review with a focus on patient safety, we summarize and discuss current literature on the incidence of severe flares following NA cessation, risk stratification for candidate selection, rules of posttreatment monitoring, and indications for treatment resumption. We also share our thoughts on the limitations of existing knowledge and suggestions for future research.

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.
Animals ; China ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Fritillaria ; chemistry ; classification ; Humans ; Molecular Structure ; Phylogeny ; Plants, Medicinal ; chemistry ; classification