Anti-hepatoma activity and mechanism of ursolic acid and its derivatives isolated from Aralia decaisneana

瞄准：为了调查 ursolic (UA ) 和它的衍生物的反肿瘤活动，在肝细胞癌上从美┦木孤立 decaisneana 在试管内和在活体内。方法：在活体内细胞毒性被 3- 首先屏蔽[4,5-dimethylthiazol-2-yl ]-2, 5-diphenyltetrazolium 溴化物(MTT ) 试金。词法观察， DNA 梯子，流动血细胞计数分析，西方的污点和实时 PCR 被采用阐明 UA 的细胞毒素的机制。植入的老鼠肝细胞瘤 H22 被用来评估生长 UA 的禁止的效果在活体内。结果：UA 能显著地禁止 HepG2 和它的药抵抗的增长紧张， R-HepG2 房间，而是首先有教养的正常老鼠 hepatocytes 上的有的不禁止的效果而 UA 的所有六衍生物不能禁止所有的生长，测试房间排队。机制上的进一步的学习证明那 apoptosis 和 G0/G1 拘捕涉及多(自动数据处理核糖) 的细胞毒性和劈开聚合酶(PARP ) 。cyclooxygenase-2 (COX-2 ) 的 Downregulation 蛋白质并且在热吃惊蛋白质(HSP ) 的规定上面， 105 mRNA 相关到与 UA 对待的 HepG2 房间的 apoptosis。另外， UA 能也禁止 H22 肝细胞瘤在活体内的生长。结论：UA 是一个有希望的反肿瘤代理人，但是推进工作需要被做改进它的溶解度。

Herbal compound 861 regulates mRNA expression of collagen synthesis- and degradation-related genes in human hepatic stellate cells

AIM:To identify the role of herbal compound 861(Cpd 861)in the regulation of mRNA expression of collagen synthesis-and degradation-related genes in human hepatic stellate cells(HSCs). METHODS:mRNA levels of collagen typesⅠand III,matrix metalloproteinase 1(MMP-1),matrix metalloproteinase 2(MMP-2),membrane type-1 matrix metalloproteinase(MT1-MMP),tissue inhibitor of metalloproteinase 1(TIMP-1),and transforming growth factorβ1(TGF-β1)in cultured-activated HSCs treated with Cpd 861 or interferon-g(IFN-g)were determined by real-time PCR. RESULTS:Both Cpd 861 and IFN-g reduced the mRNA levels of collagen typeⅢ,MMP-2 and TGF-β1.Moreover, Cpd 861 significantly enhanced the MMP-1 mRNA levels while down-regulated the TIMP-1 mRNA expression, increasing the ratio of MMP-1 to TIMP-1 to(6.3+0.3)- fold compared to the control group. CONCLUSION:The anti-fibrosis function of Cpd 861 may be mediated by both decreased interstitial collagen sythesis by inhibiting the transcription of collagen type Ⅲand TGF-β1 and increased degradation of these collagens by up-regulating MMP-1 and down-regulating TIMP-1 mRNA levels.

Distribution patterns and industry planning of commonly used traditional Chinese medicinal plants in China

Medicinal plants are the primary material basis for disease prevention and treatment in traditional Chinese medicine(TCM).The conservation and sustainable utilization of these medicinal plants is critical for the development of the TCM industry.However,wild medicinal plant resources have sharply declined in recent decades.To ameliorate the shortage of medicinal plant resources,it is essential to explore the development potential of the TCM industry in different geographical regions.For this purpose,we examined the spatial distribution of commonly used medicinal plants in China,the number of Chinese medicinal material markets,and the number of TCM decoction piece enterprises.Specifically,multispecies superimposition analysis and Thiessen polygons were used to reveal the optimal range for planting bulk medicinal plants and the ideal regions for building Chinese medicinal material markets,respectively.Furthermore,we quantitatively analyzed mismatches between the spatial distribution of commonly used medicinal plant richness,Chinese medicinal material markets,and TCM decoction piece enterprises.We found that the areas suitable for growing commonly used medicinal plants in China were mainly distributed in Hengduan Mountain,Nanling Mountain,Wuling Mountain,and Daba Mountain areas.The Thiessen polygon network based on Chinese medicinal material market localities showed there are currently fewer markets in southwestern,northwestern,and northeastern China than in central and southern China.TCM decoction piece enterprises are concentrated in a few provinces,such as Hebei and Jiangxi.We found that the distribution of commonly used medicinal plants,Chinese medicinal material markets and TCM decoction piece enterprises are mismatched in Henan,Shaanxi,Hunan,Hubei,Zhejiang,Fujian,Chongqing,and Xizang.We recommend strengthening development of the TCM industry in Henan,Hunan,Zhejiang,Shaanxi,Hubei,Chongqing,Fujian,and Xizang;building more Chinese medicinal material markets in southwestern,northwestern,and northeastern China;and establishing medicinal plant nurseries in resource-rich provinces to better protect and domesticate local medicinal plants.

Quantitative and HPLC fingerprint analysis combined with chemometrics for quality evaluation of Codonopsis Radix processed with different methods

Objective: To observe the effect of different processing methods on the quality of Codonopsis Radix and provide data reference for the reasonable processing in the producing areas.Methods: An analytical strategy that combined quantitative and HPLC fingerprint analysis with chemometrics was developed for the quality evaluation of Codonopsis Radix. Lobetyolin, polysaccharide, sucrose,glucose, and fructose were detected simultaneously in Codonopsis Radix samples treated with different processing methods including dryer-drying, sun-drying, shade-drying, sulfur fumigation, and kneading,etc.Results: The results showed that different processing methods had an obvious impact on the quality of Codonopsis Radix. Sun-drying or shade-drying was recommended, and sulfur fumigation should be avoided. And dryer-drying at 40 °C-50 °C was suggested to meet the requirement for large scale processing. In addition, based on the content of polysaccharide, glucose, and fructose, it was advised to knead for three times. As for lobetyolin and sucrose, kneading should be avoided.Conclusions: Our findings demonstrated that processing method had a big impact on the quality of Codonopsis Radix. Based on the results, the appropriate processing methods directed at different requirements were recommended. The study could lay a foundation for the reasonable processing of Codonopsis Radix in producing areas.

A phytochemical study on Dichocarpum auriculatum, an endangered medicinal plant peculiar to China

Objective:Dichocarpum auriculatum,an endangered perennial herb,is endemic to China and has been used as folk medicines for the treatment of cough,hepatitis,scrofula,and epilepsy.However,there is no phytochemical report on this herbal so far.For the resource development and protective importance of this endangered medicinal plant,a phytochemical study was undertaken.Methods:The chemical constituents were purified by silica gel column,Sephadex LH-20 column,and semi-preparative reversed phase HPLC.NMR and MS spectra were used for structural identification.Results:Thirteen compounds were isolated from D.auriculatum.Their structures were characterized as jatrorrhizine(1),berberine(2),steponine(3),magnoflorine(4),coclauril(5),menisdaurin(6),menisdaurilide(7),aquilegiolide(8),(6 R,9 S)-3-oxo-α-ionol-β-D-glucopyranoside(9),blumenol C glucoside(10),palmitic acid(11),dibutylphthalate(12),and auriculatum A(13).Conclusion:Compound 13 is a new diester terephthalate derivative.All the compounds are obtained from the genus Dichocarpum for the first time,and compounds 9 and 10 have potential chemotaxonomic significance to the genus Dichocarpum.

Simultaneous determination of 15 flavonoids from different parts of Scutellaria baicalensis and its chemometrics analysis

Objective: The aerial parts of Scutellaria baicalensis were used as Huangqin Tea for thousands of years and mainly contain flavonoids which contribute to its bioactivities. However, there is no appropriate quality evaluation method of Huangqin Tea, and three flavanones of isocarthamidin-7-O-β-D-glucuronide,carthamidin-7-O-β-D-glucuronide, and isoscutellarein-8-O-β-D-glucuronide with high contents in the aerial parts have never been defined quantitatively. Here, an HPLC-DAD method for simultaneous determination of 15 flavonoids and systematically compared their contents and distribution in the roots,stems, leaves, and flowers of S. baicalensis was established.Methods: Under the HPLC-DAD chromatographic conditions, 77 batches of samples of S. baicalensis were analyzed. Meanwhile, the chromatographic fingerprint of different parts of S. baicalensis was established.Subsequently, principal component analysis(PCA), orthogonal projections to latent structures discriminant analysis(OPLS-DA), and clustering heat map were performed based on the contents of 15 flavonoids in different parts of S. baicalensis.Results: The results showed significant differences in the contents and distributions of 15 flavonoids among the different parts of S. baicalensis. The chemical composition of stems showed some similarities to leaves, and their contents were all lower than leaves. The contents of isocarthamidin-7-O-β–glucuronide [(106.66 66 ± 22.68) mg/g], carthamidin-7-O-β-D-glucuronide [(19.82 ± 11.17) mg/g],and isoscutellarein-8-O-β-D-glucuronide [(3.10 ± 1.73) mg/g] were the highest in leaves. The content of apigenin-7-O-β-D-glucopyranoside and chrysin-7-O-β-D-glucuronide were the highest in flowers. The contents of baicalin, baicalein, wogonoside, wogonin, alpinetin, and oroxylin A were higher in roots than in other parts.Conclusion: The method was fully validated and could be effectively used to characterize the contents and distributions of main flavonoids in the different parts of S. baicalensis. It may lay a foundation to establish the quality evaluation system for Huangqin Tea.

Chemical Constituents in Plants of Genus Kadsura Kaempf. ex Juss.

Genus Kadsura Kaempf. ex Juss. includes important medicinal plants widely used in the south and southwest of China. The stems and roots are effective in activating blood and resolving stasis, promoting q/circulation to relieve pain, dispelling wind and eliminating dampness, in which lignans and triterpenoids are the major bioactive constituents. Here we summarized the chemical constituents isolated from genus Kadsura Kaempf. ex Juss., which would provide a primary and strategic platform for further exploiting the medicinal value and resources of genus Kadsura Kaempf. ex Juss.

Chemical Constituents of Plants from Tribe Chelidonieae and their Bioactivities

The tribe Chelidonieae comprises 23 species of eight genera with an extensive distribution and a long medicinal usage history both in China and Western countries. A large number of chemical constituents have been isolated and identified from the species in tribe Chelidonieae, such as alkaloids, organic acids, and their derivatives, aromatics, triterpenoids, sterols, essential oils, and proteins, most of which possess a variety of bioactivities, especially for the antibacterial, anti-inflammation, antitumor, analgesia, anti-oxidation, and antiparasitic activity. Meanwhile, potential toxicities have been discovered in some constituents. Therefore, the species in tribe Chelidonieae have become a rich source for new drug discovery, biologic study, and mechanism research. This paper presents comprehensive information of the chemical constituents, pharmacological and toxicological research on the plants in tribe Chelidoieae, which is a reference for the plants in this tribe for further development.

Genus llex L.: Phytochemistry, Ethnopharmacology, and Pharmacology

The genus Ilex L. has been used as remedies in traditional Chinese medicine in Aquifoliaceae and beverages for thousands of years due to abundant pharmaceutical bioactivities. There are 600 species in genus IlexL. containing various compounds such as terpenoids, saponins, glycosides, etc. Three species, L cornuta, I. chinensis, and L rotunda have been admitted in Chinese Pharmacopoeia 2015 to treat dyspepsia, stomatitis, and hyperactivity cough and protect the liver and kidney. Recent studies showed that several species have been daily drunk to promote human health and prevent cardiovascular diseases in the folk. Here we reviewed the genus Ilex L. in phytochemistry, ethnopharmacology, and pharmacology.

Native Medicinal Plant Richness Distribution Patterns and Environmental Determinants of Xinjiang, Northwest China

Objective To comprehensively map the distribution patterns of native medicinal plants of Xinjiang Uygur Autonomous Region, China; To find the environmental determinants and to give suggestions for the conservation planning of medicinal plants in Xinjiang region. Methods Firstly, we compiled the distribution data of native medicinal plants at a county level in Xinjiang region, including the source plants of Chinese Materia Medica （CMM）, Uygur Medicine （UM）, and Kazak Medicine （KM）; Secondly, we divided the distribution data into grid with a resolution of 0.1~ x 0.1~ and overlaid it on the topography and climate data in Arcgis 10.0; Finally, we analyzed the correlations of medicinal plant richness and environmental variables with ordinary least square （OLS） regressions and partial regressions. Results UM has more non-native species in Xinjiang region than KM. The species richness of medicinal plants is high in Altay Mountains, western Tianshan Mountains, and part of Kunlun Mountains. The richness of medicinal plants is highly correlated with the vascular plant species richness and climate, and further, the independent effects of vascular plant species richness are higher than the independent effects of climate. The whole plant, root ＆ rhizome, and seed ＆ fruit are more frequently used than stem and leaf for CMM in Xinjiang region. Conclusion The distribution patterns of medicinal plants are concordant with vascular plant species, which could be carefully considered in the conservation planning of this region. Taking full advantage of current nature reserves is a low-costing approach to the conservation of medicinal plants although they were not originally established for medicinal plant protection. Nevertheless, it is urgent to further study the distributions and protection status of medicinal plants in the nature reserves of Xinjiang region.

Rhizosphere Microbiota and Microbiome of Medicinal Plants: From Molecular Biology to Omics Approaches

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.

A Cytotoxic Neolignan from Schisandra propinqua （Wall.） Baill.

In the course of our study of bioactive natural products from Schisandra plants, we isolated a neolignan from an EtOAc extract of the stems of Schisandra propinqua （Wall.） Baill. The structure of the new com- pound was determined to be 4, 4-di （4-hydroxy-3-methoxyphenly）-2, 3-dimethylbutanol （compound 1） on the basis of 1H- and 13C-NMR spectra and 2D NMR methods. Eight known compounds, compounds 2-9, were also isolated and identified, of which compounds 3, 4, 6 and 9 were isolated for the first time from this plant. In addition, compounds 1-4 were evaluated for cytotoxicity by an 3-（4,5-dimethyl-2 thiazoyl）-2,5-diphenyl-2H- tetrazolium bromide （MTT） assay. Compound 1 showed significant potential cytotoxic ability in the bioassay.

Deep in shadows:Epigenetic and epigenomic regulations of medicinal plants

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.

Non-Camellia Tea in China: Traditional usage, phytochemistry, and pharmacology

Non-Camellia Tea, as an integral part of Chinese tea culture for several centuries, is important to prevent chronic metabolic diseases. However, it was not systematically studied until academician Pei-gen Xiao defined it. Hereby, Non-Camellia Tea was reviewed systematically in definition, classification, traditional functions, chemical compositions, and pharmacology.

Inhibition of metabolic disorders in vivo and in vitro by main constituent of Coreopsis tinctoria

Objective：To investigate the effects of the ethyl acetate extract of Coreopsis tinctoria（EAEC）on insulin resistance（IR）in rats fed a high-fat diet.Methods：Male Sprague-Dawley（SD）rats were fed a HFD（60%fat）supplemented with EAEC for 8 weeks.The administration of EAEC to the rats with HFD-induced insulin resistance reduced hyperglycemia,plasma levels of insulin,and steatosis in the liver.Metabolomic study was used to analyze the metabolic levels of the high glucose-treated cells,control cells and marein-treated cells.Results：High glucose and high fat conditions caused a significant increase in blood glucose,insulin,serum TC,TG and LDL-C levels,leading to abnormal IR in rats.However,treatment with EAEC protects against HFD-induced IR by improving the fasting serum glucose homeostasis and lipid homeostasis.The high glucose conditions significantly decreased glycogen synthesis and increased PEPCK,G6Pase and Krebs cycle-related enzyme protein levels,leading to an abnormal metabolic state in Hep G2 cells.However,treatment with marein improved IR by increasing glucose uptake and glycogen synthesis and by downregulating PEPCK and G6Pase protein levels.The statistical analysis of the HPLC/MS data demonstrated that marein could restore the normal metabolic state.Conclusion：The results revealed that EAEC ameliorates IR in rats,and marein has the potential to improve IR by ameliorating glucose metabolism disorders.

Research on Quality Markers of Moutan Cortex: Quality Evaluation and Quality Standards of Moutan Cortex

Objective To identify the quality markers of Moutan Cortex（MC） and establish the quality evaluation methods for multi-component assay and fingerprinting of MC. Methods The chemical constituents in MC were identified by HPLC-QTOF-MS. UPLC was employed for the multi-component assay and fingerprinting of MC. Furthermore, text mining was carried out to review the biosynthesis pathways and pharmacological and pharmacokinetic studies related to MC, and in silico target fishing was conducted to construct compound-target networks for MC. Results Sixteen compounds were clearly identified in MC and their structures were confirmed through comparison with literature data. In addition, the biosynthetic pathways and component specificities of the identified compounds were summarized and confirmed by text mining.Pharmacological activities, including traditional usage and modern pharmacological studies were summarized. A total of 282 targets from Homo sapiens were fished for 13 compounds. In addition, pharmacokinetic studies of different compounds were synopsized. Finally, multi-component assay and fingerprint of MC were established. Conclusion Eight major components are selected as quality markers of MC, such as oxypaeoniflorin, apiopaeonoside, albiflorin, paeonolide, paeoniflorin, 1,2,3,4,6-penta-O-galloyl-β-D-glucose, mudanpioside C and paeonol. These eight quality markers are successfully applied to the quality evaluation of MC, and could be useful in improving the current quality standards of MC.

Towards a scientific rationale for traditional properties of Chinese medicinal plants: “natures” and “flavors”

Objective: According to theory of Chinese medicine property, the ecological environment shapes properties(natures and flavors) of Chinese materia medica(CMM) and there are close relationships between certain natures and flavors. However, to date these observations have not been validated scientifically in the context of the whole flora of a region. The present study aims to address this gap.Methods: We collected geographical distributions of 3637 vascular plant species native to the Xinjiang region of northwest China, of which around 812 are medicinal plants. The CMM property characters of these medicinal plants were also collected. All medicinal plants were then analyzed in the occurrence of their natures(cold, cool, neutral, warm, and hot) and flavors(sweet, bitter, sour, salty, and pungent). Possible correlations between these properties and environmental factors, notably climate, as well as correlations with plant species richness of the wider native flora of Xinjiang were then investigated using permutation test and regression.Results: Cold species(38.5%) were more numerous than warm(21.0%) and neutral(22.3%), while bitter species(43.3%) were more numerous than pungent(25.6%), sweet(22.4%) and sour(6.7%) ones. Species with bitter flavor were most commonly also cold(48.6%) in nature, sour flavor usually coincided with cold(44.2%) or cool nature(26.0%), whereas pungent or sweet species tended to be warm(34.4%, 28.4%) or neutral(27.8%, 28.4%). The percentages of species of cold/cool nature, bitter flavor were higher in mountainous regions, and the percentages of warm/neutral and pungent/sweet/sour were higher in basins. The percentages of species of cold/cool, bitter were positively correlated with actual evapotranspiration(AET),and also plant species richness but had a bell-shaped relationship with potential evapotranspiration(PET),whereas the inverse situation was shown for warm/neutral and pungent/sweet/sour species.Conclusion: Analysis of the data in Xinjiang region of China supports the qualitative observations concerning natures and flavors in traditional theory of Chinese medicine property. Specifically,(i) certain natures and flavors co-occur more frequently than if randomly distributed;(ii) correlations between proportions of natures and flavors and climatic variables suggest a role for the environment in shaping the properties of CMM.

Genome sizes of four important medicinal species in Kadsura by flow cytometry

Objective:Dianjixueteng is a geoherb in Yunnan Province,the source plant of which is Kadsura interior.However,the formation of this geoherb is not clear in genetic mechanism,in which genome size is the first step that should be known on the genomic level.In this study we aimed to estimate the genome sizes of source plants of K.interior and three related herbs K.heteroclita,K.longipedunculata,and K.coccinea by flow cytometry(FCM)and make a comparison.Methods:The genome sizes of K.interior,K.heteroclita,K.longipedunculata and K.coccinea,i.e.,the source plants of Dianjixueteng and its relative medicinal materials,were estimated by FCM.The nuclei of K.interior were isolated using modified LB01 buffer,for the rest species,by the Galbraith’s buffer.Results:The genome sizes of K.interior,K.heteroclita,K.longipedunculata,and K.coccinea were 7.36,7.12,7.01,and 5.15 pg/1 C,respectively.Genome size of K.interior had no significant variation with those of K.heteroclita and K.longipedunculata(P=0.296),which was significantly larger than that of K.coccinea.Conclusion:Genome size can not distinguish K.interior from K.heteroclita and K.longipedunculata,but could distinguish them from K.coccinea,which lays the foundation for future studies on genetic mechanism of the geoherb formation.

Pharmaceutical resource discovery from traditional medicinal plants:Pharmacophylogeny and pharmacophylogenomics

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.