R2 R3-MYB transcription factors are ubiquitous in plants, playing a role in the regulation of plant growth, development, and secondary metabolism. In this paper, the R2 R3-MYB transcription factors were identified by bioinformatics analysis of the genomic data of Erigeron breviscapus, and their gene sequences, structures, physical and chemical properties were analyzed. The functions of R2 R3-MYB transcription factors were predicted by cluster analysis. Meanwhile, the expression patterns of R2 R3-MYB transcription factors in response to hormone treatments were analyzed. A total of 108 R2 R3-MYB transcription factors, named EbMYB1-EbMYB108, were identified from the genome of E. breviscapus. Most of the R2 R3-MYB genes carried 2-4 exons. The phylogenetic tree of MYBs in E. breviscapus and Arabidopsis thaliala was constructed, which classified 234 MYBs into 30 subfamilies. The MYBs in the five MYB subfamilies of A.thaliala were clustered into independent clades, and those in E. breviscapus were clustered into four clades. The transcriptome data showed that MYB genes were differentially expressed in different tissues of E. breviscapus and in response to the treatments with exogenous hormones such as ABA, SA, and GA for different time. The transcription of 13 R2 R3-MYB genes did not change significantly, and the expression patterns of some genes were up-regulated or down-regulated with the extension of hormone treatment time. This study provides a theoretical basis for revealing the mechanisms of R2 R3-MYB transcription factors in regulating the growth and development, stress(hormone) response, and active ingredient accumulation in E. breviscapus.
Erigeron/genetics* ; Gene Expression Regulation, Plant ; Genes, myb ; Phylogeny ; Plant Proteins/metabolism* ; Transcription Factors/metabolism*

Alzheimer's disease(AD) is a neurodegenerative disease that has no effective drug to cure it. Studies in several AD models have shown that Erigeron breviscapus and its active ingredients(scutellarin and caffeoylquinic acid) could improve/enhance the learning and memory ability, and the mechanisms are associated with inhibiting amyloid β(Aβ) production, aggregation, fibrosis and Aβ neurotoxicity toxicity, regulating cholinergic nervous system, inhibiting oxidative stress and inflammation, inhibiting tau hyperphosphorylation, improving mitochondrial function, and resisting neuronal apoptosis. This article systematically reviewed the research progress of E. breviscapus and its active ingredients for treatment of AD in AD models, in the expectation of providing references for further development of E. breviscapus's medicinal potential.
Alzheimer Disease ; Amyloid beta-Peptides ; Erigeron ; Humans ; Neurodegenerative Diseases

Dengzhan Shengmai Capsules( DZSMC),a well-known traditional Chinese medicine( TCM) formula,is comprised of the main drug of Erigeron breviscapus,and supplemented with Panax ginseng,Ophiopogon japonicus and Schisandra chinensis,with functions of supplementing Qi and nourishing Yin,promoting blood circulation and strengthening brain. DZSMC is the only Chinese patent drug with A-level evidence-based medicine in secondary prevention for stroke and ranks first among TCMs for neurological treatment. Modern studies indicate that the chemical constituents of DZSMC mainly include flavonoids,phenolic acids,lignans,saponins and so on. Pharmacological experimental studies have shown that DZSMC has such pharmacological effects as anti-oxidation,anti-inflammatory and anti-myocardial ischemia. DZSMC is mainly used in the convalescent care of ischemic cardiovascular and cerebrovascular diseases,and is often used in combination with various conventional therapeutic drugs to exert clinical efficacy through brain protection,neuroprotection,etc.,and improve clinical symptoms in patients. In this review,according to domestic and international related literature combined with research results obtained by our project,the research advances in the chemical constituents,pharmacological effects and clinical application of DZSMC have been systematically reviewed and summarized,providing reference and support for further study and secondary development of the formula.
Drugs, Chinese Herbal/pharmacology* ; Erigeron/chemistry* ; Humans ; Medicine, Chinese Traditional ; Ophiopogon ; Panax ; Phytochemicals/pharmacology* ; Phytotherapy ; Schisandra

Flavonoids are plant pigments that have been demonstrated to exert various pharmacological effects including anti-cancer, anti-diabetic, anti-atherosclerotic, anti-bacterial, and anti-inflammatory activities. However, the molecular mechanisms in terms of exact target proteins of flavonoids are not fully elucidated yet. In this study, we aimed to evaluate the anti-inflammatory mechanism of scutellarein (SCT), a flavonoid isolated from Erigeron breviscapus, Clerodendrum phlomidis and Oroxylum indicum Vent that have been traditionally used to treat various inflammatory diseases in China and Brazil. For this purpose, a nitric oxide (NO) assay, polymerase chain reaction (PCR), nuclear fractionation, immunoblot analysis, a kinase assay, and an overexpression strategy were employed. Scutellarein significantly inhibited NO production in a dose-dependent manner and reduced the mRNA expression levels of inducible NO synthase (iNOS) and tumor necrosis factor (TNF)-alpha in lipopolysaccharide (LPS)-activated RAW264.7 cells. In addition, SCT also dampened nuclear factor (NF)-kappaB-driven expression of a luciferase reporter gene upon transfection of a TIR-domain-containing adapter-inducing interferon-beta (TRIF) construct into Human embryonic kidney 293 (HEK 293) cells; similarly, NF-kappa B nuclear translocation was inhibited by SCT. Moreover, the phosphorylation levels of various upstream signaling enzymes involved in NF-kappaB activation were decreased by SCT treatment in LPS-treated RAW264.7 cells. Finally, SCT strongly inhibited Src kinase activity and also inhibited the autophosphorylation of overexpressed Src. Therefore, our data suggest that SCT can block the inflammatory response by directly inhibiting Src kinase activity linked to NF-kappaB activation.
Brazil ; China ; Clerodendrum ; Erigeron ; Flavonoids ; Genes, Reporter ; Humans ; Interferon-beta ; Kidney ; Luciferases ; Macrophages ; NF-kappa B ; Nitric Oxide ; Nitric Oxide Synthase ; Phosphorylation ; Phosphotransferases* ; Plants ; Polymerase Chain Reaction ; RNA, Messenger ; Transfection ; Tumor Necrosis Factor-alpha

BACKGROUND/OBJECTIVES: In this study, we determined the anti-inflammatory activities and the underlying molecular mechanisms of the methanol extract from Erigeron Canadensis L. (ECM) in LPS-stimulated RAW264.7 macrophage cells. MATERIALS/METHODS: The potential anti-inflammatory properties of ECM were investigated by using RAW264.7 macrophages. We used western blot assays and real time quantitative polymerase chain reaction to detect protein and mRNA expression, respectively. Luciferase assays were performed to determine the transactivity of transcription factors. RESULTS: ECM significantly inhibited inducible nitric oxide synthase (iNOS)-derived NO and cyclooxygenase-2 (COX-2) derived PGE2 production in LPS-stimulated RAW264.7 macrophages. These inhibitory effects of ECM were accompanied by decreases in LPS-induced nuclear translocations and transactivities of NFkappaB. Moreover, phosphorylation of mitogen-activated protein kinase (MAPKs) including extracellular signal-related kinase (ERK1/2), p38, and c-jun N-terminal kinase (JNK) was significantly suppressed by ECM in LPS-stimulated RAW264.7 macrophages. Further studies demonstrated that ECM by itself induced heme oxygenase-1 (HO-1) protein expression at the protein levels in dose-dependent manner. However, zinc protoporphyrin (ZnPP), a selective HO-1 inhibitor, abolished the ECM-induced suppression of NO production. CONCLUSIONS: These results suggested that ECM-induced HO-1 expression was partly responsible for the resulting anti-inflammatory effects. These findings suggest that ECM exerts anti-inflammatory actions and help to elucidate the mechanisms underlying the potential therapeutic values of Erigeron Canadensis L.
Blotting, Western ; Cyclooxygenase 2 ; Dinoprostone ; Erigeron* ; Heme Oxygenase-1* ; JNK Mitogen-Activated Protein Kinases ; Luciferases ; Macrophages* ; Methanol* ; Nitric Oxide ; Nitric Oxide Synthase Type II ; Phosphorylation ; Phosphotransferases ; Polymerase Chain Reaction ; Protein Kinases ; RNA, Messenger ; Transcription Factors ; Up-Regulation* ; Zinc

BACKGROUND/OBJECTIVES: In this study, we determined the anti-inflammatory activities and the underlying molecular mechanisms of the methanol extract from Erigeron Canadensis L. (ECM) in LPS-stimulated RAW264.7 macrophage cells. MATERIALS/METHODS: The potential anti-inflammatory properties of ECM were investigated by using RAW264.7 macrophages. We used western blot assays and real time quantitative polymerase chain reaction to detect protein and mRNA expression, respectively. Luciferase assays were performed to determine the transactivity of transcription factors. RESULTS: ECM significantly inhibited inducible nitric oxide synthase (iNOS)-derived NO and cyclooxygenase-2 (COX-2) derived PGE2 production in LPS-stimulated RAW264.7 macrophages. These inhibitory effects of ECM were accompanied by decreases in LPS-induced nuclear translocations and transactivities of NFkappaB. Moreover, phosphorylation of mitogen-activated protein kinase (MAPKs) including extracellular signal-related kinase (ERK1/2), p38, and c-jun N-terminal kinase (JNK) was significantly suppressed by ECM in LPS-stimulated RAW264.7 macrophages. Further studies demonstrated that ECM by itself induced heme oxygenase-1 (HO-1) protein expression at the protein levels in dose-dependent manner. However, zinc protoporphyrin (ZnPP), a selective HO-1 inhibitor, abolished the ECM-induced suppression of NO production. CONCLUSIONS: These results suggested that ECM-induced HO-1 expression was partly responsible for the resulting anti-inflammatory effects. These findings suggest that ECM exerts anti-inflammatory actions and help to elucidate the mechanisms underlying the potential therapeutic values of Erigeron Canadensis L.
Blotting, Western ; Cyclooxygenase 2 ; Dinoprostone ; Erigeron* ; Heme Oxygenase-1* ; JNK Mitogen-Activated Protein Kinases ; Luciferases ; Macrophages* ; Methanol* ; Nitric Oxide ; Nitric Oxide Synthase Type II ; Phosphorylation ; Phosphotransferases ; Polymerase Chain Reaction ; Protein Kinases ; RNA, Messenger ; Transcription Factors ; Up-Regulation* ; Zinc

OBJECTIVEThe SSR information in the transcriptome of Erigeron breviscapus was analyzed in this study, in order to further develop new functional genes SSR markers laid a solid foundation.

METHODSSR loci were searched in all of 52,060 unigenes by using est_timmer. Perl program and SSR primers were designed by Primer3. Furthermore, 36 pairs of primers were randomly selected for the polymorphism analysis on 13 Erigeron breviscapus plants collected from different places.

RESULTA total of 3639 SSRs were found in the transcriptome of Erigeron breviscapus, distributed in 3260 unigenes with the distribution frequency of 6.99%. Di-nucleotide repeat was the main type, account for as much as 34.41% of all SSRs, followed by mono-nucleotide (31.41%) and tri-nucleotide repeat motif (28.08%). The di-nucleotide repeat motifs of AT/AT and AC/GT were the predominant repeat types (28.71%). The tri-nucleotide repeat motifs of AAT/AT was the predominant repeat types (7.94%). For validation the availability of those SSR primers, we randomly selected 36 pairs of primers for PCR amplification. Among them, 34 pair primers (94.44%) produced clear and reproductive bands, 19 pair primers showed polymorphism (52.78%), and 13 Erigeron breviscapus plants were divided into 2 groups.

CONCLUSIONThere are numerous SSRs in Erigeron breviscapus transcriptome with high frequency and various types, this will provide abundant candidate molecular markers for genetic diversity study and genetic map in this plant.

China ; DNA Primers ; genetics ; Erigeron ; classification ; genetics ; Genetic Variation ; Microsatellite Repeats ; Phylogeny ; Polymorphism, Genetic ; Transcriptome

Two novel isocoumarins, erigeronone C (1) and D (2), were isolated from the ethanol extract of the whole plant of Erigeron breviscapus (Vant.) Hand.-Mazz (Compositae). Their structures were respectively elucidated as 8, 9-dihydroxypyrano [3, 2-c] isochromen-4, 6-dione (1) and 4, 7-dihydroxy-3-(3-hydroxy-4-oxo-4H-pyran-2-yl)-1H-isochromen-1-one (2) on the basis of spectral analyses. Both structures of 1 and 2 possess a gamma-pyrone moiety and that is rare in natural products.
Erigeron ; chemistry ; Isocoumarins ; chemistry ; isolation & purification ; Molecular Structure ; Plants, Medicinal ; chemistry

Scutellarin is the main effective constituent of breviscapine, a flavonoid mixture isolated from the dried whole plant of Erigeron breviscapus (Vant.) Hand-Mazz, and valsartan is used as an antihypertensive drug. These two drugs have already been clinically used together to treat diabetic nephropathy (DN) in China, and the combined medications showed some enhanced protection against DN. The aim of this study is to investigate the potential pharmacokinetic interaction between scutellarin and valsartan in rats. Breviscapine injection (20 mg x kg(-1), i.v.) and valsartan (15 mg x kg-, i.g.), either alone or together were given to 18 male Sprague-Dawley rats. Concentrations of scutellarin and valsartan were quantified by HPLC, and pharmacokinetic parameters were calculated by non-compartmental methods. We found that the pharmacokinetic parameters of scutellarin altered significantly after co-administration of oral valsartan. The plasma clearance (CL(p)) and the bile clearance (CL(b)) of scutellarin were reduced significantly in the presence of valsartan. After oral administration of valsartan with or without intravenous scutellarin, however, the pharmacokinetic parameters of valsartan were comparable. In conclusion, our data suggests that the concurrent use of valsartan reduces the biliary excretion of scutellarin, and this may be due to the inhibitory effect of valsartan on the biliary excretion of scutellarin mediated by Mrp2 (Multidrug resistance-associated protein 2).
Administration, Intravenous ; Administration, Oral ; Animals ; Antihypertensive Agents ; administration & dosage ; blood ; pharmacokinetics ; Apigenin ; administration & dosage ; blood ; isolation & purification ; pharmacokinetics ; Bile ; metabolism ; Chromatography, High Pressure Liquid ; Drug Interactions ; Erigeron ; chemistry ; Glucuronates ; administration & dosage ; blood ; isolation & purification ; pharmacokinetics ; Male ; Metabolic Clearance Rate ; Multidrug Resistance-Associated Proteins ; metabolism ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Valsartan ; administration & dosage ; blood ; pharmacokinetics

OBJECTIVETo study the effect of Erigeron Breviscapus (EB) at different concentrations and different intervention time points on the mRNA and protein expression of OPG/RANKL/RANK in MG63 osteoblast-like cells and RAW264. 7 pre-osteoclast cells cultured in vitro, thus exploring roles EB played in bone rebuilding and its mechanisms.

METHODSMG63 osteoblast-like cells and RAW264.7 pre-osteoclast cells were cultured in vitro. The 3rd passage cells were divided into the control group and different experimental groups. Total RNA and protein were respectively isolated from cells treated with different concentrations of EB (0, 0.001, 0.01, 0.1, and 1.0 mg/mL) for 48 h. Meanwhile, the protein was extracted from 0 and 1 mg/mL EB groups at 12, 24, and 48 h respectively. Expression of OPG mRNA and RANKL mRNA in MG63 osteoblast-like cells, and expression of RANK mRNA in RAW264.7 pre-osteoclast cells were detected by semi-quantitative RT-PCR. Expression of OPG protein and RANKL protein in MG63 osteoblast-like cells, and expression of RANK protein in RAW264. 7 pre-osteoclast cells were detected by Western blot.

RESULTSAlong with increased EB concentration, expression of OPG mRNA and protein in MG63 osteoblast-like cells was gradually lowered (P < 0.05) after 48-h intervention of EB, the expression of RANKL mRNA and protein in MG63 osteoblast-like gradually increased (P < 0.05); the expression of RANK mRNA in RAW264.7 pre-osteoclast cells increased (P < 0.05). But the expression of RANK mRNA was slightly lower in the 0.1 mg/mL EB group than in the 0.01 mg/mL EB group, and the expression of RANK protein in RAW264.7 pre-osteoclast cells gradually increased (P < 0.05). After treatment with 1 mg/mL EB for 12, 24, 48 h, the expression of OPG protein in MG63 osteoblast-like cells gradually decreased as time went by (P < 0.05), and the expression of RANKL protein in MG63 osteoblast-like and RANK protein in RAW264.7 pre-osteoclast cells gradually increased (P < 0.05). The expression of RANKL protein in RAW264.7 pre-osteoclast cells increased as time went by (P < 0.05).

CONCLUSIONEB could inhibit the expression of OPG in osteoblasts in a dose- and time-dependent manner, promote the expression of RANKL in osteoblasts and the secretion of RANK in pre-osteoclast, indicating EB might play roles in promoting bone resorption.

Animals ; Cell Differentiation ; Cell Line ; Drugs, Chinese Herbal ; pharmacology ; Erigeron ; Humans ; Mice ; Osteoblasts ; drug effects ; metabolism ; Osteoclasts ; drug effects ; metabolism ; Osteoprotegerin ; metabolism ; RANK Ligand ; metabolism ; RNA, Messenger ; genetics ; Receptor Activator of Nuclear Factor-kappa B ; metabolism