Anti-Inflammatory, Analgesic, Functional Improvement, and Chondroprotective Effects of Erigeron breviscapus (Vant.) Hand.-Mazz. Extract in Osteoarthritis: An In Vivo and In Vitro Study.

Osteoarthritis (OA) is a degenerative bone disease characterized by inflammation as a primary pathology and currently lacks therapeutic interventions to impede its progression. Erigeron breviscapus (Vant.) Hand.-Mazz. (EB) is an east Asian herbal medicine with a long history of use and a wide range of confirmed efficacy against cardiovascular and central nervous system diseases. The purpose of this study is to evaluate whether EB is worthy of further investigation as a treatment for OA based on anti-inflammatory activity. This study aims to assess the potential of EB as a treatment for OA, focusing on its anti-inflammatory properties. Analgesic effects, functional improvements, and inhibition of cartilage destruction induced by EB were evaluated in acetic acid-induced peripheral pain mice and monosodium iodoacetate-induced OA rat models. Additionally, the anti-inflammatory effect of EB was assessed in serum and cartilage tissue in vivo, as well as in lipopolysaccharide-induced RAW 264.7 cells. EB demonstrated a significant alleviation of pain, functional impairment, and cartilage degradation in OA along with a notable inhibition of pro-inflammatory cytokines, including interleukin-1ß, interleukin-6, matrix metalloproteinases 13, and nitric oxide synthase 2, both in vitro and in vivo, in a dose-dependent manner compared to the active control. Accordingly, EB merits further exploration as a potential disease-modifying drug for OA, capable of mitigating the multifaceted pathology of osteoarthritis through its anti-inflammatory properties. Nonetheless, additional validation through a broader experimental design is essential to substantiate the findings of this study.

Enhancement of methane production from anaerobic digestion of Erigeron canadensis via O2-nanobubble water supplementation.

Malignant invasive Erigeron canadensis, as a typical lignocellulosic biomass, is a formidable challenge for sustainable and efficient resource utilization, however nanobubble water (NBW) coupled with anaerobic digestion furnishes a prospective strategy with superior environmental and economic effectiveness. In this study, influence mechanism of various O2-NBW addition times on methanogenic performance of E. canadensis during anaerobic digestion were performed to achieve the optimal pollution-free energy conversion. Results showed that supplementation of O2-NBW in digestion system could significantly enhance the methane production by 10.70-16.17%, while the maximum cumulative methane production reached 343.18 mL g-1 VS in the case of one-time O2-NBW addition on day 0. Furthermore, addition of O2-NBW was conducive to an increase of 2-90% in the activities of dehydrogenase, α-glucosidase and coenzyme F420. Simultaneously, both facultative bacteria and methanogenic archaea were enriched as well, further indicating that O2-NBW might be responsible for facilitating hydrolytic acidification and methanogenesis. Based on Kyoto Encyclopedia of Genes and Genomes (KEGG) cluster analysis, provision of O2-NBW enhanced the metabolism of carbohydrate and amino acid, translation as well as membrane transport of bacteria and archaea. This study might offer the theoretical guidance and novel insights for efficient recovery of energy from lignocellulosic biomass on account of O2-NBW adhibition in anaerobic digestion system, progressing tenor of carbon-neutral vision.

Pyromeconic acid-enriched Erigeron annuus water extract as a cosmetic ingredient for itch relief and anti-inflammatory activity.

Erigeron annuus (EA), traditionally used to treat disorders such as diabetes and enteritis, contains a variety of chemicals, including caffeic acid, flavonoids, and coumarins, providing antifungal and antioxidative benefits. However, the ingredients of each part of the EA vary widely, and there are few reports on the functionality of water extracts in skin inflammation and barrier protection. We assessed the therapeutic properties of the extract of EA without roots (EEA) and its primary ingredient, pyromeconic acid (PA), focusing on their antihistamine, anti-inflammatory, and antioxidative capabilities using HMC-1(human mast cells) and human keratinocytes (HaCaT cells). Our findings revealed that histamine secretion, which is closely related to itching, was notably reduced in HMC-1 cells following pretreatment with EEA (0.1% and 0.2%) and PA (corresponding concentration, 4.7 of 9.4 µg/mL). Similarly, they led to a marked decrease in the levels of pro-inflammatory cytokines, including IL-1ß, IL-8, IL-6, and IFN-γ. Furthermore, EA and PA enhanced antioxidant enzymes, such as superoxide dismutase (SOD) and catalase (CAT), reduced malondialdehyde (MDA) production, and showed reactive oxygen species (ROS) scavenging activity in HaCaT cells. Moreover, at the molecular level, elevated levels of the pro-inflammatory cytokines IL-1ß, IL-6, TARC, and MDC induced by TNF-α/IFN-γ in HaCaT cells were mitigated by treatment with EEA and PA. We also revealed the protective effects of EEA and PA against SDS-induced skin barrier dysfunction in HaCaT cells by enhancing the expression of barrier-related proteins. Using NanoString technology, a comprehensive analysis of gene expression changes indicated significant modulation of autoimmune and inflammatory genes by EEA and PA. In summary, this study suggests that EEA and the corresponding concentration of PA as an active ingredient have functional cosmetic applications to alleviate itching and improve skin health.

Neuroprotective potential of Erigeron bonariensis ethanolic extract against ovariectomized/D-galactose-induced memory impairments in female rats in relation to its metabolite fingerprint as revealed using UPLC/MS.

Erigeron bonariensis is widely distributed throughout the world's tropics and subtropics. In folk medicine, E. bonariensis has historically been used to treat head and brain diseases. Alzheimer's disease (AD) is the most widespread form of dementia initiated via disturbances in brain function. Herein, the neuroprotective effect of the chemically characterized E. bonariensis ethanolic extract is reported for the first time in an AD animal model. Chemical profiling was conducted using UPLC-ESI-MS analysis. Female rats underwent ovariectomy (OVX) followed by 42 days of D-galactose (D-Gal) administration (150 mg/kg/day, i.p) to induce AD. The OVX/D-Gal-subjected rats received either donepezil (5 mg/kg/day) or E. bonariensis at 50, 100, and 200 mg/kg/day, given 1 h prior to D-Gal. UPLC-ESI-MS analysis identified 42 chemicals, including flavonoids, phenolic acids, terpenes, and nitrogenous constituents. Several metabolites, such as isoschaftoside, casticin, velutin, pantothenic acid, xanthurenic acid, C18-sphingosine, linoleamide, and erucamide, were reported herein for the first time in Erigeron genus. Treatment with E. bonariensis extract mitigated the cognitive decline in the Morris Water Maze test and the histopathological alterations in cortical and hippocampal tissues of OVX/D-Gal-subjected rats. Moreover, E. bonariensis extract mitigated OVX/D-Gal-induced Aß aggregation, Tau hyperphosphorylation, AChE activity, neuroinflammation (NF-κBp65, TNF-α, IL-1ß), and apoptosis (Cytc, BAX). Additionally, E. bonariensis extract ameliorated AD by increasing α7-nAChRs expression, down-regulating GSK-3ß and FOXO3a expression, and modulating Jak2/STAT3/NF-ĸB p65 and PI3K/AKT signaling cascades. These findings demonstrate the neuroprotective and memory-enhancing effects of E. bonariensis extract in the OVX/D-Gal rat model, highlighting its potential as a promising candidate for AD management.

Study on the anti-mitochondrial apoptosis mechanism of Erigeron breviscapus injection based on UPLC-Q-TOF-MS metabolomics and molecular docking in rats with cerebral ischemia-reperfusion injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Erigeron breviscapus is a common medicine of eight ethnic minorities, including Miao, Naxi, and Yi. As early as the Ming Dynasty (AD 1368-1644), Lanmao's Materia Medica of Southern Yunnan (AD 1436) recorded that the medicine is used for the treatment of "Zuo tan you huan." In modern pharmacological research, Erigeron breviscapus injection is the most commonly used preparation in the treatment of ischemic stroke caused by acute cerebral infarction, but its mechanism of action in the treatment of ischemic stroke is not well understood. AIM OF THE STUDY: In this study, a metabonomics study based on ultraperformance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS) was used in investigating the effect of a traditional Chinese medicine preparation Erigeron breviscapus injection on the rat model of focal cerebral ischemia-reperfusion and the affinity of its main components with the targets of mitochondrial apoptotic pathways. MATERIALS AND METHODS: This study used molecular docking technology to verify the effective binding ability of main effective components of Erigeron breviscapus injection to target proteins related to mitochondrial apoptosis pathway. This study developed a metabonomics method based on the ultra-performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry (UPLC Q-TOF MS) to evaluate the efficacy and study the mechanism of traditional Chinese medicine preparation. With pattern recognition analysis (principal component analysis and partial least squares-discriminate analysis) of urinary metabolites, a clear separation of focal cerebral ischemia-reperfusion model group and healthy control group was achieved. RESULTS: Erigeron breviscapus injection can significantly reduce the area of cerebral infarction, improve tissue morphological lesion in rats, and can increase the number of Nissl bodies. It may be a promoting factor by inhibiting hippocampal nerve cell apoptosis and Bax protein expression and by exerting effects against ischemia reperfusion after the induction of apoptosis. Thus, it plays a role in brain protection. Moreover, it can considerably promote the recovery of neurological deficiency signs in advance. Meanwhile, Erigeron breviscapus decreased malondialdehyde content and T-NOS activity. Its curative effect from strong to weak order: low dose > high dose > medium dose. The representative components of Erigeron breviscapus have good affinity with the active sites of mitochondrial apoptosis-related proteins. Metabolomics found that the potential biomarkers regulated by breviscapine are kynurequinolinic acid, succinylornithine, and leucine proline. It is speculated that it may participate in TRP-kynurequinolinic acid and succinylornithine-urea cycle-NO metabolic pathways. CONCLUSIONS: This paper revealed the potential biomarkers and metabolic pathways regulated by Erigeron breviscapus. It was speculated that the mechanism is related to its inhibition of mitochondrion-mediated apoptosis. Erigeron breviscapus could restore the metabolic profiles of the model animals to normal animal levels. The mechanism may be related to the potential biomarkers of quinolinic acid, succinylornithine, and leucine proline and the metabolic pathways involved. However, the exact mechanism by which Erigeron breviscapus inhibits mitochondrion-mediated apoptosis remains to be further explored.

Genome-wide identification and characterization of SRLK gene family reveal their roles in self-incompatibility of Erigeron breviscapus.

Self-incompatibility (SI) is a reproductive protection mechanism that plants acquired during evolution to prevent self-recession. As the female determinant of SI specificity, SRK has been shown to be the only recognized gene on the stigma and plays important roles in SI response. Asteraceae is the largest family of dicotyledonous plants, many of which exhibit self-incompatibility. However, systematic studies on SRK gene family in Asteraceae are still limited due to lack of high-quality genomic data. In this study, we performed the first systematic genome-wide identification of S-locus receptor like kinases (SRLKs) in the self-incompatible Asteraceae species, Erigeron breviscapus, which is also a widely used perennial medicinal plant endemic to China.52 SRLK genes were identified in the E. breviscapus genome. Structural analysis revealed that the EbSRLK proteins in E. breviscapus are conserved. SRLK proteins from E. breviscapus and other SI plants are clustered into 7 clades, and the majority of the EbSRLK proteins are distributed in Clade I. Chromosomal and duplication analyses indicate that 65% of the EbSRLK genes belong to tandem repeats and could be divided into six tandem gene clusters. Gene expression patterns obtained in E. breviscapus multiple-tissue RNA-Seq data revealed differential temporal and spatial features of EbSRLK genes. Among these, two EbSRLK genes having high expression levels in tongue flowers were cloned. Subcellular localization assay demonstrated that both of their fused proteins are localized on the plasma membrane. All these results indicated that EbSRLK genes possibly involved in SI response in E. breviscapus. This comprehensive genome-wide study of the SRLK gene family in E. breviscapus provides valuable information for understanding the mechanism of SSI in Asteraceae.

Phytochemistry and biological activity of Erigeron annuus (L.) Pers.

Erigeron annuus L. is a flowering herb of North America, Europe, Asia and Russia. This plant is used as folk medicine in China for the cure of indigestion, enteritis, epidemic hepatitis, haematuria and diabetes. Phytochemical studies showed the presence of 170 bioactive compounds like coumarins, flavonoids, terpenoids, polyacetylenic compounds; γ-pyrone derivatives, sterols and various caffeoylquinic acids derived from the essential oil and organic extracts from its various parts such as aerial parts, roots, leaves, stems and flowers. The pharmacological studies demonstrated various extracts and the compounds of E. annuus to exhibit anti-fungal, anti-atherosclerosis, anti-inflammatory, antidiabetic, phytotoxic, cytoprotective, antiobesity and antioxidant activities. This article covers a critical compendious on geographical distribution, botanical description, phytochemistry, ethnomedicinal uses and pharmacological activities of E. annuus. However, further in-depth studies are needed to determine the medical uses of E. annuus and its chemical constituents, pharmacological activities and clinical applications.

Rapid and Efficient Optimization Method for a Genetic Transformation System of Medicinal Plants Erigeron breviscapus.

Erigeron breviscapus is an important medicinal plant with high medicinal and economic value. It is currently the best natural biological drug for the treatment of obliterative cerebrovascular disease and the sequela of cerebral hemorrhage. Therefore, to solve the contradiction between supply and demand, the study of genetic transformation of E. breviscapus is essential for targeted breeding. However, establishing an efficient genetic transformation system is a lengthy process. In this study, we established a rapid and efficient optimized protocol for genetic transformation of E. breviscapus using the hybrid orthogonal method. The effect of different concentrations of selection pressure (Hygromycin B) on callus induction and the optimal pre-culture time of 7 days were demonstrated. The optimal transformation conditions were as follows: precipitant agents MgCl2 + PEG, target tissue distance 9 cm, helium pressure 650 psi, bombardment once, plasmid DNA concentration 1.0 µg·µL-1, and chamber vacuum pressure 27 mmHg. Integration of the desired genes was verified by amplifying 1.02 kb of htp gene from the T0 transgenic line. Genetic transformation of E. breviscapus was carried out by particle bombardment under the optimized conditions, and a stable transformation efficiency of 36.7% was achieved. This method will also contribute to improving the genetic transformation rate of other medicinal plants.

Effects of breviscapine on cerebral ischemia-reperfusion injury and intestinal flora imbalance by regulating the TLR4/MyD88/NF-κB signaling pathway in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The plant Erigeron breviscapus (Vant.) Hand.-Mazz.,a Chinese herbal medicine with multiple pharmacological effects and clinical applications, has been traditionally used in the treatment of paralysis caused by stroke and joint pain from rheumatism by the Yi minority people of Southwest China for generations.However, its mechanism involves many factors and has not been fully clarified. AIM OF THE STUDY: Taking intestinal flora as the target, the protective effect of extract(breviscapine) of E. breviscapus on cerebral ischemia and its possible mechanism were discussed from the perspective of brain inflammatory pathway and intestinal CYP3A4, which depends on intestinal flora. MATERIALS AND METHODS: In this study, we first verified the binding ability between major active ingredient of Erigeron breviscapus and the core target TLR4 protein by molecular docking using Vina software.We established a rat model of cerebral ischemia-reperfusion injury in vivo.The neurological function of rats was scored by Bederson score table, the cerebral infarction volume was detected by TTC staining, and the serum NSE level was detected by ELASA. 16S rRNA sequencing was used to detect the intestinal flora of rats in each group.The expression levels of cerebral TLR4/MyD88/NF-κB and CYP3A4 mRNA and protein in different intestinal segments were detected by qRT-PCR and Western blot. RESULTS: Compared with the model group, the neurological injury score, infarct volume and serum NSE concentration of breviscapine low, medium and high dose groups and nimodipine groups decreased significantly. Meanwhile, breviscapine could significantly reduce the expression level of the TLR4/MyD88/NF-κB in brain tissue and CYP3A4 in different intestinal segments of rats with cerebral ischemia-reperfusion injury. In addition, breviscapine also significantly ameliorated intestinal flora dysbiosis of rats with cerebral ischemia-reperfusion injury. CONCLUSIONS: Breviscapine can protect rats from cerebral ischemia-reperfusion injury by regulating intestinal flora, inhibiting brain TLR4/MyD88/NF-κB inflammatory pathway and intestinal CYP3A4 expression.

Phytochemical Profiles, Antioxidant, Cytotoxic, and Anti-Inflammatory Activities of Traditional Medicinal Plants: Centaurea pichleri subsp. pichleri, Conyza canadensis, and Jasminum fruticans.

Centaurea pichleri subsp. pichleri, Conyza canadensis, and Jasminum fruticans are traditionally used plants grown in Turkey. Methanol extracts were obtained from these plants and pharmacological activity studies and phytochemical analyses were carried out. To evaluate the phytochemical composition, spectrophotometric and chromatographic techniques were used. The extracts were evaluated for antioxidant activity by DPPH●, ABTS●+ radical scavenging, and FRAP assays. The cytotoxic effects of the extracts were investigated on DU145 prostate cancer and A549 lung cancer cell lines. The anti-inflammatory effects of extracts were investigated on the NO amount, TNF-α, IFN-γ, and PGE 2 levels in lipopolysaccharide-stimulated Raw 264.7 cells. The richest extract in terms of phenolic compounds (98.19 ± 1.64 mgGAE/gextract) and total flavonoids (21.85 ± 0.64 mgCA/gextract) was identified as C. pichleri subsp. pichleri methanol extract. According to antioxidant activity determinations, the C. pichleri subsp. pichleri extract was found to be the most active extract. Finally, the C. pichleri subsp. pichleri methanol extract was revealed to be the most effective inhibitor of viability in the cytotoxic activity investigation, and the extract with the best anti-inflammatory action. The findings point to C. pichleri subsp. pichleri as a promising source of bioactive compounds in the transition from natural sources to industrial uses, such as new medications, cosmeceuticals, and nutraceuticals.

Sulfur fertiliser enhancement of Erigeron breviscapus (Asteraceae) quality by improving plant physiological responses and reducing soil cadmium bioavailability.

Erigeron breviscapus (Vant.) Hand.-Mazz. is an important medicinal plant; however, its quality is severely diminished by cadmium (Cd) pollution. Sulfur fertilisation can improve the production and application of E. breviscapus. This study examined Cd stress alleviation in the soil-plant system and determined the plant growth response after the application of sulfur fertiliser. The soil Cd concentration used in the treatments was 100 g·kg-1, and the sulfur fertiliser application rates were 0.1, 0.2, and 0.3 g·kg-1. Using pot experiments, we explored the impacts of high, medium, and low amounts of sulfur fertiliser on Cd accumulation and the quality and activity of E. breviscapus. The results showed that the application of sulfur fertiliser promoted Cd transformation to residual Cd under oxidation conditions, reducing Cd accumulation in E. breviscapus. Throughout the growth period, the application of sulfur fertiliser increased the soluble protein content and antioxidant enzyme activity, which alleviated Cd toxicity. The net photosynthetic rate, transpiration rate, intercellular CO2 concentration, chlorophyll level, and leaf width increased significantly. The biomass content of E. breviscapus also increased. Sulfur fertiliser improves the quality of herbaceous medicinal plants by reducing Cd accumulation and increasing scutellarin, chlorogenic, isochlorogenic acid B, and isochlorogenic acid C contents. A reasonable application of sulfur fertiliser is essential for improving E. breviscapus quality. This study provides a new method to reduce the ecological risk of planting herbaceous medicinal plants in Cd-contaminated soil.

Dengzhan Xixin injection derived from a traditional Chinese herb Erigeron breviscapus ameliorates cerebral ischemia/reperfusion injury in rats via modulation of mitophagy and mitochondrial apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Dengzhan Xixin injection (DX), a preparation of extracts from traditional Chinese medicine Erigeron breviscapus (Vaniot) Hand.-Mazz., has been widely used in clinical treatment of cerebral ischemia sequelae in China for a long history. However, its underlying mechanisms remain unclear. AIM OF THE STUDY: The objective of this present study aimed to investigate the therapeutic effects of DX on cerebral ischemia/reperfusion (I/R) injury in a rat model. Meanwhile, its underlying molecular mechanisms on mitochondrial protection were further interpreted. MATERIALS AND METHODS: The major components of DX were detected by high-performance liquid chromatography analysis. The model of cerebral I/R injury was established by middle cerebral artery occlusion (MCAO) in SD rats. We firstly performed neurobehavioral score, the regional cerebral blood flow (rCBF) assay, and TTC, HE and Nissl staining for evaluating the effects of DX on I/R injury. And then, the cortical levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), adenosine triphosphate (ATP) and mitochondrial membrane potential (MMP) were determined by commercial kits. Whereafter, real time-PCR and transmission electron microscopy were employed to investigate the relative copy number of mitochondrial DNA (mtDNA) and neuronal ultrastructure changes, respectively. Further, the potential interactions of major components in DX with mitophagy/apoptosis-related proteins were predicted by Schrodinger molecular docking. The expression of mitophagy-related proteins LC3, p62, TOM20, PINK1 and Parkin was estimated by western blot and immunofluorescence analyses. Furthermore, TUNEL staining and western blot were used to detect the apoptotic phenomenon and the protein expression of Bax, Bcl-2, Cytochrome c (Cyto-c) and cleaved Caspase-3. RESULTS: DX mainly contains scutellarin, 3,4-O-dicaffeoylquinic acid, 3,5-O-dicaffeoylquinic acid, 4,5-O-dicaffeoylquinic acid, caffeic acid and 5-O-caffeoylquinic acid. Compared with the model group, DX could remarkably relieve ischemia-provoked neurological deficit, rCBF deficiency and cerebral infarction. Pathological changes and neuronal loss in a MCAO model of rats were memorably ameliorated by DX administration. Meanwhile, DX reduced the surged ROS and MDA, while increased the level of SOD. Notably, DX treatment conversed the collapse of ATP and MMP, along with decreased in the relative copy number of mtDNA, contributing to the maintaining of mitochondrial ultrastructure via the increased number of autophagy lysosomes. The representative ingredients in DX had a potential bind with the active sites of mitophagy/apoptosis-related proteins. DX stimulated the protein expression of LC3, PINK1 and Parkin, while reduced the levels of p62 and TOM20. In addition, DX confined TUNEL-positive cell rate with the decreased expressions of Bax, Cyto-c and cleaved Caspase-3 as well as the increased Bcl-2 level. CONCLUSIONS: We demonstrated that the protection of DX against brain ischemia could attribute to alleviating mitochondrial damage by upregulating mitophagy and inhibiting mitochondria-mediated apoptosis.

Which factor contributes most to the invasion resistance of native plant communities under the co-invasion of two invasive plant species?

Two invasive plant species (IPS) can co-invade the same plant community. As the number of IPS increases under the co-invasion of two IPS, plant taxonomic and functional diversity, community invasibility, community stability, invasion resistance, and invasion intensity and invasiveness of IPS and their interrelationships may be altered. This study aimed to quantify the contribution of plant taxonomic and functional diversity, community invasibility, community stability, and invasion intensity and invasiveness of IPS to the invasion resistance of native plant communities under the co-invasion of the two IPS Erigeron annuus (L.) Pers. and Solidago canadensis L. in eastern China. This study also defined a method to quantify the invasion resistance of native plant communities designated the invasion resistance index. The community-weighted mean trait values of native plants and plant diversity are the factors that are the most critical to determine the invasion resistance of native plant communities. Thus, the invasion resistance of native plant communities primarily depends on the three following factors: the relative abundance of natives, the growth performance of natives, and the diversity of natives. All levels of invasion significantly decrease the invasion resistance of native plant communities. The two IPS antagonistically affect the invasion resistance of native plant communities less under co-invasion compared with their independent invasion.

Chemical characteristics and significant antitussive effect of the Erigeron canadensis polyphenolic polysaccharide-protein complex.

ETHNOPHARMACOLOGICAL RELEVANCE: Erigeron canadensis has been used in traditional medicine to treat a variety of respiratory diseases, including acute upper and lower respiratory tract infections and cough-related asthma. There is as yet no relevant experimental or clinical study in the scientific literature evaluating the efficacy of plants in these disorders. AIM OF THE STUDY: To investigate the active ingredients in Erigeron canadensis, a complex isolated from flowering parts of a plant was tested for airway defense reflexes, in particular for cough reflexes and airway reactivity. Both were experimentally induced by a chemical irritant that simulated the inflammatory conditions of their formation. MATERIAL AND METHODS: The polyphenolic polysaccharide-protein (PPP) complex was isolated from the flowering parts of Erigeron canadensis by hot alkaline extraction and a multi-stage purification process. The antitussive activity was confirmed as a decrease in the number of citric acid-induced coughs and the bronchodilator effect was verified as a decrease in specific airway resistance (sRaw) in conscious guinea pigs. RESULTS: The dark brown Erigeron complex with a molecular weight of 38,000 g/mol contained phenolics (13.2% wt%), proteins (16.3% wt%), and uronic acids (6.3% wt%). The neutral carbohydrate part of Erigeron consisted mainly of xylose (12.1 wt%), glucose (13.3 wt%), arabinose (24.1 wt%), and galactose (41.0 wt%) residues. Arabinogalactan and 4-OMe-glucuronoxylan have been found to be the major polysaccharides in the Erigeron complex. Using a method of chemically-induced cough reflex and guinea pigs test system the Erigeron complex exhibited statistically significant, the dose-dependent antitussive activity, which was similar to that of the centrally-acting opioid agonist codeine. CONCLUSION: Pharmacological tests have revealed a new pharmacodynamic effect of the Erigeron complex, namely an antitussive effect. Its activity was most pronounced in comparison with all previously tested compounds from other medicinal plants and approached the effect of codeine, the most potent antitussive used in clinical practice. The results provide the scientific basis for the application of this herb in traditional medicine.

[Identification and expression profiling of R2R3-MYB transcription factors in Erigeron breviscapus].

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.

Protective mechanism of Erigeron breviscapus injection on blood-brain barrier injury induced by cerebral ischemia in rats.

This study investigates the protective effect of Erigeron breviscapus injection, a classic traditional Chinese medicine most typically used by Chinese minority to treat stroke, on cerebral ischemia-reperfusion injury and the related signaling pathways. Use network pharmacology methods to study the relationship between E. breviscapus (Vant.) Hand-Mazz. and ischemic stroke, predict the mechanism and active ingredients of E. breviscapus (Vant.) Hand-Mazz. in improving ischemic stroke disease. We study the protective effect of E. breviscapus injection on blood-brain barrier (BBB) injuries induced by cerebral ischemia in rats by regulating the ROS/RNS-MMPs-TJs signaling pathway. The rat model of focal cerebral ischemia-reperfusion injury has been prepared using the wire-suppository method. Firstly, the efficacy of E. breviscapus injection, Scutellarin and 3,5-dicaffeoylquinic acid in protecting BBB injury caused by cerebral ischemia has been evaluated. Secondly, the following two methods have been used to study the mechanism of E. breviscapus injection in regulating the ROS/RNS-MMPS-TJS signaling pathway: real-time PCR and western blot for the determination of iNOS, MMP-9, claudin-5, occludin, ZO-1 mRNA and protein expression in brain tissue. We find that PI3K-Akt signaling pathway predicted by network pharmaology affects the blood-brain barrier function, so we chose the blood-brain barrier-related MMP-9, claudin-5, iNOS, occludin and ZO-1 proteins are used for research. The results of our research show that 3 drugs can reduce the rate of cerebral infarction in rats, relieve the abnormal neuroethology of rats, reduce the degree of brain tissue lesion, increase the number of the Nissl corpuscle cells and repair the neuron ultrastructure in injured rats. At the same time, it can obviously reduce the ultrastructure damage of the BBB in rats. All three drugs significantly reduced the content of Evans blue in the ischemic brain tissue caused by cerebral ischemia in rats with BBB injury. In addition, E. breviscapus injection, Scutellarin and 3,5-dicaffeoylquinic acid can decrease the protein expression of iNOS and MMP-9 in rat ischemic brain tissue. In addition, 3,5-dicaffeoylquinic acid can increase the protein expression of claudin-5. We conclude that E. breviscapus injection, Scutellarin and 3,5-dicaffeoylquinic acid have obvious therapeutic effects on BBB and neuron injury induced by cerebral ischemia in rats. Our results from studying the mechanism of action show that E. breviscapus injection and Scutellarin inhibited the activation of MMP-9 by inhibiting the synthesis of iNOS, 3,5-dicaffeoylquinic acid inhibits the expression and activation of MMP-9 by inhibiting the activation of iNOS and reducing the generation of free radicals, thus reducing the degradation of important cytoskeleton connexin claudin-5 in the tight junction (TJ) structure by inhibiting the expression and activation of MMP-9. Finally BBB structure integrity was protected.

Metabolism and Pharmacological Mechanisms of Active Ingredients in Erigeron breviscapus.

BACKGROUND: Erigeron breviscapus (Vant.) Hand-Mazz. is a plant species in the Compositae family. More than ten types of compounds-such as flavonoids, caffeinate esters, and volatile oils-have been identified in Erigeron breviscapus; however, it remains unknown as to which compounds are associated with clinical efficacy. In recent years, flavonoids and phenolic acids have been considered as the main effective components of Erigeron breviscapus. The metabolism and mechanisms of these compounds in vivo have been extensively studied to improve our understanding of the drug. METHODS: In the present review, we summarize the relationships among these compounds, their metabolites, and their pharmacodynamics. Many methods have been implemented to improve the separation and bioavailability of these compounds from Erigeron breviscapus. RESULTS: In China, Erigeron breviscapus has been used for many years. In recent years, through the study of its metabolism and the mechanisms of its effective components, the effects of Erigeron breviscapus in the treatment of various diseases have been extensively studied. Findings have indicated that Erigeron breviscapus improves cardiovascular and cerebrovascular function and that one of its ingredients, scutellarin, has potential value in the treatment of Alzheimer's disease, cancer, diabetic vascular complications, and other conditions. In addition, phenolic acid compounds and their metabolites also play an important role in anti-oxidation, anti-inflammation, and improving blood lipids. CONCLUSION: Erigeron breviscapus plays an important role in the prevention and treatment of cardiovascular/ cerebrovascular diseases, neuroprotection, and cancer through many different mechanisms of action. Further investigation of its efficacious components and metabolites may provide more possibilities for the clinical application of traditional Chinese medicine and the development of novel drugs.

Effects of Herba Erigerontis injection on pharmacodynamics and pharmacokinetics of warfarin in rats in vivo.

Herba Erigerontis injection (HEI) is an aqueous solution derived from whole plants of Erigeron breviscapus, which may be co-administered with warfarin to treat cardiovascular and cerebrovascular disorders. This research was conducted to make sure whether HEI would affect anticoagulation of warfarin to guarantee reasonable medication. The pharmacodynamic study was designed to measure prothrombin time (PT) and activated partial thromboplastin time (APTT) values, and international normalized ratio (INR) values were calculated. For pharmacokinetic study, ultra performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) technology was applied to measure plasma concentrations of warfarin enantiomers. The influence of HEI on plasma protein binding rate of warfarin was assessed by ultrafiltration. Pharmacodynamic study demonstrated that both HEI alone and co-administered with warfarin could increase PT and INR values significantly (P < .01), whereas the APTT values were unaffected (P > .05). Pharmacokinetic study manifested that Cmax , AUC and t1/2 prolonged significantly (P < .01) for R/S-warfarin in presence of HEI. Low (3.6 mL/kg), medium (7.2 mL/kg) and high (10.8 mL/kg) doses of HEI could decrease plasma protein binding rate of warfarin significantly (P < .01). The results mean that HEI can potentiate the anticoagulant response of warfarin through both pharmacodynamics and pharmacokinetics.

High quality genome of Erigeron breviscapus provides a reference for herbal plants in Asteraceae.

Erigeron breviscapus is an important medicinal plant in Compositae and the first species to realize the whole process from the decoding of the draft genome sequence to scutellarin biosynthesis in yeast. However, the previous low-quality genome assembly has hindered the optimization of candidate genes involved in scutellarin synthesis and the development of molecular-assisted breeding based on the genome. Here, the E. breviscapus genome was updated using PacBio RSII sequencing data and Hi-C data, and increased in size from 1.2 Gb to 1.43 Gb, with a scaffold N50 of 156.82 Mb and contig N50 of 140.95 kb, and a total of 43,514 protein-coding genes were obtained and oriented onto nine pseudo-chromosomes, thus becoming the third plant species assembled to chromosome level after sunflower and lettuce in Compositae. Fourteen genes with evidence for positive selection were identified and found to be related to leaf morphology, flowering and secondary metabolism. The number of genes in some gene families involved in flavonoid biosynthesis in E. breviscapus have been significantly expanded. In particular, additional candidate genes involved in scutellarin biosynthesis, such as flavonoid-7-O-glucuronosyltransferase genes (F7GATs) were identified using updated genome. In addition, three candidate genes encoding indole-3-pyruvate monooxygenase YUCCA2 (YUC2), serine carboxypeptidase-like 18 (SCPL18), and F-box protein (FBP), respectively, were identified to be probably related to leaf development and flowering by resequencing 99 individuals. These results provided a substantial genetic basis for improving agronomic and quality traits of E. breviscapus, and provided a platform for improving other draft genome assemblies to chromosome-level.

PK-PD Correlation of Erigeron Breviscapus Injection in the Treatment of Cerebral Ischemia-Reperfusion Injury Model Rats.

By measuring the cerebral infarction rate and neurological behavioral score of rats in a sham operation group, an MCAO model control group and an Erigeron breviscapus injection treatment group, we explored the therapeutic effects of Erigeron breviscapus injection on brain tissue and neuroethological injury in rats. Plasma samples were collected at 18 time points after intravenous injection of Erigeron breviscapus. The levels of scutellarin, 4-caffeoylquinic acid, 5-caffeoylquinic acid, 3,5-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid, chlorogenic acid and isochlorogenic acid B in rat plasma at the various time points were determined by an HPLC method, and drug concentration versus time plots were constructed to estimate the pharmacokinetic parameters. Finally, a PK-PD combined model was used to analyze the relationship between the blood concentration, time and therapeutic effects of the seven active components. The results of the pharmacodynamics studies showed that the cerebral infarction rate of rats in the Erigeron breviscapus injection group decreased significantly at 5 min, 10 min, 20 min, 6 h, 8 h, 18 h, 24 h, 32 h, 40 h and 48 h after cerebral ischemia. Abnormal neurological behavior scores were significantly reduced after 4 h of cerebral ischemia. The pharmacokinetics results showed that the seven chemical constituents in Erigeron breviscapus injection reached their highest detection value after 5 min of cerebral ischemia. The lowest detection values of scutellarin and isochlorogenic acid B appeared after 6 h of cerebral ischemia but could not be detected after 8 h. The lowest detection values of 5-caffeoylquinic acid and 4,5-dicaffeoylquinic acid were found in the third hour of cerebral ischemia but not after 4 h. The lowest detection values of 4-caffeoylquinic acid, 3,5-dicaffeoylquinic acid and chlorogenic acid were found during the second hour of cerebral ischemia but not at the third hour. However, at 18 h, 24 h, 32 h and 40 h of cerebral ischemia, the cerebral infarction rates of rats in the Erigeron breviscapus injection group were significantly reduced, with decreased values of 6.22%, 11.71%, 6.92% and 4.96%, respectively, and the effects were stronger than those after 5-20 min of cerebral ischemia. The decreased values reached their highest value after 24 h of cerebral ischemia. Our results show that the effects of Erigeron breviscapus injection on reducing the cerebral infarct rate in MCAO model rats are characterized by a fast onset and long maintenance time. The 5-min blood concentration in cerebral ischemia was the highest test value, and after this time, the cerebral infarction rate of MCAO rats began to decrease. However, the peak value of the effects lagged behind that of the plasma concentration. The maximum effective time for Erigeron breviscapus injection appeared 24 h after cerebral ischemia, which provides a reference for the screening of specific drugs for ischemic stroke, optimal dosing regimens and rational clinical drug use. Graphical Abstract.