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1.
Mutat Res ; 850-851: 503147, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32247562

RESUMO

Bulbus Fritillariacirrhosa D. Don (BFC) has been widely used as an herbal medicament for respiratory diseases in China for over 2000 years. The ethnomedicinal effects of BFC have been scientifically verified, nevertheless its toxicity has not been completely studied. Previously, we have reported that the aqueous extract of BFC induces mitotic aberrations and chromosomal instability (CIN) in human colon epithelial NCM460 cells via dysfunctioning the mitotic checkpoint. Here, we extend this study and specifically focus on the influence of BFC on cytokinesis, the final step of cell division. One remarkable change in NCM460 cells following BFC treatment is the high incidence of binucleated cells (BNCs). More detailed investigation of the ana-telophases reveals that furrow ingression, the first stage of cytokinesis, is inhibited by BFC. Asynchronous cultures treatment demonstrates that furrow ingression defects induced by BFCs are highly associated with the formation of BNCs in ensuing interphase, indicating the BNCs phenotype after BFC treatment was resulted from cytokinesis failure. In line with this, the expression of genes involved in the regulation of furrow ingression is significantly de-regulated by BFC (e.g., LATS-1/2 and Aurora-B are upregulated, and YB-1 is downregulated). Furthermore, long-term treatment of BFC elucidates that the BNCs phenotype is transient and the loss of BNCs is associated with increased frequency of micronuclei and nuclear buds, two biomarkers of CIN. In supporting of these findings, the Nin Jiom Pei Pa Koa and Chuanbei Pipa Gao, two commercially available Chinese traditional medicines containing BFC, are able to induce multinucleation and CIN in NCM460 cells. Altogether, these data provide the first in vitro experimental evidence linking BFC to cytokinesis failure and suggest the resultant BNCs may be intermediates to produce CIN progenies.


Assuntos
Instabilidade Cromossômica/efeitos dos fármacos , Citocinese/efeitos dos fármacos , Fritillaria/química , Extratos Vegetais/farmacologia , Aurora Quinase B/genética , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/genética , Instabilidade Cromossômica/genética , Colo/efeitos dos fármacos , Colo/patologia , Citocinese/genética , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Mitose/efeitos dos fármacos , Extratos Vegetais/química , Raízes de Plantas/química , Proteínas Serina-Treonina Quinases/genética , Proteína 1 de Ligação a Y-Box/genética
2.
Zhongguo Zhong Yao Za Zhi ; 45(6): 1393-1398, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32281353

RESUMO

An UPLC method was established for the direct determination of six major bioactive isosteroidal alkaloids, namely peimisine, imperialine, sipeimine-3-D-glucoside, verticinone, verticine and hupehenine from the bulbus of Fritillaria(Beimu), a commonly used antitussive traditional Chinese medicinal(TCM) herb. An Acquity UPLC~(TM) CSH C_(18) column(2.1 mm×100 mm, 1.7 µm) was used for all analysis. The investigated six compounds were all separated with gradient mobile phase consisting of 0.02% diethylamine-water-methanol at a flow rate of 0.3 mL·min~(-1). The temperature of sample manager was set at 20 ℃. Drift tube temperature was 45 ℃, and spray parameter was 40% with injection volume of 1 µL. Then, the further quality assessment of Beimu was carried out by cluster analysis(CA) and principal component analysis(PCA). The investigated all had good linearity(r≥0.998 9) over the tested ranges. The method is simple, accurate and reproducible, and can be used for determining the content of six major bioactive isosteroidal alkaloids.


Assuntos
Alcaloides/análise , Medicamentos de Ervas Chinesas/química , Fritillaria/química , Alcaloides/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/isolamento & purificação , Raízes de Plantas/química
3.
Fitoterapia ; 140: 104434, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31760067

RESUMO

Fritillaria cirrhosa bulbus is a Chinese folk herb famous for its antitussive, expectorant, anti-asthma and anti-inflammatory properties, and is widely used to treat respiratory diseases. However, the impacts of F. cirrhosa bulbus on oxidative stress are still unkown. In the present study, we investigated the potential effect and mechanism of six isosteroid alkaloids with different chemical structures from F. cirrhosa bulbus on protection against cigarette smoke-induced oxidative stress in RAW264.7 macrophages. The results showed that six isosteroid alkaloids reduced reactive oxygen species (ROS) production, elevated glutathione (GSH) level and promoted heme oxygenase (HO-1) expression, which is in association with induction of NF-E2-related factor 2 (Nrf2) nuclear translocation and up-regulation of Nrf2 expression. Among these alkaloids, verticinone, verticine, imperialine-3-ß-D-glucoside, delavine and peimisine exhibited more potent effect against CSE-induced oxidative stress than that of imperialine. These findings for the first time demonstrated that F. cirrhosa bulbus may play a protective role in cellular oxidative stress by activating Nrf2-mediated antioxidant pathway. Furthermore, the differences in antioxidant effects of these alkaloids were compared, as well as the corresponding structure-activity relationships were preliminarily elucidated. This suggested that F. cirrhosa bulbus might be a promising therapeutic treatment for the prevent of oxidative stress-related diseases.


Assuntos
Alcaloides/farmacologia , Fritillaria/química , Estresse Oxidativo/efeitos dos fármacos , Fumaça/efeitos adversos , Alcaloides/isolamento & purificação , Animais , Glutationa/metabolismo , Heme Oxigenase-1/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Estrutura Molecular , Fator 2 Relacionado a NF-E2/metabolismo , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química , Plantas Medicinais/química , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade , Produtos do Tabaco
4.
J Ethnopharmacol ; 247: 112283, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31605736

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Bulbus Fritillaria cirrhosa D. Don (BFC) is a Chinese traditional herbal medicine that has long been used as an indispensable component in herbal prescriptions for bronchopulmonary diseases due to its well-established strong anti-inflammation and pulmonary harmonizing effects. Interestingly, there are few case reports in traditional Chinese medicine available where they found it to contribute in anti-tumor therapies. Imperialine is one of the most favored active substances extracted from BFC and has been widely recognized as an anti-inflammatory agent. AIM OF THE STUDY: The aim of the current work is to provide first-hand evidences both in vitro and in vivo showing that imperialine exerts anti-cancer effects against non-small cell lung cancer (NSCLC), and to explore the molecular mechanism of this anti-tumor activity. It is also necessary to examine its systemic toxicity, and to investigate how to develop strategies for feasible clinical translation of imperialine. MATERIALS AND METHODS: To investigate anti-NSCLC efficacy of imperialine using both in vitro and in vivo methods where A549 cell line were chosen as in vitro model NSCLC cells and A549 tumor-bearing mouse model was constructed for in vivo study. The detailed underlying anti-cancer mechanism has been systematically explored for the first time through a comprehensive set of molecular biology methods mainly including immunohistochemistry, western blot and enzyme-linked immunosorbent assays. The toxicity profile of imperialine treatments were evaluated using healthy nude mice by examining hemogram and histopathology. An imperialine-loaded liposomal drug delivery system was developed using thin film hydration method to evaluate target specific delivery. RESULTS: The results showed that imperialine could suppress both NSCLC tumor and associated inflammation through an inflammation-cancer feedback loop in which NF-κB activity was dramatically inhibited by imperialine. The NSCLC-targeting liposomal system was successfully developed for targeted drug delivery. The developed platform could favorably enhance imperialine cellular uptake and in vivo accumulation at tumor sites, thus improving overall anti-tumor effect. The toxicity assays revealed imperialine treatments did not significantly disturb blood cell counts in mice or exert any significant damage to the main organs. CONCLUSIONS: Imperialine exerts anti-cancer effects against NSCLC both in vitro and in vivo, and this previously unknown function is related to NF-κB centered inflammation-cancer feedback loop. Imperialine mediated anti-cancer activity is not through cytotoxicity and exhibit robust systemic safety. Furthermore, the liposome-based system we commenced would dramatically enhance therapeutic effects of imperialine while exhibiting extremely low side effects both on cellular and in NSCLC model. This work has identified imperialine as a promising novel anti-cancer compound and offered an efficient target-delivery solution that greatly facilitate practical use of imperialine.


Assuntos
Alcaloides/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cevanas/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Fritillaria/química , Neoplasias Pulmonares/tratamento farmacológico , Células A549 , Alcaloides/efeitos adversos , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Contagem de Células Sanguíneas , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Cevanas/efeitos adversos , Cevanas/química , Cevanas/isolamento & purificação , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Retroalimentação Fisiológica/efeitos dos fármacos , Humanos , Lipossomos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Masculino , Camundongos , NF-kappa B/antagonistas & inibidores , NF-kappa B/imunologia , Testes de Toxicidade , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Molecules ; 24(18)2019 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-31500338

RESUMO

Fritillariae Bulbus is a precious Chinese herbal medicine that is grown at high elevation and used to relieve coughs, remove phlegm, and nourish the lungs. Historically, Fritillariae Bulbus has been divided into two odourless crude drugs: Fritillariae Cirrhosae Bulbus and Fritillariae Thunbergii Bulbus. However, now the Chinese Pharmacopoeia has described five Fritillariae Bulbus-the new additions include Fritillariae Pallidiflorae Bulbus, Fritillariae Ussuriensis Bulbus, and Fritillariae Hupehensis Bulbus. Because the morphology of dried Fritillariae Bulbus is similar, it is difficult to accurately identify the different types of Fritillariae Bulbus. In the current study, we develop a method combining DNA barcoding and high-performance liquid chromatography (HPLC) to help distinguish Fritillariae Cirrhosae Bulbus from other Fritillariae Bulbus and guarantee species traceability of the five types of Fritillariae Bulbus. We report on the validation of an integrated analysis method for plant species identification using DNA barcoding that is based on genetic distance, identification efficiency, inter- and intra-specific variation, calculated nearest distance, neighbour-joining tree and barcoding gap. Our results show that the DNA barcoding data successfully identified the five Fritillariae Bulbus by internal transcribed spacer region (ITS) and ITS2, with the ability to distinguish the species origin of these Fritillariae Bulbus. ITS2 can serve as a potentially useful DNA barcode for the Fritillaria species. Additionally, the effective chemical constituents are identified by HPLC combined with a chemical identification method to classify Fritillaria. The HPLC fingerprint data and HCA (hierarchical clustering analysis) show that Fritillariae Cirrhosae Bulbus is clearly different from Fritillariae Thunbergii Bulbus and Fritillariae Hupehensis Bulbus, but there is no difference between Fritillariae Cirrhosae Bulbus, Fritillariae Ussuriensis Bulbus, and Fritillariae Pallidiflorae Bulbus. These results show that DNA barcoding and HPLC fingerprinting can discriminate between the five Fritillariae Bulbus types and trace species to identify related species that are genetically similar.


Assuntos
Código de Barras de DNA Taxonômico/métodos , Medicamentos de Ervas Chinesas/química , Fritillaria/classificação , Cromatografia Líquida de Alta Pressão , Análise por Conglomerados , DNA Mitocondrial/genética , DNA de Plantas/genética , Fritillaria/química , Fritillaria/genética , Filogenia , Análise de Sequência de DNA
6.
Zhongguo Zhong Yao Za Zhi ; 44(11): 2231-2235, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359647

RESUMO

In order to reveal the relationship between the amount of soil microorganisms and the quality of Fritillaria taipaiensis, both cultivated and wild F. taipaiensis were collected from Chongqing, Wuxi at different stages of their growth as objects of the research. The mycorrhizal infection rate and colonization intensity, peimisine and total alkaloid content in bulbs, the amount of microorganisms and biomass carbon content in rhizospheric soil were all determined using common methods. The results showed that the typical arbuscular-vesicle roots were formed after the AM fungi infected the F. taipaiensis roots which were collected from different origins. The mycorrhizal infection rates were ranged from 78.74% to 98.68% and the colonization intensities were ranged from 13.29% to 37.06%. The rhizospheric microorganisms of F. taipaiensis showed abundant resources. The distribution rule of them in the rhizospheric soil was as follows: the amount of bacteria>the amount of actinomycetes>the amount of fungi. The rhizospheric bacteria, decomposition inorganic phosphorus bacteria, decomposition organic phosphorus bacteria, actinomycetes amount and the total number of microbes increased first and then decreased with the increase of years, while decomposition potassium bacteria showed decreasing trend and fungi showed gradual increasing trend. The soil microbial flora content in the soil changed from "bacterial type" with a high fertility to "fungal type" with a low fertility. The mass fraction of peimisine and total alkaloid content increased first and then decreased with the increase of over the years, the same trend of culturable rhizosphere soil bacteria and actinomycetes indicated that the growth years affected the quality of soil and medicinal materials on different levels. Therefore, the diversity of microbial communities in rhizosphere soil reduced with the increase of years leading to the continuous cropping obstacles and the destruction of medicinal quality of F. taipaiensis.


Assuntos
Alcaloides/análise , Fritillaria/química , Micorrizas , Rizosfera , Microbiologia do Solo , Fritillaria/microbiologia , Raízes de Plantas
7.
Zhongguo Zhong Yao Za Zhi ; 44(3): 495-499, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-30989914

RESUMO

Twelve alkaloids were isolated from the bulbs of Fritillaria yuminensis by column chromatography over silica gel, ODS, and Sephadex LH-20, as well as RP-HPLC. Their structures were identified mainly by NMR and MS analyses as yubeinine(1), imperialine(2), delavinone(3), tortifoline(4), hupehenizioiside(5), imperialine-ß-D-glucoside(6), kuroyurinidine(7), pengbeisine A(8), walujewine A(9), peimisine-3-O-ß-D-glucopyranoside(10), solanidine-3-O-α-L-rhamnopyranosyl-(1→2)-ß-D-glucopyranoside(11), and solanidine-3-O-α-L-rhamnopyranosyl-(1→2)-[ß-D-glucopyranosyl-(1→4)]-ß-D-glucopyranoside(12). Compounds 4-12 were obtained from F. yuminensis for the first time.


Assuntos
Alcaloides/análise , Fritillaria/química , Raízes de Plantas/química , Cromatografia Líquida de Alta Pressão , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Compostos Fitoquímicos/análise
8.
Biomed Res Int ; 2019: 3163218, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31016188

RESUMO

Thirty-one compounds, including delavinone, were isolated from the methanol extract of F. cirrhosa by modern chromatographic techniques. The pharmacological action of Fritillaria is widely used in clinical practice. However, the pharmacokinetic studies on delavinone have not been reported. Therefore, the chemical constituents of this species were investigated. Therefore, it is necessary to establish an analytical method to monitor the concentration of delavinone. An UPLC-MS/MS method was established to determine delavinone in the mouse blood, and the pharmacokinetics of delavinone after intravenous (1.0 mg/kg) and intragastric (2.5, 10.0 mg/kg) administration were studied. The lower limit of quantification was 1.0 ng/mL. The intraday and interday precision RSD were less than 13%, the accuracy ranged from 96.8% to 104.9%, the average recovery was better than 80.6%, and the matrix effect was between 88.8% and 103.4%. The UPLC-MS/MS method has been successfully applied to the pharmacokinetics of delavinone in mice. The noncompartment model was used to fit the main pharmacokinetic parameters. It was found that AUC in mice was higher than that in mice given orally, and the bioavailability of delavinone was 12.4%.


Assuntos
Fritillaria/química , Extratos Vegetais/química , Extratos Vegetais/farmacocinética , Administração Intravenosa/métodos , Administração Oral , Animais , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão/métodos , Camundongos , Camundongos Endogâmicos ICR , Espectrometria de Massas em Tandem/métodos
9.
Int J Biol Macromol ; 131: 97-106, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30844453

RESUMO

In this paper, Fritillaria pallidiflora schrenk polysaccharides were extracted with different methods and isolated by anion-exchange and gel-permeation chromatography. Physicochemical properties, structural characteristics and antioxidant activities were investigated for the first time. The polysaccharides composed of glucose, galactose, arabinose, xylose, mannose and rhamnose with different molar ratio and molecular weight. Fourier transform infrared spectroscopy and nuclear magnetic resonance analysis exhibited the presence of key functional groups of polysaccharides whereas scanning electron microscopy analysis revealed the characteristic morphology of different fractions. The thermogravimetric analysis manifested the thermal stability of polysaccharides. The reducing power and antioxidant activities of polysaccharides were evaluated in vitro. Among them, the acidic fraction FPSP-H2-1 has a strong antioxidant effect against DPPH, hydroxyl and ABTS free radicals. The results revealed the polysaccharide's important role as potential natural antioxidant agents during the investigation and application of bioactive polysaccharide.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Fritillaria/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Antioxidantes/isolamento & purificação , Fracionamento Químico , Relação Dose-Resposta a Droga , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/isolamento & purificação , Depuradores de Radicais Livres/farmacologia , Peso Molecular , Monossacarídeos/química , Polissacarídeos/isolamento & purificação , Análise Espectral , Termogravimetria
10.
Cell Physiol Biochem ; 51(4): 1566-1583, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30497066

RESUMO

BACKGROUND/AIMS: Glioblastoma multiforme (GBM) is the most devastating and widespread primary central nervous system tumour in adults, with poor survival rate and high mortality rates. Existing treatments do not provide substantial benefits to patients; therefore, novel treatment strategies are required. Peiminine, a natural bioactive compound extracted from the traditional Chinese medicine Fritillaria thunbergii, has many pharmacological effects, especially anticancer activities. However, its anticancer effects on GBM and the underlying mechanism have not been demonstrated. This study was conducted to investigate the potential antitumour effects of peiminine in human GBM cells and to explore the related molecular signalling mechanisms in vitro and in vivo Methods: Cell viability and proliferation were detected with MTT and colony formation assays. Morphological changes associated with autophagy were assessed by transmission electron microscopy (TEM). The cell cycle rate was measured by flow cytometry. To detect changes in related genes and signalling pathways in vitro and in vivo, RNA-seq, Western blotting and immunohistochemical analyses were employed. RESULTS: Peiminine significantly inhibited the proliferation and colony formation of GBM cells and resulted in changes in many tumour-related genes and transcriptional products. The potential anti-GBM role of peiminine might involve cell cycle arrest and autophagic flux blocking via changes in expression of the cyclin D1/CDK network, p62 and LC3. Changes in Changes in flow cytometry results and TEM findings were also observed. Molecular alterations included downregulation of the expression of not only phospho-Akt and phospho-GSK3ß but also phospho-AMPK and phospho-ULK1. Furthermore, overexpression of AKT and inhibition of AKT reversed and augmented peiminine-induced cell cycle arrest in GBM cells, respectively. The cellular activation of AMPK reversed the changes in the levels of protein markers of autophagic flux. These results demonstrated that peiminine mediates cell cycle arrest by suppressing AktGSk3ß signalling and blocks autophagic flux by depressing AMPK-ULK1 signalling in GBM cells. Finally, peiminine inhibited the growth of U251 gliomas in vivo. CONCLUSION: Peiminine inhibits glioblastoma in vitro and in vivo via arresting the cell cycle and blocking autophagic flux, suggesting new avenues for GBM therapy.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Autofagia/efeitos dos fármacos , Neoplasias Encefálicas/tratamento farmacológico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Cevanas/uso terapêutico , Glioblastoma/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Antineoplásicos Fitogênicos/farmacologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Cevanas/farmacologia , Feminino , Fritillaria/química , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais/efeitos dos fármacos
11.
Fitoterapia ; 131: 112-118, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30336193

RESUMO

Three new isosteroidal alkaloids, frititorines A-C (1-3), were isolated from the bulbs of Fritillaria tortifolia, together with ten known ones (4-13). Their structures were elucidated by extensive spectroscopic analyses, chemical methods, and single-crystal X-ray crystallographic analysis. Compound 1 is the first 5ß-cevanine alkaloid with a cis A/B ring junction from the Fritillaria genus. Compound 2 is the first example of glycosylated isosteroidal alkaloid N-oxide. Compound 1 showed significant relaxant effect on Ach-induced tracheal contraction with pA2 and EC50 values equivalent to those of aminophylline.


Assuntos
Alcaloides/isolamento & purificação , Fritillaria/química , Raízes de Plantas/química , Traqueia/efeitos dos fármacos , Animais , China , Técnicas In Vitro , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Ratos Sprague-Dawley
12.
Molecules ; 23(7)2018 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-29958456

RESUMO

A simple and high sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous determination of peimine and peiminine in beagle dog plasma after the oral administration of Fritillariae ussuriensis Maxim and Fritillariae thunbergii Miq powder. Chromatographic separation was achieved on an ACQUIT UPLC® BEH C18 column (1.7 µm, 2.1 × 100 mm) in a gradient elution way with a mobile phase consisting of acetonitrile and water containing 0.1% formic acid at a flow rate of 0.4 mL/min. The plasma samples were prepared by a liquid⁻liquid extraction (LLE) method with ethyl acetate. The analytes were detected with a triple quadrupole tandem mass spectrometry (MS) in multiple reaction monitoring (MRM) mode and a positive ion electrospray ionization (ESI) of the transitions at m/z 432.4→414.4 for peimine and m/z 430.3→412.3 for peiminine. The method was linear for two analytes over the investigated range with all determined correlation coefficients exceeding 0.9900. The lower limit of quantification (LLOQ) was 0.988 ng/mL for peimine and 0.980 ng/mL for peiminine. The mean extraction recoveries of peimine and peiminine at three quality control samples (QC) levels were ranged from 82.56 to 88.71%, and matrix effects ranged from 92.06 to 101.2%. The intra-day and inter-day precision and accuracy were within the acceptable limits at LLOQ and QC levels. The method was effectively and successfully applied to the pharmacokinetics of peimine and peiminine after oral administration of powder to beagle dogs. The obtained results may be help to guide the clinical application of Fritillaria ussuriensis Maxim and Fritillaria thunbergii Miq.


Assuntos
Cevanas/sangue , Cevanas/farmacocinética , Cromatografia Líquida/métodos , Medicamentos de Ervas Chinesas/química , Fritillaria/química , Espectrometria de Massas em Tandem/métodos , Administração Oral , Animais , Cães , Medicamentos de Ervas Chinesas/administração & dosagem , Masculino
13.
Int J Biol Macromol ; 112: 1073-1083, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29447973

RESUMO

Rich polysaccharides were directly observed in the bulbs of Fritillaria unibracteata var. wabuensis (FUW) using the periodic acid-Schiff (PAS) method and microexamination. An acidic water-soluble heteropolysaccharide (FWPS1-1) was isolated from FUW through ethanol precipitation, decoloration, deproteinization, dialysis and separation using a DE-52 anion-exchange column and a Sepharose G-150 gel filtration column. FWPS1-1 (average molecular weight: ~7.44 kDa) has many branches and long side chains; holds the triple-helix conformation; was composed of mannose (Man), galacturonic acid (GalA), galactose (Gal), xylose (Xyl) and arabinose (Ara) with a molar ratio of 2.62:5.59:10.00:0.76:9.38; and features side chains that may be composed of Ara, Man, Gal and GalA, while the backbone may be composed of Xyl, Ara and Gal. In addition, the backbone of FWPS1-1 mainly consists of α-type glycosidic bonds. Bioactivity tests in vitro showed that the polysaccharide exhibited weak 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and low ferric reducing antioxidant power (FRAP) but high 2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)l (ABTS) radical scavenging activity, good Fe(II)-chelating ability and remarkable DNA damage protective activity. FWPS1-1 was the first heteropolysaccharide purified from FUW and showed good antioxidant activity and DNA protective effect. The results confirmed that macromolecule is also bioactive ingredient that requires attention like the small-molecule active compounds in FUW.


Assuntos
Antioxidantes/farmacologia , Fritillaria/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Benzotiazóis/química , Compostos de Bifenilo/química , Configuração de Carboidratos , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Delgada , Misturas Complexas/farmacologia , Dano ao DNA , Depuradores de Radicais Livres/química , Fritillaria/citologia , Iodo , Quelantes de Ferro/farmacologia , Monossacarídeos/análise , Oxirredução , Picratos/química , Polissacarídeos/química , Espectroscopia de Prótons por Ressonância Magnética , Padrões de Referência , Espectroscopia de Infravermelho com Transformada de Fourier , Ácidos Sulfônicos/química
14.
J Food Drug Anal ; 26(1): 337-347, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29389572

RESUMO

Thunberg fritillary bulb (the dry bulbs of Fritillaria thunbergii Miq.), a traditional Chinese Medicine, is widely applied as an expectorant and antitussive. In this investigation, the primary metabolites of bulbs, flowers, leaves, and stems of F. thunbergii were analyzed by gas chromatography-mass spectrometry. Principal component analysis, partial least squares-discriminate analysis, orthogonal projection to latent structures-discriminate analysis, and heat map analysis showed that there were dissimilar metabolites, and a negative correlation between amino acids and saccharides in different analytes. Furthermore, carbodiimide, tryptophan, glucose-6-phosphate, xylose, 2-piperidinecarboxylic acid, monoamidomalonic acid, phenylalanine, and histidine were found to play an important role in the plant metabolism net of F. thunbergii.


Assuntos
Fritillaria/química , Cromatografia Gasosa-Espectrometria de Massas , Metaboloma , Metabolômica , Biologia Computacional/métodos , Análise de Dados , Fritillaria/metabolismo , Redes e Vias Metabólicas , Metabolômica/métodos
15.
Curr Protein Pept Sci ; 19(3): 302-310, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28059041

RESUMO

Isosteroidal alkaloids are a category of promising bioactive compounds which mostly exist in plants of genus Veratrum and Fritillaria. The pharmacological activities of isosteroidal alkaloids include antihypertensive, antitussive, anti-inflammatory, antithrombosis, among others. Recently, some studies show that this kind of alkaloids exhibited significant antitumor activity. To the best of our knowledge, there is no review focusing on their antitumor activity and mechanism of their antitumor activity. To fill the gap, in this review, we summarized antitumor effects of the isosteroidal alkaloids from genus Veratrum and Fritillaria on different tumors and the mechanisms of their antitumor activity. In conclusion, this kind of alkaloids has extensive antitumor activity, and there are several main mechanisms of their antitumor activity, including the Hedgehog signaling pathway, caspase-3 dependent apoptosis, cell cycle, and autophagy.


Assuntos
Alcaloides/química , Alcaloides/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Fritillaria/química , Neoplasias/tratamento farmacológico , Veratrum/química , Alcaloides/uso terapêutico , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proteínas Hedgehog/metabolismo , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Transdução de Sinais/efeitos dos fármacos , Alcaloides de Veratrum/química , Alcaloides de Veratrum/farmacologia , Alcaloides de Veratrum/uso terapêutico
16.
J Ethnopharmacol ; 210: 39-46, 2018 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-28842340

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Fritillariae Bulbus (Beimu in Chinese) is derived from the bulbus of many Fritillaria species (family Liliaceae), which has been used as an antitussive herb in traditional Chinese medicine for more than 2000 years. Due to the complexity of plant origins and significant variations in chemical profiles, the characterization of the profile of the major bioactive constituents and its association with pharmacological activity are important for the quality control of Beimu herbs from different origins. AIM OF THE STUDY: This study aims to investigate the distribution of major bioactive isosteroidal alkaloids in Beimu herbs of different origins and its correlation with the tracheobronchial relaxant activity. METHODS: Quantification of 7 main bioactive 5α-cevanine isosteroidal alkaloids, including ebeiedine, ebeiedinone, hupehenine, isoverticine, verticine, verticinone and imperialine, in 23 Fritillaria species was performed using gas chromatography. The relaxant effect of different extracts of 4 commonly used Beimu herbs, namely Zhe-Beimu (F. thunbergii Miq.), Chuan-Beimu (F. cirrhosa D. Don), Hubei-Beimu (F. hupehensis Hsiao et K. C. Hsia) and Yi-Beimu (F. pallidiflora Schrenk), was evaluated using rat isolated tracheal and bronchial preparations pre-contracted with carbachol, the well established in vitro antitussive model. RESULTS: Amongst 23 Fritillaria species detected, significant variations of the types and quantities of 7 major isosteroidal alkaloids were determined, which served as an important indicator for the classification of different Beimu herbs with distinct geographic distributions. Based on the type and quantity of these alkaloids, different origins of Beimu could be clearly clustered into several subgroups by principal component analysis. Furthermore, both crude alkaloid and water extracts of all 4 Beimu herbs showed a dose-dependent tracheobronchial relaxation with different potencies. The total content of alkaloids (weight adjusted based on the activity of individual alkaloids) in Beimu extracts significantly correlated with their tracheobronchial relaxation effects (r2 > 0.9, p < 0.001). CONCLUSIONS: The results demonstrated that the differences in chemical profile of major bioactive isosteroidal alkaloids and pharmacological activity of Beimu could be incorporated into a simple and unified method for quality control and potential prediction of activity of Beimu herbs from different origins.


Assuntos
Alcaloides/farmacologia , Antitussígenos/farmacologia , Fritillaria/química , Extratos Vegetais/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Antitussígenos/isolamento & purificação , Brônquios/efeitos dos fármacos , Cromatografia Gasosa , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Masculino , Medicina Tradicional Chinesa , Controle de Qualidade , Ratos , Ratos Sprague-Dawley , Traqueia/efeitos dos fármacos
17.
Zhongguo Zhong Yao Za Zhi ; 42(21): 4180-4186, 2017 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-29271158

RESUMO

To investigate the effects of Fritillariae Cirrhosae Bulbus on airway remodeling and matrix metalloproteinase-2(MMP-2), matrix metalloproteinase-9(MMP-9), tissue inhibitor-1 of metalloproteinase(TIMP-1) of a murine asthma model, and explore its mechanism in treatment of asthma. BALB/C murines were randomly divided into the normal group, model group, high dose group, low dose group, and positive control group. Except for the normal group, all the other groups received ovalbumin(OVA) to establish murine asthma model. After successful modeling, the murines in high dose group and low dose group were orally administered with Fritillariae Cirrhosae Bulbus powder at the dose of 18.0 mg•kg⁻¹ and 9.0 mg•kg⁻¹, respectively; the murines in positive control group were injected intraperitoneally with dexamethasone at the dose of 0.5 mg•kg⁻¹; while the murines in normal group and the model group were orally administered with the same volume of normal saline. All the drugs were given to murines per day for 28 d. The variations of airway responsiveness, variations of the total cell count and leukocyte differential count in bronchoalveolar lavage fluid(BALF), and the variations of thicknesses of bronchial wall and airway smooth muscle of each group were observed. The levels of MMP-2, MMP-9 and TIMP-1 were measured by ELISA; and the expression levels of MMP-2, MMP-9 and TIMP-1 mRNA were detected by RT-PCR. The results showed that as compared with the normal group, the airway responsiveness, the count of total cells, neutrophils, macrophage, lymphocytes, eosinophils in BALF, and the thicknesses of bronchial wall and airway smooth muscle were increased significantly in the model group(P<0.01); as compared with the model group, the above indicators were decreased significantly in the high dose group, low dose group and positive control group (P<0.05 or P<0.01). As compared with the normal group, the levels and expressions of MMP-2, MMP-9 and TIMP-1 mRNA were increased significantly in the model group(P<0.01); while as compared with the model group, these levels were decreased significantly in the high dose group, low dose group and positive control group(P<0.01). In conclusion, Fritillariae Cirrhosae Bulbus can improve airway remodeling in a murine asthma model, and its mechanisms may be related to down-regulating MMP-2, MMP-9 and TIMP-1 levels.


Assuntos
Asma/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Fritillaria/química , Raízes de Plantas/química , Animais , Modelos Animais de Doenças , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória , Inibidor Tecidual de Metaloproteinase-1/metabolismo
18.
Molecules ; 22(9)2017 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-28832506

RESUMO

Rapid, non-destructive, and accurate quantitative determination of the effective components in traditional Chinese medicine (TCM) is required by industries, planters, and regulators. In this study, near-infrared hyperspectral imaging was applied for determining the peimine and peiminine content in Fritillaria thunbergii bulbi under sulfur fumigation. Spectral data were extracted from the hyperspectral images. High-performance liquid chromatography (HPLC) was conducted to determine the reference peimine and peiminine content. The successive projection algorithm (SPA), weighted regression coefficient (Bw), competitive adaptive reweighted sampling (CARS), and random frog (RF) were used to select optimal wavelengths, while the partial least squares (PLS), least-square support vector machine (LS-SVM) and extreme learning machine (ELM) were used to build regression models. Regression models using the full spectra and optimal wavelengths obtained satisfactory results with the correlation coefficient of calibration (rc), cross-validation (rcv) and prediction (rp) of most models being over 0.8. Prediction maps of peimine and peiminine content in Fritillaria thunbergii bulbi were formed by applying regression models to the hyperspectral images. The overall results indicated that hyperspectral imaging combined with regression models and optimal wavelength selection methods were effective in determining peimine and peiminine content in Fritillaria thunbergii bulbi, which will help in the development of an online detection system for real-world quality control of Fritillaria thunbergii bulbi under sulfur fumigation.


Assuntos
Cevanas/química , Fritillaria/química , Fumigação/métodos , Análise Espectral , Enxofre , Cevanas/análise , Análise de Regressão , Análise Espectral/métodos , Enxofre/química
19.
Biomed Pharmacother ; 94: 598-604, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28783582

RESUMO

In this study, we evaluated the cytotoxic effects of Fritillaria imperialis L. aqueous and ethanolic extracts on human liver cancer cells (LCL-PI 11), breast adenocarcinoma cells (MCF-7) and fibroblast-like cells (HSkMC). MTT, BrdU and TUNEL assays were used to detect cytotoxicity, proliferation rate and apoptotic death. Following 48h, the IC50 values for LCL-PI11 and MCF-7 cells were 4.2 and 3.9µg/mL of aqueous extract, and 1.7 and 1.3µg/mL of ethanolic extract, respectively, which was comparable to that of 5-FU. BrdU assay data verified that both extracts inhibited cell proliferation more preferentially on the two cancer cells. Exposure of LCL-PI 11 and MCF-7 cells to 2.4µg/mL of aqueous extract for 24h resulted in 29% and 32% apoptotic death. Surprisingly the ethanolic extract killed nearly all of the cells at 1.6µg/mL concentration. Collectively, our data indicated that both extracts have cytotoxic, cytostatic and pro-apoptotic activities against the two cancer cell lines. The ethanolic extract was more potent than the aqueous extract and the fibroblast cell was found to be less influenced than both cancer cell lines. Further researches are necessary for chemical characterization and in vivo evaluation especially in animal models to identify the effective anticancer ingredient of F. imperialis.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Fritillaria/química , Neoplasias Hepáticas/tratamento farmacológico , Extratos Vegetais/farmacologia , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fluoruracila/farmacologia , Humanos , Marcação In Situ das Extremidades Cortadas , Concentração Inibidora 50 , Células MCF-7
20.
Anal Chim Acta ; 977: 28-35, 2017 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-28577595

RESUMO

In this study, a new strategy combining mass spectrometric (MS) techniques with partial least squares regression (PLSR) was proposed to identify and quantify closely related adulterant herbal materials. This strategy involved preparation of adulterated samples, data acquisition and establishment of PLSR model. The approach was accurate, sensitive, durable and universal, and validation of the model was done by detecting the presence of Fritillaria Ussuriensis Bulbus in the adulteration of the bulbs of Fritillaria unibracteata. Herein, three different MS techniques, namely wooden-tip electrospray ionization mass spectrometry (wooden-tip ESI/MS), ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) and UPLC-triple quadrupole tandem mass spectrometry (UPLC-TQ/MS), were applied to obtain MS profiles for establishing PLSR models. All three models afforded good linearity and good accuracy of prediction, with correlation coefficient of prediction (rp2) of 0.9072, 0.9922 and 0.9904, respectively, and root mean square error of prediction (RMSEP) of 0.1004, 0.0290 and 0.0323, respectively. Thus, this strategy is very promising in tracking the supply chain of herb-based pharmaceutical industry, especially for identifying adulteration of medicinal materials from their closely related herbal species.


Assuntos
Contaminação de Medicamentos , Fritillaria/química , Preparações de Plantas/normas , Cromatografia Líquida de Alta Pressão , Análise dos Mínimos Quadrados , Preparações de Plantas/análise , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem
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