RESUMO
BACKGROUND: Breast cancer stands as a leading contributor to global cancer-related mortality. Progressing Research and Medical Innovations Elevate Treatment Choices and Results for Breast Cancer. Among these, Peimine, a natural steroid inherent in plants, notably within the Fritillaria species, demonstrates the capability to trigger apoptosis in breast cancer cells through the mitochondrial membrane permeation pathway. Nevertheless, its impact on an appropriate cancer model remains an area necessitating further exploration. AIM: This study explored the in vivo anticancer effects of peimine on MRMT-1 Cell-line induced breast cancer in rats. METHOD: Cancer was induced by the administration of MRMT-1 (6 x 106 cells) cells in the mammary pads of SD rats. The daily drug treatmentcommenced on day 14 and continued till 39 days. Peimine was administered in two doses (0.24 mg/kg and 0.48 mg/kg p.o) to examine its efficacy in curing breast cancer while tamoxifen was used as standard. RESULTS: A reduction in tumour size was observed in the peimine-treated groups. Peimine can correct the changed blood cell count in addition to its anti-tumour activity. In peimine-treated rats, imbalanced immune marker IgE, serum oxidative marker, and tissue apoptotic markers like cytochrome c and calcium level were shown to be restored significantly. CONCLUSION: Our findings imply that quinine has beneficial effects as an anti-neoplastic medication for breast cancer, most likely through its apoptotic activity. More research is necessary to thoroughly understand their mechanisms of action, ideal dose, and potential side effects.
Assuntos
Apoptose , Cevanas , Ratos Sprague-Dawley , Animais , Apoptose/efeitos dos fármacos , Feminino , Ratos , Linhagem Celular Tumoral , Cevanas/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/patologia , Neoplasias Mamárias Experimentais/metabolismo , Fritillaria/químicaRESUMO
Purpose: In recent years, the incidence of chronic obstructive pulmonary disease (COPD) has been increasing year by year, but therapeutic drugs has no breakthrough. The total alkaloid extract from Bulbus Fritillariae pallidiflorae (BFP-TA) is widely used in treating lung diseases. Therefore, this study aimed to investigate the protective effect and mechanism of BFP-TA in COPD mice. Methods: BFP-TA was prepared by macroporous adsorbent resin, and the material basis of BFP-TA was analyzed by HPLC-ELSD and UHPLC-MS/MS. Then, the COPD mouse model was induced by cigarette smoke (CS) for 12 weeks, administered at weeks 9-12. Subsequently, the body weight, lung-body ratio, pulmonary function, histopathology, and the levels of pro-inflammatory cytokines, matrix metalloproteinases (MMPs) and oxidative stress markers in the serum of mice were determined. The expressions of related protein of EMT and MAPK signaling pathways in the lung tissues of mice were detected by Western blot. Results: The alkaloid relative content of BFP-TA is 64.28%, and nine alkaloids in BFP-TA were identified and quantified by UHPLC-MS/MS. Subsequently, the animal experiment showed that BFP-TA could improve pulmonary function, and alleviate inflammatory cell infiltration, pulmonary emphysema, and collagen fiber deposition in the lung of COPD mice. Furthermore, BFP-TA could decrease the levels of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1ß), MMPs (MMP-9 and MMP-12) and MDA, while increase the levels of TIMP-1 and SOD. Moreover, BFP-TA could decrease the protein expressions of collagen I, vimentin, α-SMA, MMP-9, MMP-9/TIMP-1, Bax, p-JNK/JNK, p-P38/P38, and p-ERK/ERK, while increase the level of E-cadherin. Conclusion: This study is the first to demonstrate the protective effect of BFP-TA in CS-induced COPD mouse model. Furthermore, BFP-TA may improve airway remodeling by inhibiting the EMT process and potentially exert anti-inflammatory effect by inhibiting the MAPK signaling pathway.
Assuntos
Alcaloides , Anti-Inflamatórios , Citocinas , Modelos Animais de Doenças , Fritillaria , Pulmão , Estresse Oxidativo , Extratos Vegetais , Doença Pulmonar Obstrutiva Crônica , Animais , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/prevenção & controle , Alcaloides/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Masculino , Fritillaria/química , Extratos Vegetais/farmacologia , Citocinas/metabolismo , Fumaça/efeitos adversos , Mediadores da Inflamação/metabolismo , Camundongos Endogâmicos C57BL , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Remodelação das Vias Aéreas/efeitos dos fármacos , Fumar Cigarros/efeitos adversos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Antioxidantes/farmacologia , Antioxidantes/isolamento & purificação , Transdução de Sinais/efeitos dos fármacosRESUMO
A novel actinobacterium, designated strain CWNU-1T, was isolated from the rhizospheric soil of Fritillaria cirrhosa D. Don and examined using a polyphasic taxonomic approach. The organism developed pale blue aerial mycelia that was simply branched and terminated in open or closed coils of three or more volutions on International Streptomyces Project 3 agar. Spores were ellipsoidal to cylindrical with wrinkled surfaces. The strain showed high 16S rRNA gene sequence similarity to Streptomyces kurssanovii NBRC 13192T (98.8â%), Streptomyces xantholiticus NBRC 13354T (98.7â%) and Streptomyces peucetius JCM 9920T (98.6â%). The phylogenetic result based on 16S rRNA gene and genome sequences clearly demonstrated that strain CWNU-1T formed an independent phylogenetic lineage. On the basis of orthologous average nucleotide identity, CWNU-1T was most closely related to Streptomyces inusitatus NBRC 13601T with 79.3â% identity. The results of the digital DNA-DNA hybridization analysis also indicated low levels of relatedness with other species, as the highest value was observed with S. inusitatus NBRC 13601T (25.3â%). With reference to phenotypic characteristics, phylogenetic data, orthologous average nucleotide identity and digital DNA-DNA hybridization results, strain CWNU-1T was readily distinguished from its most closely related strains and classified as representing a novel species, for which the name Streptomyces albipurpureus sp. nov. is proposed. The type strain is CWNU-1T (=CGMCC 4.7758T=MCCC 1K07402T=JCM 35391T).
Assuntos
Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Fritillaria , Hibridização de Ácido Nucleico , Filogenia , RNA Ribossômico 16S , Rizosfera , Análise de Sequência de DNA , Microbiologia do Solo , Streptomyces , Streptomyces/genética , Streptomyces/classificação , Streptomyces/isolamento & purificação , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Ácidos Graxos/análise , Fritillaria/microbiologia , Vitamina K 2/análogos & derivadosRESUMO
Fritillaria cirrhosa, an endangered plant endemic to plateau regions, faces escalating cadmium (Cd) stress due to pollution in the Qinghai-Tibet Plateau. This study employed physiological, cytological, and multi-omics techniques to investigate the toxic effects of Cd stress and detoxification mechanisms of F. cirrhosa. The results demonstrated that Cd caused severe damage to cell membranes and organelles, leading to significant oxidative damage and reducing photosynthesis, alkaloid and nucleoside contents, and biomass. Cd application increased cell wall thickness by 167.89% in leaves and 445.78% in bulbs, leading to weight percentage of Cd increases of 76.00% and 257.14%, respectively. PER, CESA, PME, and SUS, genes responsible for cell wall thickening, were significantly upregulated. Additionally, the levels of metabolites participating in the scavenging of reactive oxygen species, including oxidized glutathione, D-proline, L-citrulline, and putrescine, were significantly increased under Cd stress. Combined multi-omics analyses revealed that glutathione metabolism and cell wall biosynthesis pathways jointly constituted the detoxification mechanism of F. cirrhosa in response to Cd stress. This study provides a theoretical basis for further screening of new cultivars for Cd tolerance and developing appropriate cultivation strategies to alleviate Cd toxicity.
Assuntos
Cádmio , Fritillaria , Fritillaria/genética , Fritillaria/metabolismo , Cádmio/toxicidade , Tibet , Estresse Oxidativo/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Glutationa/metabolismo , Espécies Reativas de Oxigênio/metabolismo , MultiômicaRESUMO
Fritillaria ussuriensis Maxim. (F.M.) has been widely used in both food and medication for more than 2000 years. In order to achieve its comprehensive utilization and investigate the structural characterization and biology activity, response surface methodology (RSM) was used to optimize the ultrasound-assisted extraction conditions of F.M. polysaccharides. The optimal extraction conditions were ultrasonic power of 174.2 W, ratio of liquid to material of 40.7 mL/g and ultrasonic time of 82.0 min. In addition, a neutral polysaccharide F-1 was obtained, and its structure characterization, antioxidant and immunological activity were evaluated. The structural properties of the polysaccharide were characterized by UV, IR, GC-MS, NMR and AFM. Monosaccharide composition of F-1 (MW 18.11 kDa) was rhamnose, arabinose, glucosamine hydrochloride, galactose, and glucose which under the ratio of 0.9: 3.8: 0.2: 2.9: 92.2. The fractions of F-1 were mainly linked by â 6)-α-D-Glcp-(1 â with branch chain α-D-Glcp-(1 â 4)-α-D-Glcp-(1 â and 4,6)-α-D-Glcp-(1 â residues. Moreover, F-1 has a significant scavenging activity, which can clear hydroxyl radicals, superoxide anion, DPPH and ABTS. In addition, the immunological activity showed that F-1 had an effect on macrophage phagocytic activity. And it can increase the release of inflammatory factors including TNF-α, IL-1ß and IL-6. F-1 is a novel polysaccharide with significant activity in antioxidant and immunological activity, which has great potential for antioxidant and immunizer in food, pharmaceutical and cosmetic industries. The study can provide a methodological basis for polysaccharide research and theoretical basis for the industrialized production and practical application.
Assuntos
Antioxidantes , Fritillaria , Antioxidantes/farmacologia , Antioxidantes/química , Fritillaria/química , Peso Molecular , Polissacarídeos/farmacologia , Polissacarídeos/química , MonossacarídeosRESUMO
Eleven new steroidal alkaloids, along with nine known related compounds, were isolated from the bulbs of Fritillaria sinica. Seven pairs of diastereomers were identified, including six and four 20-deoxy cevanine-type steroidal alkaloid diastereomers with molecular weights of 413 and 415, respectively. Structures were elucidated based on spectroscopic data analysis, chemical derivatization, and single-crystal X-ray diffraction analysis. Compounds 5, 9, 11, 12, 16, and 20 exhibited significant in vitro cytotoxic activity against non-small-cell lung cancer with CC50 values from 6.8 ± 3.9 to 12 ± 5 µM.
Assuntos
Alcaloides , Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Fritillaria , Neoplasias Pulmonares , Humanos , Fritillaria/química , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Estrutura Molecular , Neoplasias Pulmonares/tratamento farmacológico , Alcaloides/química , Esteroides/químicaRESUMO
Fritillaria cirrhosa D. Don, which can be used for medicine and food, contains a variety of chemicals including polyphenols, alkaloids, terpenoid, and others that have beneficial biological properties like antihypertension, bacteriostasis, and anti-inflammatory. The ethanolic extract of Fritillaria straw was obtained for this study using ultrasonic-aided extraction, and the amounts of total phenols and total flavonoids were 26.56 ± 1.36 mg GAE/g dw and 18.75 ± 0.80 mg RE/g dw, respectively. Ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry technology was utilized to identify 50 major chemicals in the Fritillaria straw extract (FSE). Meanwhile, the antioxidative activities of FSE were evaluated by 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and Ferric reducing antioxidant power assays in vitro, which pointed out the antioxidative potential of FSE. Additionally, 0.1%, 0.5%, and 1% of FSE and 0.02% butylated hydroxyanisole (BHA) + butylated hydroxytoluene (BHT) (1:1) were separately added to Chinese-style sausage to study their effects on the lipid oxidation, protein oxidation, and quality of the sausage at different storage times. The study found that the effect of adding 1% FSE on carbonyl content, total volatile basic nitrogen, and TVC of sausage could achieve the effect of the 0.02% BHA + BHT (1:1) group on the 35th day, and the thiobarbituric acid reactive substances value and peroxide value of sausage were significantly lower than the control group. Therefore, as one of the candidates to replace synthetic antioxidants, the FSE can be used in the production of Chinese sausages, which has a positive effect on improving the product's quality and extending the shelf life. PRACTICAL APPLICATION: The antioxidative activities of 50 main compounds were identified after the ethanolic extraction of Fritillaria straw. This Fritillaria straw extract was added to Chinese sausage, effectively inhibiting the oxidation of lipids and proteins as well as the decomposition of proteins. Obviously, the Fritillaria straw extract, one of the choices to replace synthetic antioxidants, may be useful for future meat processing, because of its positive impact on the product's quality and shelf life.
Assuntos
Antioxidantes , Fritillaria , Produtos da Carne , Extratos Vegetais , Antioxidantes/análise , Fritillaria/química , Lipídeos , Oxirredução , Extratos Vegetais/químicaRESUMO
BACKGROUND: Asthma is a chronic inflammatory disease that is challenging to treat. Fritillaria unibracteata var. wabuensis (FUW) is the plant origin for the famous Chinese antitussive medicine Fritillaria Cirrhosae Bulbus. The total alkaloids of Fritillaria unibracteata var. wabuensis bulbus (TAs-FUW) have anti-inflammatory properties and may be used to treat asthma. PURPOSE: To explore whether TAs-FUW have bioactivity against airway inflammation and a therapeutic effect on chronic asthma. METHODS: The alkaloids were extracted via ultrasonication in a cryogenic chloroform-methanol solution after ammonium-hydroxide percolation of the bulbus. UPLC-Q-TOF/MS was used to characterize the composition of TAs-FUW. An ovalbumin (OVA)-induced asthmatic mouse model was established. We used whole-body plethysmography, ELISA, western blotting, RT-qPCR, and histological analyses to assess the pulmonary pathological changes in these mice after TAs-FUW treatment. Additionally, TNF-α/IL-4-induced inflammation in BEAS-2B cells was used as an in vitro model, whereby the effects of various doses of TAs-FUW on the TRPV1/Ca2+-dependent NFAT-induced expression of TSLP were assessed. Stimulation and inhibition of TRPV1 receptors by capsaicin (CAP) and capsazepine (CPZ), respectively, were used to validate the effect of TAs-FUW. RESULTS: The UPLC-Q-TOF/MS analysis revealed that TAs-FUW mainly contain six compounds (peiminine, peimine, edpetiline, khasianine, peimisine, and sipeimine). TAs-FUW improved airway inflammation and obstruction, mucus secretion, collagen deposition, and leukocyte and macrophage infiltration, and downregulated TSLP by inhibiting the TRPV1/NFAT pathway in asthmatic mice. In vitro, the application of CPZ demonstrated that the TRPV1 channel is involved in TNF-α/IL-4-mediated regulation of TSLP. TAs-FUW suppressed TNF-α/IL-4-induced TSLP generation expression by regulating the TRPV1/Ca2+/NFAT pathway. Furthermore, TAs-FUW reduced CAP-induced TSLP release by inhibiting TRPV1 activation. Notably, sipeimine and edpetiline each were sufficient to block the TRPV1-mediated Ca2+ influx. CONCLUSION: Our study is the first to demonstrate that TNF-α/IL-4 can activate the TRPV1 channel. TAs-FUW can alleviate asthmatic inflammation by suppressing the TRPV1 pathway and thereby preventing the increase in cellular Ca2+ influx and the subsequent NFAT activation. The alkaloids in FUW may be used for complementary or alternative therapies in asthma.
Assuntos
Alcaloides , Asma , Fritillaria , Camundongos , Animais , Fator de Necrose Tumoral alfa , Interleucina-4 , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Asma/tratamento farmacológico , Inflamação/tratamento farmacológico , Ovalbumina , Camundongos Endogâmicos BALB C , Modelos Animais de Doenças , Canais de Cátion TRPV/uso terapêuticoRESUMO
Eight undescribed steroidal alkaloid derivatives, including three cevanine-type isosteroidal alkaloids (two N-oxide glycosides and one D-ring aromatization) (1-3), one verazine-type steroidal alkaloid derivative (4), three solanidine-type steroidal alkaloid glycosides (5-7), and one veratramine-type analogue (8), along with three known compounds (9-11) were isolated from the bulbs of Fritillaria sinica. Their structures were elucidated by comprehensive analysis of spectroscopic data, acidic hydrolysis, and X-ray crystal diffractions. In the in vitro bioassay, the anti-cancer effect, anti-oxidation and anti-inflammatory activities for the isolates were evaluated at a concentration of 10 µM.
Assuntos
Alcaloides , Fritillaria , Fritillaria/química , Alcaloides/química , Esteroides/química , Raízes de Plantas/química , Glicosídeos/análiseRESUMO
We aimed to study the mechanism of Trichosanthes-Fritillaria thunbergii in treating lung adenocarcinoma (LUAD) based on network pharmacology and experimental verification. The effective components and potential targets of Trichosanthis and Fritillaria thunbergii were collected by high-throughput experiment and reference-guided (HERB) database of traditional Chinese medicine and a similarity ensemble approach (SEA) database, and the LUAD-related targets were queried by the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. A drug-component-disease-target network was constructed by Cytoscape software. Protein-protein interaction (PPI) network, gene ontology (GO) function, and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were conducted to obtain core targets and key pathways. An aqueous extract of Trichosanthes-Fritillaria thunbergii and A549 cells were used for the subsequent experimental validation. Through the HERB database and literature search, 31 effective compounds and 157 potential target genes of Trichosanthes-Fritillaria thunbergii were screened, of which 144 were regulatory targets of Trichosanthes-Fritillaria thunbergii in the treatment of lung adenocarcinoma. The GO functional enrichment analysis showed that the mechanism of action of Trichosanthes-Fritillaria thunbergii against lung adenocarcinoma is mainly protein phosphorylation. The KEGG pathway enrichment analysis suggested that the treatment of lung adenocarcinoma by Trichosanthes-Fritillaria thunbergii mainly involves the PI3K/AKT signaling pathway. The experimental validation showed that an aqueous extract of Trichosanthes-Fritillaria thunbergii could inhibit the proliferation of A549 cells and the phosphorylation of AKT. Through network pharmacology and experimental validation, it was verified that the PI3K/AKT signaling pathway plays a vital role in the action of Trichosanthes-Fritillaria thunbergii in treating lung adenocarcinoma.
Assuntos
Adenocarcinoma de Pulmão , Fritillaria , Neoplasias Pulmonares , Trichosanthes , Humanos , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Adenocarcinoma de Pulmão/tratamento farmacológico , Bases de Dados Genéticas , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Simulação de Acoplamento MolecularRESUMO
Fritillaria cirrhosa D. Don (known as Chuan-Bei-Mu in Chinese) can synthesize isosteroidal alkaloids (ISA) with excellent medicinal value, and its bulb has become an indispensable ingredient in many patented drugs. Members of the cytochrome P450 (CYP450) gene superfamily have been shown to play essential roles in regulating steroidal alkaloids biosynthesis. However, little information is available on the P450s in F. cirrhosa. Here, we performed full-length transcriptome analysis and discovered 48 CYP450 genes belonging to 10 clans, 25 families, and 46 subfamilies. By combining phylogenetic trees, gene expression, and key F. cirrhosa ISA content analysis, we presumably identify seven FcCYP candidate genes, which may be hydroxylases active at the C-22, C-23, or C-26 positions in the late stages of ISA biosynthesis. The transcript expression levels of seven FcCYP candidate genes were positively correlated with the accumulation of three major alkaloids in bulbs of different ages. These data suggest that the candidate genes are most likely to be associated with ISA biosynthesis. Finally, the subcellular localization prediction of FcCYPs and transient expression analysis within Nicotiana benthamiana showed that the FcCYPs were mainly localized in the chloroplast. This study presents a systematic analysis of the CYP450 gene family in F. cirrhosa and provides a foundation for further functional characterization of the CYPs involved in ISA biosynthesis.
Assuntos
Alcaloides , Fritillaria , Fritillaria/genética , Fritillaria/metabolismo , Filogenia , Perfilação da Expressão Gênica , Sistema Enzimático do Citocromo P-450/genéticaRESUMO
Temperature is one of the most important environmental factors that affect organisms, especially ectotherms, due to its effects on protein stability. Understanding the general rules that govern thermostability changes in proteins to adapt high-temperature environments is crucial. Here, we report the amino acid substitutions of phosphoglucose isomerase (PGI) related to thermostability in the Glanville fritillary butterfly (Melitaea cinxia, Lepidoptera: Nymphalidae). The PGI encoded by the most common allele in M. cinxia in the Chinese population (G3-PGI), which is more thermal tolerant, is more stable under heat stress than that in the Finnish population (D1-PGI). There are 5 amino acid substitutions between G3-PGI and D1-PGI. Site-directed mutagenesis revealed that the combination of amino acid substitutions of H35Q, M49T, and I64V may increase PGI thermostability. These substitutions alter the 3D structure to increase the interaction between 2 monomers of PGI. Through molecular dynamics simulations, it was found that the amino acid at site 421 is more stable in G3-PGI, confining the motion of the α-helix 420-441 and stabilizing the interaction between 2 PGI monomers. The strategy for high-temperature adaptation through these 3 amino acid substitutions is also adopted by other butterfly species (Boloria eunomia, Aglais urticae, Colias erate, and Polycaena lua) concurrent with M. cinxia in the Tianshan Mountains of China, i.e., convergent evolution in butterflies.
Assuntos
Borboletas , Fritillaria , Animais , Borboletas/genética , Borboletas/metabolismo , Glucose-6-Fosfato Isomerase/genética , Glucose-6-Fosfato Isomerase/metabolismo , Substituição de Aminoácidos , TemperaturaRESUMO
Acute lung injury (ALI), a severe respiratory disorder, frequently develops into acute respiratory distress syndrome (ARDS) without timely treatment and scores highly in terms of morbidity and mortality rates. Fritillaria hupehensis is a famous traditional Chinese medicine with antitussive, expectorant and anti-asthmatic effect. Here, the effects of F. hupehensis extracts on lipopolysaccharide (LPS)-induced ALI mice were evaluated for the first time. We showed ethyl acetate fraction (EAF) significantly reduced the leukocytes and neutrophils of bronchoalveolar lavage fluid (BALF) and the lung index as well as pro-inflammatory cytokines (TNF-α and IL-6) of lung homogenates but increasing the anti-inflammatory cytokines (IL-4 and IL-10). Additionally, the alleviation of EAF treatment on lung injury was verified through histopathological observations. Subsequent phytochemical investigation on bioactive fraction led to isolation of 17 compounds including two new, in which compounds 2, 5 and 6 exhibited better anti-inflammatory effect on LPS-induced 16 human airway epithelial (16HBE) cells model by inhibiting the production of CRP and PCT. Furthermore, compound 2 suppressed the LPS-induced upregulation of proteins containing p-p65, COX-2, Caspase-1 and IL-18. In summary, F. hupehensis alleviating LPS-induced ALI in mice may be associated with the anti-inflammatory activity of steroidal alkaloids by suppressing the NF-κB-regulated pro-inflammatory proteins.
Assuntos
Lesão Pulmonar Aguda , Alcaloides , Antiasmáticos , Antitussígenos , Fritillaria , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Animais , Antiasmáticos/efeitos adversos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Caspases/metabolismo , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Expectorantes/efeitos adversos , Humanos , Interleucina-10/efeitos adversos , Interleucina-18/efeitos adversos , Interleucina-4/efeitos adversos , Interleucina-6 , Lipopolissacarídeos/toxicidade , Camundongos , Estrutura Molecular , NF-kappa B/metabolismo , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Fator de Necrose Tumoral alfaRESUMO
Five previously undescribed steroidal glycoalkaloids(SGAs)and a rare ring B-seco isosteroidal alkaloid, were isolated from Fritillaria pallidiflora Schrenk, along with six known alkaloids. The structures of these alkaloids were established by comprehensive analyses of the 1D, 2D-NMR and HR-ESI-MS data. Configurations of sugar moieties were resolved by chemical derivations. The isolated compounds showed nitric oxide (NO) inhibitory activities in lipopolysaccharide (LPS) induced RAW264.7 cells, and yibeinone exhibited the strongest inhibitory effects among them. This study revealed that the alkaloids from F. pallidiflora might have significant anti-inflammatory potentials.
Assuntos
Alcaloides , Antineoplásicos , Fritillaria , Alcaloides/química , Fritillaria/química , Lipopolissacarídeos/farmacologia , Óxido Nítrico , AçúcaresRESUMO
BACKGROUND: Bulbus Fritillariae Cirrhosae (BFC) is an endangered high-altitude medicine and food homology plant with anti-tumor, anti-asthmatic, and antitussive activities as it contains a variety of active ingredients, especially steroidal alkaloids. Bulbus Fritillariae Thunbergia (BFT) is another species of Fritillaria that grows at lower altitude areas. Production of plant-derived active ingredients through a synthetic biology strategy is one of the current hot topics in biological research, which requires a complete understanding of the related molecular pathways. Our knowledge of the steroidal alkaloid biosynthesis in Fritillaria species is still very limited. RESULTS: To promote our understanding of these pathways, we performed non-target metabolomics and transcriptome analysis of BFC and BFT. Metabolomics analysis identified 1288 metabolites in BFC and BFT in total. Steroidal alkaloids, including the proposed active ingredients of Fritillaria species peimine, peimisine, peiminine, etc., were the most abundant alkaloids detected. Our metabolomics data also showed that the contents of the majority of the steroidal alkaloids in BFC were higher than in BFT. Further, our comparative transcriptome analyses between BFC and BFT identified differentially expressed gene sets among these species, which are potentially involved in the alkaloids biosynthesis of BFC. CONCLUSION: These findings promote our understanding of the mechanism of steroidal alkaloids biosynthesis in Fritillaria species.
Assuntos
Alcaloides , Fritillaria , Fritillaria/genética , Perfilação da Expressão Gênica , Metaboloma , Raízes de PlantasRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Forsythia suspensa (Thunb.) Vahl and Fritillaria thunbergii Miq are traditional Chinese medicines that exhibit the ability to clear heat and toxic material effects. In China, the combination of these two medicines is widely used to treat mucopurulent sputum and bloody phlegm, arising due to phlegm-heat obstruction in respiratory diseases. However, very limited information is available regarding the combined anti-inflammatory effect of important effective components of Forsythia suspensa (Thunb.) Vahl and Fritillaria thunbergii Miq, namely peimine, peiminine, and forsythoside A. AIM OF THIS STUDY: To investigate synergistic anti-inflammatory effects of combined administration of peimine, peiminine, and forsythoside A on LPS-induced acute lung injury compared to combined administration of two compounds or individual administration, and unravel the underlying mechanism. MATERIAL AND METHODS: In the present study, male BALB/c mice received an oral dosage of sodium carboxymethylcellulose (CMC-Na) (0.5%, 1 mL/100 g), peimine, peiminine, forsythoside A, peimine + forsythoside A, peiminine + forsythoside A, and peimine + peiminine + forsythoside A (suspended in CMC-Na; 0.5%), once daily for 7 days. Subsequently, intratracheal instillation of LPS was applied to establish acute lung injury model. After 6 h of administration, the mice were sacrificed, and bronchoalveolar lavage fluid (BALF) and lung tissues were collected. These samples were further used to determine lung W/D (wet/dry) weight ratio, total protein (TP) levels, inflammatory cytokines (IL-6, TNF-α, IL-1ß, and IL-17), and expression of proteins involved in TLR4/MAPK/NF-κB pathway and IL-17 pathway. Further, tissue sections were subjected to H&E staining to assess the pathological alterations induced by LPS. The expression of IL-6 and TNF-α proteins in lung tissues was also analyzed using immunohistochemical staining. RESULTS: A synergistic anti-inflammatory effect of peimine, peiminine, and forsythoside A was observed when administered in combination to LPS-induced acute lung injury. The combined administration of peimine, peiminine, and forsythoside A had a strongly inhibitory effects on the W/D weight ratio, total protein (TP) level and the inflammatory cytokines (TNF-α, IL-6, IL-1ß, and IL-17) level in acute lung injury mice, compared to combined administration of two compounds or individual administration. The infiltration of inflammatory cells and thickened bronchoalveolar walls induced by LPS were also ameliorated through the combined administration of peimine, peiminine, and forsythoside A. More importantly, the upregulation of protein related to TLR4/MAPK/NF-κB signaling pathway and the activation of IL-17 were significantly suppressed by pretreatment with each of the three compounds alone, while the effects of individual compounds were synergistically augmented by the combined pretreatment of these three compounds. CONCLUSION: The combined administration of peimine, peiminine, and forsythoside A ameliorated inflammatory response in acute lung injury mice induced by LPS in a synergistic manner, the mechanism may be related to the dampening of the TLR4/MAPK/NF-κB signaling pathway and IL-17 activation.
Assuntos
Lesão Pulmonar Aguda , Forsythia , Fritillaria , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/patologia , Animais , Anti-Inflamatórios/efeitos adversos , Cevanas , Citocinas/metabolismo , Fritillaria/química , Glicosídeos , Interleucina-17 , Interleucina-6 , Lipopolissacarídeos/toxicidade , Pulmão/patologia , Masculino , Camundongos , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfaRESUMO
Objective: To investigate the effect of Danggui Beimu Kushen Pills on renal cell carcinoma patients undergoing laparoscopic radical resection and their effects on renal function and immune function. Methods: 106 patients with renal cell carcinoma who underwent retroperitoneal laparoscopic radical surgery in our hospital from March 2015 to February 2017 were selected, and they were divided into control group and treatment group. The control group was treated with interferon and the treatment group was treated with Danggui Beimu Kushen pills on the basis of the control group. The clinical efficacy, incidence of adverse reactions, survival rate, and the relationship with clinical stages were detected in the two groups. The renal function index levels, immune function index levels, and quality of life levels were measured in the two groups after treatment. Results: Compared with the control group, the total clinical effective rate was increased, the abnormal renal function, abnormal liver function, and platelet decline were decreased, and the survival rate was significantly elevated in the treatment group. The patients with clinical stage Iâ¼II' survival rate was increased, relative to patients with clinical stage III. After treatment, the levels of ß2-MG, SCr, BUN, and CD8+ in the two groups were decreased, while the levels of CD3+, CD4+, and CD4+/CD8+ were increased. Moreover, the scores of physical function, social function, emotional function, role function, cognitive function, and total score of the two groups were improved. Compared with the control group, the treatment group changes were more obvious. Conclusion: The Danggui Beimu Kushen Pill has significant clinical effects on the treatment of renal cancer, which can improve the clinical symptoms, enhance the immune function, restore the health renal function, improve the quality of life, prolong the survival time of patients, reduce the incidence of adverse reactions, and provide high safety.
Assuntos
Angelica , Carcinoma de Células Renais , Fritillaria , Neoplasias Renais , Laparoscopia , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Medicamentos de Ervas Chinesas , Humanos , Imunidade , Rim/fisiologia , Rim/cirurgia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Nefrectomia , Qualidade de VidaRESUMO
Three novel steroidal glycosides (1-3) and a previously described steroidal alkaloid glycoside (4) have been isolated from the bulbs of Fritillaria camtschatcensis (L.) Ker Gawl. (Liliaceae). The structures of novel compounds 1-3 were characterized based on NMR spectroscopy and chemical transformations. Compounds 1-3 are furospirostanol glycosides bearing a (3S)-3-hydroxy-3-methylglutaryl moiety at C-26 in the aglycone. Compounds 1-4 were evaluated in terms of their cytotoxic activities toward HL-60 human promyelocytic leukemia cells, A549 human lung adenocarcinoma cells, and SBC-3 human lung small cell carcinoma cells. Only 4 showed moderate cytotoxicity against HL-60, A549, and SBC-3 cells with IC50 values of 22.9, 13.3, and 11.9 µM, respectively. Compound 4 was found to cause necrotic-like cell death in HL-60 cells.
Assuntos
Alcaloides , Antineoplásicos , Fritillaria , Liliaceae , Alcaloides/farmacologia , Glicosídeos/química , Glicosídeos/farmacologia , Células HL-60 , Humanos , Liliaceae/química , Estrutura MolecularRESUMO
A new alkaloid named zhebeisine (1), together with four known compounds, eduardine (2), zhebeirine (3), isoverticine (4), and verticine (5), was isolated from the bulbs of Fritillaria thunbergii Miq. The structure of the new compound was elucidated on the basis of extensive spectroscopic methods and the in vitro biological activities of it were evaluated as well. Compound 1 features a veratramine skeleton with a rare 6/6/5/6/6/6 fused-ring system, representing the first reported veratramine-type alkaloid with a new oxazinane ring (ring-F) in Fritillaria genus. The cytotoxic activities study revealed that compound 1 inhibited the cell proliferation of HT29 and DLD1 (IC50 values of 25.1 and 48.8 µM, respectively) and also induced apoptosis of the above-mentioned two cancer cell lines.[Formula: see text].
Assuntos
Alcaloides , Antineoplásicos , Medicamentos de Ervas Chinesas , Fritillaria , Alcaloides/química , Antineoplásicos/análise , Medicamentos de Ervas Chinesas/química , Fritillaria/química , Raízes de Plantas/químicaRESUMO
One new cevanine isosteroidal alkaloid named 5,6-anhydrohupehenine (1), together with five known alkaloids (2-6) were isolated from Fritillaria hupehensis Hsiao et K.C.Hsia, among which 5,6-anhydrohupehenine (1) exhibited strong inhibitory activity against HepG2 (IC50 = 12.21 µM) and MCF-7 (IC50 = 22.05 µM) cancer cells. Therefore, a total of 33 5,6-anhydrohupehenine derivatives (9a-9s, 10a-10f, 11a-11b, and 12a-12f) were synthesized and evaluated for their cytotoxic activity. The cytotoxicity evaluation of all 5,6-anhydrohupehenine derivatives against HepG2 and MCF-7 human cancer cells revealed that 9s displayed best activity against HepG2 cells with IC50 at 1.27 µM. Further biological evaluations on 9s showed that it inhibited the proliferation of HepG2 cells and induced apoptosis of the HepG2 cells by activating cleaved caspase-3. Moreover, 9s exhibited strong antimetastatic potential. These results suggest that 5,6-anhydrohupehenine is a promising compound to be designed as novel cytotoxic agents.