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1.
J Pharm Biomed Anal ; 217: 114836, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35662013

RESUMO

In this study, the inter-individual variability of antitussive effect of Farfarae Flos was observed, and then the Farfarae Flos treated mice were divided into the mice with good or poor antitussive effect. Then a UHPLC-Q TOF-MS method was developed and validated to quantify 13 fecal metabolites of Farfarae Flos, and the results showed concentrated differences between the two subgroups. The results of 16 S rRNA gene sequencing analysis showed that mice with good or poor antitussive effects were also different at the structure of gut microbiota in phylum and genus, as well as the related 6 pathways. In addition, the differential fecal metabolites of Farfarae Flos between the two subgroups were probably related with 5 bacterial that participating in the CQAs and flavonoids metabolism. This study explained the inter-individual variability of the antitussive effect of Farfarae Flos from the perspective of gut microbiota. However, the specific bacterial that participate in the metabolism of Farfarae Flos as well as the antitussive effects of Farfarae Flos need to be further validated.


Assuntos
Antitussígenos , Microbioma Gastrointestinal , Tussilago , Animais , Antitussígenos/análise , Antitussígenos/farmacologia , Antitussígenos/uso terapêutico , Cromatografia Líquida de Alta Pressão/métodos , Flores/química , Camundongos , Tussilago/química
2.
Chin J Nat Med ; 20(4): 301-308, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35487600

RESUMO

Chemical fractionation of the n-BuOH partition, which was generated from the EtOH extract of the flower buds of Tussilago farfara, afforded a series of polar constituents including four new sesquiterpenoids (1-4), one new sesquiterpenoid glucoside (5) and one known analogue (6) of the eudesmane type, as well as five known quinic acid derivatives (7-11). Structures of the new compounds were unambiguously characterized by detailed spectroscopic analyses, with their absolute configurations being established by X-ray crystallography, electronic circular dichroism (ECD) calculation and induced ECD experiments. The inhibitory effect of all the isolates against LPS-induced NO production in murine RAW264.7 macrophages was evaluated, with isochlorogenic acid A (7) showing significant inhibitory activity.


Assuntos
Sesquiterpenos de Eudesmano , Sesquiterpenos , Tussilago , Animais , Flores/química , Glucosídeos/análise , Glucosídeos/farmacologia , Camundongos , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sesquiterpenos de Eudesmano/análise , Sesquiterpenos de Eudesmano/farmacologia , Tussilago/química
3.
Chembiochem ; 23(3): e202100539, 2022 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-34850523

RESUMO

The discovery of a bioactive inhibitor tool for human polypeptide N-acetylgalactosaminyl transferases (GalNAc-Ts), the initiating enzyme for mucin-type O-glycosylation, remains challenging. In the present study, we identified an array of quinic acid derivatives, including four new glycerates (1-4) from Tussilago farfara, a traditional Chinese medicinal plant, as active inhibitors of GalNAc-T2 using a combined screening approach with a cell-based T2-specific sensor and purified enzyme assay. These inhibitors dose-dependently inhibited human GalNAc-T2 but did not affect O-linked N-acetylglucosamine transferase (OGT), the other type of glycosyltransferase. Importantly, they are not cytotoxic and retain inhibitory activity in cells lacking elongated O-glycans, which are eliminated by the CRISPR/Cas9 gene editing tool. A structure-activity relationship study unveiled a novel quinic acid-caffeic acid conjugate pharmacophore that directs inhibition. Overall, these new natural product inhibitors could serve as a basis for developing an inhibitor tool for GalNAc-T2.


Assuntos
Inibidores Enzimáticos/farmacologia , N-Acetilgalactosaminiltransferases/antagonistas & inibidores , Ácido Quínico/farmacologia , Tussilago/química , Células Cultivadas , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Flores/química , Flores/metabolismo , Glicosilação , Células HEK293 , Humanos , Conformação Molecular , N-Acetilgalactosaminiltransferases/isolamento & purificação , N-Acetilgalactosaminiltransferases/metabolismo , Ácido Quínico/química , Ácido Quínico/metabolismo , Relação Estrutura-Atividade , Tussilago/metabolismo , Polipeptídeo N-Acetilgalactosaminiltransferase
4.
J Ethnopharmacol ; 283: 114694, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34601084

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The flower buds of Tussilago farfara L. (Abbreviated as FTF) were widely used in traditional Chinese medicine (TCM) to treat respiratory diseases, including asthma, dry throat, great thirst, turbid saliva, stinky pus, and coughs caused by various causes. AIM OF STUDY: The aim of study is to explore the efficiency of FTF in vitro and in vivo for the treatment of lung inflammation, and to illustrate the possible mechanisms of FTF in treating inflammation-related respiratory diseases targeting NOD-like receptor 3 (NLRP3) inflammasome, nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear transcription factor-κB (NF-κB). METHODS: Lung inflammation model in vivo was induced by exposure of mice to cigarette smoke (CS) for two weeks. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), inflammatory factors, and histology in lung tissues were investigated in presence or absence of ethanol extract of the flower buds of T. farfara L. (FTF-EtOH). In the cell-based models, nitric oxide (NO) assay, flow cytometry assay, enzyme-linked immunosorbent assay (Elisa), and glutathione (GSH) assay were used to explore the anti-inflammatory and anti-oxidant effects of FTF-EtOH. Possible anti-inflammatory mechanisms of FTF targeting NLRP3 inflammasome, Nrf2, and NF-κB have been determined using western blot, quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), immunofluorescence assay, nuclear and cytoplasmic extraction, and ubiqutination assay. RESULTS: FTF-EtOH suppressed CS-induced overproduction of inflammatory factors [e.g., tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß)], and upregulation of the content of intracellular MDA in the lung homogenate of mice. In cell-based models, FTF-EtOH reduced the lipopolysaccharide (LPS)-induced overproduction of inflammatory factors, and attenuated the CS extract-induced overgeneration of reactive oxygen species (ROS). Furthermore, FTF-EtOH up-regulated Nrf2 and its downstream genes through enhancing the stability of Nrf2 protein, and inhibited the activation of NF-κB and NLRP3 inflammasome, which have been confirmed by detecting the protein levels in the mouse model. CONCLUSIONS: FTF-EtOH effectively attenuated lung inflammation in vitro and in vivo. The protection of FTF-EtOH against inflammation was produced by activation of Nrf2 and inhibitions of NF-κB and NLRP3 inflammasome. These datas definitely support the ethnopharmacological use of FTF as an anti-inflammatory drug for treating respiratory diseases in TCM.


Assuntos
Inflamação/tratamento farmacológico , Pneumopatias/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Fumaça/efeitos adversos , Tussilago/química , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Flores/química , Humanos , Inflamação/induzido quimicamente , Pneumopatias/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/química , Mucosa Respiratória/citologia , Nicotiana
5.
J Mass Spectrom ; 56(2): e4697, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33484014

RESUMO

Farfarae Flos (FF) has been used in China for a long time as an anti-tussive and expectorant herbal drugs, and it was usually honey-fried FF (HFF). To clarify the mechanism of honey processing, it is important to know the chemical difference between FF and HFF firstly. In this study, UHPLC-Orbitrap-MS was used to characterize the chemical compounds in FF, honey and HFF. Then the metabolomic approach based on UHPLC-Orbitrap-MS revealed 68 differential compounds between the FF and HFF, and chemical reactions occurring during processing were also proposed to elucidate the honey processing mechanisms of FF. In order to investigate the chemical difference between FF and HFF comprehensively and accurately, the components derived from the honey and the moisture content in FF and HFF were considered for the first time. In summary, this study investigated the chemical differences between FF and HFF in a holistic way, which laid the basis for the quality control of HFF and further explaining the honey processing mechanisms of FF. In addition, eight native compounds derived from the honey could be used as the index to authenticate the HFF prepared by the genuine honey.


Assuntos
Medicamentos de Ervas Chinesas , Mel , Preparações de Plantas , Tussilago , Alcaloides/análise , Alcaloides/química , Alcaloides/metabolismo , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/química , Flavonas/análise , Flavonas/química , Flavonas/metabolismo , Flores/química , Flores/metabolismo , Espectrometria de Massas , Metaboloma , Metabolômica , Preparações de Plantas/química , Preparações de Plantas/metabolismo , Sesquiterpenos/análise , Sesquiterpenos/química , Sesquiterpenos/metabolismo , Tussilago/química , Tussilago/metabolismo
6.
Bioorg Chem ; 107: 104632, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33450544

RESUMO

Eleven new compounds including five bisabolane (1-5) and three oplopane (6-8) sesquiterpenoids, a pair of benzopyran enantiomers (9 & 10) and a benzofuran derivative (11), along with six known sesquiterpenoid co-metabolites (12-17), have been obtained from the flower buds of Tussilago farfara. Their structures were elucidated by comprehensive spectroscopic analyses and comparison with structurally related known analogues. The absolute configurations of all the compounds except 11 were unequivocally assigned by various techniques, including Mosher's method and time-dependent density functional theory (TD-DFT) based calculations of 13C NMR and electronic circular dichroism (ECD) data. The C-8 absolute configuration on the sidechain of this group of bisabolane sesquiterpenoids was assigned for the first time. Our bioassays have established that compounds 3, 4, 13 and 14 showed significant α-glucosidase inhibitory activities, while 6, 8 and 14 displayed moderate antiproliferative effects against two human tumor cell lines A549 and MDA-MB-231. Further flow cytometric analysis revealed that 14 effectively induced cell apoptosis and arrested cell cycle at the S/G2 phases in A549 cells, in a dose-dependent manner.


Assuntos
Sesquiterpenos/química , Tussilago/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dicroísmo Circular , Flores/química , Flores/metabolismo , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Espectroscopia de Ressonância Magnética , Conformação Molecular , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/metabolismo , Sesquiterpenos/farmacologia , Estereoisomerismo , Tussilago/metabolismo , alfa-Glucosidases/química , alfa-Glucosidases/metabolismo
7.
Int J Med Sci ; 18(2): 555-563, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390825

RESUMO

Farfarae Flos is a traditional Chinese medicine that has long been used to treat allergies. In this study, we aimed to investigate the effect of a petroleum extract of Farfarae Flos (PEFF) in a mouse model of allergic rhinitis (AR) and to explore the underlying molecular mechanisms of action. An animal model of AR was established by sensitization and challenge of BALB/c mice with ovalbumin (OVA). PEFF was administered intranasally and AR nasal symptoms were assessed on a semi-quantitative scale according to the frequencies of nose rubbing and sneezing and the degree of rhinorrhea. The mechanism of action of PEFF was evaluated by histological analysis of nasal mucosa architecture and inflammatory status; ELISA-based quantification of serum OVA-specific IgE, interferon-γ (IFN-γ), and interleukin-4 (IL-4) concentrations; and immunohistochemical and western blot analysis of T-bet and GATA3 protein expression in nasal mucosa and spleen tissues. The results showed intranasal administration of PEFF alleviated AR symptom scores and reduced both the infiltration of inflammatory cells and tissue damage in the nasal mucosa. PEFF significantly decreased serum concentrations of OVA-specific IgE (P<0.01) and IL-4 (P<0.05) and significantly increased IFN-γ (P<0.01). PEFF also upregulated the expression of T-bet protein (P<0.05) but downregulated GATA3 protein (P<0.05) in nasal mucosa and spleen tissues. In conclusion, PEFF effectively reduces AR nasal symptoms and serum IgE levels in a mouse model and may act by correcting the imbalance between Th1 and Th2 responses.


Assuntos
Extratos Vegetais/farmacologia , Rinite Alérgica/tratamento farmacológico , Equilíbrio Th1-Th2/efeitos dos fármacos , Tussilago/química , Administração Intranasal , Animais , Modelos Animais de Doenças , Feminino , Flores/química , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/imunologia , Ovalbumina/administração & dosagem , Ovalbumina/imunologia , Petróleo , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Rinite Alérgica/sangue , Rinite Alérgica/imunologia
8.
J Ethnopharmacol ; 267: 113478, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33069788

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Tussilago farfara L. (commonly called coltsfoot), known as a vital folk medicine, have long been used to treat various respiratory disorders and consumed as a vegetable in many parts of the world since ancient times. AIM OF THE REVIEW: This review aims to provide a critical evaluation of the current knowledge on the ethnobotanical value, phytochemistry, pharmacology, toxicity and quality control of coltsfoot, thus provide a basis for further investigations. MATERIALS AND METHODS: A detailed literature search was obtained using various online search engines (e.g. Google Scholar, Web of Science, Science Direct, Baidu Scholar, PubMed and CNKI). Additional information was sourced from ethnobotanical literature focusing on Chinese and European flora. The plant synonyms were validated by the database 'The Plant List' (www.theplantlist.org). RESULTS: Coltsfoot has diverse uses in local and traditional medicine, but similarities have been noticed, specifically for relieving inflammatory conditions, respiratory and infectious diseases in humans. Regarding its pharmacological activities, many traditional uses of coltsfoot are supported by modern in vitro or in vivo pharmacological studies such as anti-inflammatory activities, neuro-protective activity, anti-diabetic, anti-oxidant activity. Quantitative analysis (e.g. GC-MS, UHPLC-MRMHR) indicated the presence of a rich (>150) pool of chemicals, including sesquiterpenes, phenolic acids, flavonoids, chromones, pyrrolizidine alkaloids (PAs) and others from its leaves and buds. In addition, adverse events have resulted from a collection of the wrong plant which contains PAs that became the subject of public concern attributed to their highly toxic. CONCLUSIONS: So far, remarkable progress has been witnessed in phytochemistry and pharmacology of coltsfoot. Thus, some traditional uses have been well supported and clarified by modern pharmacological studies. Discovery of therapeutic natural products and novel structures in plants for future clinical and experimental studies are still a growing interest. Furthermore, well-designed studies in vitro particularly in vivo are required to establish links between the traditional uses and bioactivities, as well as ensure safety before clinical use. In addition, the good botanical identification of coltsfoot and content of morphologically close species is a precondition for quality supervision and control. Moreover, strict quality control measures are required in the studies investigating any aspect of the pharmacology and chemistry of coltsfoot.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Tussilago , Animais , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/normas , Medicamentos de Ervas Chinesas/toxicidade , Etnobotânica , Etnofarmacologia , Humanos , Medicina Tradicional Chinesa/normas , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/normas , Compostos Fitoquímicos/toxicidade , Fitoterapia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/normas , Extratos Vegetais/toxicidade , Controle de Qualidade , Tussilago/química
9.
Bull Exp Biol Med ; 170(1): 171-174, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33231808
10.
J Nat Prod ; 83(9): 2559-2566, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32881525

RESUMO

Tussilago farfara is a traditional herbal medicine used to treat coughs, bronchitis, and asthma. Its bioactive compounds include sesquiterpenoids with anti-inflammatory, antiproliferative, neuroprotective, and other effects. Biochemical studies have highlighted the mechanisms of action, but the investigations of related molecular pathways have not specified direct molecular targets. Therefore, this study profiled cellular target proteins of a sesquiterpenoid isolated from T. farfara using quantitative chemical proteomics in MDA-MB-231 and MCF-7 human breast cancer cells. Compound 8, 7ß-(3'-ethyl-cis-crotonoyloxy)-1α-(2'-methyl butyryloxy)-3,14-dehydro-Z-notonipetranone, exhibited potent antiproliferative activity based on its α,ß-unsaturated carbonyl moiety, and its potential cellular target proteins were identified using a compound 8-based clickable probe. Among >200 identified proteins, 17 showed enrichment ratios of >3 in both cell lines, while recombinant 14-3-3 protein zeta and peroxiredoxin-1 were verified using isothermic calorimetry and their alkylation sites. Considering the interaction between the α,ß-unsaturated carbonyl moiety of compound 8 and cysteine residues of the proteins, peptides containing Cys25 and Cys94 of 14-3-3 protein zeta and Cys83 of peroxiredoxin-1 were significantly reduced by this sesquiterpene ester. Although the results did not elucidate the effects of compound 8 in breast cancer cells, identification of potential target proteins contributes to enhanced understanding of its antiproliferative and anti-inflammatory effects.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Sesquiterpenos/uso terapêutico , Tussilago/química , Alquilação , Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Estrutura Molecular , Proteômica , Sesquiterpenos/isolamento & purificação
11.
Fitoterapia ; 146: 104729, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32956711

RESUMO

Six new compounds including four prenylated indole alkaloids (1-4) and two lignans (5-6), along with eight known cometabolites (7-14), were isolated from the flower buds of Tussilago farfara. Structures of the new compounds were elucidated by comparison with structurally related known analogues and also by comprehensive spectroscopic analyses. Their absolute configurations were determined by a variety of means including Mosher's method, Marfey's analysis, electronic circular dichroism (ECD) exciton chirality method and ECD calculations. Our bioassays have established that compounds 1 and 2 showed potent α-glucosidase inhibitory activity with IC50 values of 105 ± 4.7 and 35.2 ± 3.2 µM, respectively, while the known 13 and 14 exerted moderate DPPH radical scavenging activity with IC50 values of 45.2 ± 2.9 and 29.2 ± 2.0 µM, respectively.


Assuntos
Flores/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Alcaloides Indólicos/farmacologia , Lignanas/farmacologia , Tussilago/química , China , Sequestradores de Radicais Livres/isolamento & purificação , Sequestradores de Radicais Livres/farmacologia , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Alcaloides Indólicos/isolamento & purificação , Lignanas/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Prenilação , Saccharomyces cerevisiae/enzimologia , alfa-Glucosidases
12.
Mol Med Rep ; 22(4): 3525-3532, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32945423

RESUMO

α­glucosidase is a key enzyme that plays a role in glucose absorption in the gastrointestinal tract, and the inhibition of its activity induces the prevention of postprandial hyperglycemia. Several α­glucosidase inhibitors have been used as medicines for type 2 diabetes, but a similar effect is observed in natural resources, including traditional herbs and their phytochemicals. To identify the presence of the α­glucosidase inhibitory activity in herbs, in which various functional effects have been known to occur, the present study investigated the effects of hot­water extracts of 26 types of herbs on α­glucosidase activity in an in vitro assay. The results indicated significant increases in the inhibition of α­glucosidase activity in 1,000 µg/ml olive (P<0.01), white willow (P<0.01) and red rooibos hot­water extracts. Furthermore, ≥50% inhibition of α­glucosidase activity was determined to be significant in 1,000 µg/ml coltsfoot, green tea and bearberry hot­water extracts. In addition, the effects of bearberry, green tea and coltsfoot hot­water extracts on α­glucosidase activity in vivo were evaluated according to the blood glucose levels (BGLs) in maltose and glucose load model rats. It was indicated that the administration of these three herb extracts significantly reduced the increasing BGLs after maltose loading until 0.5 h compared with the control group. However, only coltsfoot extract significantly reduced the increasing BGLs after glucose loading until 0.5 h compared with the control group. Thus, the present results may facilitate the understanding of a novel functionality in traditional herbs, which could be useful for the prevention of disease onset and progression, such as in hyperglycemia and type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores de Glicosídeo Hidrolases/administração & dosagem , Plantas Medicinais/química , Água/administração & dosagem , alfa-Glucosidases/metabolismo , Animais , Arctostaphylos/química , Aspalathus/química , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/enzimologia , Modelos Animais de Doenças , Glucose/efeitos adversos , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Temperatura Alta , Masculino , Maltose/efeitos adversos , Olea/química , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Salix/química , Chá/química , Tussilago/química , Água/química , Água/farmacologia
13.
Biochem Biophys Res Commun ; 531(4): 508-514, 2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-32807498

RESUMO

Osteoporosis is a degenerative disease characterized by reduced bone mass, in which deregulated bone remodeling by osteoclasts and osteoblasts is a main pathogenesis. Although recently tussilagone, a major active component of flower buds of Tussilago farfara, has been shown to inhibit osteoclastogenesis, its effect on estrogen deficiency-induced osteoporosis remains unknown. This study examined the effect of tussilagone on bone loss in ovariectomized mice and further explored its impact on osteoclast apoptosis and osteoblast formation in addition to osteoclastogenesis. Tussilagone suppression of osteoclastogenesis was confirmed in bone marrow derived macrophages, which was observed with the 1/10 concentration of that of the previous study. As demonstrated by ApoPercentage dye staining and Western blotting, tussilagone enhanced apoptosis in differentiated osteoclasts by increasing estrogen receptor α and Fas ligand expression. On the contrary, either osteoblast differentiation or mineralization was not affected by tussilagone. Lastly, administering tussilagone to mice for 6 weeks prevented trabecular microarchitecture impairment in ovariectomized mice compared to vehicle control groups. These findings suggest that tussilagone or Tussilago farfara prevents osteoporotic bone loss by suppressing osteoclast differentiation and inducing osteoclast apoptosis, and that it may therefore offer a possible remedy against resorptive bone diseases.


Assuntos
Osteoclastos/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Sesquiterpenos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Estrogênios/deficiência , Feminino , Macrófagos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Osteoclastos/patologia , Osteogênese/efeitos dos fármacos , Osteoporose/metabolismo , Osteoporose/patologia , Ovariectomia , Sesquiterpenos/isolamento & purificação , Tussilago/química
14.
Bull Exp Biol Med ; 169(3): 378-382, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32749562

RESUMO

One of prospective methods for immunotherapy of tumors is modulation via immunological checkpoints, specifically, via the PD-1(CD279)/PD-L1(CD274) system. Interactions between tumor cell receptor (CD279) and the ligand on lymphocytes (CD274) leads to lymphocyte inactivation, which allows tumor escape from the immune control. Experiments on C57BL/6 mice with Lewis lung carcinoma demonstrate the possibility of reducing the expression of CD279 and CD274 on the peripheral blood and tumor tissue lymphocytes under the effects of Tussilago farfara L. polysaccharides. This phenomenon can underlie the antitumor and antimetastatic effects of these substances.


Assuntos
Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Carcinoma Pulmonar de Lewis/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Polissacarídeos/uso terapêutico , Receptor de Morte Celular Programada 1/metabolismo , Tussilago/química , Animais , Feminino , Citometria de Fluxo , Imunoterapia , Camundongos , Camundongos Endogâmicos C57BL
15.
J Ethnopharmacol ; 260: 113038, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-32526340

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Farfarae Flos (FF; dried flower buds of Tussilago farfara L.), a widely used traditional Chinese medicine (TCM), is also known as "Kuandonghua" (Chinese: ). It has a wide range of pharmacological effects and has long been used to treat various respiratory conditions including cough, asthma, and acute or chronic bronchitis. AIMS: This study reviews the current advances in the research on the botany, ethnopharmacology, phytochemistry, pharmacology, and toxicology of Farfarae Flos. Prospects for future investigation and application of this herb are also discussed. MATERIALS AND METHODS: Information on FF was collected from both published materials (such as ancient and modern books, Ph.D. and M. Sc. dissertations, monographs on medicinal plants, and pharmacopoeia) and electronic databases (such as CNKI, SciFinder, WanFang data, PubMed, ScienceDirect, Web of Science, Taylor&Francis, ACS Publications, Wiley, Springer, Europe PMC, EBSCOhost, J-STAGE, and Google Scholar). RESULTS: Approximately 175 chemical compounds, including terpenoids, organic acids, flavonoids, alkaloids, chromones, volatile oils, and other compounds, have been isolated from FF. This TCM has been reported to produce pharmacological effects on the respiratory, cardiovascular, and digestive systems, and exert antioxidant, anti-inflammatory, and neuroprotective activities. FF is safe in the traditional dose range, but the potential toxicity due to the emergence of pyrrolidine alkaloids needs to be paid more attention. CONCLUSIONS: FF is a commonly used TCM with pharmacological activities mainly on the respiratory system. This study suggests that the further expansion of the pharmacological effect of FF and in-depth study of its prescription need to be concerned about. The investigations of the role of more active substances and the pharmacokinetics of the hepatotoxic components of FF will help to maximize the therapeutic potential and promote its popularization and application. Meanwhile, it is important to pay attention to pursue research on the similarities and differences between the leaves and the flower buds to find their respective advantages and make rational use of T. farfara L.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa , Tussilago/química , Animais , Medicamentos de Ervas Chinesas/efeitos adversos , Etnofarmacologia , Flores , Humanos , Folhas de Planta
16.
Molecules ; 25(8)2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32294941

RESUMO

Recently, potent neuroprotective and anti-diabetic effects of 7ß-(3-Ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (ECN), a sesquiterpenoid isolated from Tussilago farfara Linnaeus, have been elucidated. To facilitate further pre-clinical evaluation in rats, an analytical method for the determination of ECN in rat plasma was developed and optimized by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma samples were pretreated by the protein precipitation method with an acetonitrile solution of losartan (LST) as the internal standard. Chromatographic separation was performed using a an Octadecyl-silica (ODS) column (2.6 µm, 100 x 4.6 mm) in the isocratic mode. The mobile phase, comprising 10 mM ammonium formate in water pH 5.75) and acetonitrile (11:89, v/v), was eluted at a flow rate of 0.4 mL/min. Mass spectrometric detection was performed in the multiple reaction monitoring mode with positive electrospray ionization, and the mass transitions of ECN and LST were m/z 431.3 to 97.3 and m/z 423.1 to 207.2, respectively. The calibration curves of spiked plasma samples were linear in the 10.0-10,000 ng/mL range (r2 > 0.996). The lower limit of quantification (LLOQ) was determined as 10.0 ng/mL. Validation was conducted in the LLOQ, and three quality control (QC) sample levels (10.0, 25.0, 3750, and 7500 ng/mL) were studied. Among them, the relative standard deviation for the within- and between-run precisions was under 9.90%, and the relative error of the accuracies was within the -8.13% to 0.42% range. The validated method was successfully employed to investigate the pharmacokinetic properties of ECN in rats, which revealed the linear pharmacokinetic behavior of ECN for the first time.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Extratos Vegetais/farmacocinética , Sesquiterpenos/farmacocinética , Espectrometria de Massas em Tandem/métodos , Acetonitrilas/química , Administração Oral , Animais , Calibragem , Cromatografia Líquida de Alta Pressão/instrumentação , Formiatos/química , Limite de Detecção , Losartan/química , Masculino , Farmacocinética , Extratos Vegetais/sangue , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Controle de Qualidade , Ratos , Ratos Sprague-Dawley , Sesquiterpenos/administração & dosagem , Sesquiterpenos/sangue , Sesquiterpenos/química , Espectrometria de Massas em Tandem/instrumentação , Tussilago/química
17.
Am Nat ; 195(3): 485-503, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32097036

RESUMO

Organisms encounter a wide range of toxic compounds in their environments, from chemicals that serve anticonsumption or anticompetition functions to pollutants and pesticides. Although we understand many detoxification mechanisms that allow organisms to consume toxins typical of their diet, we know little about why organisms vary in their ability to tolerate entirely novel toxins. We tested whether variation in generalized stress responses, such as antioxidant pathways, may underlie variation in reactions to novel toxins and, if so, their associated costs. We used an artificial diet to present cabbage white butterfly caterpillars (Pieris rapae) with plant material containing toxins not experienced in their evolutionary history. Families that maintained high performance (e.g., high survival, fast development time, large body size) on diets containing one novel toxic plant also performed well when exposed to two other novel toxic plants, consistent with a generalized response. Variation in constitutive (but not induced) expression of genes involved in oxidative stress responses was positively related to performance on the novel diets. While we did not detect reproductive trade-offs of this generalized response, there was a tendency to have less melanin investment in the wings, consistent with the role of melanin in oxidative stress responses. Taken together, our results support the hypothesis that variation in generalized stress responses, such as genes involved in oxidative stress responses, may explain the variation in tolerance to entirely novel toxins and may facilitate colonization of novel hosts and environments.


Assuntos
Aristolochia/química , Borboletas/fisiologia , Passiflora/química , Toxinas Biológicas/metabolismo , Tussilago/química , Animais , Evolução Biológica , Borboletas/genética , Borboletas/crescimento & desenvolvimento , Larva/genética , Larva/crescimento & desenvolvimento , Larva/fisiologia
18.
Molecules ; 25(3)2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32023945

RESUMO

Farfarae Flos (FF) is the dried flower bud of Tussilago farfara L, which has antitussive, expectorant, and anti-inflammatory effects. However, little research on the main active composition of FF has been reported. The purpose of this study is to find the main active compounds responsible for the three pharmacological effects (i.e., antitussive, expectorant, and anti-inflammatory effects) of Farfarae Flos, based on the spectrum-effect relationship combined with chemometrics. First, this study uses the UPLC-QDA method to establish the chromatography fingerprint of Farfarae Flos, which is combined with chemometrics to analyze 18 batches of samples. Then, we study the antitussive, expectorant, and anti-inflammatory effects of Farfarae Flos. Finally, the spectrum-effect relationship between the fingerprint and the three pharmacological effects are studied by grey correlation analysis and partial least squares regression. The results show that four, four, and three main active constituents were found for the antitussive, expectorant, and anti-inflammatory pharmacological effects, respectively. In conclusion, we found the main active compounds corresponding to the main pharmacodynamic effects of Farfarae Flos. To our knowledge, this is the first time that spectrum-effect relationships in FF have been established using both raw and processed samples, which provides an experimental basis for further studies on the pharmacodynamic material basis of Farfarae Flos, as well as providing reference for the comprehensive evaluation of Farfarae Flos quality and the development of substitute resources.


Assuntos
Anti-Inflamatórios/isolamento & purificação , Antitussígenos/isolamento & purificação , Expectorantes/isolamento & purificação , Tussilago/química , Cromatografia Líquida de Alta Pressão , Análise por Conglomerados , Flores/química , Análise dos Mínimos Quadrados , Metabolômica/métodos , Estrutura Molecular , Extratos Vegetais/isolamento & purificação , Análise de Componente Principal
19.
Nat Prod Res ; 34(4): 545-548, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30257572

RESUMO

The chemical composition of Tussilago farfara L. essential oil from the Saguenay-Lac-St-Jean region of Quebec, Canada was analyzed by gas chromatography-flame ionisation detector (GC-FID) and gas chromatography-mass spectrometry (GC-MS), and the antibacterial activity of the oil was tested against Escherichia coli and Staphylococcus aureus. Forty-five (45) compounds were identified from the GC profile. The main components were 1-nonene (40.1%), α-phellandrene (26.0%) and ρ-cymene (6.6%). The essential oil demonstrated antibacterial activity against E. coli (MIC50 = 468 µg·mL-1; MIC90 = 6869 µg·mL-1) and S. aureus (MIC50 = 368 µg·mL-1; MIC90 = 773 µg·mL-1). Dodecanoic acid was found to be active against both bacteria having a MIC50 and MIC90 of 16.4 µg·mL-1 and 95 µg·mL-1, respectively for E. coli and a MIC50 and MIC90 of 9.8 µg·mL-1 and 27.3 µg·mL-1, respectively for S. aureus. In addition, 1-decene and (E)-cyclodecene were also found to be active against E. coli.


Assuntos
Antibacterianos/isolamento & purificação , Óleos Voláteis/química , Tussilago/química , Alcanos/análise , Alcanos/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Ciclodecanos/análise , Ciclodecanos/farmacologia , Monoterpenos Cicloexânicos/análise , Cimenos/análise , Escherichia coli/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Ácidos Láuricos/análise , Ácidos Láuricos/farmacologia , Testes de Sensibilidade Microbiana , Quebeque , Staphylococcus aureus/efeitos dos fármacos
20.
Environ Sci Pollut Res Int ; 27(4): 4089-4103, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31828708

RESUMO

The purpose of this study was to examine the accumulation potential of spontaneously developed Tussilago farfara populations colonizing sites with different levels of anthropogenic pollution. Physical characteristics of the soil are presented, together with the concentrations of macroelements and microelements (Ca, Mg, Fe, S, Al, Pb, Zn, Cu, Cd, Mn, As, Sb, Ag, Ti, and Sr) in both soil and plants. The biological concentration, accumulation, and translocation factors were used to assess the potential for heavy metal accumulation. Considerable differences were found among assessions from unevenly contaminated habitats, particularly in comparison with an unpolluted site. In line with the ore's characteristics, substrate samples from polluted sites were heavily contaminated with Pb, Zn, As, and Sb. Increased levels of microelements were also detected in plant samples from flotation tailings. Despite active absorption of Zn, Cu, Cd, Mn, and Sr by the plants from mining sites, the detected quantities of these elements in all samples were below the hyperaccumulation threshold. However, the obtained results indicate that the use of T. farfara from such sites in traditional medicine could pose a risk to human health due to accumulation of several toxic elements in the plant's aboveground tissues. Additionally, as a successful primary colonizer and stabilizer of technogenic substrates, T. farfara has an important role in the initial phases of revegetation of highly contaminated sites.


Assuntos
Metais Pesados/análise , Poluentes do Solo/análise , Oligoelementos/análise , Tussilago/química , Sérvia , Solo/química
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