RESUMEN
BACKGROUND: Scutellaria baicalensis root is traditionally used for the treatment of common cold, fever and influenza. Flavonoids are the major chemical components of S. baicalensis root. PURPOSE: To evaluate the therapeutic effects and action mechanism of flavonoids-enriched extract from S. baicalensis root (FESR) on acute lung injury (ALI) induced by influenza A virus (IAV) in mice. METHODS: The anti-influenza, anti-inflammatory and anti-complementary properties of FESR and the main flavonoids were evaluated in vitro. Mice were challenged intranasally with influenza virus H1N1 (A/FM/1/47) 2 â¯h before treatment. FESR (50, 100 and 200⯠mg/kg) was administrated intragastrically. Baicalin (BG), the most abundant compound in FESR was given as reference control. Survival rates, life spans and lung indexes of IAV-infected mice were measured. Histopathological changes, virus levels, inflammatory markers and complement deposition in lungs were analyzed. RESULT: Compared with the main compound BG, FESR and lower content aglycones (baicalein, oroxylin A, wogonin and chrysin) in FESR significantly inhibited H1N1 activity in virus-infected Madin-Darby canine kidney (MDCK) cells and markedly decreased nitric oxide (NO) production from lipopolysaccharide (LPS)-stimulated RAW264.7 cells. In vitro assays showed that FESR and BG had no anti-complementary activity whereas baicalein, oroxylin A, wogonin and chrysin exhibited obvious anti-complementary activity. Oral administration of FESR effectively protected the IAV-infected mice, increased the survival rate (FESR: 67%; BG: 33%), decreased the lung index (FESR: 0.90; BG: 1.00) and improved the lung morphology in comparing with BG group. FESR efficiently decreased lung virus titers, reduced haemagglutinin (HA) titers and inhibited neuraminidase (NA) activities in lungs of IAV-infected mice. FESR modulated the inflammatory responses by decreasing the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1), and increasing the levels of interferon-γ (IFN-γ) and interleukin-10 (IL-10) in lung tissues. Although showing no anti-complementary activity in vitro, FESR obviously reduced complement deposition and decreased complement activation product level in the lung . CONCLUSION: FESR has a great potential for the treatment of ALI induced by IAV and the underlying action mechanism might be closely associated with antiviral, anti-inflammatory and anti-complementary properties. Furthermore, FESR resulted in more potent therapeutic effect than BG in the treatment of IAV-induced ALI.
Asunto(s)
Lesión Pulmonar Aguda/tratamiento farmacológico , Antivirales/farmacología , Flavonoides/farmacología , Infecciones por Orthomyxoviridae/complicaciones , Scutellaria baicalensis/química , Lesión Pulmonar Aguda/virología , Animales , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/farmacología , Antivirales/química , Perros , Flavonoides/análisis , Humanos , Subtipo H1N1 del Virus de la Influenza A/patogenicidad , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/virología , Células de Riñón Canino Madin Darby , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Extractos Vegetales/farmacología , Raíces de Plantas/químicaRESUMEN
1H NMR-based metabolomic approach combined with multivariate statistical analysis was used to evaluate the quality of 21 Farfarae Flos (FF) samples from different growth regions. Principal component analysis showed that wild and cultivated FF could be separated clearly, suggesting a big chemical difference existed between them. Supervised PLS-DA analysis indicated that the wild samples showed higher levels of secondary metabolites, such as bauer-7-ene-3ß, 16α-diol, chlorogenic acid, rutin, 7-(3'-ethylcrotonoyloxy)-1α-(2'-methyl-butyryloxy)-3, 14-dehydro-Z-notonipetranone (EMDNT), tussilagone, ß-sitosterol and sitosterone. This is consistent with traditional experience that the quality of wild samples are better than that of cultivated ones. The content of pyrrolizidine alkaloids senkirkine also differed greatly among samples from different habitats. The Pearson correlation analysis showed that senkirkine is positively correlated with 4, 5-O-dicaffeoylquinic acid, 3,5-O-dicaffeoylquinic acid, 3,4-O-dicaffeoylquinic acid, rutin, kampferol analogues, to a statistically significant extent. The correlation between the toxic compounds and the bioactive components in FF should be further studied.
Asunto(s)
Medicamentos Herbarios Chinos/química , Flores/química , Metabolómica , Tussilago/química , Ácido Clorogénico , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Ácido Quínico/análogos & derivados , Rutina , SitoesterolesRESUMEN
This study aims to find metabolites responsible for antitussive and expectorant activities of Tussilago farfara L. by metabolomic approach. Different parts (roots, flower buds, and leaves) of the title plant were analyzed systematically. The in vivo study revealed that the leaves and flower buds had strong antitussive and expectorant effects. Then ¹H NMR spectrometry together with principal component analysis (PCA) and partial least squares discriminant (PLS-DA) analysis were used to investigate the compounds responsible for the bioactivities. PCA was used to find the differential metabolites, while PLS-DA confirmed a strong correlation between the observed effects and the metabolic profiles of the plant. The result revealed that chlorogenic acid, 3,5-dicaffeoylquinic acid, and rutin may be closely related with the antitussive and expectorant activities. The overall results of this study confirm the benefits of using metabolic profiling for screening active principles in medicinal plants.
Asunto(s)
Antitusígenos/análisis , Descubrimiento de Drogas , Medicamentos Herbarios Chinos/química , Expectorantes/análisis , Tussilago/química , Animales , Antitusígenos/farmacología , Antitusígenos/uso terapéutico , Ácido Clorogénico/análogos & derivados , Ácido Clorogénico/análisis , Ácido Clorogénico/farmacología , Ácido Clorogénico/uso terapéutico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Etnofarmacología , Expectorantes/farmacología , Expectorantes/uso terapéutico , Femenino , Flores/química , Flores/crecimiento & desarrollo , Flores/metabolismo , Espectroscopía de Resonancia Magnética , Masculino , Metabolómica/métodos , Ratones , Ratones Endogámicos ICR , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Raíces de Plantas/química , Raíces de Plantas/metabolismo , Distribución Aleatoria , Rutina/análisis , Rutina/farmacología , Rutina/uso terapéutico , Estadística como Asunto , Tussilago/crecimiento & desarrollo , Tussilago/metabolismoRESUMEN
INTRODUCTION: The flower bud of Tussilago farfara L. is widely used for the treatment of coughs, bronchitis and asthmatic disorders in traditional Chinese medicine. In Europe, the plant has been used as herbal remedies for virtually the same applications, but the leaves are preferred over flowers. OBJECTIVE: To systematically evaluate the chemical profiles of Tusssilago farfara leaves and flowers along with the identification of the polar and non-polar metabolites. METHODOLOGY: Metabolic profiling carried out by means of ¹H-NMR spectroscopy and multivariate data analysis was applied to crude extracts from flowers and leaves. Metabolites were identified directly from the crude extracts through one-dimensional and two-dimensional NMR spectra. RESULTS: A broad range of metabolites were detected without any chromatographic separation. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) of ¹H-NMR data provided a clear separation between the samples. The corresponding loadings plot indicated that higher levels of phenylpropanoids, amino acids, organic acids and fatty acids, as well as lower levels of sugars, terpenoids and sterols were present in the leaves, as compared with flowers. For the flowers, more phenylpropanoids were present in fully open flowers, while more sugars and fatty acids were present in flower buds. CONCLUSION: NMR spectra (one- and two-dimensional) are useful for identifying metabolites, especially for the overlapped signals. The NMR-based metabolomics approach has great potential for chemical comparison study of the metabolome of herbal drugs.
Asunto(s)
Flores/química , Espectroscopía de Resonancia Magnética/métodos , Metaboloma , Metabolómica/métodos , Hojas de la Planta/química , Tussilago/metabolismo , Aminoácidos/química , Aminoácidos/aislamiento & purificación , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/metabolismo , Ácidos Grasos/química , Ácidos Grasos/aislamiento & purificación , Flores/metabolismo , Análisis de los Mínimos Cuadrados , Análisis Multivariante , Fitosteroles/química , Fitosteroles/aislamiento & purificación , Hojas de la Planta/metabolismo , Análisis de Componente Principal , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Tussilago/químicaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Flower bud of Tussilago farfara L. is widely used for the treatment of cough, bronchitis and asthmatic disorders in the Traditional Chinese Medicine. However, due to the increasing demands, adulteration with rachis is frequently encountered in the marketplace. No report demonstrated the chemical and pharmacological differences between flower bud and rachis before. MATERIALS AND METHODS: The water extracts were orally administrated to mice. Ammonia induced mice coughing model was used to evaluate the antitussive activity. The expectorant activity was evaluated by volume of phenol red in mice's tracheas. Metabolites were identified directly from the crude extracts through 1D- and 2D-NMR spectra. A metabolic profiling carried out by (1)H NMR spectroscopy and multivariate data analysis was applied to crude extracts from flower bud and rachis. RESULTS: Flower bud significantly lengthened the latent period of cough, decreased cough frequency caused by ammonia and enhanced tracheal phenol red output in expectorant evaluation. Principal component analysis (PCA) yielded good separation between flower bud and rachis, and corresponding loading plot showed that the phenolic compounds, organic acid, sugar, amino acid, terpene and sterol contributed to the discrimination. CONCLUSIONS: These findings provide pharmacological and chemical evidence that only flower bud can be used as the antitussive and expectorant herbal drug. The high concentration of chlorogenic acid, 3,5-dicaffeoylquinic acid, rutin in flower buds may be related with the antitussive and expectorant effects of Flos Farfara. To guarantee the clinical effect, rachis should be picked out before use.