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By consulting ancient and modern literature， the herbal textual research of Farfarae Flos has been conducted to verify the name， origin， producing area， quality evaluation， harvesting and processing methods， so as to provide reference for the development and utilization of the famous classical formulas containing Farfarae Flos. According to the research， the results showed that Farfarae Flos was first described as a medicinal material by the name of Kuandonghua in Shennong Bencaojing（《神农本草经》）， and the name was used and justified by later generations. The main origin was the folwer buds of Tussilago farfara， in addition， the flower buds of Petasites japonicus were used as medicine in ancient times. The ancient harvesting time of Farfarae Flos was mostly in the twelfth month of the lunar calendar， and the modern harvesting time is in December or before the ground freeze when the flower buds have not been excavated. Hebei， Gansu， Shaanxi are the authentic producing areas with the good quality products. Since modern times， its quality is summarized as big， fat， purple-red color， no pedicel is better. Processing method from soaking with licorice water in the Northern and Southern dynasties to stir-frying with honey water followed by micro-fire in the Ming dynasty， and gradually evolved to the modern mainstream processing method of honey processing. Based on the research results， it is suggested that the dried flower buds of T. farfara， a Compositae plant， should be selected for the development of famous classical formulas containing Farfarae Flos， and the corresponding processed products should be selected according to the specific processing requirements of the formulas， and raw products are recommended for medicinal use without indicating processing requirements.
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Objective: To investigate the mechanism of Farfarae Flos (FF) in Qingfei Paidu Decoction against coronavirus disease 2019 (COVID-19) based on network pharmacology and molecular docking. Methods: Based on our previous study, the main compounds in FF were selected. The potential targets of FF were searched by Swiss Target Prediction and BATMAN-TCM database. GenCLiP 3 and GeneCard were used to predict and screen the therapeutic targets of COVID-19, and then Cytoscape 3.7.1 was used to build the compound-target-disease network. The String database was used to build the target PPI network. Gene ontology (GO) function enrichment analysis and KEGG pathway enrichment analysis were performed in the DAVID database. Molecular docking was performed based on the above compounds and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3CL hydrolase and angiotensin converting enzyme II (ACE2). Results: The compound-target-disease network contained 14 compounds, 104 targets and four diseases. GO function enrichment analysis revealed 444 GO items (P < 0.05), including 325 biological process (BP) items, 44 cell composition (CC) items and 75 molecular function (MF) items. A total of 94 signal pathways (P < 0.05) were screened out by KEGG pathway enrichment analysis. The results of molecular docking showed that the affinity of 3,4-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid with proteins were better than Remdesivir. Conclusion: The compounds in FF can bind with SARS-CoV-2 3CL hydrolase and ACE2, and then act on many targets to regulate multiple signaling pathways, thus exerting the therapeutic effect on COVID-19.
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Objective: For the adulteration phenomenon of Farfarae Flos, the chemical composition of the flower buds and the rachis, rhizome, and the roots were compared, to provide the basis for the quality control of Farfarae Flos. Methods: The content of tussilagone was determined by high performance liquid chromatography (HPLC) according to the Chinese Pharmacopeia. The HPLC based fingerprint was also generated, and the similarity and the relative contents of the common peaks between the flower buds and adulteration parts were calculated. The pearson correlation between the relative content of the major compounds and the flower buds ratio, as well as principal component analysis and clustering analysis were also performed. Results: The content of tussilagone and the peak areas of 13 common peaks in the HPLC fingerprint were significantly higher than those in the rachis, rhizome, and the roots, and positively correlated with the flower buds ratio. The results of the principal component analysis and clustering analysis showed that the flower buds showed distinct separation with those adulteration parts. In addition, the compounds within the caffeoyl quinic acids and flavonoids showed positive correlations with each other, and the correlations were also observed between different kinds of components. Conclusion: The major compounds of Farfarae Flos were mainly present in the flower buds, and the quality of Farfarae Flos will be greatly affected when there are more impurities such as pedicel, taproot and rhizome in the crude drugs. Currently, there is no impurity in the Chinese pharmacopeia for Farfarae Flos, and the limit of the impurities should be added to guarantee the quality of Farfarae Flos.
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<b>Objective::To establish an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for the simultaneous determination of 15 pyrrolidine alkaloids (PAs) and their nitrogen oxides, and determine the content of the 15 PAs in the 15 batches of Farfarae Flos samples obtained from different sources, in order to understand the distribution status of these 15 PAs in Farfarae Flos from different sources, and provide relevant references for the safe and rational use of this medicinal materials. <b>Method::The method was achieved by Agilent Eclipse Plus C<sub>18</sub> column (3.0 mm×150 mm, 1.8 μm) using a mobile phase made up of 0.05%formic acid and 2.5 mmol·L<sup>-1</sup> ammonium formate in water (A)-0.05%formic acid and 2.5 mmol·L<sup>-1</sup> ammonium formate in methanol(B). The flow rate and the injection volume were 0.4 mL·min<sup>-1</sup> and 2 μL, respectively. The column temperature was 40 ℃. The instrument was Agilent 1290-6470 QQQ ultra high performance liquid chromatography-triple quaternary bar mass spectrometer. The components were detected in multiple reaction monitoring mode by mass spectrometry with ionizationmode of ESI<sup>+</sup>. The content of the components measured in the samples was calculated by using the external standard method, and the difference between samples was analyzed based on RSD of different components. <b>Result::The established method had a high sensitivity and good separation degree. The results of methodological investigation met the requirements. The results showed that all of the 15 batches of Farfarae Flos contained PAs and their nitrogen oxides. These PAs had almost the same types of structure. There were significant differences in the content and distribution of PAs in Farfarae Flos obtained from different sources. <b>Conclusion::In general, Farfarae Flos contains pyrrolidine alkaloids and their nitrogen oxides. Senkirkine with a significant hepatotoxicity is the main compound. The content determination of PAs will provide scientific fundaments for the safe and effective use of Farfarae Flos.
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OBJECTIVE: To analyze the effect of different drying methods on the major compounds in Farfarae Flos(FF). METHODS: The content of moisture and tussilagone were determined, and the common peaks in the HPLC fingerprint were calculated and subjected to the principal component analysis. RESULTS: The results showed that the moisture content was the highest when the FF was dried in the shade, and the drying method showed little effect on the content of tussilagone. The results of the principal component analysis showed that the FF dried in the shade was different from those of FF being dried under heat. The relative content of major compounds were the highest for the FF dried in the shade. In addition, the caffeoyl quinic acids and flavonoids were greatly affected after heating, however the heat drying showed little effect on the sesquiterpenoids. Among the different drying temperature, 55 ℃ showed smallest effect on the main components in the FF. CONCLUSION: The components in FF can be protected when drying in the shade, which reveals the scientific basis for the traditional experience of drying. However, in order to facilitate the drying process on a large scale, and minimizing the effect of drying on the compounds in the FF, drying temperature of 55 ℃ is recommended.
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Objective: To compare the toxicity of the flower buds and leaves from Tussilago farfara, and provide scientific basis for the utilization of the leaves of T. farfara. Methods: The 3 dpf (day post fertilization) healthy AB and transgene zebrafish were selected. The flowers, the leaves, the flowers coupled with Aster tataricus, and the leaves coupled with A. tataricus were prepared at the concentration of 0.5, 1.0, and 1.5 mg/mL. The fluorescent area of the liver and ALT and AST levels were measured after 72 h of drug treatment. For the renal toxicity assay, the morphology of zebrafish and the nutrient solution protein were also determined. Results: Compared with the control group, there were no significant differences in liver biochemical indexes in the four drug treatment groups. However, the fluorescence area of liver decreased in the flowers and flowers coupled with A. tataricus group at the concentration of 1.5 mg/mL. No significant difference was observed in the four groups of the nephrotoxicity assay. Conclusion: The flower and the flower coupled with A. tataricus showed minor hepatotoxicity at higher doses, and the leaves showed no stronger toxicity than the flower buds in comparison with the flower buds. It can provide refercences for the resource utilization of the leaves of T. farfara.
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Objective To predict the action targets of antitussive and expectorant active ingredients of Farfarae Flos (FF) to understand the “multi-components, multi-targets, and multi-pathways” mechanism. Methods Using network pharmacology, the main components in FF [chlorogenic acid, 3,5-O-dicaffeoylquinic acid, 3,4-O-dicaffeoylquinic acid, 4,5-O-dicaffeoylquinic acid, rutin, caffeic acid, quercetin, kampferol, hyperoside, β-sitosterol, tussilagone, and 7β-(3-Ethyl-ciscrotonoyloxy)-1α-(2-methylbutyryloxy)-3(14)- dehydro-Z-notonipetranone] reported in previous studies, were used to predict the targets of main active ingredients of FF according to the PharmMapper method. The prediction was made by screening of the antitussive and expectorant targets approved by the CooLGeN database and annotating the information of targets with the aid of MAS 3.0 biological molecular function software. Based on the molecular docking, the tight binding of active ingredients with potential protein targets was explored by Systems Dock Web Site. The Cytoscape software was used to construct the FF ingredients-targets-pathways network. Results The network analysis indicated that the active ingredients in FF involve 18 targets, such as IL-2, COX-2, and RNASE3, as well as the signal transduction-inflammation-energy metabolism relevant biological processes and metabolic pathways. Conclusion The antitussive and expectorant effect of FF showed the characteristics of traditional Chinese medicine in multi-components, multi-targets, and multi-pathways. This research provides a scientific basis for elucidation of the antitussive and expectorant pharmacological mechanism of FF.
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Objective To analyze the accumulation patterns of active constituents in Farfarae Flos with different flower bud colors (yellow, purple, and deep purple) at different growth stages, and provide theoretical guidance for the production and quality control of Farfarae Flos. Methods The medicinal materials of Farfarae Flos of different growth stages with different colors were determinated by HPLC method. The Similarity Evaluation System for Chromatographic Fingerprint of TCM (2012 A edition) was used to evaluate the similarity of the samples. The differences among samples were identified by chemical pattern recognition methods including hierarchical principal component analysis (PCA) and partial least squares discriminate analysis (PLS-DA). Results The HPLC fingerprint of different flower bud colors of Farfarae Flos at different growth stages was obtained, 27 common peaks were found in the chromatography, and 11 of them were identified. Similarities of samples of all batches with reference fingerprint were among 0.901-0.995. There were differences in the accumulation characteristics of Farfarae Flos at different growth stages according to the peak area, and showing significant differences among different flower bud colors. PCA and PLS-DA results demonstrated obvious distinction among different flower bud colors. Twelve constituents, such as gallic acid, chlorogenic acid, rutin, hyperin, isochlorogenic acid B and quercetin, were screened as biomarkers, representing major differences among colors. The quality evaluation demonstrated that deep purple buds was the best, followed by purple buds and yellow buds for the worst. Conclusion The HPLC fingerprint can reflect the accumulation characteristics of the active constituents of Farfarae Flos in different growth stages and the differences among different flower bud colors. Combining chemical pattern recognition can provide reference for the production and quality evaluation of Farfarae Flos.
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Objective To establish an HPLC fingerprint of raw and honey baked Farfarae Flos for its quality control and samples differentiation. Methods An HPLC method has been developed for the fingerprinting and evaluation of 36 batches of raw and honey baked Farfarae Flos collected from different locations. The Similarity Evaluation System for Chromatographic Fingerprint of TCM (2012A edition) was used to evaluate the similarity of 36 batches. The difference between raw and honey baked Farfarae Flos was identified by chemical pattern recognition methods including hierarchical cluster analysis (HCA), principal component analysis (PCA), and partial least squares discriminate analysis (PLS-DA). Results A standard fingerprint containing 20 common peaks was constructed from 36 batches of raw and honey baked Farfarae Flos, and identified 10 of them. The similarity of all batches with reference fingerprint was between 0.723-0.984. The similarity of 16 batches of raw Farfarae Flos was between 0.862-0.998, and the similarity of 20 batches of honey baked Farfarae Flos was between 0.687-0.993. HCA, PCA and PLS-DA results demonstrated that there were obvious distinction between raw and honey baked Farfarae Flos. According to the VIP plot, ten constituents including gallic acid, chlorogenic acid, isochlorogenic acid A, and tussilagone were primarily response for the discrimination. Conclusion The combination of HPLC fingerprint and chemical pattern recognition could provide a comprehensive reference for the quality control and quality evaluation of raw and honey baked Farfarae Flos.
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Objective: The chemical constituents in the methanol extract from Farfarae Flos were rapidly identified using UPLC-Q-TOF-MS in positive and negative ion modes. Methods: The analysis was performed on an Agilent Poroshell 120 EC-C18 chromatographic column (100 mm × 2.1 mm, 2.7 μm). The mobile phase consisted of acetonitrile and 0.1% aq formic acid. In positive ion mode, gradient elution: 0-1 min, 5%-17% B; 1-3 min, 17%-19% B; 3-14 min, 19%-44% B; 14-16 min, 44%-66% B; 16-26 min, 66%-87% B; 26-28 min, 87%-95% B; 28-33 min, 95% B. In negative ion mode, gradient elution: 0-2 min, 5%-14% B; 2-10 min, 14%-32% B; 10-15 min, 32% B. The flow rate was 0.4 mL/min, and the injection volume was 5 μL. The information of the compounds was analyzed by positive and negative ion modes mass spectrum information, elements composition, reference substance retention time or mass spectrum parameters of compounds in literature. Results: Thirty-four compounds in Farfarae Flos extracts were identified, combined with provided accurate molecular weight compounds by UPLC-Q-TOF-MS, including 12 kinds of terpenoids, eight kinds of flavonoids, seven kinds of phenolic acids, two kinds of pyran compounds, one kind of phenolic ketones, one kind of fat ketones, and three kinds of alkaloids. Conclusion: The method provides the theory basis for quality control and the clinical reasonable application and provides the reference for clarifying its efficacy material base.
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Farfarae Flos (FF) is derived from the flower buds of Tussilago farfara, and belongs to the Compositae family. It is one of the commonly used herbal drugs in the clinic and industry of Chinese materia medica. FF contained a series of chemical components, such as sesquiterpenes, triterpenes, flavonoids, phenolic acid, and pyrrolizidine alkaloids. Sesquiterpenes are present as the characteristic components in FF, and the quality evaluation indicator is tussilagone in Chinese Pharmacopoeia. Bisabolane and oplopane are the main skeletons for sesquiterpenes in FF, and the reported sesquiterpenes possessed a series of pharmacological properties, such as anti-inflammatory, anti-allergic, anticancer, neuroprotection, and platelet activating factor inhibition. This paper summarizes the chemical structures and biological activities of sesquiterpenes in FF, and provides the scientific basis for the further development and utilization.
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Farfarae Flos, one of the important herbal drugs in Chinese materia medica (CMM), is commonly used to in the clinical and pharmaceutical industry of CMM. The quality of Farfarae Flos is closed related with its safety and efficacy in the clinic. In this review, the previous studies on the quality evaluation of Farfarae Flos were summarized and analyzed from morphological identification, microscopic identification, thin-layer chromatography, physicochemical analysis, fingerprinting, commodity specification and grade, etc, which provides the necessary reference and scientific basis for improving the quality standards of Farfarae Flos.
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Objective: To compare the toxicity of two kinds of Ziwansan, which were prepared by Asteris Radix with Farfarae Flos (FF) and the leaves of Tussilago farfara (FL), respectively, The results will provide scientific basis for the utilization of leaves of T. farfarae. Methods: The FF and FL were in combination ratio of 1:1 with Asteris Radix, respectively, and given to mice at a dose of 40 g/kg for 14 d. The drug toxicology was evaluated by serum biochemical indicators and histopathological examination, as well as 1H-NMR based metabonomic approach. Results: The mice liver showed obvious damage as revealed by serum biochemical indicators and histopathological examination. Totally 15 biomarkers related to liver toxicity were determined by multivariate statistics and KEGG metabolic pathway analysis. By analyzing the distance between drug treated groups and blank group in scatter plots and the level changes of hepatoxicity related biomarkers, it was found that Ziwansan prepared by FF and FL showed different toxic effects on mice metabolome. However, there was no evidence that Ziwansan made from FL showed stronger toxicity than that made from FF. Conclusion: These results suggest that FL and FF show equivalent toxicity in Ziwansan, which lays the foundation for the utilization of leaves of T. farfara.
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Objective: To explore the scientific basis for Farfarae Flos baked with honey. Methods: NMR-based metabolomic approach combined with PAC, OPLS-DA, and univariate analysis was used to investigate the differences between the raw Farfarae Flos (RFF) and Farfarae Flos baked with honey (HFF). Results: Forty metabolites were identified in the NMR spectra, and the multivariate statistical results showed that RFF and HFF could be clearly separated. The levels of 1-O-ethyl-β-D-glucoside, β-glucose, sucrose, and α-glucose were higher and those of valine, aspartate, and threonine were lower in HFF compared with RFF. In light of secondary metabolites, RFF contained more chlorogenic acid and caffeic acid whereas HFF contained more tussilagone and rutin. Conclusion: The results reveal the chemical differences between RFF and HFF in a holistic way, and lay the foundation for the scientific explanation of Farfarae Flos processing.