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Farfarae Flos (FF), also known as "Kuandonghua" in Chinese, is a commonly used traditional Chinese medicine (TCM) with various therapeutic properties, including antitussive, expectorant, antioxidant, and anti-inflammatory effects. Despite the widespread consumption of processed FF, there has been limited progress in improving quality control measures for both raw FF and honey-processed Farfarae Flos (PFF). This study aimed to establish a comprehensive strategy for quality evaluation and distinguish between FF and PFF by integrating high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis with chemometric techniques. Additionally, the antioxidant activities of FF and PFF were assessed using radical-scavenging experiments. The spectrum-effect relationship is the association of chemical composition information of the fingerprint with antioxidant activity, which was used to predict the primary active components that influence the antioxidant activity of FF. The results indicated that FF and PFF samples showed a clear distinction, and the most potent pharmacologically active ingredients were hyperoside, quercetin, caffeic acid, isoquercitrin, neochlorogenic acid, rutin, cryptochlorogenic acid, and isochlorogenic acid C. Moreover, the comprehensive efficacy of the honey-processed FF was better than for raw FF. In conclusion, the findings of this study provide a scientific foundation for future evaluation of the quality, further research, and practical use of FF herbs. [ABSTRACT FROM AUTHOR]

Introduction: Due to its remarkable anti-inflammatory pharmacological activity, Farfarae Flos has gained extensive usage in the treatment of various inflammatory diseases such as bronchitis, pneumonia, prostatitis and colitis. And Farfarae Flos come in two color types depending on the color of the flowers: yellowish-white (YW), and purplish-red (PR). However, the difference in anti-inflammatory activity and metabolic profiles between the two flower colors remains unexplored. Methods: This study aims to explore the difference in the anti-inflammatory potential between YW and PR variants of Farfarae Flos and unravel the mechanisms responsible for the observed differences in anti-inflammatory activity through an integrated approach encompassing untargeted metabolomics and in vivo/vitro experimental studies. Initially, we verified the contrasting effects of YW and PR on the inhibition of the inflammatory factors interleukin-6 (IL-6) and nitric oxide (NO) by utilizing an in vitro RAW 264.7 cell inflammation model. Subsequently, a comprehensive evaluation of the systemic inhibitory capacity of YW and PR on IL-6, Interleukin-10 (IL-10), and tumor necrosis factor-a (TNF-a) was conducted using a validated whole-body mouse model, followed by the analysis of inflammatory factors and histological examination of collected serum, liver, and spleen after 7 days. Furthermore, non-targeted metabolomics profiling was employed to analyze the metabolite profiles of Farfarae Flos with different colors, and quantitative analysis was conducted to identify differential metabolites between YW and PR. The correlation between the anti-inflammatory activities of differentially accumulated metabolites (DAMs) and Farfarae Flos was investigated, resulting in the identification of 48 compounds exhibiting significant anti-inflammatory activity. Additionally, KEGG pathway enrichment analysis was performed to elucidate the underlying mechanisms. Results: Our findings demonstrate that both YW and PR possess antiinflammatory abilities, with PR exhibiting significantly superior efficacy. The integration of in vivo/vitro experiments and non-targeted metabolomics confirmed the exceptional anti-inflammatory potential of PR and solidified its classification as the "purplish-red better" of Farfarae Flos. Discussion: This study provides valuable insights into the breeding and medical transformation of Farfarae Flos varieties, along with a scientific basis for the establishment of quality standards and the development of new drugs utilizing Farfarae Flos. [ABSTRACT FROM AUTHOR]

Introduction: Due to its remarkable anti-inflammatory pharmacological activity, Farfarae Flos has gained extensive usage in the treatment of various inflammatory diseases such as bronchitis, pneumonia, prostatitis and colitis. And Farfarae Flos come in two color types depending on the color of the flowers: yellowish-white (YW), and purplish-red (PR). However, the difference in anti-inflammatory activity and metabolic profiles between the two flower colors remains unexplored., Methods: This study aims to explore the difference in the anti-inflammatory potential between YW and PR variants of Farfarae Flos and unravel the mechanisms responsible for the observed differences in anti-inflammatory activity through an integrated approach encompassing untargeted metabolomics and in vivo / vitro experimental studies. Initially, we verified the contrasting effects of YW and PR on the inhibition of the inflammatory factors interleukin-6 (IL-6) and nitric oxide (NO) by utilizing an in vitro RAW 264.7 cell inflammation model. Subsequently, a comprehensive evaluation of the systemic inhibitory capacity of YW and PR on IL-6, Interleukin-10 (IL-10), and tumor necrosis factor- α (TNF- α ) was conducted using a validated whole-body mouse model, followed by the analysis of inflammatory factors and histological examination of collected serum, liver, and spleen after 7 days. Furthermore, non-targeted metabolomics profiling was employed to analyze the metabolite profiles of Farfarae Flos with different colors, and quantitative analysis was conducted to identify differential metabolites between YW and PR. The correlation between the anti-inflammatory activities of differentially accumulated metabolites (DAMs) and Farfarae Flos was investigated, resulting in the identification of 48 compounds exhibiting significant anti-inflammatory activity. Additionally, KEGG pathway enrichment analysis was performed to elucidate the underlying mechanisms., Results: Our findings demonstrate that both YW and PR possess anti-inflammatory abilities, with PR exhibiting significantly superior efficacy. The integration of in vivo / vitro experiments and non-targeted metabolomics confirmed the exceptional anti-inflammatory potential of PR and solidified its classification as the "purplish-red better" of Farfarae Flos., Discussion: This study provides valuable insights into the breeding and medical transformation of Farfarae Flos varieties, along with a scientific basis for the establishment of quality standards and the development of new drugs utilizing Farfarae Flos., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhou, Peng, Jing, Luo, Yan, Zhang, Guo and Yang.)

• SWATH and IDA data acquisition modes were used to identify Farfarae Flos metabolites in mice serum. • 56 compounds of Farfarae Flos were identified in mice serum. • A newly developed and rigorously validated analytical method was utilized to determine 12 absorbed metabolites. Farfarae Flos is a traditional herb widely employed for treating coughs, bronchitis, and asthmatic disorders. In the current study, we utilized SWATH and IDA data acquisition modes in combination with multiple data processing techniques to identify Farfarae Flos metabolites in mice serum. A total of 56 compounds were characterized, including 31 phenolic acids, 13 flavonoids, 11 sesquiterpenoids and 1 alkaloid. Further quantitative analysis was conducted on 12 absorbed metabolites, utilizing a newly developed and rigorously validated analytical method. Our approach demonstrated an acceptable level of specificity, accuracy, precision, and stability. When applied to compare the serum of mice treated with FF, all 12 metabolites showed the highest concentration at 0.5 h. Overall, this study presented a novel strategy for unraveling the active compounds of FF via serum pharmacochemistry analysis, which made a foundation for exploring the pharmacodynamic material basis of FF. [ABSTRACT FROM AUTHOR]

Farfarae Flos, a frequently used traditional herbal medicine with outstanding antitussive and anti-asthmatic effects. As an herbal rich in natural flavonoids, the quantitative determination of multi-flavonoids can be helpful to comprehensively evaluate its quality. Herein, an efficient, sensitive and accurate UHPLC-MS/MS method was established to simultaneous determinate nine flavonoids (rutin, hyperin, kaempferol-3-O-rutinoside, hesperidin, luteolin, quercetin, kaempferol, apigenin, and genkwanin) in Farfarae Flos. The calibration curves of the analytes had good linearity (R2 ≥ 0.9991). Limit of detection and limit of quantitation of each analytes was in the range of 1.06 × 10−5–2.26 × 10−3 μg·mL−1 and 3.52 × 10−5–7.53 × 10−3 μg·mL−1. The relative standard deviation (RSD) of the intra-day and inter-day precision was less than 2.71% and 2.94%. The RSD of repeatability test and stability test was less than 2.35% and 2.56%. The recovery rates were in the range of 95.27%–103.60%. The method was further applied to determinate 40 batches of samples that derived from different plant parts and with definite habitat. The results of chemometric statistical analysis showed that, firstly, the content of flavonoids can effectively reflect the differences between traditional medicinal parts and impurities. Secondly, the geographical environment has impact on the quality. In conclusion, this study provides a valuable methodological reference for the quality evaluation and further resource utilization of Farfarae Flos. [ABSTRACT FROM AUTHOR]

A solid‐phase extraction cartridge was fabricated using diallyl isophthalate as the monomer with the addition of porous organic cage material via in situ free‐radical polymerization in a stainless‐steel column. The resulting monolithic adsorbent exhibited a relatively uniform porous structure, a high specific surface area of 113.98 m2/g, and multiple functional chemical groups according to the characterization results. An online solid‐phase extraction–high‐performance liquid chromatography procedure was fabricated to extract and determine tussilagone from Farfarae Flos. The results show that the complex sample matrices can be removed in the solid‐phase extraction procedure. Simultaneously, tussilagone can remain, which can be subsequently switched to an octadecylsilane bonded analytical column. The methodological validation showed that the correlation coefficient was 0.9999 with a linear range of 0.6–200.0 µg/mL, the limit of detection was 0.2 µg/mL, the limit of quantification was 0.6 µg/mL, accuracy was 100.3–100.6%, and relative standard deviation of precision was ≤1.9%. The present monolithic cartridge exhibits good reusability of not more than 100 times. The real sample of Farfarae Flos was determined with a tussilagone content of 0.74 mg/g. [ABSTRACT FROM AUTHOR]

Farfarae Flos is a frequently used traditional herbal medicine, with outstanding antitussive, anti-asthmatic and expectorant effects. The current quality standard cannot effectively evaluate the quality of decoction pieces, or reflect the quality difference between medicinal parts and impurities. Herein, a simple, rapid, and accurate ultra high-performance liquid-chromatography diode-array (UHPLC-DAD) method was established for the simultaneous determination of 14 components in Farfarae Flos within 15 minutes. Different parts of the plant (flower bud, corolla, pedicel and stem) of 20 batches of decoction pieces were determined by the established method. Chemometrics was applied to assess the proposed method and analyze the quantitative results. Principal component analysis showed that the phenolic acids, flavonoids and terpenoids were effective quality control markers for Farfarae Flos. The quality of traditional medicinal part (flower bud) was significantly different from that of impurities (pedicel and stem). ANOVA showed that the content of phenolic acids in the pedicel and stem was significantly higher than that in the flower bud, while the content of flavonoids in the pedicel and stem was significantly lower than that in the flower bud. This study provides an efficient and low-cost methodology with adequate sensitivity for the quality control of Farfarae Flos decoction pieces. [ABSTRACT FROM AUTHOR]

Sulfur fumigation is adopted in the post-harvest processing of herbal drugs. In addition to the sulfur dioxide residual, sulfur fumigation could also lead to chemical transformations of native compounds in the herbs to generate sulfur-containing derivatives. In this study, influence of sulfur fumigation on the chemical composition of Farfarae Flos (FF) was investigated by the ultra-high-performance liquid chromatography-Q exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-orbitrap HRMS). In addition to 103 native compounds in FF, 12 sulfur-containing caffeoylquinic acids were also detected after sulfur fumigation. The further screening results showed that the diagnostic sulfate/sulfite derivatives were effective for rapid discrimination of sulfur-fumigated FF samples. In brief, sulfur fumigation can induce chemical transformations of phenylpropanoids, and the corresponding sulfur-containing derivatives could be regarded as the characteristic chemical markers of sulfur-fumigated FF. [ABSTRACT FROM AUTHOR]

Pyrrolizidine alkaloids (PAs) that are plant toxin naturally produced for protection against herbivores in some plant families. They are associated with the potential hepatotoxic and carcinogenic diseases serious hepatic disease in humans and animals. As the concern of human health risk posed by exposure to PAs has been gradually increased, precise and reliable analysis is required for monitoring PAs. The present study developed a new and simple pretreatment using 50% MeOH (methanol) for quantification analysis of the PAs contained with high content in the herbal medicines. Another pretreatment method using cation-ion exchange solid-phase extraction (MCX-SPE) was employed for determining most of the PAs that are not contained in the herbal medicines. That is, the proposed LC–MS/MS method coupled with MCX-SPE extraction and 50% MeOH extraction method was developed. And to evaluate the reliability of its application for Farfarae Flos and Lithospermi Radix, a validation study was conducted. In addition, monitory study was performed with ten samples in each herbal medicine. As a result, the proposed method had good linearity with r2 ≥ 0.997. Also, the recoveries indicated to be in the ranges of 70.4–118.0% for the Farfarae Flos, 70.2–119.7% for the Lithospermi Radix. In two herbal medicines, the intra-day precision was revealed to satisfy the reference criteria in most of the PAs. In monitoring results, most of the PAs were not contained in two herbal medicines, whereas a part of PAs revealed to have high concentration in Farfarae Flos and Lithospermi Radix. The proposed method is considered as a simple and reliable method to quantify 28 PAs present in two herbal medicines. Especially, the simple MeOH extraction method seems to be available for quantification analysis of certain PAs in herbal medicines with high content. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The flower bud of Tussilago farfara L., also known as Farfarae Flos (FF), is commonly used in the traditional Chinese medicine (TCM) for the treatment of cough, bronchitis and asthmatic disorders. In this study, 26 samples from five provinces across northern China were collected, and internal transcribed spacer-polymerase chain reaction (ITS-PCR) coupled with high performance liquid chromatography (HPLC) fingerprint profiling was used for the quality evaluation of FF. The results of the ITS sequence analysis showed the high similarity values among these samples. ITS2 sequence exhibited less molecular diversity compared with ITS1, and no obvious correlation was found between the variation of ITS with the production areas or cultivation methods. The results of HPLC fingerprints in combination with the similarity analysis suggested that relative contents of phenylpropanoids and flavonoids varied among the 26 FF samples, and there was also no obvious difference among the different habitats. The phenylpropanoids and the flavonoids showed similar fluctuating patterns, and positive correlation among them was also observed. The results presented in this study suggested that FF from different habits showed high similarities, and ITS-PCR coupled with HPLC fingerprint profiling could be used as a valuable approach for the quality evaluation of FF. [ABSTRACT FROM AUTHOR]

Objectives: Farfarae Flos has the effect of cough suppression and phlegm elimination, with cough suppression as the main function. Studies have revealed that certain components of Farfarae Flos may be related to its cough suppressant effect, and some components have been confirmed to have cough suppressant activity. However, the antitussive material basis of Farfarae Flos has not been systematically elucidated. This study aims to elucidate the group of active ingredients in Farfarae Flos with cough suppressant activity by correlating the high performance liquid chromatography (HPLC) fingerprint of Farfarae Flos extract with its cough suppressant activity., Methods: HPLC was used to establish the fingerprint profiles of 10 batches of Farfarae Flos extract and obtain their chemical composition data. Guinea pigs were selected as experimental animals and the citric acid-induced cough model was used to evaluate the antitussive efficacy data of 10 batches of Farfarae Flos extract. SPF-grade healthy male Hartley guinea pigs were randomly divided into the S1 to S10 groups, a positive control group, and a blank control group (12 groups in total), with 10 guinea pigs in each group. The S1 to S10 groups were respectively administered Farfarae Flos extract S1 to S10 (4 g/kg), the positive control group was administered pentoverine citrate (10 mg/kg), and the blank control group was administered purified water. Each group received continuous oral administration for 5 days. The guinea pigs were placed in 5 L closed wide-mouth bottles, and 17.5% citric acid was sprayed into the bottle with an ultrasonic atomizer at the maximum spray intensity for 0.5 minutes. The cough latency period and cough frequency in 5 minutes were recorded for each guinea pig. Grey relational analysis (GRA) and partial least squares regression (PLSR) were used to conduct spectral-effect correlation analysis of the chemical composition data of Farfarae Flos extract and the antitussive efficacy data, and predict the group of active ingredients in Farfarae Flos with antitussive activity. The bioequivalence verification was conducted to verify the predicted group of active ingredients in Farfarae Flos with antitussive activity: SPF-grade healthy male Hartley guinea pigs were randomly divided into a S9 group, an active ingredient group, a positive control group, and a blank control group (4 groups in total), with 10 guinea pigs in each group. The S9 group was administered Farfarae Flos extract S9 (4 g/kg), the active ingredient group was administered the predicted combination of antitussive active ingredients (dose equivalent to 4 g/kg of Farfarae Flos extract S9), the positive control group was administered pentoverine citrate (10 mg/kg), and the blank control group was administered purified water. Each group received continuous oral administration for 5 days, and animal modeling and observation of efficacy indicators were the same as above., Results: The HPLC fingerprint of 10 batches of Farfarae Flos extract was established, and the peak area data of 14 main common peaks were obtained. The antitussive effect data of 10 batches of Farfarae Flos extract were obtained. Compared with the blank control group, the cough latence in the positive control group and S1, S2, S3, S4, S6, S7, S8, S9, S10 groups was prolonged (all P <0.01), while the cough frequency in 5 minutes in the positive control group and S1, S2, S4, S6, S8, S9, S10 groups was decreased (all P <0.05). The analysis of spectrum-effect relationship revealed that isochlorogenic acid C, isochlorogenic acid A, chlorogenic acid, isochlorogenic acid B, isoquercitrin, and rutin had high contribution to the antitussive effect of Farfarae Flos, and the 6 components were predicted to be the antitussive component group of Farfarae Flos. The verification of bioequivalence showed that there were no statistically significant differences in the antitussive effect between the S9 group and the antitussive component composition group(all P> 0.05), which confirmed that isochlorogenic acid C, isochlorogenic acid A, chlorogenic acid, isochlorogenic acid B, isoquercetin, and rutin were the antitussive component group of Farfarae Flos., Conclusions: The analysis of spectrum-effect relationship combined with the verification of bioequivalence could be used to study the antitussive material basis of Farfarae Flos. The antitussive effect of Farfarae Flos is the result of the joint action of many components.

Lung cancer shows the highest incidence rate in the world. Thus, it has become increasingly important to find therapeutic drugs to treat lung cancer. Farfarae Flos (FF) has been used in traditional Chinese medicine to treat pulmonary diseases such as cough, bronchitis and asthmatic disorders. In this study, the anti‐proliferation effects of petroleum extracts of FF (PEFF) on Lewis lung cancer cells and the corresponding mechanisms were studied using cell metabolomics. Fifteen differential metabolites in the cell extracts and the corresponding medium related to the anti‐proliferation effect of PEFF were identified, which were probably involved in pyruvate metabolism and glycine, serine and threonine metabolism. For the cellular uptake compounds in PEFF, six metabolites derived from two prototype compounds were also tentatively identified by UHPLC‐Q‐Orbitrap high‐resolution MS. Network pharmacology analysis demonstrated that the anti‐proliferation mechanism of PEFF was also probably related to the target genes, including, Aurora‐A, glutathione S‐transferase Mu 1 (GSTM1), glutathione S‐transferase P 1 (GSTP1), progesterone receptor and heme oxygenase‐1 (HO‐1), and further associated with the proteoglycans and PI3K/Akt signaling pathway. Cell metabolomics and network pharmacology analysis provided a holistic method to investigate the anti‐proliferation mechanisms of PEFF. However, further studies were still needed to validate the potential target genes, pathways and active compounds in PEFF. [ABSTRACT FROM AUTHOR]

Farfarae Flos is a commonly used traditional herb for the treatment of respiratory disorders. In this study, ultra-high-performance liquid chromatography coupled with time-of-flight mass spectrometry combined with the mass defect filter method was used for the qualitative analysis of Farfarae Flos metabolites in the lung tissues. Then a method for the simultaneous determination of 14 Farfarae Flos metabolites was developed and validated in terms of specificity, linearity, precision and accuracy, matrix effect and recovery. The method was applied to compare the lung tissue of Farfarae Flos treated mice, and 10 caffeoylquinic acid metabolites were higher in the mice with better antitussive effect. Further network pharmacology analysis and molecular docking results showed that these metabolites played an important role in the antitussive effect of Farfarae Flos. This study presented a novel strategy for deciphering the active compounds of herbal medicine by inter-individual variability of bioactivities. [Display omitted] • MDF was used for the identification of Farfarae Flos metabolites in lung tissue. • A method was developed for the quantification of 14 Farfarae Flos metabolites. • Ten caffeoylquinic acids were higher in the mice with better antitussive effect. • The bioactive metabolites were deciphered by the inter-individual variability. [ABSTRACT FROM AUTHOR]

This study aimed to clarify the difference between the effective compounds of raw and processed Farfarae flos using a network pharmacology-integrated metabolomics strategy. First, metabolomics data were obtained by ultra high-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF/MS). Then, metabolomics analysis was developed to screen for the influential compounds that were different between raw and processed Farfarae flos. Finally, a network pharmacology approach was applied to verify the activity of the screened compounds. As a result, 4 compounds (chlorogenic acid, caffeic acid, rutin and isoquercitrin) were successfully screened, identified, quantified and verified as the most influential effective compounds. They may synergistically inhibit the p38, JNK and ERK-mediated pathways, which would induce the inhibition of the expression of the IFA virus. The results revealed that the proposed network pharmacology-integrated metabolomics strategy was a powerful tool for discovering the effective compounds that were responsible for the difference between raw and processed Chinese herbs. [ABSTRACT FROM AUTHOR]

Farfarae Flos (FF) is widely used for the treatment of cough, bronchitis, and asthmatic disorders in the Traditional Chinese Medicine (TCM). According to the experience of TCM, only the flower bud can be used as herbal drug, and its medicinal quality becomes lower after blooming. However, the underlying scientific basis for this phenomenon is not fully understood. In this study, the chemical components and the bioactivities of the FF collected at three different development stages were compared systematically. NMR based fingerprint coupled with multivariate analysis showed that the flower buds differed greatly from the fully opened flower both on the secondary and primary metabolites, and the animal experiments showed that the fully opened flower exhibited no antitussive or expectorant effect. In addition, the endogenous metabolites correlated with the antitussive and expectorant effect of FF were also identified. These findings are useful for understanding the rationality of the traditional use of FF, and also suggested the components responsible for the antitussive and expectorant effect of FF. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancers (TNBCs) are hard-to-treat breast tumors with poor prognosis, which need to be treated by chemotherapy. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor involved in proliferation, metastasis, and invasion of cancer cells. Therefore, research on searching for promising compounds with metabolism that suppress phosphorylation or transcription of STAT3 in TNBC cells is important. Farfarae Flos is well known as a traditional medicine for treating inflammation. However, few studies have shown that sesquiterpenoids from Farfarae Flos have an anticancer effect. In this study, efficient separation methods and an MTT assay were conducted to isolate an anticancer compound from Farfarae Flos against TNBC MDA-MB-231 cells. Here, 7β-(3-Ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (ECN), a compound isolated from Farfarae Flos showed a potent cytotoxic effect on MDA-MB-231 cells. ECN inhibited JAK−STAT3 signaling and suppressed the expression of STAT3 target genes. In addition, ECN induced apoptosis through both extrinsic and intrinsic pathways. Furthermore, we investigated that ECN inhibited the growth of tumors by intraperitoneal administration in mice injected with MDA-MB-231 cells. Therefore, ECN can be an effective chemotherapeutic agent for breast cancer treatment.

Farfarae Flos (FF) is a commonly used herbal drug which has been used for a long time in the Tradition Chinese Medicines (TCM). Nowadays, the cultivated FF in the Northern China is the main source of FF used in the clinic of TCM. The chemical compositions of the herbal drugs are always influenced by the weather, geographic location, soil conditions, and cultivation patterns. Thus it is difficult to guarantee the homogeneity or uniformity of the herbal drugs. In this study, a metabolomic approach was used to compare three batches of FF collected from different growing regions. The results showed that three batches of FFs differed from each other both in the primary and secondary metabolites, and there also existed in vivo differences among three groups of FFs. The clustering pattern of n-butanol extracts was similar to those of crude water extracts and serum, indicating that the polar compounds, such as phenylpropanoids and flavonoids, play an important role in the water extracts of FF. The results presented here suggested that the metabolomic approach can be used as a valuable method to evaluate the difference of herbal drugs from various origins. [ABSTRACT FROM AUTHOR]

In this study, an ionic liquids (ILs) based extraction approach has been successfully applied to the extraction of essential oil from Farfarae Flos, and the effect of lithium chloride was also investigated. The results indicated that the oil yields can be increased by the ILs, and the extraction time can be reduced significantly (from 4 h to 2 h), compared with the conventional water distillation. The addition of lithium chloride showed different effect according to the structures of ILs, and the oil yields may be related with the structure of cation, while the chemical compositions of essential oil may be related with the anion. The reduction of extraction time and remarkable higher efficiency (5.41–62.17% improved) by combination of lithium salt and proper ILs supports the suitability of the proposed approach. [ABSTRACT FROM AUTHOR]

Alcohol soluble extractive values play an important role in the quality evaluation of herbal drugs. Farfarae Flos were collected from four locations in this study, and their alcohol soluble extractives were compared systematically. The values were determined according to the procedures described in Chinese Pharmacopoeia, and the chemical compositions of alcohol soluble extractives were compared by nuclear magnetic resonance (NMR) fingerprinting approach combined with the multivariate analysis. A principal component analysis biplot showed better discrimination and revealed the contribution of each variable to the clustering model. Material from Zhangjiakou contained higher concentrations of tussilagone and tussilagonone, while Qinxian samples contained more chlorogenic acid, caffeic acid, rutin, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, and 4,5-dicaffeoylquinic acid. This study demonstrates that the alcohol soluble extractives of Farfarae Flos may be used to trace its cultivation locations. [ABSTRACT FROM PUBLISHER]

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. [Display omitted] • The inter-individual variability of antitussive effect of FF was observed. • The differential fecal metabolites of FF were related with gut microbiota. • The inter-individual variability of antitussive effect was related with the gut. [ABSTRACT FROM AUTHOR]

Activated microglia produce diverse neurotoxic factors such as nitric oxide (NO) and prostaglandin E2 (PGE2) that may cause neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. From the EtOAc soluble fraction of Farfarae flos ( Tussilago farfara), we purified tussilagone as a bioactive compound by monitoring the inhibitory potential of NO production in activated microglia through the purification procedures. Tussilagone showed dose-dependent inhibition of NO and PGE2 production in LPS-activated microglia with IC50 values of 8.67 μM and 14.1 μM, respectively. It suppressed the expression of protein and mRNA of inducible nitric oxide synthase and cyclooxygenase-2 through the inhibition of 1-κBα degradation and nuclear translocation of p65 subunit of NF-κB. Therefore tussilagone from Farfarae flos may have therapeutic potential in the treatment of neuro-inflammatory diseases through the inhibition of overproduction of NO and PGE2. [ABSTRACT FROM AUTHOR]

In this study, the polysaccharide of Farfarae Flos (FFP) was utilized as a reducing agent to the green synthesis of FFP@AgNPs, and the anticancer activity was evaluated using the HT29 cells. The results showed that the FFP@AgNPs could significantly decrease proliferation ability, inhibit migration, and promote cell apoptosis of HT29 cells, which suggested that the FFP@AgNPs showed significant, strong cytotoxicity against HT29 cells. The cell metabolomic analysis coupled with the heatmap showed an obvious metabolome difference for the cells with and without FFP@AgNPs treatment, which was related to 51 differential metabolites. Four metabolic pathways were determined as the key pathways, and the representative functional metabolites and metabolic pathways were validated in vitro . Nicotinic acid (NA) was revealed as the key metabolite relating with the effect of FFP@AgNPs, and it was interesting that NA supplementation could inhibit the proliferation ability of HT29 cells in vitro , lead to mitochondrial dysfunction, reduce intracellular ATP, and damage the integrity of the cell membrane, which exhibited a similar effect as FFP@AgNPs. In conclusion, this study not only revealed the anticancer mechanism of FFP@AgNPs against the HT29 cells but also provided the important reference that NA shows a potential role in the development of a therapy for colorectal cancer.

Farfarae Flos (FF; dried flower buds of Tussilago farfara L.), a widely used traditional Chinese medicine (TCM), is also known as "Kuandonghua" (Chinese: 款冬花). 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. 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. 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). 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. 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. resources. [ABSTRACT FROM AUTHOR]

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., (© 2020 John Wiley & Sons, Ltd.)

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., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Triple-negative breast cancers (TNBCs) are hard-to-treat breast tumors with poor prognosis, which need to be treated by chemotherapy. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor involved in proliferation, metastasis, and invasion of cancer cells. Therefore, research on searching for promising compounds with metabolism that suppress phosphorylation or transcription of STAT3 in TNBC cells is important. Farfarae Flos is well known as a traditional medicine for treating inflammation. However, few studies have shown that sesquiterpenoids from Farfarae Flos have an anticancer effect. In this study, efficient separation methods and an MTT assay were conducted to isolate an anticancer compound from Farfarae Flos against TNBC MDA-MB-231 cells. Here, 7β-(3-Ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (ECN), a compound isolated from Farfarae Flos showed a potent cytotoxic effect on MDA-MB-231 cells. ECN inhibited JAK–STAT3 signaling and suppressed the expression of STAT3 target genes. In addition, ECN induced apoptosis through both extrinsic and intrinsic pathways. Furthermore, we investigated that ECN inhibited the growth of tumors by intraperitoneal administration in mice injected with MDA-MB-231 cells. Therefore, ECN can be an effective chemotherapeutic agent for breast cancer treatment. [ABSTRACT FROM AUTHOR]