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The trend towards alternative medicine and naturopathy increases the interest in the use of natural products. This requires larger quantities of qualitative raw material of medicinal plants, including the well-known genus Echinacea. The purpose of this study was to evaluate the quality of E. purpurea and pallida cultivated in Kazanlak, Bulgaria. We developed and validated a rapid, reliable, and inexpensive HPLC method for the quantitative determination of chicoric, caftaric, and caffeic acids, and of cynarin, echinacoside, quercetin, and apigenin. The amount of chicoric and caftaric acids was monitored in different phases of plant development in aerial parts and roots. Maximal concentrations of chicoric acid (3.4%) were reported in roots in the seed-formation phase, and a concentration of 2.8% was reported in aerial parts in the vegetative phase. Caftaric acid was 0.9% in aerial parts in the vegetative and flowering phases and 0.5% in roots in the vegetative and seeding phases. Their amounts significantly exceed the requirements of the European Pharmacopoeia 8.0. Therefore, Kazanlak-grown E. purpurea could be a reliable raw material for the formulation of phytopreparations. In addition, the proposed method was applied to the detection and determination of the above-described substances in phytopreparations containing Echinacea from commercial sources. The amounts of the tested substances were found to vary widely. [ABSTRACT FROM AUTHOR]

Introduction: Dandelion is widely used in clinical practice due to its beneficial effects. Polyphenolic compounds are considered the main anti-inflammatory active ingredient of dandelion, but the gene expression patterns of polyphenolic compounds in different dandelion tissues are still unclear. Methods: In this study, we combined a nontargeted metabolome, PacBio Iso-seq transcriptome, and Illumina RNA-seq transcriptome to investigate the relationship between polyphenols and gene expression in roots, flowers, and leaves of flowering dandelion plants. Results: Eighty-eight flavonoids and twenty-five phenolic acids were identified, and 64 candidate genes involved in flavonoid biosynthesis and 63 candidate genes involved in chicoric acid biosynthesis were identified. Most flavonoid and chicoric acid-related genes demonstrated the highest content in flowers. RNA-seq analysis revealed that genes involved in polyphenol biosynthesis pathways, such as CHS, CHI, F3H, F3'H, FLS, HQT, and CAS, which are crucial for the accumulation of flavonoids and chicoric acid, were upregulated in flowers. Discussion: The combination of transcriptomic and metabolomic data can help us better understand the biosynthetic pathways of polyphenols in dandelion. These results provide abundant genetic resources for further studying the regulatory mechanism of dandelion polyphenol biosynthesis. [ABSTRACT FROM AUTHOR]

SUMMARY: Chicoric acid is the major active ingredient of the world‐popular medicinal plant purple coneflower (Echinacea purpurea (L.) Menoch). It is recognized as the quality index of commercial hot‐selling Echinacea products. While the biosynthetic pathway of chicoric acid in purple coneflower has been elucidated recently, its regulatory network remains elusive. Through co‐expression and phylogenetic analysis, we found EpMYB2, a typical R2R3‐type MYB transcription factor (TF) responsive to methyl jasmonate (MeJA) simulation, is a positive regulator of chicoric acid biosynthesis. In addition to directly regulating chicoric acid biosynthetic genes, EpMYB2 positively regulates genes of the upstream shikimate pathway. We also found that EpMYC2 could activate the expression of EpMYB2 by binding to its G‐box site, and the EpMYC2–EpMYB2 module is involved in the MeJA‐induced chicoric acid biosynthesis. Overall, we identified an MYB TF that positively regulates the biosynthesis of chicoric acid by activating both primary and specialized metabolic genes. EpMYB2 links the gap between the JA signaling pathway and chicoric acid biosynthesis. This work opens a new direction toward engineering purple coneflower with higher medicinal qualities. [ABSTRACT FROM AUTHOR]

IntroductionEnteritis and dysbiosis are the major causes of high morbidity and mortality of juvenile ostriches. Chicory (CC) has been proven to have excellent antioxidant, anti-inflammatory, and antibacterial activities. However, it’s unclear whether CC could improve the survival rate of juvenile ostriches by relieving enteritis and correcting dysbiosis.Materials and methodsSouth African ostrich hatchlings (Struthio camelus domesticus) were fed with and without a CC-supplemented diet, and the body weight gain and mortality were compared over 4 months of age. Fresh fecal samples of clinically healthy ostriches were collected, and 16S DNAs were analyzed. Moreover, ostrich chicks with LPS-induced enteritis were fed with different dosages (0, 20, 40, and 80 mg/kg) of chicoric acid (CA), a major bioactive component of CC, for five consecutive days. The expression levels of tight junction (TJ)-related proteins and inflammatory mediators in the ilea were detected with western blot and immunofluorescence.ResultsThe ostrich chicks fed on the CC-supplemented diet began to increase in weight at the 1st month of age and became remarkably heavier at the fourth month (p 4) and Bacteroidota (26.7% vs. 17.7%, respectively) as well as decreased the enrichment of Clostridium (5.0% vs. 9.1%, respectively) in the ostrich ilea compared to the diet without CC. The supplementation of CA at a dose of 80 mg/kg significantly increased the expression level of ZO-1 and claudin-3 (p

INTRODUCTION. Current scientific research aims to discover new plant sources of hydroxycinnamic acids for the development of novel medicinal products. Most commonly, the quantitative determination of hydroxycinnamic acids in herbal drugs involves testing procedures based on spectrophotometry and its modifications.AIM. This study aimed to establish the possibility of the quantification of hydroxycinnamic acids in herbal drugs by direct spectrophotometry.DISCUSSION. This review presents organised information on the use of direct spectrophotometry to quantify hydroxycinnamic acids in 70 plant species growing or cultivated in the Russian Federation. The review covers publications in Russian for the period from 2007 to 2023. According to the reviewed publications, direct spectrophotometry is an easy-to-use and highly reproducible method that does not require additional reagents or labour-intensive steps. Direct spectrophotometry may result in an overestimation of the hydroxycinnamic acid content due to overlapping absorption bands of polyphenolic compounds with different structures.CONCLUSIONS. Direct spectrophotometry can be considered as a method for measuring the total content of phenolic compounds (as well as hydroxycinnamic acids) in herbal drugs. Different approaches to direct spectrophotometric quantification of hydroxycinnamic acids in herbal drugs by can serve as a methodological basis for developing analytical procedures specific to the chemical compositions of biologically active compounds in herbal drugs and their extracts.

INTRODUCTION. Currently the development of novel resourceand cost-effective extraction techniques for herbal medicinal products is a priority for pharmaceutical technology. A unique position among these herbal medicinal products belongs to the medicinal products of Echinacea purpurea, which stimulate the innate immune system.AIM. The study aimed to investigate the effect of E. purpurea herb defatting on the extraction of hydroxycinnamic acids (HCAs) from the herbal drug and to evaluate the suitability of this treatment for the production of E. purpurea tinctures.MATERIALS AND METHODS. On the basis of previous experimental findings, heptane was chosen as the defatting solvent. The production of E. purpurea tinctures included an additional step of herbal drug heating. The content of total HCAs was determined using a pharmacopoeial method, while the content of individual HCAs was determined using high-performance liquid chromatography. The residual defatting solvent was quantified by gas chromatography. The experiment used reference standards for HCAs.RESULTS. The study showed that a single one-hour defatting treatment of the herbal drug with heptane at a 1 g to 5 mL ratio increased the yield of HCAs extracted from Е. purpurea herb. The optimal production process for E. purpurea tinctures involved grinding the herbal drug to 500–2000 μm, macerating the powder with 60% ethanol (v/v) at a 1 g to 10 mL ratio for 7 days, mechanically stirring the mixture for 60 min, and settling the crude extract for 3 days. Heating the herbal drug prior to extraction resulted in the highest yield of HCAs.CONCLUSIONS. The newly developed production technology for E. purpurea tinctures with a preliminary defatting step increases the HCA content in the tinctures. This technology can be used for the industrial production of tinctures high in HCAs.

INTRODUCTION. Polyphenolic compounds of various classes have pronounced absorption bands overlapping in almost the same ultraviolet region. This superposition of bands complicates the quantification of total hydroxycinnamic acids in herbal drugs by direct spectrophotometry without additional sample preparation.AIM. This study aimed to establish the possibility of quantifying hydroxycinnamic acids in herbal drugs by spectrophotometry in the presence of other polyphenolic compounds.DISCUSSION. This review analyses publications on analytical procedures for the spectrophotometric quantification of hydroxycinnamic acids that are based on the preliminary separation or chemical modification of polyphenolic compounds (combining the use of spectrophotometry, chromatography, extraction, Arnow’s reagent, etc.). The described sample preparation can help to resolve absorption bands in the spectra of polyphenolic compounds. The results of assessing the characteristic parameters of these analytical procedures (selectivity, sensitivity, labour intensity, etc.) can serve as a basis for searching novel approaches to the quantitative determination of hydroxycinnamic acids in plants.CONCLUSIONS. To determine the content of hydroxycinnamic acids in mixtures of polyphenolic compounds, analysts may use special sample preparation (combining spectrophotometry with chromatography and extraction) or chemical modification of the initial compounds. The acquired spectra could benefit from specific mathematical processing (derivative photometry and Vierordt’s method). However, even with the abovementioned approaches, it may not always be possible to increase the selectivity of an analytical procedure. Therefore, there is a need to further improve existing analytical procedures for the quantification of hydroxycinnamic acids and develop new ones.

Alzheimer's disease (AD) is the most common progressive neurodegenerative disease. The accumulation of amyloid-beta (Aβ) plaques is a distinctive pathological feature of AD patients. The aims of this study were to evaluate the therapeutic effect of chicoric acid (CA) on AD models and to explore its underlying mechanisms. APPswe/Ind SH-SY5Y cells and 5xFAD mice were treated with CA. Soluble Aβ1–42 and Aβ plaque levels were analyzed by ELISA and immunohistochemistry, respectively. Transcriptome sequencing was used to compare the changes in hippocampal gene expression profiles among the 5xFAD mouse groups. The specific gene expression levels were quantified by qRT-PCR and Western blot analysis. It was found that CA treatment reduced the Aβ1–42 levels in the APPswe/Ind cells and 5xFAD mice. It also reduced the Aβ plaque levels as well as the APP and BACE1 levels. Transcriptome analysis showed that CA affected the synaptic-plasticity-related genes in the 5xFAD mice. The levels of L1CAM, PSD-95 and synaptophysin were increased in the APPswe/Ind SH-SY5Y cells and 5xFAD mice treated with CA, which could be inhibited by administering siRNA-L1CAM to the CA-treated APPswe/Ind SH-SY5Y cells. In summary, CA reduced Aβ levels and increased the expression levels of synaptic-function-related markers via L1CAM in AD models. [ABSTRACT FROM AUTHOR]

Chicory is one of the most useful plants in traditional medicine and has various therapeutic properties and chemical compounds. Due to the variety of climatic conditions of Iran, the chemical composition and biological stress of chicory grown in different regions of Iran may be different from chicory grown in other countries. Therefore, this research was conducted to investigate phytochemistry including the identification and measurement of some phenolic compounds in the hydroalcoholic extracts of the Cichorium intybus L. (collected from 6 localities) in order to compare with chicory grown in other parts of the world. Based on the studied articles and existing standards, 9 compounds including chicoric acid, chlorogenic acid, rosmarinic acid, caffeic acid, salicylic acid, gallic acid, catechin, quercetin, and rutin were selected and examined in the extract of the aerial part and roots of the plant by HPLC. Among the studied compounds, chicoric acid (0.55 to 6.04 mg per gram of dry plant), chlorogenic acid (0.50 to 5.37 mg per gram of dry plant), and rutin (0.56 to 2.25 mg per gram of dry plant) were found in the extracts of aerial parts and chicoric acid (0.03% to 0.29 mg per gram of dry plant) and chlorogenic acid (0.84% to 2.88 mg per gram of dry plant) were found in the extracts of roots of all samples. Among the studied populations, the highest amounts of major compounds (chicoric acid and chlorogenic acid) were observed in the aerial parts of the sample collected from the National Botanical Garden of Iran with 6.04 mg of chicoric acid and 5.37 mg chlorogenic acid. The results show that although the amount of main compounds of the cultivated sample is different from of that of wild samples, but the nature of the main compounds and the pattern of the HPLC spectrum of all the samples are close to each other and similar to the chicory grown outside of Iran. [ABSTRACT FROM AUTHOR]

The aim of the present study is to investigate and compare the physicochemical properties of the essential oil obtained from the oleo-gumresin of two Ferula gummosa populations from Isfahan and Fars habitats. For this purpose, the oleo-gum-resin of F. gummosa was collected from two areas in Maragh, Kashan and Eqlid, Fars. The essential oil was then extracted from the fresh oleo-gum-resin by water and steam distillation. The essential oil was analyzed quantitatively and qualitatively using GC and GC/MS devices. The appearance and physical and chemical characteristics of the essential oil of two populations of F. gummosa including their relative density, refractive index, optical rotation, and phytochemicals were investigated and compared. According to the results, F. gummosa essential oil is a transparent and colourless liquid with a turpentine odour and a green woody scent. The essential oils of two populations of Kashan and Eqlid have relative densities of 0.874 and 0.869, refractive indices of 1.4810 and 1.4795, and optical rotations of 11.35° and 23.52°, respectively. The comparison of the average physical traits of the essential oils of two F. gummosa populations shows that there is no significant difference in the characteristics of relative density and refractive index while there is a significant difference in the amount of optical rotation, which is due to the difference in the content of optically active compounds in the profiles of the two essential oil samples. Based on the essential oil analysis, hydrocarbon monoterpenes including β-pinene (71% and 68.8%), δ-3-carne (9.4% and 5.2%), limonene (2.4% and 15.6%), myrcene (3.9% and 2.4%), and α-pinene (3.6% and 3.4%) were identified as the main compounds in two F. gummosa populations from Kashan and Eqlid, respectively. The difference between two F. gummosa populations in the amount of essential oil components is related to factors such as altitude, climate and precipitation of the two habitats. Although the physicochemical properties of the essential oil of two F. gummosa populations studied are in good agreement with the international standard (ISO), the advantage of Fars F. gummosa is the high content of limonene in the essential oil, and this indicates the ability of Iranian galbanum to compete in foreign markets. [ABSTRACT FROM AUTHOR]

Echinacea purpurea L. (EP) preparations are globally popular herbal supplements known for their medicinal benefits, including anti-inflammatory activities, partly related to their phenolic composition. However, regarding their use for the management of inflammation-related intestinal diseases, the knowledge about the fate of orally ingested constituents throughout the human gastrointestinal tract and the exposition of in vitro digested extracts in relevant inflammatory models are unknown. This study investigated for the first time the impact of in vitro gastrointestinal digestion (INFOGEST) on the phenolic composition and anti-inflammatory properties of EP extracts from flowers (EF), leaves (EL), and roots (ER) on IL-1β-treated human colon-derived CCD-18Co cells. Among the seven hydroxycinnamic acids identified using HPLC-UV-MS/MS, chicoric and caftaric acids showed the highest concentrations in EL, followed by EF and ER, and all extracts exerted significant reductions in IL-6, IL-8, and PGE2 levels. After digestion, despite reducing the bioaccessibility of their phenolics, the anti-inflammatory effects were preserved for digested EL and, to a lesser extent, for EF, but not for digested ER. The lower phenolic content in digested EF and ER could explain these findings. Overall, this study emphasizes the potential of EP in alleviating intestinal inflammatory conditions and related disorders. [ABSTRACT FROM AUTHOR]

ABSTRACT: Chicoric acid (CA) is a natural nutrient found in plants, showcasing diverse biological activities, including anti-inflammatory and antioxidant properties. Despite its valuable properties, CA faces limitations in bioavailability and susceptibility to oxidative breakdown during utilization. Previous research introduced synthesized dihydrocaffeic acid grafted chitosan self-assembled nanomicelles (DA-g-CS), demonstrating its potential to enhance CA absorption. This study aims to investigate the pharmacokinetics, tissue distribution, and antioxidant activity of both CA and DA-g-CS loaded CA (DA-g-CS/CA) in broilers. An IPEC-J2 cell model was established and evaluated to delve deeper into the transport mechanism and antioxidant potential. The in vivo pharmacokinetic analysis in broilers highlighted a substantial difference: the maximum plasma concentration (Cmax) of DA-g-CS/CA exceeded CA by 2.6-fold, yielding a notable increased relative bioavailability to 214%. This evidence underscores the significant enhancement in CA's oral absorption, facilitated by DA-g-CS. The collective evaluation outcomes affirm the successful development of the cell model, indicating its suitability for drug transporter experiments. The findings from the intestinal transit analysis revealed that both CA and DA-g-CS/CA underwent passive entry into IPEC-J2 cells. Notably, the cellular uptake rate of DA-g-CS loaded with CA was significantly amplified, reaching 2.1 times higher than that of CA alone. Intracellular transport mechanisms involved microtubules, lysosomes, and the endoplasmic reticulum, with an additional pathway involving the endoplasmic reticulum observed specifically for DA-g-CS/CA, distinguishing it from CA. Moreover, the results from both in vivo and in vitro antioxidant assessments highlight the potent antioxidant activity of DA-g-CS/CA, showcasing its efficacy in preventing and treating cellular damage induced by oxidative stress. In summary, these findings underscore the significant enhancement of CA's efficacy facilitated by DA-g-CS, establishing a robust theoretical foundation for the prospective application of CA within livestock and poultry farming.

The trend towards alternative medicine and naturopathy increases the interest in the use of natural products. This requires larger quantities of qualitative raw material of medicinal plants, including the well-known genus Echinacea. The purpose of this study was to evaluate the quality of E. purpurea and pallida cultivated in Kazanlak, Bulgaria. We developed and validated a rapid, reliable, and inexpensive HPLC method for the quantitative determination of chicoric, caftaric, and caffeic acids, and of cynarin, echinacoside, quercetin, and apigenin. The amount of chicoric and caftaric acids was monitored in different phases of plant development in aerial parts and roots. Maximal concentrations of chicoric acid (3.4%) were reported in roots in the seed-formation phase, and a concentration of 2.8% was reported in aerial parts in the vegetative phase. Caftaric acid was 0.9% in aerial parts in the vegetative and flowering phases and 0.5% in roots in the vegetative and seeding phases. Their amounts significantly exceed the requirements of the European Pharmacopoeia 8.0. Therefore, Kazanlak-grown E. purpurea could be a reliable raw material for the formulation of phytopreparations. In addition, the proposed method was applied to the detection and determination of the above-described substances in phytopreparations containing Echinacea from commercial sources. The amounts of the tested substances were found to vary widely.

Chicoric acid (CA) has been reported to exhibit biological activities; it remains unclear, however, whether CA could regulate colitis via modulation of the gut microbiota and metabolites. This study aimed to assess CA's impact on dextran sulfate sodium (DSS)-induced colitis, the gut microbiota, and metabolites. Mice were induced with 2.5% DSS to develop colitis over a 7-day period. CA was administered intragastrically one week prior to DSS treatment and continued for 14 days. The microbial composition in the stool was determined using 16S rRNA sequencing, while non-targeted metabolomics was employed to analyze the metabolic profiles of each mouse group. The results show that CA effectively alleviated colitis, as evidenced by an increased colon length, lowered disease activity index (DAI) and histological scores, and decreased tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression levels. CA intervention restored the structure of gut microbiota. Specifically, it decreased the abundance of Bacteroidetes and Cyanobacteria at the phylum level and Bacteroides, Rosiarcus, and unclassified Xanthobacteraceae at the genus level, and increased the abundance of unclassified Lachnospiraceae at the genus level. Metabolomic analysis revealed that CA supplementation reversed the up-regulation of asymmetric dimethylarginine, N-glycolylneuraminic acid, and N-acetylneuraminic acid, as well as the down-regulation of phloroglucinol, thiamine, 4-methyl-5-thiazoleethanol, lithocholic acid, and oxymatrine induced by DSS. Our current research provides scientific evidence for developing CA into an anti-colitis functional food ingredient. Further clinical trials are warranted to elucidate the efficacy and mechanism of CA in treating human inflammatory bowel disease (IBD). [ABSTRACT FROM AUTHOR]

Although several anticolitic drugs are available, their application is associated with numerous side effects. Chicoric acid (CA) is a hydroxycinnamic acid found naturally in chicory (Cichorium intybus), purple coneflower (Echinacea purpurea), and basil with numerous health benefits, such as antioxidative and anti-inflammatory activities. Here, the potential anticolitic efficiency of CA against dextran sulfate sodium (DSS)-induced colitis in rats was examined in rats. Animals were randomly assigned to the following five groups: control, CA (100 mg/kg body weight), DSS [(DSS); 4% w/v], CA + DSS (100 mg/kg), and the 5-aminosalicylic acid (100 mg/kg) + DSS group. The obtained data revealed that CA significantly prevented the shortening of colon length. Meanwhile, the oxidative stress-related enzymes were increased, while malondialdehyde and nitric oxide, were markedly decreased significantly by CA. The results also indicated that CA administration decreased significantly the pro-apoptogenic indices (Bax and caspase-3) and enhanced significantly Bcl-2, the anti-apoptogenic protein. Moreover, DSS caused a significant elevation of pro-inflammatory mediators, including interleukin-1β, tumor necrosis factor-α, myeloperoxidase, cyclooxygenase II, prostaglandin E2, and peroxisome proliferator-activated receptor gamma. Interestingly, these changes were significantly decreased following the CA administration. At the molecular level, CA supplementation has increased significantly the expression level of nuclear factor erythroid 2-related factor-2 (Nrf2) and decreased the expressions of nitric oxide synthase and mitogen-activated protein kinase 14. CA has been determined to significantly lessen DSS-induced colitis by activating Nrf2 and its derived antioxidant molecules and suppressing inflammation and apoptosis cascades associated with the development of colitis; suggesting that CA could be used as an alternative naturally-derived anticolitic agent. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) is a highly morbid inflammatory lung disease with limited pharmacological interventions. The present study aims to evaluate and compare the potential pulmonoprotective effects of natural prolyl oligopeptidase (POP) inhibitors namely rosmarinic acid (RA), chicoric acid (CA), epigallocatechin-3-gallate (EGCG) and gallic acid (GA), against lipopolysaccharide (LPS)-induced ARDS. Cell viability and expression of pro-inflammatory mediators were measured in RAW264.7 cells and in primary murine lung epithelial and bone marrow cells. Nitric oxide (NO) production was also assessed in unstimulated and LPS-stimulated RAW264.7 cells. For subsequent in vivo experiments, the two natural products (NPs) with the most favorable effects, RA and GA, were selected. Protein, cell content and lipid peroxidation levels in bronchoalveolar lavage fluid (BALF), as well as histopathological changes and respiratory parameters were evaluated in LPS-challenged mice. Expression of key mediators involved in ARDS pathophysiology was detected by Western blotting. RA and GA favorably reduced gene expression of pro-inflammatory mediators in vitro, while GA decreased NO production in macrophages. In LPS-challenged mice, RA and GA co-administration improved respiratory parameters, reduced cell and protein content and malondialdehyde (MDA) levels in BALF, decreased vascular cell adhesion molecule-1 (VCAM-1) and the inducible nitric oxide synthase (iNOS) protein expression, activated anti-apoptotic mechanisms and down-regulated POP in the lung. Conclusively, these synergistic pulmonoprotective effects of RA and GA co-administration could render them a promising prophylactic/therapeutic pharmacological intervention against ARDS. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) is the most common progressive neurodegenerative disease. The accumulation of amyloid-beta (Aβ) plaques is a distinctive pathological feature of AD patients. The aims of this study were to evaluate the therapeutic effect of chicoric acid (CA) on AD models and to explore its underlying mechanisms. APPswe/Ind SH-SY5Y cells and 5xFAD mice were treated with CA. Soluble Aβ1–42 and Aβ plaque levels were analyzed by ELISA and immunohistochemistry, respectively. Transcriptome sequencing was used to compare the changes in hippocampal gene expression profiles among the 5xFAD mouse groups. The specific gene expression levels were quantified by qRT-PCR and Western blot analysis. It was found that CA treatment reduced the Aβ1–42 levels in the APPswe/Ind cells and 5xFAD mice. It also reduced the Aβ plaque levels as well as the APP and BACE1 levels. Transcriptome analysis showed that CA affected the synaptic-plasticity-related genes in the 5xFAD mice. The levels of L1CAM, PSD-95 and synaptophysin were increased in the APPswe/Ind SH-SY5Y cells and 5xFAD mice treated with CA, which could be inhibited by administering siRNA-L1CAM to the CA-treated APPswe/Ind SH-SY5Y cells. In summary, CA reduced Aβ levels and increased the expression levels of synaptic-function-related markers via L1CAM in AD models.

Echinacea purpurea L. (EP) preparations are globally popular herbal supplements known for their medicinal benefits, including anti-inflammatory activities, partly related to their phenolic composition. However, regarding their use for the management of inflammation-related intestinal diseases, the knowledge about the fate of orally ingested constituents throughout the human gastrointestinal tract and the exposition of in vitro digested extracts in relevant inflammatory models are unknown. This study investigated for the first time the impact of in vitro gastrointestinal digestion (INFOGEST) on the phenolic composition and anti-inflammatory properties of EP extracts from flowers (EF), leaves (EL), and roots (ER) on IL-1β-treated human colon-derived CCD-18Co cells. Among the seven hydroxycinnamic acids identified using HPLC-UV-MS/MS, chicoric and caftaric acids showed the highest concentrations in EL, followed by EF and ER, and all extracts exerted significant reductions in IL-6, IL-8, and PGE2 levels. After digestion, despite reducing the bioaccessibility of their phenolics, the anti-inflammatory effects were preserved for digested EL and, to a lesser extent, for EF, but not for digested ER. The lower phenolic content in digested EF and ER could explain these findings. Overall, this study emphasizes the potential of EP in alleviating intestinal inflammatory conditions and related disorders.

Chicoric acid (CA), a functional food ingredient, is a caffeic acid derivative that is mainly found in lettuce, pulsatilla, and other natural plants. However, the anti-inflammatory effects of CA in acute lung injury (ALI) remain poorly understood. This study was conducted to investigate potential drug usage of CA for ALI and the underlying molecular mechanisms of inflammation. C57BL/6 mice were given injections of liposaccharide (LPS) to establish the in vivo model. Meanwhile, BMDM cells were stimulated with LPS+ATP to build the in vitro model. CA significantly alleviated inflammation and oxidative stress in both the in vivo and in vitro models of ALI through the inhibition of NLR family pyrin domain-containing 3 (NLRP3)-mediated pyroptosis. In addition, CA attenuated mitochondrial damage to suppress NLRP3-mediated pyroptosis in the in vivo and in vitro models of ALI by suppressing the production of reactive oxygen species (ROS) via inhibiting the Akt/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. CA inhibited the interaction between Akt at T308 and phosphoinositide-dependent kinase-1 (PDPK1) at S549, thus promoting the phosphorylation of the Akt protein. Furthermore, CA directly targeted the PDPK1 protein and accelerated PDPK1 ubiquitination, indicating that 91-GLY, 111-LYS, 126-TYR, 162-ALA, 205-ASP, and 223-ASP might be responsible for the interaction between PDPK1 and CA. In conclusion, CA from Lettuce alleviated NLRP3-mediated pyroptosis in the ALI model through ROS-induced mitochondrial damage by activating Akt/Nrf2 pathway via PDPK1 ubiquitination. The present study suggests that CA might be a potential therapeutic drug to treat or prevent ALI in pneumonia or COVID-19. [ABSTRACT FROM AUTHOR]

The main goal of our study was to find an optimal combination of tested factors to achieve lettuce rich in bioactive compounds sustaining its pleasant taste. We examined three red and three green cultivars in a greenhouse using two microbiological fertilisers (EM Aktiv and Vital Tricho), and their combination. Plants were grown in three consecutive growing seasons (autumn, winter, and spring). Lactones accumulated in autumn, whereas phenolics' concentration rose during winter. Red cultivars showed higher phenolics and lactone content, where chicoric acid and luteolin-7-glucoside were the most abundant in the 'Gaugin' winter trial. Lactucopicrin was the predominant lactone among tested cultivars with the highest value in the red cultivar 'Carmesi'. Solely applicated, the fertiliser EM Aktiv and Vital Tricho led to significantly higher phenolic acid and dihydrolactucopicrin content, while combined, there were notably increased levels of all detected lactones. Application of single fertilisers had no effect on flavonoid content, while the combination even reduced it. A sensory analysis showed a negative correlation between overall taste and total sesquiterpene lactones, lactucopicrin, caffeoylmalic, and chlorogenic acid, indicating a less bitter taste with decreasing content of these compounds. Our findings indicate that the cultivar, fertiliser, and growing season jointly affected all of the tested parameters, highlighting the differences in the application of EM Aktiv, Vital Tricho, and their combination. [ABSTRACT FROM AUTHOR]

Chemotherapy‐induced neuropathy represents the main dose‐limiting toxicity of several anticancer drugs, such as oxaliplatin, leading to chronic pain and an impairment of the quality of life. Echinacea purpurea n‐hexane extract (EP4–RE; rich in alkamides) and butanolic extract (EP4–RBU; rich in polyphenols) have been characterized and tested in an in vivo model of oxaliplatin‐induced neuropathic pain, addressing the endocannabinoid system with alkamides and counteracting the redox imbalance with polyphenols. Thermal hypersensitivity was evaluated by the Cold Plate test. EP4–RE showed a dose‐dependent anti‐hyperalgesic profile. The extract was more effective than its main constituent, dodeca‐2 E,4 E,8Z,10 E/Z‐tetraenoic acid isobutylamide (18 mg kg−1, twofold to equimolar EP4–RE 30 mg kg−1), suggesting a synergy with other extract constituents. Administration of cannabinoid type 2 (CB2) receptor‐selective antagonist completely blocked the anti‐allodynic effect of EP4–RE, differently from the antagonism of CB1 receptors. EP4–RBU (30 mg kg−1) exhibited anti‐neuropathic properties too. The effect was mainly exerted by chicoric acid, which administered alone (123 μg kg−1, equimolar to EP4–RBU 30 mg kg−1) completely reverted oxaliplatin‐induced allodynia. A synergy between different polyphenols in the extract had not been highlighted. Echinacea extracts have therapeutic potential in the treatment of neuropathic pain, through both alkamides CB2‐selective activity and polyphenols protective properties. [ABSTRACT FROM AUTHOR]

Plant-derived antioxidants are intrinsic components of human diet and factors implicated in tolerance mechanisms against environmental stresses in both plants and humans. They are being used as food preservatives and additives or ingredients of cosmetics. For nearly forty years, Rhizobium rhizogenes-transformed roots (hairy roots) have been studied in respect to their usability as producers of plant specialized metabolites of different, primarily medical applications. Moreover, the hairy root cultures have proven their value as a tool in crop plant improvement and in plant secondary metabolism investigations. Though cultivated plants remain a major source of plant polyphenolics of economic importance, the decline in biodiversity caused by climate changes and overexploitation of natural resources may increase the interest in hairy roots as a productive and renewable source of biologically active compounds. The present review examines hairy roots as efficient producers of simple phenolics, phenylethanoids, and hydroxycinnamates of plant origin and summarizes efforts to maximize the product yield. Attempts to use Rhizobium rhizogenes-mediated genetic transformation for inducing enhanced production of the plant phenolics/polyphenolics in crop plants are also mentioned. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is associated with lipid accumulation and lipotoxicity. The main aim of this study is to evaluate the synergistic treatment effect of fish oils (FOs) and chicoric acid (CA) in palmitate (PA)-induced NAFLD HepG2 model. HepG2 cells were pre-treated with palmitate (0.75 mM) for 24 h, and then were exposed to CA, FOs and combination of these chemicals for another 24 h. Gene expression and protein levels were determined using qRT-PCR and western blotting or ELISA analysing, respectively. The combination index (CI) values of FOs and CA in HepG2 cells were calculated according to the Chou-Talalay equation using the CompuSyn software. FOs and CA acid together synergistically reduced lipid accumulation as indicated by decreased oil red O staining (vehicle-treated control: 1 ± 0.1; PA-treated control: 4.7 ± 0.4; PA + CA100: 3.9 ± 0.4; PA + CA200: 2.4 ± 0.3; PA + FOs: 2.7 ± 0.1; PA + CA200 + FOs: 1.5 ± 0.1) and triglyceride (vehicle-treatedcontrol:10 ± 1.2; PA-treated control: 25.8 ± 2.7; PA + CA100: 18.9 ± 2.5; PA + CA200: 14.4 ± 1.8; PA + FOs: 15.2 ± 2.4; PA + CA200 + FOs: 11.9 ± 1.5) levels in PA-treated HepG2 cells. Gene expression and Immunoblotting analysis confirmed the combination effect of FOs and CA in up-regulation of AMPK-mediated PPARα/UCP2 and down-regulation of AMPK-mediated SREBP-1/FAS signalling pathways. Collectively, these results suggest that combining FOs with CA can serve as a potential combination therapy for NAFLD. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (METS) is a complex disorder that predisposes an affected person to an increased risk of diabetes and cardiovascular disease. Bitter Asteraceae plants contain several compounds active against METS that can be used as an alternative preventive therapy. Our previous work showed that a natural chicory extract (NCRAE) containing chicoric acid (CRA) and chlorogenic acid (CGA) in a molar ratio of 70/30 exhibited an antioxidant, insulin sensitization and anti-hyperglycemic effect. The present study was designed to evaluate the preventive effects of an NCRAE-like extract against METS in a complementary natural pharmacotherapeutic approach. An original Asteraceae infused drink containing the NCRAE CRA/CGA molecular ratio equivalent was prepared from dandelion (Taraxacum officinale L.) and burdock (Arctium lappa L.). The anti-METS effect of this drink was evaluated on the fructose-rat model for 8 weeks. Body weight, blood biochemistry, hepatic glucose-6-phosphatase, arterial blood pressure glucose and insulin tolerance were evaluated after 8 weeks. Our results show that daily oral intake of the Asteraceae infused drink led to a reduction of body weight gain, hyperglycemia, hypertriglyceridemia, insulin resistance and hypertension. Moreover, rat-by-rat analysis of the insulinemia measures revealed two types of responders. One sub-group of subjects demonstrated normal insulinemia and the other subgroup demonstrated hyperinsulinemia. This hyperinsulinemia, associated with the inhibition of the glucose-6-phosphatase activity in the liver tissue, may suggest an insulin release caused by CGA. The present study suggests that this original infusion of dandelion leaves and burdock roots may be used as an adjuvant therapy to prevent metabolic syndrome. [ABSTRACT FROM AUTHOR]

Chicoric acid (CA) has been reported to exhibit biological activities; it remains unclear, however, whether CA could regulate colitis via modulation of the gut microbiota and metabolites. This study aimed to assess CA’s impact on dextran sulfate sodium (DSS)-induced colitis, the gut microbiota, and metabolites. Mice were induced with 2.5% DSS to develop colitis over a 7-day period. CA was administered intragastrically one week prior to DSS treatment and continued for 14 days. The microbial composition in the stool was determined using 16S rRNA sequencing, while non-targeted metabolomics was employed to analyze the metabolic profiles of each mouse group. The results show that CA effectively alleviated colitis, as evidenced by an increased colon length, lowered disease activity index (DAI) and histological scores, and decreased tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression levels. CA intervention restored the structure of gut microbiota. Specifically, it decreased the abundance of Bacteroidetes and Cyanobacteria at the phylum level and Bacteroides, Rosiarcus, and unclassified Xanthobacteraceae at the genus level, and increased the abundance of unclassified Lachnospiraceae at the genus level. Metabolomic analysis revealed that CA supplementation reversed the up-regulation of asymmetric dimethylarginine, N-glycolylneuraminic acid, and N-acetylneuraminic acid, as well as the down-regulation of phloroglucinol, thiamine, 4-methyl-5-thiazoleethanol, lithocholic acid, and oxymatrine induced by DSS. Our current research provides scientific evidence for developing CA into an anti-colitis functional food ingredient. Further clinical trials are warranted to elucidate the efficacy and mechanism of CA in treating human inflammatory bowel disease (IBD).

ABSTRACT: Thiacloprid (TH) is a neonicotinoid insecticide employed in agriculture to protect fruits and vegetables against different insects. It showed different deleterious effects on the general health of non-target organisms including birds and animals, however, its developmental toxicity has yet to be fully elucidated. Chicoric (CA) and rosmarinic (RA) acids are polyphenolic compounds with a wide range of beneficial biological activities. In this study, the possible protective effects of CA and RA were investigated in chick embryos exposed in ovo to TH (1µg/egg) with or without CA (100 µg/egg) or RA (100 µg/egg) co-exposure. TH reduced the hatchling body weight, body weight/egg weight, and relative weight of bursa of Fabricius in the one-day-old hatchlings. Examination of the 7-day-old chicks revealed a decline in feed intake, daily weight gain, feed conversion ratio (FCR), and plasma levels of T3, T4, and growth hormone. Serum ALT, AST activities, and total cholesterol levels showed significant elevations. Hepatic MDA was increased with a reduction in SOD activity and GSH level and downregulation of the liver SOD and GST gene expression pattern. Serum IgG and IgM levels were reduced, and various histopathological alterations were noticed in the liver. Co-administration of CA or RA with TH mitigated the toxic effects on hatchlings. When both CA and RA are combined, they present a synergistic protective effect. CA and RA can be used as protective agents against TH toxicity as they improve growth performance and have hepatoprotective and immunostimulant effects in newly hatched chicks.

Eryngo (Eryngium caucasicum Trautv) a widespread species of the Apiaceae reveals high nutritional value and therapeutic properties due to the significant content of biologically active metabolites such as essential oils, phenolic compounds, and flavonoids. The present study was performed to evaluate the morphological and biochemical variability and antioxidant properties of naturally grown populations of eryngo. One‐way ANOVA showed significant (p <.01) differences in the majority of parameters measured among the studied populations. The range of fresh weight was from 1.3 to 12.0 g/plant, while dry weight varied from 0.01 to 6.0 g/plant. The highest variation was observed for essential oil yield (CV = 205.32%) followed by essential oil content (CV = 126.23%) and chicoric acid content (CV = 71.18%). Total phenolics content varied from 8.85 to 88.15 mg GAE/g extract. Total flavonoids value ranged from 5.41 to 134.40 mg QE/g extract. Rosmarinic acid and chicoric acid contents varied from 0.118–1.234 and 0.014–0.597 μg/g DW, respectively. DPPH free radical scavenging activity varied from 76.12 to 513.5 μg/mL, while it ranged from 156.7 to 477.1 μg/mL with the ferrous ions (Fe2+) chelating assay. Rosmarinic acid and chicoric acid showed a significant and positive correlation (r0.01 = 0.81 and r0.05 = 0.40) with total phenolics, respectively. The Ward dendrogram analysis revealed two different clusters based on the parameters measured, confirming high morpho‐phytochemical variability among the individuals and populations. Principal component analysis (PCA) revealed eight PCs which contributed to 99.97% of the overall variance, and leaf length, essential oil content, and antioxidant activity in terms of DPPH and Fe2+ chelating techniques were the most effective attributes for characterizing and selecting the studied population. Based on the traits related to vegetative yield and antioxidant properties, eight individuals from two populations were superior for breeding and/or farming programs. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) is a highly morbid inflammatory lung disease with limited pharmacological interventions. The present study aims to evaluate and compare the potential pulmonoprotective effects of natural prolyl oligopeptidase (POP) inhibitors namely rosmarinic acid (RA), chicoric acid (CA), epigallocatechin-3-gallate (EGCG) and gallic acid (GA), against lipopolysaccharide (LPS)-induced ARDS. Cell viability and expression of pro-inflammatory mediators were measured in RAW264.7 cells and in primary murine lung epithelial and bone marrow cells. Nitric oxide (NO) production was also assessed in unstimulated and LPS-stimulated RAW264.7 cells. For subsequent in vivo experiments, the two natural products (NPs) with the most favorable effects, RA and GA, were selected. Protein, cell content and lipid peroxidation levels in bronchoalveolar lavage fluid (BALF), as well as histopathological changes and respiratory parameters were evaluated in LPS-challenged mice. Expression of key mediators involved in ARDS pathophysiology was detected by Western blotting. RA and GA favorably reduced gene expression of pro-inflammatory mediators in vitro, while GA decreased NO production in macrophages. In LPS-challenged mice, RA and GA co-administration improved respiratory parameters, reduced cell and protein content and malondialdehyde (MDA) levels in BALF, decreased vascular cell adhesion molecule-1 (VCAM-1) and the inducible nitric oxide synthase (iNOS) protein expression, activated anti-apoptotic mechanisms and down-regulated POP in the lung. Conclusively, these synergistic pulmonoprotective effects of RA and GA co-administration could render them a promising prophylactic/therapeutic pharmacological intervention against ARDS.

The effects of dandelion addition (DA) on the physiochemical properties, antioxidant activity, inhibitory activity against xanthine oxidase (XOD) and flavor of craft beer were investigated. It was found that DA changed the pH value, total acid content, thiobarbituric-acid-value, sugar content and color of beer, and increased the contents of total polyphenols and flavonoids and thus the antioxidant activity of beer. HPLC analysis showed that DA provided beer with chlorogenic, caffeic, ferulic, and chicoric acid, contributing to the inhibition activity against XOD that is a key enzyme in uric acid production. GC-MS analysis showed that 3-methyl-1-butanol, isopentyl acetate and ethyl caprylate were main aroma components of all samples. Although DA introduced the special aroma component of azulene, it did not significantly affect the appearance, bubble, aroma and taste evaluation of beer. Conclusively, DA potentially improved the beer properties of antioxidant and inhibition of uric acid production without changing its sensory characteristics.

Echinacea purpurea (L.) Moench is one of the most economically important medicinal plants, cultivated worldwide for its high medicinal value and with several industrial applications in both pharmaceutical and food industries. Thanks to its various phytochemical contents, including caffeic acid derivatives (CADs), E. purpurea extracts have antioxidant, anti-inflammatory, and immuno-stimulating properties. Among CADs, chicoric acid is one of the most important compounds which have shown important pharmacological properties. The present research was aimed at optimizing the production of chicoric acid in E. purpurea cell culture. Methyl jasmonate (MeJa) at different concentrations and for different duration of treatments was utilized as elicitor, and the content of total polyphenols and chicoric acid was measured. Several genes involved in the chicoric acid biosynthetic pathway were selected, and their expression evaluated at different time points of cell culture growth. This was performed with the aim of identifying the most suitable putative molecular markers to be used as a proxy for the early prediction of chicoric acid contents, without the need of expensive quantification methods. A correlation between the production of chicoric acid in response to MeJa and an increased response to oxidative stress was also proposed. [ABSTRACT FROM AUTHOR]

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The combination of extraction with different solvents with HPLC-MS2 was used to identify chemotaxonomic markers (sesquiterpene lactones and hydroxycinnamic acids) to confirm whether the 200-year-old historical material is chicory extract. To compare and verify this approach, an analysis of current dry chicory root was performed simultaneously. Although it was not possible to prove the presence of selected sesquiterpene lactones or hydroxycinnamic acids in the historical sample analyzed, arteincultone was found to be a suitable chemotaxonomic marker to prove that this sample was prepared from chicory in the past. Moreover, this is the first evidence of this substance in the plant Cichorium intybus. In addition, the presence of other substances typical of chicory confirms the positive authentication of the sample. Mass spectrometric fragmentation of arteincultone, selected sesquiterpene lactones, and chicoric acid has also been studied in detail. [ABSTRACT FROM AUTHOR]

Ubiquitin-like containing plant homeodomain Ring Finger 1 (UHRF1) protein is recognized as a cell-cycle-regulated multidomain protein. UHRF1 importantly manifests the maintenance of DNA methylation mediated by the interaction between its SRA (SET and RING associated) domain and DNA methyltransferase-1 (DNMT1)-like epigenetic modulators. However, overexpression of UHRF1 epigenetically responds to the aberrant global methylation and promotes tumorigenesis. To date, no potential molecular inhibitor has been studied against the SRA domain. Therefore, this study focused on identifying the active natural drug-like candidates against the SRA domain. A comprehensive set of in silico approaches including molecular docking, molecular dynamics (MD) simulation, and toxicity analysis was performed to identify potential candidates. A dataset of 709 natural compounds was screened through molecular docking where chicoric acid and nystose have been found showing higher binding affinities to the SRA domain. The MD simulations also showed the protein ligand interaction stability of and in silico toxicity analysis has also showed chicoric acid as a safe and nontoxic drug. In addition, chicoric acid possessed a longer interaction time and higher LD50 of 5000 mg/kg. Moreover, the global methylation level (%5 mC) has been assessed after chicoric acid treatment was in the colorectal cancer cell line (HCT116) at different doses. The result showed that 7.5 pM chicoric acid treatment reduced methylation levels significantly. Thus, the study found chicoric acid can become a possible epidrug-like inhibitor against the SRA domain of UHRF1 protein. [ABSTRACT FROM AUTHOR]

Among the most frequent causes of respiratory infections in humans are influenza A virus H1N1 (H1N1), influenza B virus (IVB), and respiratory syncytial virus (RSV). Echinacea is a perennial wildflower belonging to the Asteraceae family. Echinacea purpurea (L.) Moench is a species belonging to the Echinacea genus. Its characteristic compound, chicoric acid (CA), is known for its physiological activities, including antiviral effects and immune enhancement. Activities of E. purpurea 60% ethanol extract (EPE) and CA in inhibiting infections caused by H1N1, IVB, and RSV subtype A (RSV-A) were evaluated through plaque inhibition tests, quantification of viral gene expression, and analysis of transmission electron microscopy (TEM) images. Additionally, inhibitory activities of EPE and CA for hemagglutination and neuraminidase (NA) of H1N1 and IVB were determined. In the plaque reduction assays, both EPE and CA reduced infectivity against H1N1, IVB, and RSV-A. Furthermore, quantitative real-time polymerase chain reaction analysis revealed that EPE and CA reduced gene expression levels for H1N1, IVB, and RSV-A, whereas TEM image analysis confirmed their inhibitory effects on host cell infection by these viruses. Hemagglutination assays exhibited the ability of EPE and CA to hinder H1N1 and IVB attachment to host cell receptors. Furthermore, EPE and CA displayed inhibition activity against the NA of H1N1 and IVB. These findings suggest that EPE and CA can suppress the infection and propagation of H1N1, IVB, and RSV-A, demonstrating their potential as preventive and therapeutic agents for viral respiratory infections or as ingredients for health functional foods., Competing Interests: AUTHOR DISCLOSURE STATEMENT Author SKL, DRL, DEM, SHP, DGK, EJK, and BKC were employed by the company NUON Co., Ltd. The remaining authors declare no conflict of interest., (© 2024 The Korean Society of Food Science and Nutrition.)

Introduction: Enteritis and dysbiosis are the major causes of high morbidity and mortality of juvenile ostriches. Chicory (CC) has been proven to have excellent antioxidant, anti-inflammatory, and antibacterial activities. However, it's unclear whether CC could improve the survival rate of juvenile ostriches by relieving enteritis and correcting dysbiosis., Materials and Methods: South African ostrich hatchlings ( Struthio camelus domesticus ) were fed with and without a CC-supplemented diet, and the body weight gain and mortality were compared over 4 months of age. Fresh fecal samples of clinically healthy ostriches were collected, and 16S DNAs were analyzed. Moreover, ostrich chicks with LPS-induced enteritis were fed with different dosages (0, 20, 40, and 80 mg/kg) of chicoric acid (CA), a major bioactive component of CC, for five consecutive days. The expression levels of tight junction (TJ)-related proteins and inflammatory mediators in the ilea were detected with western blot and immunofluorescence., Results: The ostrich chicks fed on the CC-supplemented diet began to increase in weight at the 1st month of age and became remarkably heavier at the fourth month ( p  < 0.01) compared with those fed on the non-CC-supplemented diet. Additionally, the mortality percentage was lower in the chicks fed on the CC-supplemented diet than those fed on the non-CC-supplemented diet (19% vs. 36%, respectively). The diet with the CC supplementation significantly increased the abundance of Phascolactobacteria (linear discriminant analysis; LDA >4) and Bacteroidota (26.7% vs. 17.7%, respectively) as well as decreased the enrichment of Clostridium (5.0% vs. 9.1%, respectively) in the ostrich ilea compared to the diet without CC. The supplementation of CA at a dose of 80 mg/kg significantly increased the expression level of ZO-1 and claudin-3 ( p  < 0.0001) and suppressed the levels of IL-1β, IL-6, and TNF-α ( p  < 0.0001) in ostriches with LPS-induced ileitis., Conclusion: Our results substantiate that CC or CA supplementation in a diet could effectively improve growth performance and reduce mortality in juvenile ostriches via modulating the gut microbiota and attenuating enteritis., Competing Interests: ML was employed by Henan Jinlu Special Breeding Farm. The remaining 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 Li, Abouelfetouh, Salah, Kiani, Nan, Ding and Ding.)

Introduction: Dandelion is widely used in clinical practice due to its beneficial effects. Polyphenolic compounds are considered the main anti-inflammatory active ingredient of dandelion, but the gene expression patterns of polyphenolic compounds in different dandelion tissues are still unclear., Methods: In this study, we combined a nontargeted metabolome, PacBio Iso-seq transcriptome, and Illumina RNA-seq transcriptome to investigate the relationship between polyphenols and gene expression in roots, flowers, and leaves of flowering dandelion plants., Results: Eighty-eight flavonoids and twenty-five phenolic acids were identified, and 64 candidate genes involved in flavonoid biosynthesis and 63 candidate genes involved in chicoric acid biosynthesis were identified. Most flavonoid and chicoric acid-related genes demonstrated the highest content in flowers. RNA-seq analysis revealed that genes involved in polyphenol biosynthesis pathways, such as CHS, CHI, F3H, F3'H, FLS, HQT, and CAS, which are crucial for the accumulation of flavonoids and chicoric acid, were upregulated in flowers., Discussion: The combination of transcriptomic and metabolomic data can help us better understand the biosynthetic pathways of polyphenols in dandelion. These results provide abundant genetic resources for further studying the regulatory mechanism of dandelion polyphenol biosynthesis., 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 Zhao, Li, Huang, Shen, Xu and Li.)

Ubiquitin-like containing plant homeodomain Ring Finger 1 (UHRF1) protein is recognized as a cell-cycle-regulated multidomain protein. UHRF1 importantly manifests the maintenance of DNA methylation mediated by the interaction between its SRA (SET and RING associated) domain and DNA methyltransferase-1 (DNMT1)-like epigenetic modulators. However, overexpression of UHRF1 epigenetically responds to the aberrant global methylation and promotes tumorigenesis. To date, no potential molecular inhibitor has been studied against the SRA domain. Therefore, this study focused on identifying the active natural drug-like candidates against the SRA domain. A comprehensive set of in silico approaches including molecular docking, molecular dynamics (MD) simulation, and toxicity analysis was performed to identify potential candidates. A dataset of 709 natural compounds was screened through molecular docking where chicoric acid and nystose have been found showing higher binding affinities to the SRA domain. The MD simulations also showed the protein ligand interaction stability of and in silico toxicity analysis has also showed chicoric acid as a safe and nontoxic drug. In addition, chicoric acid possessed a longer interaction time and higher LD50 of 5000 mg/kg. Moreover, the global methylation level (%5 mC) has been assessed after chicoric acid treatment was in the colorectal cancer cell line (HCT116) at different doses. The result showed that 7.5 µM chicoric acid treatment reduced methylation levels significantly. Thus, the study found chicoric acid can become a possible epidrug-like inhibitor against the SRA domain of UHRF1 protein.

The main goal of our study was to find an optimal combination of tested factors to achieve lettuce rich in bioactive compounds sustaining its pleasant taste. We examined three red and three green cultivars in a greenhouse using two microbiological fertilisers (EM Aktiv and Vital Tricho), and their combination. Plants were grown in three consecutive growing seasons (autumn, winter, and spring). Lactones accumulated in autumn, whereas phenolics’ concentration rose during winter. Red cultivars showed higher phenolics and lactone content, where chicoric acid and luteolin-7-glucoside were the most abundant in the ‘Gaugin’ winter trial. Lactucopicrin was the predominant lactone among tested cultivars with the highest value in the red cultivar ‘Carmesi’. Solely applicated, the fertiliser EM Aktiv and Vital Tricho led to significantly higher phenolic acid and dihydrolactucopicrin content, while combined, there were notably increased levels of all detected lactones. Application of single fertilisers had no effect on flavonoid content, while the combination even reduced it. A sensory analysis showed a negative correlation between overall taste and total sesquiterpene lactones, lactucopicrin, caffeoylmalic, and chlorogenic acid, indicating a less bitter taste with decreasing content of these compounds. Our findings indicate that the cultivar, fertiliser, and growing season jointly affected all of the tested parameters, highlighting the differences in the application of EM Aktiv, Vital Tricho, and their combination.

Chicoric acid (CA), an active phenolic acid of Echinacea purpurea (Linn.) Moench, has been demonstrated to exhibit antioxidative, antiviral and immunological activities. A prior study showed that CA is a water-soluble compound with low bioavailability. The current study was performed to study the intestinal absorption mechanism of CA and improve its bioavailability using natural biodegradable chitosan. A Caco-2 monolayer cell model was established to characterise the mechanisms involved in the intestinal absorption of CA. The bioavailability improvement of CA was studied in Sprague–Dawley rats after oral (20 mg/kg) administration of 0.5% chitosan. In vitro, the results showed that the absorption transport of CA was fairly poor, with Papp values of 8.2 × 10−8 to 2.1 × 10−7 cm/s in the absorption direction and 1.5 × 10−7 to 2.6 × 10−7 cm/s in the secretory direction. The permeability was increased by EDTA and chitosan in both directions. Moreover, the transport through the intestinal monolayer was H+ dependent, and P-glycoprotein and OATP2B1 transporters were involved in the intestinal transport of CA. In vivo, the absorption of CA was increased and accelerated with chitosan in rats because the bioavailability was 1.74-fold that of the prototype drug. The above mentioned results indicated that CA was a poor absorption drug and that paracellular and carrier-mediated trancellular transport both participated in its transport route. Chitosan is an excellent absorption enhancer for CA. The transport characteristics uncovered in this study lay the groundwork for further studies directed toward the development and utilisation of its new formulations.

Chicoric acid has been widely used in food, medicine, animal husbandry, and other commercial products because of its significant pharmacological activities. However, the shortage of chicoric acid limits its further development and utilization. Currently, Echinacea purpurea (L.) Moench serves as the primary natural resource of chicoric acid, while other sources of it are poorly known. Extracting chicoric acid from plants is the most common approach. Meanwhile, chicoric acid levels vary in different plants as well as in the same plant from different areas and different medicinal parts, and different extraction methods. We comprehensively reviewed the information regarding the sources of chicoric acid from plant extracts, its chemical synthesis, biosynthesis, and bioactive effects.

Chicoric acid (CA) is a natural nutrient found in plants, showcasing diverse biological activities, including anti-inflammatory and antioxidant properties. Despite its valuable properties, CA faces limitations in bioavailability and susceptibility to oxidative breakdown during utilization. Previous research introduced synthesized dihydrocaffeic acid grafted chitosan self-assembled nanomicelles (DA-g-CS), demonstrating its potential to enhance CA absorption. This study aims to investigate the pharmacokinetics, tissue distribution, and antioxidant activity of both CA and DA-g-CS loaded CA (DA-g-CS/CA) in broilers. An IPEC-J2 cell model was established and evaluated to delve deeper into the transport mechanism and antioxidant potential. The in vivo pharmacokinetic analysis in broilers highlighted a substantial difference: the maximum plasma concentration (Cmax) of DA-g-CS/CA exceeded CA by 2.6-fold, yielding a notable increased relative bioavailability to 214%. This evidence underscores the significant enhancement in CA's oral absorption, facilitated by DA-g-CS. The collective evaluation outcomes affirm the successful development of the cell model, indicating its suitability for drug transporter experiments. The findings from the intestinal transit analysis revealed that both CA and DA-g-CS/CA underwent passive entry into IPEC-J2 cells. Notably, the cellular uptake rate of DA-g-CS loaded with CA was significantly amplified, reaching 2.1 times higher than that of CA alone. Intracellular transport mechanisms involved microtubules, lysosomes, and the endoplasmic reticulum, with an additional pathway involving the endoplasmic reticulum observed specifically for DA-g-CS/CA, distinguishing it from CA. Moreover, the results from both in vivo and in vitro antioxidant assessments highlight the potent antioxidant activity of DA-g-CS/CA, showcasing its efficacy in preventing and treating cellular damage induced by oxidative stress. In summary, these findings underscore the significant enhancement of CA's efficacy facilitated by DA-g-CS, establishing a robust theoretical foundation for the prospective application of CA within livestock and poultry farming. [ABSTRACT FROM AUTHOR]

Plant-derived antioxidants are intrinsic components of human diet and factors implicated in tolerance mechanisms against environmental stresses in both plants and humans. They are being used as food preservatives and additives or ingredients of cosmetics. For nearly forty years, Rhizobium rhizogenes-transformed roots (hairy roots) have been studied in respect to their usability as producers of plant specialized metabolites of different, primarily medical applications. Moreover, the hairy root cultures have proven their value as a tool in crop plant improvement and in plant secondary metabolism investigations. Though cultivated plants remain a major source of plant polyphenolics of economic importance, the decline in biodiversity caused by climate changes and overexploitation of natural resources may increase the interest in hairy roots as a productive and renewable source of biologically active compounds. The present review examines hairy roots as efficient producers of simple phenolics, phenylethanoids, and hydroxycinnamates of plant origin and summarizes efforts to maximize the product yield. Attempts to use Rhizobium rhizogenes-mediated genetic transformation for inducing enhanced production of the plant phenolics/polyphenolics in crop plants are also mentioned.

The antiradical properties and possible mechanisms of action of the tautomers of curcumin, caffeic acid phenethyl ester (CAPE), and chicoric acid (CA) have been studied within density functional theory (DFT). We calculated global chemical reactivity descriptors from conceptual DFT, pKa, bioavailability, and toxicity to evaluate the antiradical properties and characterize these species. Our final level of theory is the M06-2X functional with the 6–31 + G* basis set; we selected this level after performing a benchmark calibration and validation among different levels. Solvent effects were modeled via the continuum solvation model based on density (SMD). We used water and pentyl ethanoate as solvents to simulate the physiological conditions. The free radical scavenger capacity was analyzed for three possible oxidative stress mechanisms: single electron transfer (SET), hydrogen atom transfer (HAT), and xanthine oxidase (XO) inhibition. The results indicate that neutral curcumin, CA, and CAPE behave as antireductants. The most favorable mechanism turns out to be HAT, where CA and CAPE stand out. In conclusion, our DFT study strongly indicates that neutral curcumin, CAPE, and CA would very likely perform well as antiradical drugs with recommended therapeutic use, supported by their non-toxic nature. [ABSTRACT FROM AUTHOR]

Hyperphophorylation of tau protein is typical pathological features of Alzheimer's disease. Chicoric acid (CA) has been reported to inhibit formation of β amyloid peptide, it's hard to transport through blood brain barrier (BBB) and its role in inhibiting tau phosphorylation is unknown. In this study, we employed ferritin as a nanocage to encapsulate CA (Ft-CA), and stability, cell survival and BBB permeability of CA were improved by ferritin encapsulation, suggesting ferritin to be an effective vector for bioactive molecules. Meanwhile, both CA and Ft-CA were proved to inhibit tau phosphorylation in SH-SY5Y cells, and effects of Ft-CA are more obvious than CA. Roles of CA were proposed to regulate glucose metabolism by increasing GluT1 and promote glycosylation of tau protein. Meanwhile, CA was proved to inhibit phosphorylation of AMPK, which may further inhibit tau phosphorylation. These findings may provide a novel strategy to prevent neurodegenerative diseases by using dietary polyphenols.

Objectives: Dandelion has been shown to exert anti-inflammatory and anti-bacterial effects. Our study aimed to identify the effect and mechanism of dandelion flower extracts on H. pylori-induced gastritis and screen for novel antimicrobial substances., Methods: Anti-H. pylori activities of water extracts(WEDF) and ethanol extracts (EEDF) of dandelion flowers were performed with disk diffusion method assay, MIC, and MBC. The H. pylori-induced model was constructed to examine the gastroprotective of EEDF using RUT, pathological analysis, and ELISA., Results: EEDF exhibited better anti- H. pylori and urease inhibition activities than WEDF. In vivo studies, EEDF can reduce the adhesion of H. pylori to the gastric mucosa, alleviate gastric damage, and concurrently reduce the levels of TNF-α and IL-6 in gastric tissues. The six phenolic compounds showed urease inhibition effect (IC 50 : 2.99±0.15 to 66.08±6.46 mmol/mL). Among them, chlorogenic acid, caffeic acid, and luteolin also had anti-H. pylori activity (MIC: 64-256 μg/mL)., Conclusion: EEDF exhibited anti-H. pylori, gastroprotective and anti-inflammatory effects. Chicoric acid and luteolin may be the main active compounds of dandelion flowers to exert anti-H. pylori, and worthy of further investigation., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Chicoric acid (ChA) is present in various plants, and it is known to have interesting biological properties, e. g., antioxidant activity. In this work, a detailed analysis of the electrochemical oxidation mechanism of L‐(ChA) in DMSO on glassy carbon is reported, for the first time. Since geometry optimization of ChA using Density Functional Theory, confirms a C2 symmetry, three mechanistic routes involving electron transfers (E) and deprotonation reactions (C) were proposed for the simulation work: 1) EECCEECC, 2) ECECECEC, and 3) two simultaneous 2(ECE) steps. Thermodynamic and kinetic parameters of the electrochemical and chemical steps were estimated by fitting the voltammetric simulation with the experimental voltammograms at different scan rates. Results showed that only the ECECECEC mechanism presented an adequate fitting with respect to experimental voltammograms. Homogeneous kinetic constants were close to a diffusion‐limited process (ca. 1×1010 M−1 s−1, for bimolecular reactions) and equilibrium constants, within the range of 1.5–12.0. [ABSTRACT FROM AUTHOR]

To investigate the effects and potential mechanisms of chicoric acid (CA) on LPS-induced inflammatory response in A549 cells. 0–800 μM CA was added to A549 cells to determine the toxicity of CA using MTT assay. Then, 2 μg/mL LPS and 50 μM CA were simultaneously added to A549 cells to investigate the effects of CA. In order to investigate the effects of miR-130a-3p and IGF-1 on LPS-induced A549 cells, cells were infected with inhibitor of miR-130a-3p and si RNA IGF-1. The levels of inflammatory cytokines such as IL-1β, IL-6, and TNF-α were measured by real-time RT-PCR and enzyme-linked immunosorbent (ELISA) assay. The IGF-1 pathway and NF-κB expression were measured using immunoblot assay. Moreover, a luciferase activity assay was used to indicate the binding site of miR-130a-3p on the 3′UTR of IGF-1. 0–50 μM CA had no toxicity on A549 cells. Thus, we chose 50 μM CA for the following study. CA attenuated the inflammatory response by LPS through decreasing IL-1β, IL-6, and TNF-α levels and increasing IGF-1/IGF-1R expression. Inhibition of miR-130a-3p reduced the inflammatory response and restored IGF-1/IGF-1R pathway induced by LPS. Furthermore, luciferase activity results indicated that miR-130a-3p directly targeted IGF-1 to regulate inflammatory response. CA alleviates LPS-induced inflammatory response through miR-130a-3p/IGF-1pathway in A549 cells. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction is a driving force during the development and progression of cardiovascular complications in diabetes. Targeting endothelial injury may be an attractive avenue for the management of diabetic vascular disorders. Chicoric acid is reported to confer antioxidant and anti-inflammatory properties in various diseases including diabetes. However, the role and mechanism of chicoric acid in hyperglycemia-induced endothelial damage are not well understood. In the present study, human umbilical vein endothelial cells (HUVECs) were incubated with high glucose/high fat (HG + HF) to induce endothelial cell injury. We found that exposure of HUVECs to HG + HF medium promoted the release of cytochrome c (cytc) from mitochondrion into the cytoplasm, stimulated the cleavage of caspase-3 and poly ADP-ribose-polymerase (PARP), then inducing cell apoptosis, the effects that were prevented by administration of chicoric acid. Besides, we found that chicoric acid diminished HG + HF-induced phosphorylation and degradation of IκBα, and subsequent p65 NFκB nuclear translocation, thereby contributing to its anti-inflammatory effects in HUVECs. We also confirmed that chicoric acid mitigated oxidative/nitrative stresses under HG + HF conditions. Studies aimed at exploring the underlying mechanisms found that chicoric acid activated the AMP-activated protein kinase (AMPK) signaling pathway to attenuate HG + HF-triggered injury in HUVECs as AMPK inhibitor Compound C or silencing of AMPKα1 abolished the beneficial effects of chicoric acid in HUVECs. Collectively, chicoric acid is likely protected against diabetes-induced endothelial dysfunction by activation of the AMPK signaling pathway. Chicoric acid could be a novel candidate for the treatment of the diabetes-associated vascular endothelial injury. [ABSTRACT FROM AUTHOR]

Echinacea purpurea (L.) Moench is one of the most economically important medicinal plants, cultivated worldwide for its high medicinal value and with several industrial applications in both pharmaceutical and food industries. Thanks to its various phytochemical contents, including caffeic acid derivatives (CADs), E. purpurea extracts have antioxidant, anti-inflammatory, and immuno-stimulating properties. Among CADs, chicoric acid is one of the most important compounds which have shown important pharmacological properties. The present research was aimed at optimizing the production of chicoric acid in E. purpurea cell culture. Methyl jasmonate (MeJa) at different concentrations and for different duration of treatments was utilized as elicitor, and the content of total polyphenols and chicoric acid was measured. Several genes involved in the chicoric acid biosynthetic pathway were selected, and their expression evaluated at different time points of cell culture growth. This was performed with the aim of identifying the most suitable putative molecular markers to be used as a proxy for the early prediction of chicoric acid contents, without the need of expensive quantification methods. A correlation between the production of chicoric acid in response to MeJa and an increased response to oxidative stress was also proposed.