Unveiling the anti-inflammatory potential of 11ß,13-dihydrolactucin for application in inflammatory bowel disease management.

Management of inflammatory bowel disease (IBD) poses significant challenges, and there is a need for innovative therapeutic approaches. This study investigates the anti-inflammatory properties of the dietary sesquiterpene lactone (SL) 11ß,13-dihydrolactucin, which can be found in chicory, in three distinct complementary models of intestinal inflammation (two cell models and a zebrafish model), offering comprehensive insights into its potential application for IBD treatment alternatives. In a triple cell co-culture composed of Caco-2, HT29-MTX-E12, and Raji B, 11ß,13-dihydrolactucin demonstrated remarkable anti-inflammatory activity at several levels of the cellular inflammatory response. Notably, 11ß,13-dihydrolactucin prevented the activation of critical signalling pathways associated with inflammation, namely NF-κB and MAPK p38. This SL also decreased the release of the neutrophil-recruiting chemokine IL-8. Additionally, the compound reduced the gene expression of IL-6 and TNF-α, as well as the gene and protein expression of the inflammatory inducible enzymes iNOS and COX-2. In a myofibroblast-like human cell model, 11ß,13-dihydrolactucin decreased the release of the cytokine TNF-α and the COX-2-derived inflammation mediator PGE2. Finally, in a zebrafish model of gut inflammation, 11ß,13-dihydrolactucin effectively reduced neutrophil infiltration, further supporting its anti-inflammatory efficacy in a physiological context. Collectively, our findings highlight the promising anti-inflammatory potential of 11ß,13-dihydrolactucin across various facets of intestinal inflammation, providing a foundation for the consideration of chicory as a promising candidate for incorporation in food or nutraceutical products for the potential prevention of IBD.

Phytochemistry, pharmacological applications, and therapeutic effects of green synthesized nanomaterials using Cichorium species-a comprehensive review.

Cichorium is a genus of potential medicinal herbs that finds widespread cultivation in regions spanning Asia and Europe. Belonging to the Asteraceae family, these plants are typically biennial or perennial in nature. Among the various explored varieties of chicory plants, the most commonly studied ones include Cichorium intybus, Cichorium endivia, and Cichorium pumilum. In Ayurveda, chicory has long been used as a remedy for many health problems. This versatile plant is renowned for its efficacy in managing conditions such as gallstones, gastroenteritis, sinus ailments, and the treatment of skin abrasions and wounds. Numerous bioactives, including polysaccharides, caffeic acid, flavonoids, coumarins, steroids, alkaloids, organic acids, triterpenoids, sesquiterpenoids, and essential oils, are present, according to a thorough phytochemical examination. The phytochemicals isolated from chicory have displayed significant therapeutic activities, including antidiabetic effects, hepatoprotective benefits, anti-obesity properties, and anti-cancer potential, as extensively documented by numerous researchers. The incorporation of these bioactive compounds into one's diet as part of a healthy lifestyle has demonstrated considerable advantages for human well-being. Green synthesis is a recent technology in which plant extracts or phytochemicals are used for synthesizing nanoparticles since plant extracts are generally less toxic and contain capping and reducing agents. This review summarizes current developments in green synthesis employing phytoconstituents from Cichorium species and extracts from various plant parts and their application to scientific problems. In order to preserve lifestyles and cure human diseases, the investigation emphasizes the therapeutic effects of the chemical components and nanoparticles obtained from the extract of Cichorium species.

Edible wild plants, chicory and purslane, alleviated diabetic testicular dysfunction, and insulin resistance via suppression 8OHdg and oxidative stress in rats.

Testicular dysfunction is a prevalent health problem frequently reported in individuals with diabetes mellitus (DM). Oxidative-inflammatory reactions, hormonal and spermatic abnormalities often accompany this illness. Herbal remedies "particularly wild plants" including chicory (Chicorium Intybus) and purslane (Portulaca Oleracea) are emerging as popular agents for people dealing with these issues due to their ability to act as antioxidants, reduce inflammation, and exhibit antidiabetic effects. According to the collected data, the daily administration of chicory (Ch) seed-extract (250 mg/kg) or purslane (Pu) seed-extract (200 mg/kg) to streptozotocin (STZ)-induced diabetic rats (50 mg/kg) for 30 days resulted in the normalization of fasting blood glucose (FBG), serum fructosamine, insulin levels, and insulin resistance (HOMA-IR), as well as reducing lipid peroxidation end-product malondialdehyde (MDA) level, aldehyde oxidase (AO) and xanthene oxidase (XO) activities. While caused a considerable improvement in glutathione (GSH) content, superoxide dismutase (SOD), catalase (CAT) activity, and total antioxidant capacity (TAC) when compared to diabetic rats. Ch and Pu extracts had a substantial impact on testicular parameters including sperm characterization, testosterone level, vimentin expression along with improvements in body and testis weight. They also mitigated hyperlipidemia by reducing total lipids (TL), total cholesterol (TC) levels, and low-density lipoprotein cholesterol (LDL-C), while increasing high-density lipoprotein cholesterol (HDL-C). Furthermore, oral administration of either Ch or Pu notably attuned the elevated proinflammatory cytokines as tumor necrotic factor (TNF-α), C-reactive protein (CRP), and Interleukin-6 (IL-6) together with reducing apoptosis and DNA damage. This was achieved through the suppression of DNA-fragmentation marker 8OHdG, triggering of caspase-3 immuno-expression, and elevation of Bcl-2 protein. The histological studies provided evidence supporting the preventive effects of Ch and Pu against DM-induced testicular dysfunction. In conclusion, Ch and Pu seed-extracts mitigate testicular impairment during DM due to their antihyperglycemic, antilipidemic, antioxidant, anti-inflammatory, and antiapoptotic properties.

Antidiabetic Effect of Combined Leaf Extracts of Portulaca oleracea L., Beta vulgaris L., and Cichorium intybus L. in Streptozotocin-Induced Diabetic Rats.

Purslane (P), chard (CHA), and chicory (CHI) leaf extracts are individually and traditionally used in the treatment of diabetes mellitus. Polyphenols, flavonoids, the polyphenolic profile of the extracts, and their antioxidant activity were determined. This study evaluated the antidiabetic activity of combinations of these extracts in streptozotocin-induced diabetic rats. Diabetic groups were administered orally and daily for 40 days with the investigated extracts at 250 mg/kg body weight (b.w.) or metformin (100 mg/kg b.w.) as a drug. Fasting blood glucose, oral glucose tolerance, insulin, and fructosamine were assessed. The combined extracts with high levels of P or CHI exerted potent hypoglycemic activity compared with metformin in addition to the restoration of the histopathological changes in the liver and pancreas of diabetic rats to a near-normal state. Therefore, these combined extracts could be developed as natural drugs for diabetes.

Purification and characterization of a chicory polysaccharide and its application in stabilizing genistein for cancer therapy.

Genistein is an isoflavone with chemopreventive and therapeutic effects on various types of cancers. Apparently, in contrast to the advantages of multi-target therapy, the poor water solubility of this molecule is a major obstacle to its clinical application. In this work, zein/chicory polysaccharide nanoparticles (G-zein-P NPs) were prepared by pH-induced antisolvent precipitation method for the encapsulation of genistein. Firstly, an acidic polysaccharide (CIP70-2) with a molecular weight of 66.7 kDa was identified from the roots of chicory (Cichorium intybus). This natural macromolecule was identified as a plant pectin, for which the structure included RG-I (rhamnogalacturonan I) and HG (homogalacturonan) regions. Using this polysaccharide, G-zein-P NPs were prepared, in which the water solubility of genistein was improved by encapsulation. The encapsulation efficiency and loading efficiency of genistein by composite nanoparticles reached 99.0 % and 6.96 %, respectively. In vitro tumor inhibition experiments showed that the inhibitory effect of G-zein-P NPs on HepG2 cells was twice that of unencapsulated genistein. Moreover, the significant inhibition of tumor development and metastasis by G-zein-P NPs was observed in zebrafish xenograft models. The results suggested that zein/chicory polysaccharide nanoparticles may be a promising delivery carrier for genistein application in cancer prevention and therapy.

In ovo protective effects of chicoric and rosmarinic acids against Thiacloprid-induced cytotoxicity, oxidative stress, and growth retardation on newly hatched chicks.

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.

Re-Visiting Antioxidant Therapy in Murine Advanced Atherosclerosis with Brussels Chicory, a Typical Vegetable in Mediterranean Diets.

Brussels chicory, a typical vegetable in Mediterranean diets, has been recently reported to stabilize advanced atherosclerotic plaques in the brachiocephalic artery of apoE-deficient (Apoe-/-) mice. Herein, we investigated whether Brussels chicory can stabilize advanced plaques in the aorta via improving oxidative stress. Thirty week old Apoe-/- mice were fed the AIN-93G diet or supplemented with 0.5% freeze-dried Brussels chicory for twenty weeks. Aortic plaque size and stability, aortic relaxation, monocyte adhesion to aortic endothelium, free radicals, and enzymatic and non-enzymatic factors involved in free radical production and elimination in aorta and serum were measured. Brussels chicory consumption did not alter aortic plaque size, however, it stabilized aortic plaques, promoted aortic relaxation, and also inhibited monocyte adhesion to aortic endothelium. Moreover, this administration reduced oxidized LDL (ox-LDL) and 4-hydroxynonenal (4-HNE) content in aortic plaques, associated with inhibited aortic NADPH oxidase (NOX) and uncoupled endothelial nitric oxide synthase (eNOS)-mediated free radical production. However, Brussels chicory consumption did not appreciably alter aortic and serum superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, aortic glutathione (GSH), as well as serum non-enzymatic antioxidants, such as bilirubin, uric acid, and GSH. Collectively, improved oxidative stress might contribute to the atheroprotective effect of Brussels chicory, supporting the prospect of the antioxidant therapy in advanced atherosclerosis progression.

A rice-chicory rotation pattern ensures safe grain production and phytoremediation of cadmium-contaminated paddy fields: A four-year field experiment in southern China.

Cadmium (Cd) contamination in paddy systems is a serious problem, and a strategy must be devised that ensures safe grain production and rapid remediation of soil Cd contamination. To investigate the remediation potential of crop rotation and its effect on Cd accumulation in rice, a four-year (seven-season) rice-chicory rotation field trial was conducted on a moderately acidic Cd-contaminated paddy soil. Rice was planted in summers, followed by straw removal, and chicory, a Cd-enrichment plant, was planted during winter fallows. Rotation effects were compared with those with rice only (control). Rice yields between the rotation and control were not significantly different, whereas Cd concentrations in rice tissues decreased in the rotation. Cd concentration in brown rice of the low-Cd variety decreased to less than 0.2 mg/kg (national food safety standard) from the third season onward, whereas in the high-Cd variety, it decreased from 0.43 mg/kg in the first season to 0.24 mg/kg in the fourth season. The highest Cd concentration in chicory aboveground parts was 24.47 mg/kg, with an enrichment factor of 27.81. Chicory had high regenerative capacity and was repeatedly harvested for biomass in multiple mowings, with average aboveground biomass over 2000 kg/ha in a single mowing. Theoretical phytoextraction efficiency (TPE) of one rice season with straw removal was 0.84%-2.44%, whereas the highest TPE of one chicory season reached 8.07%. The seven seasons of rice-chicory rotation extracted up to 407 g/ha Cd from soil with a TPE exceeding 20%. Therefore, rice-chicory rotation and straw removal can effectively reduce Cd accumulation in subsequent rice crops, without interrupting production and simultaneously rapidly remediating Cd-contaminated soil. Thus, the production potential of light to moderately Cd-contaminated paddy fields can be realized with crop rotation.

Effects of Chicory and Fumitory on Hot Flashes Among Breast Cancer Survivors: A Randomized, Double-Blind Placebo-Controlled Trial.

Objectives: Hot flashes are unpleasant long-term complications of breast cancer. This study aimed to evaluate the effects of a traditional Persian medicine containing extracts of Cichorium intybus L. (chicory) and Fumaria parviflora L. (Fumitory) extract syrup (CFS) compared with placebo when used as intended. Design: Randomized, double-blind, placebo-controlled clinical trial. Setting/Location: The Oncology Ward of Shahid Modarres Hospital (Tehran, Iran). Subjects: Breast cancer survivors undergoing hormone deprivation therapy. Interventions: Patients were randomly allocated to receive 5 mL CFS or placebo syrup three times a day, for 4 weeks. Outcome measures: The co-primary outcomes were self-reported daily hot flashes frequency and severity scores assessed using self-reported daily dairies, including 1 week of baseline data. Results: Of the 148 patients screened, 137 were eligible, and 96 were randomly allocated to receive either CFS (n = 48) or placebo (n = 48). All participants who returned their dairies were compliant and analyzed as randomized in the a priori per-protocol analysis. After 4 weeks of treatment, both the mean daily hot flashes frequency and severity score had reduced by 57% in the CFS group and 10% in the placebo group. The overall weekly mean daily hot flashes frequency (effect size ηp2 0.221, p < 0.001, n = 66) and severity scores (effect size ηp2 0.160, p = 0.001, n = 66) were significantly lower in the CFS group compared with the placebo group (one-within one-between repeated-measures analysis of variance adjusted for baseline). CFS was well tolerated, with similar proportions of serious and nonserious adverse events occurring in both groups. Conclusions: This is the first study to report the effects of chicory or fumitory for the treatment of hot flashes. The findings provide preliminary evidence that CFS can improve hot flashes in breast cancer survivors undergoing hormone deprivation therapy. More research is warranted to confirm its effectiveness, safety, and mechanisms of action. Clinical Trial Registration: IRCT20210226050506N1.

Discovery of potential mTOR inhibitors from Cichorium intybus to find new candidate drugs targeting the pathological protein related to the breast cancer: an integrated computational approach.

Breast cancer is the most common malignancy among women. It is a complex condition with many subtypes based on the hormone receptor. The mammalian target of the rapamycin (mTOR) pathway regulates cell survival, metabolism, growth, and protein synthesis in response to upstream signals in both normal physiological and pathological situations, primarily in cancer. The objective of this study was to screen for a potential target to inhibit the mTOR using a variety of inhibitors derived from Cichorium intybus and to identify the one with the highest binding affinity for the receptor protein. Initially, AutoDock Vina was used to perform structure-based virtual screening, as protein-like interactions are critical in drug development. For the comparative analysis, 110 components of Cichorium intybus were employed and ten FDA-approved anticancer medicines, including everolimus, an mTOR inhibitor. Further, the drug-likeness and ADMET properties were investigated to evaluate the anti-breast cancer activity by applying Lipinski's rule of five to the selected molecules. The promising candidates were then subjected to three replica molecular dynamics simulations run for 100 ns, followed by binding free energy estimation using MM-GBSA. The data were analyzed using root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), and protein-ligand interactions to determine the stability of the protein-ligand complex. Based on the results, taraxerone (98) revealed optimum binding affinities with mTOR, followed by stigmasterol (110) and rutin (104), which compared favorably to the control compounds. Subsequently, bioactive compounds derived from Cichorium intybus may serve as lead molecules for developing potent and effective mTOR inhibitors to treat breast cancer.

Lactucin, a Bitter Sesquiterpene from Cichorium intybus, Inhibits Cancer Cell Proliferation by Downregulating the MAPK and Central Carbon Metabolism Pathway.

Lung cancer, especially adenocarcinoma, is the second most occurring and highest fatality-causing cancer worldwide. Many natural anticancer compounds, such as sesquiterpene lactones (SLs), show promising anticancer properties. Herein, we examined Lactucin, an SL from the plant Cichorium intybus, for its cytotoxicity, apoptotic-inducing, cell cycle inhibiting capacity, and associated protein expression. We also constructed a biotinylated Lactucin probe to isolate interacting proteins and identified them. We found that Lactucin stops the proliferation of A549 and H2347 lung adenocarcinoma cell lines while not affecting normal lung cell MRC5. It also significantly inhibits the cell cycle at G0/G1 stage and induces apoptosis. The western blot analysis shows that Lactucin downregulates the MAPK pathway, cyclin, and cyclin-dependent kinases, inhibiting DNA repair while upregulating p53, p21, Bax, PTEN, and downregulation of Bcl-2. An increased p53 in response to DNA damage upregulates p21, Bax, and PTEN. In an activity-based protein profiling (ABPP) analysis of A549 cell's protein lysate using a biotinylated Lactucin probe, we found that Lactucin binds PGM, PKM, and LDHA PDH, four critical enzymes in central carbon metabolism in cancer cells, limiting cancer cells in its growth; thus, Lactucin inhibits cancer cell proliferation by downregulating the MAPK and the Central Carbon Metabolism pathway.

Sesquiterpene lactones with anti-inflammatory and cytotoxic activities from the roots of Cichorium intybus.

Cichorium intybus L. (Asteraceae), belonging to the tribe Cichorieae of the family Asteraceae, has a long history as an edible and medicinal food. Sesquiterpene lactones are commonly considered as its major active constituents. In the current study, five unreported sesquiterpene lactones, including one 12,8-guaianolide and four 12,6-guaianolides were isolated from C. intybus roots, as well as 16 known analogues. The planar structures and relative configurations of these compounds were elucidated by extensive spectroscopic analysis. The absolute configurations were determined by the time-dependent density functional theory (TDDFT)-based electronic circular dichroism (ECD) calculation method. Bioassay results showed that seven of the isolates exhibited remarkable NO production inhibitory activity in LPS-stimulated RAW264.7 macrophages, with IC50 values ranging from 1.83 to 38.81 µM. Some of them can significantly decrease the secretion of inflammatory cytokines (TNF-α and IL-6). Cytotoxicity assays demonstrated that intybusins B, as well as four known compounds, displayed obvious inhibitory activities against four human tumor cells, with IC50 values ranging from 9.01 to 27.07 µM.

Cichorium intybus bio-callus synthesized silver nanoparticles: A promising antioxidant, antibacterial and anticancer compound.

Cichorium intybus, commonly called chicory, has been widely used as a coffee substitute. It display a wide range of natural compounds and medicinally uses in treatment of gastrointestinal disorders. This study synthesized silver nanoparticles (Ci-AgNPs) using C. intybus leaf-derived callus extract to evaluate phytochemical content, antibacterial, antioxidant and anti-proliferative activities against human breast cancer cells (MDA-MB231). The optimal shape, size and stability of Ci-AgNPs was confirmed using UV-visible spectrophotometry, FESEM, EDX, XRD, DLS, Zeta potential, FTIR and sp-ICP-MS studies. The antibacterial activity of Ci-AgNPs was assessed using disk diffusion method against Staphylococcus aureus and Escherichia coli, and they displayed distinct zones of inhibition. Colorimetric phytochemical analysis of Ci-AgNPs revealed their higher total phenolic (TP) and total flavonoid (TF) content. Ci-AgNPs also indicated a high level of antioxidant activity using FRAP and DPPH assays. The Ci-AgNPs were investigated for their anticancer activities on the cancerous MDA-MB231 cells viability and apoptosis using MTT and flow cytometry, respectively. Ci-AgNPs showed dose dependent cytotoxicity against MDA-MB231 cells with IC50 value of 187.6 µg/mL at 48 h through induction of apoptosis. The biocompatibility test showed that Ci-AgNPs induced neglectable cytotoxicity (lower than 3 %) toward human erythrocytes. This is the first study that reports the bio-callus mediated synthesis of silver nanoparticle using C. intybus callus extract which provided a promising anticancer activity against human breast cancer MDA-MB231 cells and therefore could be used as an alternative and interesting benign strategy for biosynthesis of silver nanoparticles useful in cancer therapy.

The genomes of chicory, endive, great burdock and yacon provide insights into Asteraceae palaeo-polyploidization history and plant inulin production.

Inulin is an important reserve polysaccharide in Asteraceae plants, and is also widely used as a sweetener, a source of dietary fibre and prebiotic. Nevertheless, a lack of genomic resources for inulin-producing plants has hindered extensive studies on inulin metabolism and regulation. Here, we present chromosome-level reference genomes for four inulin-producing plants: chicory (Cichorium intybus), endive (Cichorium endivia), great burdock (Arctium lappa) and yacon (Smallanthus sonchifolius), with assembled genome sizes of 1.28, 0.89, 1.73 and 2.72 Gb, respectively. We found that the chicory, endive and great burdock genomes were shaped by whole genome triplication (WGT-1), and the yacon genome was shaped by WGT-1 and two subsequent whole genome duplications (WGD-2 and WGD-3). A yacon unique whole genome duplication (WGD-3) occurred 5.6-5.8 million years ago. Our results also showed the genome size difference between chicory and endive is largely due to LTR retrotransposons, and rejected a previous hypothesis that chicory is an ancestor of endive. Furthermore, we identified fructan-active-enzyme and transcription-factor genes, and found there is one copy in chicory, endive and great burdock but two copies in yacon for most of these genes, except for the 1-FEH II gene which is significantly expanded in chicory. Interestingly, inulin synthesis genes 1-SST and 1-FFT are located close to each other, as are the degradation genes 1-FEH I and 1-FEH II. Finally, we predicted protein structures for 1-FFT genes to explore the mechanism determining inulin chain length.

Synergistic effect of probiotic, chicory root powder and coriander seed powder on growth performance, antioxidant activity and gut health of broiler chickens.

Gut health plays an important role on production and performance of broilers. This trial was undertaken with an aim to evaluate the synergistic effect of probiotic, chicory root powder and coriander seed powder on the performance and gut health of broiler chicken. For this purpose, a total of 240 day-old broiler chicks were randomly allotted to six dietary treatments with 8 replicates of 5 birds in each. Treatment groups included T1 as control i.e., basal diet (BD) without any growth promoter and T2-BD + antibiotic (BMD 0.05%). In the remaining experimental diets, T3-probiotic (@ 0.01%) + chicory root powder (@ 1.0%), T4-probiotic (@ 0.01%) + coriander seed powder (@ 1.5%), T5-chicory root powder (@ 1.0%) + coriander seed powder (@ 1.5%) and T6-probiotic (@ 0.01%) + chicory root powder (@ 1.0%) + coriander seed powder (@ 1.5%). The results indicated that supplementation of probiotic + chicory (T3), probiotic + coriander (T4), chicory + coriander (T5) and probiotic + chicory + coriander (T6) in combination resulted in significantly (P<0.05) higher weight gain and better FCR compared to control and antibiotic groups at 42 d of age. Supplementation of different dietary groups did not show any significant (P>0.05) effect on feed intake of broilers. Supplementation of all the test diets (T3 to T6) significantly (P<0.05) increased the glutathione peroxidase (GSHPx), glutathione reductase (GSHRx) and superoxide dismutase (SOD) enzyme activity when compared to control and antibiotic groups at 42 d of age. Supplementation of all the test diets (T3 to T6) significantly (P<0.05) lowered the pH in the gut, increased Lactobacillus counts, and reduced E. coli and Salmonella counts in the ileum compared to control and antibiotic groups. Supplementation of all the test diets (T3 to T6) significantly (P<0.05) increased the villus height (VH), crypt depth (CD), VH:CD ratio and villus width (VW) in the duodenum and only VH and CD in the ileum compared to control and antibiotic groups. Significantly (P<0.05) higher jejunal VH and VW and increased the goblet cell number in duodenum, jejunum and ileum was recorded in all test diets (T3 to T6) compared to control and antibiotic groups. Therefore, combinations of probiotic (0.01%), chicory root powder (1.0%) and coriander seed powder (1.5%) can be used as feed additive for improving performance and gut health of broiler chicken.

Consecutive action of two BAHD acyltransferases promotes tetracoumaroyl spermine accumulation in chicory.

Fully substituted phenolamide accumulation in the pollen coat of Eudicotyledons is a conserved evolutionary chemical trait. Interestingly, spermidine derivatives are replaced by spermine derivatives as the main phenolamide accumulated in the Asteraceae family. Here, we show that the full substitution of spermine in chicory (Cichorium intybus) requires the successive action of two enzymes, that is spermidine hydroxycinnamoyl transferase-like proteins 1 and 2 (CiSHT1 and CiSHT2), two members of the BAHD enzyme family. Deletion of these genes in chicory using CRISPR/Cas9 gene editing technology evidenced that CiSHT2 catalyzes the first N-acylation steps, whereas CiSHT1 fulfills the substitution to give rise to tetracoumaroyl spermine. Additional experiments using Nicotiana benthamiana confirmed these findings. Expression of CiSHT2 alone promoted partially substituted spermine accumulation, and coexpression of CiSHT2 and CiSHT1 promoted synthesis and accumulation of the fully substituted spermine. Structural characterization of the main product of CiSHT2 using nuclear magnetic resonance revealed that CiSHT2 preferentially catalyzed N-acylation of secondary amines to form N5,N10-dicoumaroyl spermine, whereas CiSHT1 used this substrate to synthesize tetracoumaroyl spermine. We showed that spermine availability may be a key determinant toward preferential accumulation of spermine derivatives over spermidine derivatives in chicory. Our results reveal a subfunctionalization among the spermidine hydroxycinnamoyl transferase that was accompanied by a modification of free polyamine metabolism that has resulted in the accumulation of this new phenolamide in chicory and most probably in all Asteraceae. Finally, genetically engineered yeast (Saccharomyces cerevisiae) was shown to be a promising host platform to produce these compounds.

Sulfur enhances cadmium bioaccumulation in Cichorium intybus by altering soil properties, heavy metal availability and microbial community in contaminated alkaline soil.

Cadmium (Cd) contamination seriously threatens the soil health and food safety. Combination of amendment and accumulator plant is a green and effective technique to improve phytoremediation of Cd-contaminated alkaline soil. In this study, a potting experiment was conducted to investigate the effect of sulfur on Cd phytoextraction by Cichorium intybus (chicory). Soil chemical and microbial properties were determined to reveal the mechanism of sulfur-assisting Cd phytoremediation by chicory. Soil pH decreased from 7.77 to the lowest 7.30 with sulfur addition (0.6, 0.9 and 1.2 g kg-1, LS, MS and HS treatment); Electric conductivity, sulfate anion and available cadmium concentration increased gradually with increasing sulfur doses. Cd concentration of shoot and root significantly increased from 1.47 to 4.43 mg kg-1, 6.15 to 20.16 mg kg-1 by sulfur treatment relative to CK, which were attributed to increased available Cd concentration induced by decreased pH. Sulfur treatments significantly increased the Cd bioconcentration factor by 64.1%, 118.6%, 201.0% for shoot, 76.3%, 145.6% and 227.7% for root under LS, MS and HS relative to CK treatment, respectively (P < 0.05). However, only MS treatment significantly improved the Cd removal efficiency by 82.9% in comparison of CK treatment (P < 0.05). Microbial community diversity measured by 16SrRNA showed that Thiobacillus and Actinobacteria were the key and dominant strains of soil microbial communities after sulfur addition, which played a pivotal role in the process of sulfur oxidation involved in decrease of soil pH and the transformation of Cd forms. Correlation analysis and path analysis by structural equation model indicated that soil sulfate anion and Thiobacillus directly affected Cd removal efficiency by chicory in Cd-contaminated alkaline soil. This suggests that combination of sulfur and chicory may provide a way to promote Cd bioaccumulation for phytoremediation of Cd-contaminated alkaline soil.

Brussels Chicory Stabilizes Unstable Atherosclerotic Plaques and Reshapes the Gut Microbiota in Apoe-/- Mice.

BACKGROUND: Adherence to a Mediterranean dietary pattern can protect against atherosclerosis in part by reducing intestinal permeability and gut microbial LPS production. Brussels chicory, a typical Mediterranean vegetable, has been shown to inhibit the formation of early-stage atherosclerosis in mice. OBJECTIVES: We evaluated whether Brussels chicory affects advanced atherosclerosis progression, intestinal permeability, and gut microbial LPS production. METHODS: Thirty-week-old male apoE-deficient mice with unstable atherosclerotic plaques in the brachiocephalic artery were fed the AIN-93G diet alone (control) or supplemented with 0.5% freeze-dried Brussels chicory for 20 wk. Plaque volume and features of plaque stability, plaque macrophage polarization, fecal and serum LPS concentrations, serum lipid profiles and inflammation-related cytokines, and gut microbial profiles were measured. RESULTS: Compared with the control treatment, Brussels chicory consumption did not significantly change plaque volume and serum lipid profiles. However, it increased plaque stability (P < 0.05), as evidenced by reduced necrotic core size (42.3%), and increased fibrous cap thickness (55.0%) and collagen content (68.4%). Moreover, Brussels chicory consumption reduced intestinal permeability (56.3%), fecal and serum LPS concentrations (52.2% and 39.4%), serum IL1ß and TNFα (52.0% and 33.8%), promoted plaque macrophage polarization towards the M2-like phenotype, and altered gut microbial composition, the latter indicated by increased relative abundance of certain members of the Ruminococcaceae family, such as Ruminiclostridium_9, Ruminiclostridium_5, and Intestinimonas (P < 0.05). Spearman correlation analyses further showed that these bacterial genera were significantly correlated with intestinal permeability, fecal and serum LPS, serum proinflammatory cytokines, and several features of plaque stability. CONCLUSIONS: Brussels chicory might help stabilize atherosclerotic plaques in mice by reducing intestinal permeability and gut microbial LPS production. This study provides a promising approach to slow the progression of atherosclerosis.

Three-season rotation of chicory-tobacco-peanut with high biomass and bioconcentration factors effectively remediates cadmium-contaminated farmland.

Traditional phytoremediation is one approach to remediate heavy metal pollution. In developing countries, the key factor in promoting practical application of phytoremediation in polluted soils is selecting suitable plants that are tolerant to heavy metals and also produce products with economic value. Therefore, a field experiment was conducted with a three-season chicory-tobacco-peanut rotation to determine effects on remediation of cadmium (Cd)-contaminated farmland in China. All crops had strong Cd accumulation capacity, with bioconcentration factors of 6.61 to 11.97 in chicory, 3.85 to 21.61 in tobacco, and 1.36 to 7.0 in peanut. Yield of total dry biomass reached 32.4 t ha-1, and the Cd phytoextraction efficiency was 10.3% per year. Aboveground tissues of the three crops accounted for 83.9 to 91.2% of total biomass in the rotation experiment. Cd content in peanut grain and oil met the National Food Safety Standard of China (0.5 mg kg-1, GB 2762-2017) and the Food Contaminant Limit of the European Union (0.1 mg kg-1, 18,812,006). Therefore, in addition to phytoremediation of Cd-contaminated soils, the chicory-tobacco-peanut rotation system can also produce economic benefits for local farmers.

Construction of inulin-based selenium nanoparticles to improve the antitumor activity of an inulin-type fructan from chicory.

Cancer has become one of the leading causes of death worldwide. It is urgent to develop new antitumor drugs with high efficiency and low toxicity. In this study, an inulin-type fructan CIP70-1 was purified and characterized from chicory and showed weak antitumor activity. To improve its antitumor effects, inulin-based selenium nanoparticles (CIP-SeNPs) were constructed and characterized. CIP-SeNPs were spherical nanoparticles (60 nm), which remained stable in water for more than 3 months. A cellular antitumor assay revealed that CIP-SeNPs had stronger inhibitory effects on cancer cells (MCF-7, A549, and HepG2) than CIP70-1 alone. Furthermore, the in vivo antitumor effects of CIP-SeNPs were confirmed using zebrafish models. The results showed that CIP-SeNPs significantly inhibited the proliferation and migration of tumors as well as the angiogenesis of transgenic zebrafish in the concentration range of 1-4 µg/mL.