Membrane transport of nobilin conjugation products and use of the extract of Chamomillae romanae flos influence absorption of nobilin in the Caco-2 model

Thormann, Ursula; Hänggi, R.; Kreuter, Matthias; Imanidis, Georgios

doi:10.1016/j.ejps.2014.11.011

Cited by 3 publications

(5 citation statements)

References 56 publications

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“…This compound may be able to interact with calcineurin or through its exposed sulfhydryl groups present in its catalytic subunit [ 36 , 37 ]. Although α-methylene-γ-lactones rings are the most bioactive group, they may also present the ability to create conjugates via Michael-type addition with glutathione intracellularly—a process already described for other chicory SLs, lactucin and lactucopicrinand other SLs such as noblin—that become unavailable for further reaction with the target proteins [ 38 , 39 ].…”

Section: Resultsmentioning

confidence: 99%

Supercritical CO2 Extraction as a Tool to Isolate Anti-Inflammatory Sesquiterpene Lactones from Cichorium intybus L. Roots

et al. 2021

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Cichorium intybus L. or chicory plants are a natural source of health-promoting compounds in the form of supplements such as inulin, as well as other bioactive compounds such as sesquiterpene lactones (SLs). After inulin extraction, chicory roots are considered waste, with most SLs not being harnessed. We developed and optimized a new strategy for SL extraction that can contribute to the conversion of chicory root waste into valuable products to be used in human health-promoting applications. In our work, rich fractions of SLs were recovered from chicory roots using supercritical CO2. A response surface methodology was used to optimize the process parameters (pressure, temperature, flow rate, and co-solvent percentage) for the extraction performance. The best operating conditions were achieved at 350 bar, 40 °C, and 10% EtOH as a co-solvent in a 15 g/min flow rate for 120 min. The extraction with supercritical CO2 revealed to be more selective for the SLs than the conventional solid–liquid extraction with ethyl acetate. In our work, 1.68% mass and a 0.09% sesquiterpenes yield extraction were obtained, including the recovery of two sesquiterpene lactones (8-deoxylactucin and 11β,13-dihydro-8-deoxylactucin), which, to the best of our knowledge, are not commercially available. A mixture of the abovementioned compounds were tested at different concentrations for their toxic profile and anti-inflammatory potential towards a human calcineurin/NFAT orthologue pathway in a yeast model, the calcineurin/Crz1 pathway. The SFE extract obtained, rich in SLs, yielded results of inhibition of 61.74 ± 6.87% with 50 µg/mL, and the purified fraction containing 8-deoxylactucin and 11β,13-dihydro-8-deoxylactucin inhibited the activation of the reporter gene up to 53.38 ± 3.9% at 10 µg/mL. The potential activity of the purified fraction was also validated by the ability to inhibit Crz1 nuclear translocation and accumulation. These results reveal a possible exploitable green technology to recover potential anti-inflammatory compounds from chicory roots waste after inulin extraction.

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Section: Resultsmentioning

confidence: 99%

Supercritical CO2 Extraction as a Tool to Isolate Anti-Inflammatory Sesquiterpene Lactones from Cichorium intybus L. Roots

et al. 2021

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“…In fact, the identification of cysteine conjugates of some SLs on the apical side of Caco-2 suggests that these SLs were either formed by enzymatic action within the cell, followed by efflux through membrane transporters back to the apical side, or underwent a nonenzymatic conjugation with cysteine. Both mechanisms have already been described in Caco-2 cells for nobilin, a sesquiterpene lactone of the germacranolide type [38]. In fact, Caco-2 cells express the transporters P-gp, BCRP, MRP1, MRP2, MRP3, and OATP as well as phase II conjugating enzymes including glutathione S-transferase and UDP-glucuronosyltransferase [39].…”

Section: Discussionmentioning

confidence: 86%

“…In fact, Caco-2 cells express the transporters P-gp, BCRP, MRP1, MRP2, MRP3, and OATP as well as phase II conjugating enzymes including glutathione S-transferase and UDP-glucuronosyltransferase [39]. The extensive bioconversion of nobilin by Caco-2 cells results in the formation of three conjugation products, i.e., with glucuronic acid, cysteine, and glutathione [38]. Based on these reports, the SL-cysteine species detected may result from a glutathione conjugate formed intracellularly then hydrolyzed by the brush border membrane enzymes, γ-glutamyltranspeptidase and/or dipeptidases, yielding the cysteine conjugate, a process already described for other glutathione conjugates and also observed for nobilin [38,40].…”

Section: Discussionmentioning

confidence: 99%

“…The extensive bioconversion of nobilin by Caco-2 cells results in the formation of three conjugation products, i.e., with glucuronic acid, cysteine, and glutathione [38]. Based on these reports, the SL-cysteine species detected may result from a glutathione conjugate formed intracellularly then hydrolyzed by the brush border membrane enzymes, γ-glutamyltranspeptidase and/or dipeptidases, yielding the cysteine conjugate, a process already described for other glutathione conjugates and also observed for nobilin [38,40]. Alternatively, a direct conjugation with cysteine by a nonenzymatic reaction with the SLs might have taken place.…”

Section: Discussionmentioning

confidence: 99%

“…Overall, we observed differential in vitro absorption and evidence of bioconversion of the main chicory SLs and to the best of our knowledge, there are still no reports about their in vivo bioavailability. Indeed, little is known about the ADME of chicory SLs and SLs in general, with the few published studies with Caco-2 cells suggesting that sesquiterpene lactones are well absorbed by diffusion [47][48][49] and undergo carrier mediated efflux and influx [38].…”

Section: Discussionmentioning

confidence: 99%

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Assessing the Intestinal Permeability and Anti-Inflammatory Potential of Sesquiterpene Lactones from Chicory

et al. 2020

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Cichorium intybus L. has recently gained major attention due to large quantities of health-promoting compounds in its roots, such as inulin and sesquiterpene lactones (SLs). Chicory is the main dietary source of SLs, which have underexplored bioactive potential. In this study, we assessed the capacity of SLs to permeate the intestinal barrier to become physiologically available, using in silico predictions and in vitro studies with the well-established cell model of the human intestinal mucosa (differentiated Caco-2 cells). The potential of SLs to modulate inflammatory responses through modulation of the nuclear factor of activated T-cells (NFAT) pathway was also evaluated, using a yeast reporter system. Lactucopicrin was revealed as the most permeable chicory SL in the intestinal barrier model, but it had low anti-inflammatory potential. The SL with the highest anti-inflammatory potential was 11β,13-dihydrolactucin, which inhibited up to 54% of Calcineurin-responsive zinc finger (Crz1) activation, concomitantly with the impairment of the nuclear accumulation of Crz1, the yeast orthologue of human NFAT.

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Costunolide and parthenolide: Novel blood-brain barrier permeable sesquiterpene lactones to improve barrier tightness

Ávila-Gálvez,

Marques,

Figueira

et al. 2023

Biomedicine & Pharmacotherapy

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Membrane transport of nobilin conjugation products and use of the extract of Chamomillae romanae flos influence absorption of nobilin in the Caco-2 model

Cited by 3 publications

References 56 publications

Supercritical CO2 Extraction as a Tool to Isolate Anti-Inflammatory Sesquiterpene Lactones from Cichorium intybus L. Roots

Supercritical CO2 Extraction as a Tool to Isolate Anti-Inflammatory Sesquiterpene Lactones from Cichorium intybus L. Roots

Assessing the Intestinal Permeability and Anti-Inflammatory Potential of Sesquiterpene Lactones from Chicory

Costunolide and parthenolide: Novel blood-brain barrier permeable sesquiterpene lactones to improve barrier tightness

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