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Keywords = EA 575

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23 pages, 3048 KiB  
Article
Ivy Leaf Dry Extract EA 575® Is a Potent Immunomodulator Acting on Dendritic Cells
by Miodrag Čolić, Sergej Tomić, Marina Bekić, Anđela Dubovina, Hanns Häberlein, André Rademaekers, Srđan Mašić and Dejan Bokonjić
Pharmaceutics 2025, 17(6), 773; https://doi.org/10.3390/pharmaceutics17060773 - 12 Jun 2025
Cited by 1 | Viewed by 744
Abstract
Background/Objectives: Ivy leaf extract has been shown to alleviate bronchial infection symptoms through various mechanisms, including anti-inflammatory effects. However, its impact on adaptive immunity, particularly dendritic cell (DC)/T-cell interactions, remains unexplored. This study investigated the immunomodulatory potential of ivy leaf extract (EA [...] Read more.
Background/Objectives: Ivy leaf extract has been shown to alleviate bronchial infection symptoms through various mechanisms, including anti-inflammatory effects. However, its impact on adaptive immunity, particularly dendritic cell (DC)/T-cell interactions, remains unexplored. This study investigated the immunomodulatory potential of ivy leaf extract (EA 575®) using human monocyte-derived DCs (MoDCs). Methods: Immature MoDCs (imMoDCs) were differentiated with IL-4/GM-CSF and matured with LPS/IFN-γ (mMoDCs). MoDCs, treated with EA 575® during differentiation, were co-cultured with purified T cells. Results: EA 575® (non-cytotoxic up to 100 µg/mL) inhibited MoDC differentiation and maturation by reducing the expression of CD1a, CD83, CD40, CD86, HLA-DR, Dectin-1, CD206, CD209, HIF-1α, and proinflammatory cytokines (IL-12, IL-23, IL-27, IL-1β, IL-6, TNF-α). EA 575®-treated mMoDCs suppressed allogeneic T-cell proliferation and reduced Th1 (IFN-γ), Th17 (IL-17A, IL-22), Th9 (IL-9), Th21 (IL-21), TNF-α, and IL-6 responses. Effects were dose-dependent, with higher concentrations (100 µg/mL) showing stronger inhibition. At lower concentrations (20 µg/mL), EA 575® increased Th2 (IL-4, IL-5) and IL-10 responses, and the frequencies of CD4+ T cells with Treg properties, such as CD25hiFoxp3+, Tr1 (IL-10+Foxp3−), and IL-35+ Foxp3+ cells. Immunoregulatory mechanisms mediated by EA 575®-treated mMoDCs correlated with the upregulation of tolerogenic markers (PD-L1, ILT3, ILT4, IDO1) on mMoDCs and the increased frequency of exhausted CD4+ T cells (PD-1+CD69+) and cytotoxic T cells (Granzyme B+PD-1+). Conclusions: EA 575® induces tolerogenic DCs with significant anti-inflammatory and immunoregulatory properties, a previously undescribed phenomenon. Lower concentrations primarily enhance immunoregulatory responses, while higher concentrations exert more pronounced anti-inflammatory effects. Full article
(This article belongs to the Section Gene and Cell Therapy)
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13 pages, 1642 KiB  
Article
Efficacy and Safety of a Single Ivy Extract Versus Two Herbal Extract Combinations in Patients with Acute Bronchitis: A Multi-Center, Randomized, Open-Label Clinical Trial
by Peter Kardos, Justus de Zeeuw, Inga Trompetter, Simon Braun and Yuliya Ilieva
Pharmaceuticals 2025, 18(5), 754; https://doi.org/10.3390/ph18050754 - 20 May 2025
Cited by 1 | Viewed by 1876
Abstract
Background: The combination therapy for acute bronchitis with several plant extracts, such as Ivy and Thyme or Primrose and Thyme, is assumed to offer added benefit over single extract preparations. However, no clinical trials have yet demonstrated such a therapeutic advantage. Methods [...] Read more.
Background: The combination therapy for acute bronchitis with several plant extracts, such as Ivy and Thyme or Primrose and Thyme, is assumed to offer added benefit over single extract preparations. However, no clinical trials have yet demonstrated such a therapeutic advantage. Methods: In this three-arm, open-label, randomized clinical trial, patients with acute bronchitis were assigned to groups receiving Ivy extract EA 575 (Prospan® Cough Drops), Ivy/Thyme extract combination (Bronchipret® Drops), or Thyme/Primrose extract combination (Bronchicum® Drops) according to their respective labels. The primary endpoint was the assessment of non-inferiority, and the second endpoint was the assessment of superiority of Ivy vs. each of the two comparators (Ivy/Thyme and Thyme/Primrose) regarding the change in Bronchitis Severity Score between baseline and day 7. In total, 325 adult patients were considered for evaluation. Results: Non-inferiority of Ivy extract was statistically significant against both comparators (both p < 0.0001). Superiority of Ivy extract was statistically significant against Ivy/Thyme extract (p < 0.0001) but missed statistical significance against Thyme/Primrose extract (p < 0.0607). The incidence of adverse events was low and comparable between the groups. All adverse events were non-serious. Conclusions: these data revealed that Ivy extract EA 575 is non-inferior in acute bronchitis treatment compared to both comparators and superior to Ivy/Thyme. Full article
(This article belongs to the Section Natural Products)
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11 pages, 681 KiB  
Article
The Impact of Ivy Leaf Dry Extract EA 575 on Subsequent Antibiotic Use and Its Therapeutic Value in Children and Adolescents with the Common Cold: A Retrospective Prescription Database Analysis
by Christian Vogelberg, Georg Seifert, Simon Braun, Rebecca Zingel and Karel Kostev
Children 2025, 12(4), 518; https://doi.org/10.3390/children12040518 - 17 Apr 2025
Cited by 1 | Viewed by 717
Abstract
Background: Dried ivy leaf extract EA 575® (Prospan®) is commonly used to treat coughs and may help reduce inappropriate antibiotic use for the common cold. This retrospective study investigated whether prescribing EA 575 is associated with reduced subsequent antibiotic use [...] Read more.
Background: Dried ivy leaf extract EA 575® (Prospan®) is commonly used to treat coughs and may help reduce inappropriate antibiotic use for the common cold. This retrospective study investigated whether prescribing EA 575 is associated with reduced subsequent antibiotic use in children and adolescents with the common cold. Repeated EA 575 prescriptions were also analyzed to estimate treatment satisfaction. Methods: Data were sourced from the IQVIA Disease Analyzer database, including patients under 18 diagnosed with a common cold and prescribed either EA 575 or antibiotics between 2017 and 2020 (index date). Propensity score matching controlled for confounding factors. Antibiotic prescriptions were assessed 4–30 and 31–365 days after the index date, along with bacterial infections 4–40 days post-index. Repeated EA 575 prescriptions 2–5 years post-index were analyzed as a proxy for treatment satisfaction. Results: Overall, 10,390 children and adolescents were included in each matched cohort. Compared to antibiotics, EA 575 prescriptions were associated with significantly lower odds of antibiotic use 4–30 days (OR: 0.56; 95% CI: 0.49–0.64; p < 0.001) and 31–365 days (OR: 0.58; 95% CI: 0.54–0.62; p < 0.001) after the index date. The odds of bacterial infection 4–30 days after EA 575 prescription were also lower (OR: 0.67; 95% CI: 0.45–0.99; p = 0.047). Of the 42,677 patients in the EA 575 analysis, 50.5% had at least one repeated prescription, with the highest rates among children aged 0–2 years (54.7%) and the lowest in those aged 13–17 years (19.9%). Conclusions: EA 575 prescription was associated with reduced subsequent antibiotic use in children and adolescents with common colds. Frequent repeated prescription rates emphasize the therapeutic value of EA 575 as a treatment option for cold symptoms, especially in younger children. Full article
(This article belongs to the Section Pediatric Allergy and Immunology)
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16 pages, 2990 KiB  
Article
Ivy Leaf Dry Extract EA 575® Has an Inhibitory Effect on the Signalling Cascade of Adenosine Receptor A2B
by Fabio Meurer, Hanns Häberlein and Sebastian Franken
Int. J. Mol. Sci. 2023, 24(15), 12373; https://doi.org/10.3390/ijms241512373 - 3 Aug 2023
Cited by 2 | Viewed by 3038
Abstract
Ivy leaf dry extract EA 575® is used to improve complaints of chronic inflammatory bronchial diseases and acute inflammation of the respiratory tract accompanied by coughing. Its mechanism of action has so far been explained by influencing β2-adrenergic signal transduction. [...] Read more.
Ivy leaf dry extract EA 575® is used to improve complaints of chronic inflammatory bronchial diseases and acute inflammation of the respiratory tract accompanied by coughing. Its mechanism of action has so far been explained by influencing β2-adrenergic signal transduction. In the present study, we investigated a possible influence on adenosine receptor A2B (A2BAR) signalling, as it has been described to play a significant and detrimental role in chronic inflammatory airway diseases. The influence of EA 575® on A2BAR signalling was assessed with measurements of dynamic mass redistribution. Subsequently, the effects on A2BAR-mediated second messenger cAMP levels, β-arrestin 2 recruitment, and cAMP response element (CRE) activation were examined using luciferase-based HEK293 reporter cell lines. Lastly, the impact on A2BAR-mediated IL-6 release in Calu-3 epithelial lung cells was investigated via the Lumit™ Immunoassay. Additionally, the adenosine receptor subtype mediating these effects was specified, and A2BAR was found to be responsible. The present study demonstrates an inhibitory influence of EA 575® on A2BAR-mediated general cellular response, cAMP levels, β-arrestin 2 recruitment, CRE activation, and IL-6 release. Since these EA 575®-mediated effects occur within a time frame of several hours of incubation, its mode of action can be described as indirect. The present data are the first to describe an inhibitory effect of EA 575® on A2BAR signalling. This may offer an explanation for the beneficial clinical effects of the extract in adjuvant asthma therapy. Full article
(This article belongs to the Section Molecular Plant Sciences)
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