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Peer-reviewedCC BYMolecules (Basel, Switzerland)

Anti-Neuroinflammatory Effects of Cardenolides in IL-1β-Activated SK-N-SH Cells

  • Lu Sun1
  • Matthias Apweiler1,2
  • Rami Schulzki1
  • Christoph W. Grathwol3
  • Claus Normann2
  • Stefan Bräse3,4
  • Bernd L. Fiebich1
4 affiliations
  1. 1Neuroimmunology and Neurochemistry Research Group, Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany
  2. 2Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany
  3. 3Institute of Biological and Chemical Systems-Functional Molecular Systems (IBCS-FMS), Karlsruhe Institute of Technology (KIT), Kaiserstrasse 12, 76131 Karlsruhe, Germany
  4. 4Institute of Organic Chemistry, Karlsruhe Institute of Technology (KIT), 76131 Karlsruhe, Germany
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Abstract

Neuroinflammation is a key feature of neurological disorders such as Alzheimer’s or Parkinson’s disease, depression or amyotrophic lateral sclerosis. This study investigates the anti-neuroinflammatory effects of three cardenolide derivatives, digitoxigenin, digitoxigenone, and coroglaucigenin (all at concentrations of 1, 5, 10, and 25 µM), in IL-1β-stimulated human neuroblastoma SK-N-SH cells. All compounds significantly reduced PGE2 production without affecting cell viability by downregulation of cyclooxygenase (COX)-2 and microsomal prostaglandin E synthases (mPGES)-1 expression and synthesis. Among them, digitoxigenin notably inhibited phosphorylation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) and suppressed interleukin (IL)-6 and IL-8 expression and release. These findings demonstrate that cardenolide derivatives exert potent anti-neuroinflammatory effects by at least partially targeting key enzymes of the arachidonic acid pathway and modulating MAPK/NF-κB signaling, highlighting their potential as novel therapeutic candidates for neuroinflammatory diseases. Future research should focus on effects of the cardenolides in mixed-cell cultures, organoids and in vivo experiments, to evaluate possible side effects and the potential in disease models.

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Cite

BibTeXRIS
BibTeX
@article{sun2026antineuroinflammatory,
  title = {{Anti-Neuroinflammatory Effects of Cardenolides in IL-1β-Activated SK-N-SH Cells}},
  author = {Lu Sun and Matthias Apweiler and Rami Schulzki and Christoph W. Grathwol and Claus Normann and Stefan Bräse and Bernd L. Fiebich},
  journal = {Molecules (Basel, Switzerland)},
  year = {2026},
  month = oct,
  doi = {10.3390/molecules31193501},
  url = {https://europepmc.org/article/PMC/PMC13666663},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Anti-Neuroinflammatory Effects of Cardenolides in IL-1β-Activated SK-N-SH Cells
AU  - Lu Sun
AU  - Matthias Apweiler
AU  - Rami Schulzki
AU  - Christoph W. Grathwol
AU  - Claus Normann
AU  - Stefan Bräse
AU  - Bernd L. Fiebich
PY  - 2026
DA  - 2026/10/01
JO  - Molecules (Basel, Switzerland)
DO  - 10.3390/molecules31193501
UR  - https://europepmc.org/article/PMC/PMC13666663
AB  - Neuroinflammation is a key feature of neurological disorders such as Alzheimer’s or Parkinson’s disease, depression or amyotrophic lateral sclerosis. This study investigates the anti-neuroinflammatory effects of three cardenolide derivatives, digitoxigenin, digitoxigenone, and coroglaucigenin (all at concentrations of 1, 5, 10, and 25 µM), in IL-1β-stimulated human neuroblastoma SK-N-SH cells. All compounds significantly reduced PGE2 production without affecting cell viability by downregulation of cyclooxygenase (COX)-2 and microsomal prostaglandin E synthases (mPGES)-1 expression and synthesis. Among them, digitoxigenin notably inhibited phosphorylation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) and suppressed interleukin (IL)-6 and IL-8 expression and release. These findings demonstrate that cardenolide derivatives exert potent anti-neuroinflammatory effects by at least partially targeting key enzymes of the arachidonic acid pathway and modulating MAPK/NF-κB signaling, highlighting their potential as novel therapeutic candidates for neuroinflammatory diseases. Future research should focus on effects of the cardenolides in mixed-cell cultures, organoids and in vivo experiments, to evaluate possible side effects and the potential in disease models.
SN  - 1420-3049
ER  -