Cited by 27NF-κB Signaling PathwaysNatural product bioactivities and synthesisCell Adhesion Molecules Research

Maslinic acid alleviates ischemia/reperfusion-induced inflammation by downregulation of NFκB-mediated adhesion molecule expression

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Ampofo, Emmanuel, Berg, Julian J., Menger, Michael D., Laschke, Matthias W.·2019·Scientific Reports

Abstract

Ischemia/reperfusion (I/R)-induced inflammation is associated with enhanced leukocyte rolling, adhesion and transmigration within the microcirculation. These steps are mediated by hypoxia-triggered signaling pathways, which upregulate adhesion molecule expression on endothelial cells and pericytes. We analyzed whether these cellular events are affected by maslinic acid (MA). Mitochondrial activity and viability of MA-exposed endothelial cells and pericytes were assessed by water-soluble tetrazolium (WST)-1 and lactate dehydrogenase (LDH) assays as well as Annexin V/propidium iodide (PI) stainings. Effects of MA on hypoxia and reoxygenation-induced expression of E-selectin, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 were determined by flow cytometry. The subcellular localization of the NFκB subunit p65 was analyzed by immunofluorescence and Western blot. I/R-induced leukocytic inflammation was studied in MA- and vehicle-treated mouse dorsal skinfold chambers by intravital fluorescence microscopy and immunohistochemistry. MA did not affect viability, but suppressed the mitochondrial activity of endothelial cells. Furthermore, MA reduced adhesion molecule expression on endothelial cells and pericytes due to an inhibitory action on NFκB signaling. Numbers of adherent and transmigrated leukocytes were lower in post-ischemic tissue of MA-treated mice when compared to vehicle-treated controls. In addition, MA affected reactive oxygen species (ROS) formation, resulting in a diminished oxidative DNA damage. Hence, MA represents an attractive compound for the establishment of novel therapeutic approaches against I/R-induced inflammation.

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Authors
Ampofo, E., Berg, J. J., Menger, M. D., & Laschke, M. W.
Affiliations
Saarland University (DE)
Corresponding author
Ampofo, Emmanuel
Venue
Scientific Reports
Published
2019-04-16
Volume
9
Issue
1
Pages
6119-6119
ISSN
2045-2322 (ISSN-L)
OpenAlex
W2936431047
Cited by
27
References
61
Citations by year
2026: 1 · 2025: 3 · 2023: 3 · 2022: 7 · 2021: 7 · 2020: 4 · 2019: 1
FWCI
1.50
Type
journal article
Language
en
Open access
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Publications of the UdS (Saarland University)
Funders
  • Deutsche Forschungsgemeinschaft
  • Universität des Saarlandes
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Natural product bioactivities and synthesis
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Keywords
maslinic acid, ischemia-reperfusion injury, inflammation, NF-κB signaling, adhesion molecules, leukocyte transmigration, endothelial cells, pericytes, hypoxia, mitochondrial activity, E-selectin, ICAM-1, VCAM-1, reactive oxygen species, oxidative DNA damage, leukocyte rolling
MeSH terms
Animals, Cell Adhesion, Cell Line, Cell Movement, Disease Models, Animal, Female, Humans, Leukocytes, Male, Oleanolic Acid, Triterpenes, Signal Transduction, Reperfusion Injury, Down-Regulation, Cell Hypoxia, Cell Adhesion Molecules, Reactive Oxygen Species, Pericytes, Endothelial Cells, Mice, Transcription Factor RelA

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