Excel · study · 2026
Obacunone alleviates ischemia-induced blood-brain barrier disruption and brain injury via targeting MIF signaling
Listed in NCBI GEO
Blood-brain barrier (BBB) breakdown is one of the hallmarks of stroke pathology, which is characterized by the death of brain capillary endothelial cells and the disassembly of intercellular tight junction.
Description
Damaged BBB is associated with poor stroke prognosis, and few treatment of BBB breakdown is applicable. Obacunone (Oba) is a highly oxygenated triterpenoid with known pharmacological activities on mitigating colonic epithelial cell injury, however whether Oba could be effective to endothelial cell integrity remains unknown.
In the present study, with the use of transient middle cerebral artery occlusion (tMCAO) mice model, we found that gavage Oba significantly alleviated tMCAO-induced BBB leakage, brain injury and neurological deficit. In the oxygen-glucose deprivation (OGD) model of mice brain microvascular endothelial cells (MBMECs), synergistic application of Oba and ISO-1 revealed the protective effect of Oba against MBMECs monolayer leakage via inhibiting MBMECs-derived macrophage migration inhibitory factor (MIF).
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In mechanism, with the use of bulk RNA sequencing and a battery of molecular approaches, we found that inhibition of MIF by Oba attenuated the activation of pro-apoptotic signals, including P38 and RIPK1, and promoted the distribution of tight junction ZO-1 onto MBMECs membrane, which was accompanied with the upregulation of intracellular LCN2. In consistent, pharmacological inhibition of LCN2 by ZINC00640089 protected against OGD-induced MBMECs death and monolayer leakage.
These results collectively conclude that Oba alleviates ischemia-induced BBB breakdown and brain injury via, at least partially, inhibiting MIF-mediated endothelial cell death and intercellular junction loss. Oba may represent a therapeutic candidate for neurological disorders caused by cerebral stroke.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE317nnn/GSE317846 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE317846 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1415670 ncbi.nlm.nih.gov/bioproject/PRJNA1415670 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- RNA sequencing 75% · Sequencing 75%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE317846 | 15 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |