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06:01
A Thrombotic Stroke Model Based On Transient Cerebral Hypoxia-ischemia
Published on: August 18, 2015
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Network-based drug repurposing for potential stroke therapy
Qihui Wu1,2,3, Cuilan Chen4, Weihua Liu2
1Clinical Research Center, Hainan Provincial Hospital of Traditional Chinese Medicine, Hainan Medical University, Haikou 571000, China.
Computational and Structural Biotechnology Journal
|May 19, 2023
Summary
Drug repurposing identified 185 potential stroke drug candidates using a network approach. Six drugs, including cinnarizine and phenelzine, showed anti-stroke effects by reducing inflammation markers like IL-6 and COX-2.
Area of Science:
- Neuroscience
- Pharmacology
- Computational Biology
Background:
- Stroke is a leading global cause of death and disability with limited therapeutic options.
- Drug repurposing offers a cost-effective and time-efficient strategy for identifying new stroke treatments.
- Existing therapies for stroke are insufficient, necessitating novel therapeutic approaches.
Purpose of the Study:
- To computationally identify potential drug candidates for stroke by repurposing approved drugs from the DrugBank database.
- To validate the efficacy of identified drug candidates through experimental testing.
- To elucidate the anti-stroke mechanisms of promising drug candidates.
Main Methods:
- Development of a drug-target network for approved drugs.
- Application of a network-based approach for drug repurposing to identify stroke candidates.
- Experimental validation of drug candidates using oxygen-glucose deprivation/reoxygenation (OGD/R) induced BV2 cell models.
- Mechanism of action studies using Western blot and Olink inflammation panels.
Main Results:
- Identified 185 potential drug candidates for stroke through computational repurposing.
- Validated 36.8% (68 out of 185) of candidates with existing literature supporting therapeutic effects on stroke.
- Six selected drugs, including cinnarizine and phenelzine, demonstrated significant anti-stroke activity in OGD/R induced BV2 cells.
- Cinnarizine and phenelzine were found to exert anti-stroke effects by inhibiting Interleukin-6 (IL-6) and Cyclooxygenase-2 (COX-2) expression.
Conclusions:
- The study presents an efficient network-based methodology for *in silico* identification of stroke drug candidates.
- Drug repurposing via network analysis is a viable strategy for discovering novel stroke therapeutics.
- Cinnarizine and phenelzine show promise as potential anti-stroke agents with specific anti-inflammatory mechanisms.
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