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Obacunone Inhibits Microglia-Mediated Neuroinflammation and Ischemic Injury by Targeting Mitogen-Activated Protein
Jing Huang1,2, Zuobin Hu1,2, Jie Zhang1,2
1Department of Neurology, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, People's Republic of China.
Journal of Inflammation Research
|March 9, 2026
Summary
Obacunone (OB) shows neuroprotective effects against ischemic stroke by inhibiting inflammation and brain injury. It directly binds to MAPK1, suggesting its potential as a therapeutic agent for stroke.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Ischemic stroke is a leading cause of death and disability worldwide.
- Neuroinflammation plays a critical role in the pathogenesis of ischemic stroke.
- Obacunone (OB) is known for its anti-inflammatory and antioxidant properties.
Purpose of the Study:
- To investigate the neuroprotective effects of Obacunone (OB) in an ischemic stroke model.
- To elucidate the underlying mechanisms of OB's neuroprotection, focusing on the MAPK/NF-κB pathway and MAPK1 interaction.
Main Methods:
- In vitro studies using primary microglia stimulated with lipopolysaccharide (LPS) and treated with OB.
- In vivo studies using a middle cerebral artery occlusion (MCAO) mouse model treated with OB.
- Assessment of inflammatory cytokines, signaling pathway activation (MAPK/NF-κB), infarct size, blood-brain barrier permeability, and neurological function.
- Network pharmacology, molecular docking, surface plasmon resonance (SPR), CETSA, and DARTS to identify and validate OB's molecular target.
Main Results:
- OB significantly reduced microglia-mediated inflammatory cytokine production in vitro and in vivo.
- OB attenuated ischemic brain injury and improved memory function in MCAO mice.
- OB directly bound to MAPK1, with ARG-146 identified as a critical binding site, inhibiting the MAPK/NF-κB pathway.
Conclusions:
- Obacunone (OB) exerts neuroprotective effects against ischemic stroke by targeting MAPK1.
- OB alleviates neuroinflammation and ischemic brain injury, highlighting its potential as a therapeutic agent for ischemic stroke.

