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Published on: June 20, 2025
Curcumin Protects against Ischemic Stroke by Titrating Microglia/Macrophage Polarization
Zongjian Liu1,2, Yuanyuan Ran1,2, Shuo Huang1,2
1China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical UniversityBeijing, China.
Insights
Curcumin administration after ischemic stroke in mice reduced brain damage and improved sensorimotor function by shifting microglia to an anti-inflammatory M2 state. This suggests curcumin is a promising therapeutic for stroke recovery.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Stroke, particularly ischemic stroke, is a major cause of death and disability.
- Current therapeutic options for acute ischemic stroke are limited.
- Modulating microglial polarization from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotypes shows therapeutic potential for stroke.
Purpose of the Study:
- To investigate the effects of curcumin on microglial polarization and functional recovery after ischemic stroke.
- To determine if curcumin post-treatment can reduce brain damage and improve outcomes in a mouse model of ischemic stroke.
Main Methods:
- Mice underwent distal middle cerebral artery occlusion (dMCAO) to induce ischemic stroke.
- Curcumin was administered intraperitoneally immediately after ischemia and 24 hours later.
- Histological analysis, sensorimotor function tests, RT-PCR, and immunofluorescent staining were used to assess brain damage, function, and microglial polarization.
Main Results:
- Curcumin post-treatment significantly reduced cerebral ischemic damage and improved sensorimotor functions at multiple time points post-stroke.
- Curcumin increased M2 microglial/macrophage markers (e.g., CD206) and decreased M1 markers (e.g., CD16) in the brain.
- In vitro studies confirmed curcumin inhibited M1 polarization and reduced pro-inflammatory cytokine expression without affecting cell viability.
Conclusions:
- Curcumin effectively promotes M2 microglial polarization and inhibits M1-mediated inflammation.
- Curcumin post-treatment reduces brain damage and enhances functional recovery after ischemic stroke.
- Curcumin represents a potential therapeutic strategy for treating ischemic stroke.
Abstract:
Stroke is the most common type of cerebrovascular disease and is a leading cause of disability and death. Ischemic stroke accounts for approximately 80% of all strokes. The remaining 20% of strokes are hemorrhagic in nature. To date, therapeutic options for acute ischemic stroke are very limited. Recent research suggests that shifting microglial phenotype from the pro-inflammatory M1 state toward the anti-inflammatory and tissue-reparative M2 phenotype may be an effective therapeutic strategy for ischemic stroke. The dietary phytochemical curcumin has shown promise in experimental stroke models, but its effects on microglial polarization and long-term recovery after stroke are unknown. Here we address these gaps by subjecting mice to distal middle cerebral artery occlusion (dMCAO) and administering curcumin intraperitoneally (150 mg/kg) immediately after ischemia and 24 h later. Histological studies revealed that curcumin post-treatment significantly reduced cerebral ischemic damage 3 days after dMCAO. Sensorimotor functions-as measured by the adhesive removal test and modified Garcia scores-were superior in curcumin-treated mice at 3, 5, 7 and 10 days after stroke. RT-PCR measurements revealed an elevation of M2 microglia/macrophage phenotypic markers and a reduction in M1 markers in curcumin-treated brains 3 days after dMCAO. Immunofluorescent staining further showed that curcumin treatment significantly increased the number of CD206+Iba1+ M2 microglia/macrophages and reduced the number of CD16+Iba1+ M1 cells 10 days after stroke. In vitro studies using the BV2 microglial cell line confirmed that curcumin inhibited lipopolysaccharide (LPS) and interferon-γ (IFN-γ)-induced M1 polarization. Curcumin treatment concentration-dependently reduced the expression of pro-inflammatory cytokines, including TNF-α, IL-6 and IL-12p70, in the absence of any toxic effect on microglial cell survival. In conclusion, we demonstrate that curcumin has a profound regulatory effect on microglial responses, promoting M2 microglial polarization and inhibiting microglia-mediated pro-inflammatory responses. Curcumin post-treatment reduces ischemic stroke-induced brain damage and improves functional outcomes, providing new evidence that curcumin might be a promising therapeutic strategy for stroke.
