期刊
TRANSLATIONAL STROKE RESEARCH
卷 12, 期 4, 页码 660-675出版社
SPRINGER
DOI: 10.1007/s12975-020-00842-9
关键词
Intracerebral hemorrhage; Wogonin; PPAR-gamma; Hematoma clearance; Anti-inflammation; Anti-oxidative stress
资金
- National Natural Science Foundation of China [81571106, 81771246, 81971099, 81870908, 81801144, 81870910]
- National Key R&D Program of China [2018YFC1312600, 2018YFC1312603]
- Key Research and Development Project of Zhejiang Province [2018C03011]
- Natural Science Foundation of Zhejiang Province [LQ20H090015]
- Innovative Talents Plan of Zhejiang Province [2020380752]
- Scientific Research Fund of Zhejiang Provincial Education Department [Y201941838]
- andMedical and Health Scientific Research Project of Zhejiang Province [2018KY408]
Wogonin enhances phagocytosis, reduces inflammation, and oxidative stress, facilitating hematoma clearance and improving neurobehavioral recovery after ICH.
Intracerebral hemorrhage (ICH) is a cerebrovascular disease with high mortality and morbidity for which effective treatments are currently lacking. Wogonin is a major flavonoid compound isolated fromScutellaria radix. Accumulating evidence suggests that wogonin plays a crucial role in anti-inflammatory and anti-oxidative stress. Treatment of microglia with nuclear receptor agonists augments the expression of phagocytosis-related genes. However, the neuroprotective effects of wogonin in ICH remain obscure. In this study, we elucidated an innovative mechanism by which wogonin acts to enhance phagocytosis in a murine model of ICH. Wogonin promoted hematoma clearance and improved neurological recovery after ICH by upregulating the expression of Axl, MerTK, CD36, and LAMP2 in perihematomal microglia and BV2 cells. Treatment of a murine model of ICH with wogonin stimulated microglial phagocytosis in vitro. Further, we demonstrated that wogonin dramatically attenuated inflammatory and oxidative stress responses in a murine model of ICH by reducing the expression of pro-inflammatory cytokines and pro-oxidant enzymes such as TNF-alpha, IL-1 beta, and inducible nitric oxide synthase (iNOS) after ICH. The effects of wogonin were abolished by administration of the PPAR-gamma inhibitor GW9662. In conclusion, our data suggest that wogonin facilitates hematoma clearance and neurobehavioral recovery by targeting PPAR-gamma.
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