Shionone protects cerebral ischemic injury through alleviating microglia-mediated neuroinflammation.
10.1016/S1875-5364(25)60812-0
- Author:
Lushan XU
1
;
Chenggang LI
2
;
ChenChen ZHAO
3
;
Zibu WANG
3
;
Zhi ZHANG
3
;
Xin SHU
3
;
Xiang CAO
4
;
Shengnan XIA
5
;
Xinyu BAO
5
;
Pengfei SHAO
5
;
Yun XU
6
Author Information
1. Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing 210008, China.
2. School of Pharmacy, Faculty of Medicine, Macau University of Science and Technology, Macau 999078, China.
3. Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing 210008, China; Department of Neurology, Drum Tower Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing 210008, China.
4. Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing 210008, China; Jiangsu Provincial Key Discipline of Neurology, Nanjing 210008, China.
5. Department of Neurology, Drum Tower Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing 210008, China; Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing 210008, China.
6. Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing 210008, China; School of Pharmacy, Faculty of Medicine, Macau University of Science and Technology, Macau 999078, China; Department of Neurology, Drum Tower Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing 210008, China; Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing 210008, China; Jiangsu Provincial Key Discipline of Neurology, Nanjing 210008, China. Electronic address: xuyun20042001@aliyun.com.
- Publication Type:Journal Article
- Keywords:
AKT-mTOR-STAT3 Signaling Pathway;
Ischemic Stroke;
Microglial Activation;
Neuroinflammation;
Shionone
- MeSH:
Animals;
Microglia/immunology*;
Mice;
Male;
Mice, Inbred C57BL;
Brain Ischemia/immunology*;
Neuroinflammatory Diseases/drug therapy*;
Neuroprotective Agents/administration & dosage*;
Interleukin-1beta/genetics*;
STAT3 Transcription Factor/genetics*;
TOR Serine-Threonine Kinases/genetics*;
Tumor Necrosis Factor-alpha/genetics*;
Proto-Oncogene Proteins c-akt/immunology*;
Nitric Oxide Synthase Type II/genetics*;
Lipopolysaccharides
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(4):471-479
- CountryChina
- Language:English
-
Abstract:
Microglia, the resident immune cells in the central nervous system (CNS), rapidly transition from a resting to an active state in the acute phase of ischemic brain injury. This active state mediates a pro-inflammatory response that can exacerbate the injury. Targeting the pro-inflammatory response of microglia in the semi-dark band during this acute phase may effectively reduce brain injury. Shionone (SH), an active ingredient extracted from the dried roots and rhizomes of the genus Aster (Asteraceae), has been reported to regulate the inflammatory response of macrophages in sepsis-induced acute lung injury. However, its function in post-stroke neuroinflammation, particularly microglia-mediated neuroinflammation, remains uninvestigated. This study found that SH significantly inhibited lipopolysaccharide (LPS)-induced elevation of inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS), in microglia in vitro. Furthermore, the results demonstrated that SH alleviated infarct volume and improved behavioral performance in middle cerebral artery occlusion (MCAO) mice, which may be attributed to the inhibition of the microglial inflammatory response induced by SH treatment. Mechanistically, SH potently inhibited the phosphorylation of serine-threonine protein kinase B (AKT), mammalian target of rapamycin (mTOR), and signal transducer and activator of transcription 3 (STAT3). These findings suggest that SH may be a potential therapeutic agent for relieving ischemic stroke (IS) by alleviating microglia-associated neuroinflammation.
