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  3. Beyond lipid management: Clofibrate's anti-neuroinflammation role via NF-κB inhibition in ischemic stroke

Beyond lipid management: Clofibrate's anti-neuroinflammation role via NF-κB inhibition in ischemic stroke

  • Neuroscience. 2025 Jun 21:577:144-153. doi: 10.1016/j.neuroscience.2025.05.009.
Jiaxin Sun 1,  Guolei Liao 2,  Ping Wang 3,  Jingyuan Zhang 4,  Hongling Jing 5,  Feng Lin 6,  Yuhang Wang 7,  Xinying Chen 8,  Lei Zhang 9,  Wenli Chen 10
Affiliations

Affiliations

  • 1 Department of Cerebrovascular Disease, Sun Yat-Sen University, The Fifth Affiliated Hospital, Zhuhai 519000 Guangdong, PR China. Electronic address: sunjx23@mail2.sysu.edu.cn.
  • 2 Department of Cerebrovascular Disease, Sun Yat-Sen University, The Fifth Affiliated Hospital, Zhuhai 519000 Guangdong, PR China. Electronic address: liaoglei@mail2.sysu.edu.cn.
  • 3 Department of Cerebrovascular Disease, Sun Yat-Sen University, The Fifth Affiliated Hospital, Zhuhai 519000 Guangdong, PR China. Electronic address: wangp_2014@163.com.
  • 4 Department of Cerebrovascular Disease, Sun Yat-Sen University, The Fifth Affiliated Hospital, Zhuhai 519000 Guangdong, PR China. Electronic address: zhangjy653@mail2.sysu.edu.cn.
  • 5 Department of Cerebrovascular Disease, Sun Yat-Sen University, The Fifth Affiliated Hospital, Zhuhai 519000 Guangdong, PR China. Electronic address: jinghling0@163.com.
  • 6 Department of Cerebrovascular Disease, Sun Yat-Sen University, The Fifth Affiliated Hospital, Zhuhai 519000 Guangdong, PR China. Electronic address: linf0909@163.com.
  • 7 School of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107 Guangdong, PR China. Electronic address: wangyh127166@163.com.
  • 8 School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107 Guangdong, PR China. Electronic address: chxiny@mail2.sysu.edu.cn.
  • 9 Department of Cerebrovascular Disease, Sun Yat-Sen University, The Fifth Affiliated Hospital, Zhuhai 519000 Guangdong, PR China. Electronic address: zhangl92@sysu.edu.cn.
  • 10 Department of Pharmacy, Sun Yat-Sen University, The Fifth Affiliated Hospital, Zhuhai 519000 Guangdong, PR China; Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000 Guangdong, PR China. Electronic address: chenwenl@mail3.sysu.edu.cn.
PMID: 40339898 DOI: 10.1016/j.neuroscience.2025.05.009
Abstract

Ischemic stroke(IS) is the second leading cause of mortality and disability worldwide and neuroimmunity plays an important role in its occurrence and development. The pathogenesis of IS is associated with various metabolic disorders. Yet reports on the amelioration of neuroinflammation by modulating metabolic disorders in clinical practice are scarce. By screening drugs targeting the inflammatory cytokine pro IL-1β in the metabolism-related compound library, we first found that clofibrate, an antihyperlipidemic drug, has an anti-neuroinflammatory effect. However, the role of clofibrate in exerting anti-inflammatory effects in IS and its underlying mechanisms remain unclear. To further investigate the role of clofibrate, we administered clofibrate in an LPS-stimulated microglial cell model and in mice with transient middle cerebral artery occlusion. Notably, clofibrate lowered IL-1β expression, both in vivo and in vitro. Simultaneously, clofibrate reduced infarct volume after ischemia and reperfusion. Moreover, clofibrate affected IS by regulating the expression of NF-κB p65 and NLRP3, thus suppressing the expression of inflammatory factors. These findings suggest that clofibrate could be a prospective medication to alleviate neuroinflammation in IS.

Keywords

Clofibrate; Inflammation; Ischemic stroke; Lipid metabolism; NF-κB/NLRP3 signaling pathway.

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