2. Academic Validation
  3. Danlou tablet attenuates ischemic stroke injury and blood‒brain barrier damage by inhibiting ferroptosis

Danlou tablet attenuates ischemic stroke injury and blood‒brain barrier damage by inhibiting ferroptosis

  • J Ethnopharmacol. 2023 Dec 23:322:117657. doi: 10.1016/j.jep.2023.117657.
Chang Liu 1,  Enran Liu 2,  Zhixi Li 3,  Wenqiang Li 4,  Jiaqi Jin 5,  Haijing Sui 6,  Guangmin Chen 7,  Zhenyu Sun 8,  Hongjie Xi 9
Affiliations

Affiliations

  • 1 Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150001, PR China; Heilongjiang Province Key Laboratory of Research on Anesthesiology and Critical Care Medicine, 246 Xuefu Road, Harbin, 150001, PR China; The Key Laboratory of Myocardial Ischemia, Ministry of Education, Heilongjiang Province, 246 Xuefu Road, Harbin, 150001, PR China. Electronic address: [email protected].
  • 2 Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150001, PR China; Heilongjiang Province Key Laboratory of Research on Anesthesiology and Critical Care Medicine, 246 Xuefu Road, Harbin, 150001, PR China. Electronic address: [email protected].
  • 3 Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150001, PR China; Heilongjiang Province Key Laboratory of Research on Anesthesiology and Critical Care Medicine, 246 Xuefu Road, Harbin, 150001, PR China; The Key Laboratory of Myocardial Ischemia, Ministry of Education, Heilongjiang Province, 246 Xuefu Road, Harbin, 150001, PR China. Electronic address: [email protected].
  • 4 Department of Vascular Surgery, Jinshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, PR China. Electronic address: [email protected].
  • 5 The Key Laboratory of Myocardial Ischemia, Ministry of Education, Heilongjiang Province, 246 Xuefu Road, Harbin, 150001, PR China; Department of Neurology, Xuanwu Hospital, Capital Medical University, 45 Changchun Road, Beijing, 100053, PR China. Electronic address: [email protected].
  • 6 Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150001, PR China; Heilongjiang Province Key Laboratory of Research on Anesthesiology and Critical Care Medicine, 246 Xuefu Road, Harbin, 150001, PR China. Electronic address: [email protected].
  • 7 Department of Anesthesiology, The First Affiliated Hospital of Harbin Medical University, 199 Dazhi Road, Harbin, 150001, PR China. Electronic address: [email protected].
  • 8 Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150001, PR China; Heilongjiang Province Key Laboratory of Research on Anesthesiology and Critical Care Medicine, 246 Xuefu Road, Harbin, 150001, PR China. Electronic address: [email protected].
  • 9 Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150001, PR China; Heilongjiang Province Key Laboratory of Research on Anesthesiology and Critical Care Medicine, 246 Xuefu Road, Harbin, 150001, PR China. Electronic address: [email protected].
PMID: 38145861 DOI: 10.1016/j.jep.2023.117657
Abstract

Ethnopharmacological relevance: Danlou tablet (DLT) is a traditional Chinese medicinal formulation known for replenishing Qi, promoting blood circulation, and resolving stasis. Its pharmacological actions primarily involve anti-inflammatory, antioxidant stress reduction, antiapoptotic, proangiogenic, and improved energy metabolism. DLT has been confirmed to have favorable therapeutic effects on ischemic stroke (IS). However, the underlying mechanism through which DLT affects IS-induced brain injury remains unknown.

Aim of the study: This study aims to investigate the effects and underlying mechanisms of danlou tablet on ischemic stroke based on network pharmacology and experimental verification.

Materials and methods: Using a transient middle cerebral artery occlusion (tMCAO) mouse model, the impact of DLT on the blood‒brain barrier (BBB) and brain injury in mice was assessed. Network pharmacology and bioinformatics analyses were utilized to explore the potential mechanisms of DLT in treating IS. Endothelial cells were cultured to observe the effects of DLT on vascular endothelial cells after oxygen-glucose deprivation/reperfusion, and these findings were validated in the brains of tMCAO mice.

Results: DLT alleviated oxidative stress and brain damage in tMCAO mice, mitigating BBB damage. A total of 185 potential targets through which DLT regulates IS were identified, including COX2, a known critical marker of Ferroptosis, which identified as a key target. In vitro and in vivo experiments demonstrated that DLT significantly (p < 0.05) improved cell death and vascular barrier damage in IS, reducing intracellular oxidative stress and COX2 protein levels while increasing SLC7A11 and GPX4 protein levels.

Conclusions: This study demonstrated that DLT maintained BBB integrity and alleviated brain injury of tMCAO mice by inhibiting Ferroptosis. The study partially unraveled the mechanism through which DLT functioned in treating IS and further clarified the pivotal active components of DLT, thereby providing a theoretical scientific basis for treating IS with DLT.

Keywords

Blood brain barrier; Danlou tablet; Ferroptosis; Ischemic stroke; Network pharmacology.

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