Ginsenoside Rg1 ameliorates blood–brain barrier disruption and traumatic brain injury via attenuating macrophages derived exosomes miR-21 release

Acta Pharmaceutica Sinica B

Siyu Zhao¹  Wei Wang²  Mengting Wang³  Kiran Thakur⁴  Jianbo Xiao⁵  Kefeng Zhai⁶  Zhaojun Wei⁶  Hong Duan⁶  Chao Wu⁶  Ghulam Jilany Khan⁶  Yuhan Zhang⁶  Xuemei Fang⁶ 

[1] Corresponding authors. Tel./fax: [phone].;Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Guangxi Normal University), Guilin 541004, China;School of Biological and Food Engineering, Anhui Polytechnic University, Wuhu 241000, China;Department of Pharmacology and Therapeutics, Faculty of Pharmacy, University of Central Punjab, Lahore 54000, Pakistan;School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China;Suzhou Engineering Research Center of Natural Medicine and Functional Food, School of Biological and Food Engineering, Suzhou University, Suzhou 234000, China;

关键词: Traumatic brain injury;    Exosome;    MiRNA-21;    Blood–brain barrier;    Ginsenoside Rg1;    Nonmuscle myosin IIA;   

DOI  :  

来源: DOAJ

【 摘 要 】

During the traumatic brain injury (TBI), improved expression of circulatory miR-21 serves as a diagnostic feature. Low levels of exosome-miR-21 in the brain can effectively improve neuroinflammation and blood–brain barrier (BBB) permeability, reduce nerve apoptosis, restore neural function and ameliorate TBI. We evaluated the role of macrophage derived exosomes-miR-21 (M-Exos-miR-21) in disrupting BBB, deteriorating TBI, and Rg1 interventions. IL-1β-induced macrophages (IIM)-Exos-miR-21 can activate NF-κB signaling pathway and induce the expressions of MMP-1, -3 and -9 and downregulate the levels of tight junction proteins (TJPs) deteriorating the BBB. Rg1 reduced miR-21-5p content in IIM-Exos (RIIM-Exos). The interaction of NMIIA–HSP90 controlled the release of Exos-miR-21, this interaction was restricted by Rg1. Rg1 could inhibit the Exos-miR-21 release in peripheral blood flow to brain, enhancing TIMP3 protein expression, MMPs proteolysis, and restricting TJPs degradation thus protected the BBB integrity. Conclusively, Rg1 can improve the cerebrovascular endothelial injury and hold the therapeutic potential against TBI disease.

【 授权许可】

Unknown