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

• 作者: Kefeng Zhai Hong Duan Wei Wang Siyu Zhao Ghulam Jilany Khan Mengting Wang Yuhan Zhang Kiran Thakur Xuemei Fang Chao Wu Jianbo Xiao Zhaojun Wei
• 来源期刊: 药学学报（英文版）
• 年，卷（期）: 2021,（11）
• 所属期刊栏目: Origimal articles
• 页码范围: 3493-3507
• 页数: 15页
• 语种: 英文

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 neuroinflamma-tion 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 downregu-late 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 pro-tected the BBB integrity.Conclusively,Rg1 can improve the cerebrovascular endothelial injury and hold the therapeutic potential against TBI disease.