Astragaloside Ⅳ suppresses post-ischemic natural killer cell infiltration and activation in the brain:involvement of histone deacetylase inhibition

作     者：Baokai Dou Shichun Li Luyao Wei Lixin Wang Shiguo Zhu Zhengtao Wang Zunji Ke Kaixian Chen Zhifei Wang Baokai Dou;Shichun Li;Luyao Wei;Lixin Wang;Shiguo Zhu;Zhengtao Wang;Zunji Ke;Kaixian Chen;Zhifei Wang

作者机构：School of Basic Medical SciencesShanghai University of Traditional Chinese MedicineShanghai 201203China Institute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai 201203China Academy of Integrative MedicineShanghai University of Traditional Chinese MedicineShanghai 201203China 

出 版 物：《Frontiers of Medicine》 (医学前沿（英文版）)

年 卷 期：2021年第15卷第1期

页      面：79-90页

核心收录：

学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(Nos.81503055 and 81873029) Shanghai Youth Eastern Scholar(No.QD2015037) 

主　　题：astragalosideⅣ brain ischemia natural killer cells histone deacetylase nuclear factor-κB 

摘      要：Natural killer(NK)cells,a type of cytotoxic lymphocytes,can infiltrate into ischemic brain and exacerbate neuronal cell *** Ⅳ(ASIV)is the major bioactive ingredient of Astragalus membranaceus,a Chinese herbal medicine,and possesses potent immunomodulatory and neuroprotective *** study investigated the effects of ASIV on post-ischemic brain infiltration and activation of NK *** reduced brain infarction and alleviated functional deficits in MCAO rats,and these beneficial effects persisted for at least 7 *** NK cells infiltrated into the ischemic hemisphere on day 1 after brain ischemia,and this infiltration was suppressed by ***,ASIV reversed NK cell deficiency in the spleen and blood after brain *** inhibited astrocyte-derived CCL2 upregulation and reduced CCR2+NK cell levels in the ischemic ***,ASIV attenuated NK cell activating receptor NKG2D levels and reduced interferon-γ*** restored acetylation of histone H3 and the p65 subunit of nuclear factor-κB in the ischemic brain,suggesting inhibition of histone deacetylase(HDAC).Simultaneously,ASIV prevented p65 nuclear *** effects of ASIV on reducing CCL2 production,restoring acetylated p65 levels and preventing p65 nuclear translocation were mimicked by valproate,an HDAC inhibitor,in astrocytes subjected to oxygen-glucose *** findings suggest that ASIV inhibits post-ischemic NK cell brain infiltration and activation and reverses NK cell deficiency in the periphery,which together contribute to the beneficial effects of ASIV against brain ***,ASIV’s effects on suppressing NK cell brain infiltration and activation may involve HDAC inhibition.