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Front. Pharmacol. | doi: 10.3389/fphar.2018.00250

Transcriptomic study reveals recovery of impaired astrocytes contribute to neuroprotective effects of Danhong Injection against cerebral ischemia/reperfusion-induced injury

 Jing Qian1, Xiaoping Zhao2*,  Weiting Wang3,  Shujing Zhang1,  Zhuping Hong1, Xiaoling Chen2, Chunhua Hao3, Zhuanyou Zhao3 and  Yi Wang1*
  • 1College of Pharmaceutical Sciences, Zhejiang University, China
  • 2Zhejiang Chinese Medical University, China
  • 3Tianjin Pharmaceutical Research Institute Pharmaceutical Co., Ltd., China

Danhong Injection (DHI) is widely used in clinic for treating cardiovascular and cerebrovascular diseases in China. However, the mode of action of DHI for neuroprotection remains unclear. In the present study, we deemed to investigate the effects of DHI on a rat model of cerebral ischemia/reperfusion injury (IRI) with an emphasis on its regulated gene profile obtained from microarray assays. Firstly, we showed that a 14-day DHI treatment effectively ameliorated severity of neurological deficits, reduced size of ischemic damage, improved status of oxidation stress as well as systemic inflammation for IRI rats, along with which was a pronounced reduced cell infiltration in the area of periaqueductal gray matter. Secondly, bioinformatic analyses for the 429 differentially expressed genes (DEGs) regulated by DHI treatment pointed out ECM-receptor interaction, neuroactive ligand-receptor interaction, and endocytosis as the top 3 biological processes, whilst Toll like recptor 4 (TLR4) as the most relavant singalling molecule. Lastly, we provided evidences showing that DHI might directly protect primary astrocytes from oxygen and glucose deprivation/re-oxygenation (OGD/Re) injury, the effects of which was associated with LAMC2 and ADRB3, two DEGs related to the top 3 biological processes according to transcriptomic analysis. In conlusion, we reported that DHI might work through maintaining the integrity for brain blood barrier (BBB) and to regulate TLR4 related signaling pathway to diminish the inflammation, therefore effectively improved the outcomes of IRI. Our findings suggested that the attenuated astrocytic dysfunction could be a novel mechanism contributing to the neuroprotective effects of DHI against cerebral ischemia/reperfusion-induced damage.

Keywords: cerebral ischemic/reperfusion injury, Danhong injection, Microarray, astrocyte, Inflammation, brain-blood barrier

Received: 16 Jan 2018; Accepted: 06 Mar 2018.

Edited by:

Anna Rita Bilia, Università degli Studi di Firenze, Italy

Reviewed by:

Jianxin Chen, Beijing University of Chinese Medicine, China
Songxiao Xu, Artron BioResearch Inc., Canada  

Copyright: © 2018 Qian, Zhao, Wang, Zhang, Hong, Chen, Hao, Zhao and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Xiaoping Zhao, Zhejiang Chinese Medical University, Hangzhou, China,
Prof. Yi Wang, Zhejiang University, College of Pharmaceutical Sciences, Yuhangtang Road 866, Hangzhou, 310058, Zhejiang, China,