Xuefu zhuyu decoction improves cognitive impairment in experimental traumatic brain injury via synaptic regulation

Abstract

// Jing Zhou 1 , Tao Liu 1, 2 , Hanjin Cui 1 , Rong Fan 1 , Chunhu Zhang 1 , Weijun Peng 3 , Ali Yang 4 , Lin Zhu 1 , Yang Wang 1 and Tao Tang 1 1 Laboratory of Ethnopharmacology, Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, 410008 Changsha, China 2 Department of Gerontology, Traditional Chinese Medicine Hospital Affiliate to Xinjiang Medical University, 830000 Urumqi, China 3 Department of Traditional Chinese Medicine, 2nd Xiangya Hospital, Central South University, 410011 Changsha, China 4 Department of Neurology, Henan Province People’ Hospital, 450003 Zhengzhou, China Correspondence to: Yang Wang, email: wangyang_xy87@csu.edu.cn Tao Tang, email: falcontang@126.com Keywords: xuefu zhuyu decoction, traditional Chinese medicine, traumatic brain injury, cognitive impairment, synaptic regulation Received: February 24, 2017      Accepted: June 12, 2017      Published: June 30, 2017 ABSTRACT An overarching consequence of traumatic brain injury (TBI) is the cognitive impairment. It may hinder individual performance of daily tasks and determine people’s subjective well-being. The damage to synaptic plasticity, one of the key mechanisms of cognitive dysfunction, becomes the potential therapeutic strategy of TBI. In this study, we aimed to investigate whether Xuefu Zhuyu Decoction (XFZYD), a traditional Chinese medicine, provided a synaptic regulation to improve cognitive disorder following TBI. Morris water maze and modified neurological severity scores were performed to assess the neurological and cognitive abilities. The PubChem Compound IDs of the major compounds of XFZYD were submitted into BATMAN-TCM, an online bioinformatics analysis tool, to predict the druggable targets related to synaptic function. Furthermore, we validated the prediction through immunohistochemical, RT-PCR and western blot analyses. We found that XFZYD enhanced neuroprotection, simultaneously improved learning and memory performances in controlled cortical impact rats. Bioinformatics analysis revealed that the improvements of XFZYD implied the Long-term potentiation relative proteins including NMDAR1, CaMKII and GAP-43. The further confirmation of molecular biological studies confirmed that XFZYD upregulated the mRNA and protein levels of NMDAR1, CaMKII and GAP-43. Pharmacological synaptic regulation of XFZYD could provide a novel therapeutic strategy for cognitive impairment following TBI.