Neural Regeneration Research ›› 2019, Vol. 14 ›› Issue (3): 470-479.doi: 10.4103/1673-5374.245471

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Xiao-Xu-Ming decoction extract regulates differentially expressed proteins in the hippocampus after chronic cerebral hypoperfusion

Yue-Hua Wang 1, 2 , Ying-Lin Yang 2 , Xiao Cheng 2 , Jun Zhang 2 , Wan Li 1, 2 , Guan-Hua Du 1, 2   

  1. 1 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China 2 Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
  • Online:2019-03-15 Published:2019-03-15
  • Contact: Yue-Hua Wang, PhD, wangyuehua@pku.org.cn; Guan-Hua Du, PhD, dugh@imm.ac.cn.
  • Supported by:

    This study was supported in part by the National Natural Science Foundation of China, No. 81473383 (to YHW); the Significant New-Drugs Creation of Science and Technology Major Projects in China, No. 2018ZX09711001-003-019 (to YHW); the Innovation Fund for Graduate of Beijing Union Medical College of China, No. 2017-1007-02 (to XC).

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Abstract:

Xiao-Xu-Ming decoction has been widely used to treat stroke and sequelae of stroke. We have previously shown that the active fractions of Xiao-Xu-Ming decoction attenuate cerebral ischemic injury. However, the global protein profile and signaling conduction pathways reg­ulated by Xiao-Xu-Ming decoction are still unclear. This study established a two-vessel occlusion rat model by bilateral common carotid artery occlusion. Rats were intragastrically administered 50 or 150 mg/kg Xiao-Xu-Ming decoction for 4 consecutive weeks. Learning and memory abilities were measured with Morris water maze. Motor ability was detected with prehensile test. Coordination ability was exam­ined using the inclined screen test. Neuronal plasticity was observed by immunofluorescent staining. Differentially expressed proteins of rat hippocampus were analyzed by label-free quantitative proteomics. Real time-polymerase chain reaction and western blot assay were used to identify the changes in proteins. Results showed that Xiao-Xu-Ming decoction dramatically alleviated learning and memory deficits, and motor and coordination dysfunction, and increased the expression of microtubule-associated protein 2. Xiao-Xu-Ming decoction extract remarkably decreased 13 upregulated proteins and increased 39 downregulated proteins. The regulated proteins were mainly involved in oxidation reduction process, intracellular signaling cascade process, and protein catabolic process. The signaling pathways were mainly involved in ubiquitin mediated proteolysis and the phosphatidylinositol signaling system. Furthermore, there was an interaction among Rab2a, Ptpn1, Ppm1e, Cdk18, Gorasp2, Eps15, Capza2, Syngap1 and Mt-nd1. Protein analyses confirmed the changes in expression of MT-ND1. The current findings provide new insights into the molecular mechanisms of Xiao-Xu-Ming decoction extract’s effects on chronic cerebral hypoperfusion.

Key words: nerve regeneration, chronic cerebral hypoperfusion, vascular dementia, bilateral common carotid artery occlusion, Xiao-Xu-Ming decoction, label-free quantitative proteomics, Morris water maze test, Nano-LC-ESI LTQ-Orbitrap MS/MS technology, neural regeneration