Proteomic analysis provides insights into the molecular regulatory mechanism of Dengzhan Shengmai capsule in a rat model of vascular dementia

Abstract

Abstract Dengzhan Shengmai (DZSM) capsule is a compound Chinese medicine that is widely used in the clinic for the treatment of ischemic cerebrovascular diseases along with symptoms of dementia and forgetfulness. DZSM can improve the cognitive function and quality of life of patients with vascular dementia (VD), but little is known about the therapeutic mechanisms. In this study, we found that DZSM rescued spatial memory impairment in VD rats. We next employed an isobaric tag for relative and absolute quantitation (iTRAQ)-based quantitative proteomic approach to uncover the specific proteins and biological pathways underlying the exacerbation of cognitive deficits observed in VD and to investigate the molecular mechanism of the effect of DZSM against VD. We discovered that the proteome was broadly changed in VD rat brains; among the 222 identified proteins with altered expression after VD modeling, 136 were upregulated and 86 were downregulated. Gene ontology and ingenuity pathway analysis indicated that the altered proteins in VD brains strongly interacts with the TCA cycle, 14-3-3-mediated signaling, actin cytoskeleton signaling, the synaptogenic signaling pathway, etc. These top-ranked canonical pathways, key regulators of glucose metabolism, synaptic plasticity and synaptogenesis, were predicted to be downregulated in VD. We also examined the proteomic profile of DZSM-treated VD rat brains and identified 23 potential DZSM-targeting proteins. Our results suggest that DZSM may function by regulating key modulators, such as RAP1A and H2AFX, which are involved in signaling pathways important for neuronal functions. Our study offers resources to characterize the biological functions of DZSM regulating proteins and may aid in the identification of the molecular mechanism by which DZSM can treat VD.