Effects of schisandrin B on hypoxia-related cognitive function and protein expression in vascular dementia rats

• Published in: Journal of Toxicology and Environmental Health, Part A Part A, 2024-05, Vol.87 (10), p.421-427
• Main Authors: He, Jing-Bo, Zhang, He, Zheng, Hong-Xia, Jia, Jian-Xin, Zhang, Yi-Chi, Yan, Xu-Sheng, Li, Xiao-Xu, Wei, Kai-Wen, Mao, Jun, Chen, Hong, Li, Jing, Wang, He, Zhang, Ming, Zhao, Zhi-Ying
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Animals; bilateral common carotid artery occlusion (BCAO) dementia model; Blood flow; Brain; Carotid arteries; Carotid artery; Cell death; Cerebral blood flow; Cerebrovascular diseases; Cognition; Cognitive ability; Cyclooctanes; Dementia; Dementia disorders; Dementia, Vascular - drug therapy; Dementia, Vascular - etiology; Dementia, Vascular - metabolism; Hippocampus; Humans; Hypoxia; Hypoxia-inducible factor 1; Hypoxia-inducible factor 1a; hypoxia-upregulated mitochondrial movement regulator (HUMMR) protein; Ischemia; Kinesin; Lignans; Maze Learning - physiology; Morris water maze; Neuroblastoma; Neurodegenerative diseases; Occlusion; Oxygen; Oxygen - pharmacology; Perfusion; Polycyclic Compounds; Protein expression; Protein transport; Proteins; Rats; Regulatory mechanisms (biology); Risk factors; Schisandrin B; Sexually transmitted diseases; STD; trafficking protein kinesin 2 (TRAK2); Vascular dementia; β-Amyloid
• ISSN: 1528-7394; 1087-2620; 2381-3504
• DOI: 10.1080/15287394.2024.2334247

Vascular dementia (VD) a heterogenous group of brain disorders in which cognitive impairment is attributable to vascular risk factors and cerebrovascular disease. A common phenomenon in VD is a dysfunctional cerebral regulatory mechanism associated with insufficient cerebral blood flow, ischemia and hypoxia. Under hypoxic conditions oxygen supply to the brain results in neuronal death leading to neurodegenerative diseases including Alzheimer's (AD) and VD. In conditions of hypoxia and low oxygen perfusion, expression of hypoxia-inducible factor 1 alpha (HIF-1α) increases under conditions of low oxygen and low perfusion associated with upregulation of expression of hypoxia-upregulated mitochondrial movement regulator (HUMMR), which promotes anterograde mitochondrial transport by binding with trafficking protein kinesin 2 (TRAK2). Schisandrin B (Sch B) an active component derived from Chinese herb Wuweizi prevented β-amyloid protein induced morphological alterations and cell death using a SH-SY5Y neuronal cells considered an AD model. It was thus of interest to determine whether Sch B might also alleviate VD using a rat bilateral common carotid artery occlusion (BCAO) dementia model. The aim of this study was to examine the effects of Sch B in BCAO on cognitive functions such as Morris water maze test and underlying mechanisms involving expression of HIF-1α, TRAK2, and HUMMR levels. The results showed that Sch B improved learning and memory function of rats with VD and exerted a protective effect on the hippocampus by inhibition of protein expression of HIF-1α, TRAK2, and HUMMR factors. Evidence indicates that Sch B may be considered as an alternative in VD treatment.