Puerarin Alleviates Vascular Cognitive Impairment in Vascular Dementia Rats

Abstract

Cerebral ischemia triggers vascular dementia (VD), which is characterized by memory loss, cognitive deficits, and vascular injury in the brain. Puerarin (Pur) represents the major isoflavone glycoside of Radix Puerariae, with verified neuroprotective activity and cardiovascular protective effects. However, whether Pur ameliorates cognitive impairment and vascular injury in rats with permanent occlusion of bilateral common carotid arteries (BCCAO) remains unknown. This work aimed to assess Pur’s effects on BCCAO-induced VD and to dissect the underlying mechanisms, especially examining the function of transient receptor potential melastatin-related 2 (TRPM2) in alleviating cognitive deficits and vascular injuries. Rats with BCCAO developed VD. Pur (50, 100, and 150 mg/kg) dose-dependently attenuated the pathological changes, increased synaptic structural plasticity in the dorsal CA1 hippocampal region and decreased oxidative stress, which eventually reduced cognitive impairment and vascular injury in BCCAO rats. Notably, Pur-improved neuronal cell loss, synaptic structural plasticity, and endothelial vasorelaxation function might be mediated by the reactive oxygen species (ROS)-dependent TRPM2/NMDAR pathway, evidenced by decreased levels of ROS, malondialdehyde (MDA), Bax, Bax/Bcl2, and TRPM2, and increased levels of superoxide dismutase (SOD), Bcl2, and NR2A. In conclusion, Pur has therapeutic potential for VD, alleviating neuronal cell apoptosis and vascular injury, which may be related to the ROS-dependent TRPM2/NMDAR pathway.

Effects of puerarin on chronic inflammation: Focus on the heart, brain, and arteries

“…In a vascular dementia rat model induced by permanent occlusion of bilateral common arteries, puerarin treatment substantially prevented neuronal loss, which was linked to a decrease in ROS stress and anti‐apoptosis, and importantly this treatment markedly improved cognitive decline. 65 In vitro study shows that an exposure of intracellular overloaded ROS neurons isolated from sporadic AD to puerarin markedly attenuated the apoptotic‐related caspase 3 activity, stress molecules p38, and JNK signaling, contributing to a decrease in neural damage. 82 Consequently, puerarin administration markedly enhanced the survival capability of the overloaded ROS neurons while diminished the number of apoptotic neurons.…”

Structural Plasticity of the Hippocampus in Neurodegenerative Diseases

“…In rat models of VD with bilateral common carotid artery occlusion (BCCAO), impaired basal synaptic transmission [ 225 ] and damaged synaptic ultrastructure [ 222 ] were observed. Most plasticity changes were alleviated with antioxidative therapies [ 65 , 225 ], supporting the strong correlation between hippocampal synaptic dysfunction and oxidative stress in VD [ 226 ]. FTD and ALS are discussed for their common pathogenic mechanisms that have different outcomes [ 227 ].…”

“…Total dendritic length, dendrite numbers, and dendrite crossings were significantly reduced in both CA1 and DG regions of rat models of VD with BCCAO [ 65 , 299 ]. Hippocampal dendritic branching and outgrowth were reduced in primary cultured rat hippocampal neurons with TDP-43 overexpression, as in an in vitro model of ALS/FTD [ 67 ].…”

“…In VD rats, densities of dendritic spines in both DG [ 65 , 300 ] and CA1 [ 301 , 302 ] regions of the hippocampus were decreased, largely due to the decrease in mushroom spines [ 65 , 301 , 305 ]. Moreover, expressions of spinophilin, a spine marker protein [ 301 ], and BDNF [ 302 ] were significantly lower in the CA1 region of VD rats.…”

“…Furthermore, hippocampal neurons readily respond to environmental cues by showing differential pattern changes in dendritic and spine morphology [ 61 ]. The hippocampus is one of the brain areas that shows neuronal remodeling under several neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), multiple sclerosis (MS), vascular dementia (VD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS) [ 62 , 63 , 64 , 65 , 66 , 67 ].…”