Frontiers in Behavioral Neuroscience (Oct 2021)

Puerarin Alleviates Vascular Cognitive Impairment in Vascular Dementia Rats

  • Tiantian Zhu,
  • Tiantian Zhu,
  • Tiantian Zhu,
  • Moli Zhu,
  • Moli Zhu,
  • Moli Zhu,
  • Yue Qiu,
  • Yue Qiu,
  • Yue Qiu,
  • Zeqing Wu,
  • Zeqing Wu,
  • Zeqing Wu,
  • Ning Huang,
  • Ning Huang,
  • Ning Huang,
  • Guangrui Wan,
  • Guangrui Wan,
  • Guangrui Wan,
  • Jian Xu,
  • Jian Xu,
  • Jian Xu,
  • Ping Song,
  • Ping Song,
  • Ping Song,
  • Shuangxi Wang,
  • Shuangxi Wang,
  • Shuangxi Wang,
  • Yaling Yin,
  • Yaling Yin,
  • Yaling Yin,
  • Peng Li,
  • Peng Li,
  • Peng Li

DOI
https://doi.org/10.3389/fnbeh.2021.717008
Journal volume & issue
Vol. 15

Abstract

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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.

Keywords