Frontiers in Neuroscience (Dec 2022)

Isorhynchophylline ameliorates stress-induced emotional disorder and cognitive impairment with modulation of NMDA receptors

  • Chen Wang,
  • Ming-Hao Zhu,
  • Na Sun,
  • Wei Shen,
  • Ning Jiang,
  • Qin-Shi Zhao,
  • Yong-Xiang Zhang,
  • Yan Huang,
  • Wen-Xia Zhou

DOI
https://doi.org/10.3389/fnins.2022.1071068
Journal volume & issue
Vol. 16

Abstract

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IntroductionIsorhynchophylline is one of the main active ingredients from Uncaria rhynchophylla, the effects and mechanisms of isorhynchophylline on stress-induced emotional disorders and cognitive impairment remain unclear.MethodsLong-term potentiation (LTP) in vivo was used for synaptic plasticity evaluation; chronic unpredictable mild stress (CUMS) model was used to evaluate the effect of isorhynchophylline on stress induced emotional disorders and cognitive impairment; sucrose preference test (SPT), open field test (OFT), and elevated plus maze (EPM) were used to evaluate emotional disorders; morris water maze (MWM) test was used to evaluate cognitive impairment; Western blotting (WB) was used to the expression of proteins; high performance liquid chromatography (HPLC) was used to quantify neurotransmitters; Nissl staining was used to identify pathological changes induced by stress.ResultsIn this study, we found that isorhynchophylline improved corticosterone-induced in vivo LTP impairment significantly, indicating positive effects on stress. Therefore, 28-day CUMS model was adopted to evaluate the anti-stress effects of isorhynchophylline. The results showed that isorhynchophylline improved CUMS-induced weight loss, anxiety- and depression-like behaviors, and spatial memory impairment. Isorhynchophylline reduced CUMS-induced corticosterone elevation. N-methyl-D-aspartic acid (NMDA) receptors play an important role in the process of emotion and memory. Glutamate and the expression of GluN2B increased in the CUMS mice, while D-serine and the expression of serine racemase (SR) decreased significantly, and isorhynchophylline restored these changes to normal level.ConclusionThese results indicated that isorhynchophylline ameliorated stress-induced emotional disorders and cognitive impairment, modulating NMDA receptors might be one of the underlying mechanisms.

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