Cornel iridoid glycoside inhibits tau pathology via regulating cross-talk between GSK-3beta and PP2A signaling

P301S transgenic mice are an animal model of tauopathy and Alzheimer’s disease (AD), exhibiting tau pathology and synaptic dysfunction. Cornel iridoid glycoside (CIG) is an active ingredient extracted from Cornus officinalis, a traditional Chinese herb. In the present study, the purpose was to investigate the effects and mechanisms of CIG on tau pathology and synaptic dysfunction using P301S transgenic mice. The results showed that intragastric administration of CIG for 3.5 months improved cognitive impairments and the survival rate of P301S mice. Electrophysiological recordings and transmission electron microscopy study showed that CIG improved synaptic plasticity and increased the ultrastructure and number of synapse. Moreover, CIG increased the expression levels of N-methyl-D-aspartate receptors (NMDAR) subunits GluN1, GluN2A, and GluN2B, and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit GluA1. We inferred that the major mechanism of CIG involving in the regulation of synaptic dysfunctions was inhibiting the activation of Janus kinase-2 (JAK2)/signal transducer and activator of transcription 1 (STAT1) signaling pathway and alleviating STAT1-induced suppression of NMDAR expressions. Based on our findings, we thought CIG might be a promising candidate for the therapy of tauopathy such as AD.

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Cornel Iridoid Glycoside Inhibits Tau Hyperphosphorylation via Regulating Cross-Talk Between GSK-3β and PP2A Signaling

Frontiers in Pharmacology ◽

10.3389/fphar.2018.00682 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 10

Author(s):

Cuicui Yang ◽

Xuelian Li ◽

Wenbin Gao ◽

Qi Wang ◽

Li Zhang ◽

...

Keyword(s):

Cross Talk ◽

Iridoid Glycoside ◽

Tau Hyperphosphorylation ◽

Cornel Iridoid Glycoside ◽

Gsk 3Β

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IC-P-169: Effects of cornel iridoid glycoside on CNS microenvironment related to neurogenesis in Alzheimer-like rat model induced by fimbria-fornix transaction

Alzheimer s & Dementia ◽

10.1016/j.jalz.2009.05.142 ◽

2009 ◽

Vol 5 (4S_Part_2) ◽

pp. P66-P66

Author(s):

Lin Li ◽

Yue-xia Ding ◽

Lan Zhang

Keyword(s):

Rat Model ◽

Iridoid Glycoside ◽

Cornel Iridoid Glycoside

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Cornel Iridoid Glycoside Improves Locomotor Impairment and Decreases Spinal Cord Damage in Rats

BioMed Research International ◽

10.1155/2016/6725381 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12

Author(s):

Wen-jing Tang ◽

Deng-lei Ma ◽

Cui-cui Yang ◽

Li Zhang ◽

Ya-li Li ◽

...

Keyword(s):

Spinal Cord ◽

Rating Scale ◽

Iridoid Glycoside ◽

Neurotrophin Receptor ◽

Intragastric Administration ◽

P75 Neurotrophin Receptor ◽

Lesion Site ◽

Cord Injury ◽

Locomotor Impairment ◽

Cornel Iridoid Glycoside

Purpose. This study was to investigate the effects of cornel iridoid glycoside (CIG) on spinal cord injury (SCI) in rats. Methods. The thoracic cord (at T9) of rats was injured by clip compression for 30 sec. Locomotor function was assessed using the Basso, Beattie, and Bresnahan (BBB) rating scale. Neuroanatomic stereological parameters as well as Nogo-A, p75 neurotrophin receptor (p75NTR), and ROCKII expression were measured by histological processing, immunohistochemistry, and stereological analyses. The axons passing through the lesion site were detected by BDA tracing. Results. Intragastric administration of CIG (60 and 180 mg/kg) improved the locomotor impairment at 10, 17, 24, and 31 days post-injury (dpi) compared with untreated SCI model rats. CIG treatment decreased the volume of the lesion epicenter (LEp) and increased the volume of spared tissue and the number of surviving neurons in the injured spinal cord at 31 dpi. CIG promoted the growth of BDA-positive axons and their passage through the lesion site and decreased the expression of Nogo-A, p75NTR, and ROCKII both in and around the LEp. Conclusion. CIG improved the locomotor impairment, decreased tissue damage, and downregulated the myelin-associated inhibition signaling pathway in SCI rats. The results suggest that CIG may be beneficial for SCI therapy.

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