scholarly journals Cornel iridoid glycoside protected synaptic function by inhibiting tau hyperphosphorylation

2018 ◽  
Vol WCP2018 (0) ◽  
pp. PO1-1-63
Author(s):  
Lan Zhang
Keyword(s):  
Iridoid Glycoside ◽  
Synaptic Function ◽  
Tau Hyperphosphorylation ◽  
Cornel Iridoid Glycoside

scholarly journals Cornel Iridoid Glycoside Attenuates Tau Hyperphosphorylation by Inhibition of PP2A Demethylation

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Cui-cui Yang ◽  
Xue-xian Kuai ◽  
Ya-li Li ◽  
Li Zhang ◽  
Jian-chun Yu ◽  
...  
Keyword(s):  
Cultured Cells ◽  
Glycogen Synthase ◽  
Iridoid Glycoside ◽  
Tau Hyperphosphorylation ◽  
Human Neuroblastoma ◽  
Microtubular Cytoskeleton ◽  
Gf 109203X ◽  
Phosphatase 2A ◽  
Cornel Iridoid Glycoside ◽  
Underlying Mechanisms

Aim. The aim of the present study was to investigate the effect of cornel iridoid glycoside (CIG) on tau hyperphosphorylation induced by wortmannin (WT) and GF-109203X (GFX) and the underlying mechanisms.Methods. Human neuroblastoma SK-N-SH cells were preincubated with CIG (50, 100, and 200 µg/ml, resp.) for 24 h and then exposed to 10 µM WT and 10 µM GFX for 3 h after washing out CIG. Immunohistochemistry was used to observe the microtubular cytoskeleton of the cultured cells. Western blotting was used to measure the phosphorylation level of tau protein, glycogen synthase kinase 3β(GSK-3β), and protein phosphatase 2A (PP2A). The activity of PP2A was detected by a biochemical assay.Results. Preincubation of CIG significantly attenuated the WT/GFX-induced tau hyperphosphorylation at the sites of Thr205, Thr212, Ser214, Thr217, Ser396, and PHF-1 and improved the damage of morphology and microtubular cytoskeleton of the cells. CIG did not prevent the decrease in p-AKT-ser473 and p-GSK-3β-ser9 induced by WT/GFX. However, CIG significantly elevated the activity of PP2A by reducing the demethylation of PP2A catalytic subunit (PP2Ac) at Leu309 and the ratio of PME-1/LCMT in the WT/GFX-treated cells. The results suggest that CIG may be beneficial to the treatment of AD.

Cornel Iridoid Glycoside Suppresses Tau Hyperphosphorylation and Aggregation in a Mouse Model of Tauopathy through Increasing Activity of PP2A

2020 ◽  
Vol 16 (14) ◽  
pp. 1316-1331 ◽  
Author(s):  
Denglei Ma ◽  
Yi Luo ◽  
Rui Huang ◽  
Zirun Zhao ◽  
Qi Wang ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Chinese Herb ◽  
Iridoid Glycoside ◽  
Synaptic Proteins ◽  
Intragastric Administration ◽  
Tau Hyperphosphorylation ◽  
Phosphatase 2A ◽  
Cornel Iridoid Glycoside ◽  
The Brain

Background: rTg4510 mice are transgenic mice expressing P301L mutant tau and have been developed as an animal model of tauopathy including Alzheimer’s Disease (AD). Cornel Iridoid Glycoside (CIG) is an active ingredient extracted from Cornus officinalis, a traditional Chinese herb. The purpose of the present study was to investigate the effects of CIG on tau pathology and underlying mechanisms using rTg4510 mice. Methods: The cognitive functions were detected by Morris water maze and objective recognition tests. Western blotting and immunofluorescence were conducted to measure the levels of phosphorylated tau and related proteins. Serine/threonine phosphatase assay was applied to detect the activity of protein phosphatase 2A (PP2A). Results: Intragastric administration of CIG for 3 months improved learning and memory abilities, prevented neuronal and synapse loss, halted brain atrophy, elevated levels of synaptic proteins, protected cytoskeleton, reduced tau hyperphosphorylation and aggregation in the brain of rTg4510 mice. In the mechanism studies, CIG increased the activity of PP2A, elevated the methylation of PP2A catalytic C (PP2Ac) at leucine 309, decreased the phosphorylation of PP2Ac at tyrosine 307, and increased protein expression of leucine carboxyl methyltransferase 1 (LCMT-1), protein tyrosine phosphatase 1B (PTP1B), and protein phosphatase 2A phosphatase activator (PTPA) in the brain of rTg4510 mice. Conclusion: CIG might have the potential to treat tauopathy such as AD via activating PP2A.

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

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.

Cornel Iridoid Glycoside Inhibits Inflammation and Apoptosis in Brains of Rats with Focal Cerebral Ischemia

2010 ◽  
Vol 35 (5) ◽  
pp. 773-781 ◽  
Author(s):  
Bai-liu Ya ◽  
Chun-yang Li ◽  
Lan Zhang ◽  
Wen Wang ◽  
Lin Li
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Iridoid Glycoside ◽  
Cornel Iridoid Glycoside

scholarly journals Cornel Iridoid Glycoside Protects Against STAT1-Dependent Synapse and Memory Deficits by Increasing N-Methyl-D-aspartate Receptor Expression in a Tau Transgenic Mice

2021 ◽  
Vol 13 ◽  
Author(s):  
Denglei Ma ◽  
Rui Huang ◽  
Kaiwen Guo ◽  
Zirun Zhao ◽  
Weipeng Wei ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Chinese Herb ◽  
Microscopy Study ◽  
Iridoid Glycoside ◽  
Receptor Expression ◽  
Janus Kinase ◽  
Synaptic Dysfunction ◽  
Intragastric Administration ◽  
Tau Pathology ◽  
Cornel Iridoid Glycoside

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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