Gastrodin Alleviates Vascular Dementia in a 2-VO-Vascular Dementia Rat Model by Altering Amyloid and Tau Levels

Shi, Rui; Zheng, Chang‐Bo; Wang, Hongyan; Rao, Qiang; Du, Tingyan; Bai, Chun-Yun; Xiao, Chuang; Dai, Zelan; Zhang, Changhong; Chen, Chen; Li, Xian; Tian, Minglei; Yu, Xin; Ji, Bai-xi; Weng, Zhiying; Ye, Weimin

doi:10.1159/000504056

Cited by 32 publications

(29 citation statements)

References 39 publications

(47 reference statements)

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“…GAS alleviated memory dysfunction, inflammation and Aβ accumulation in the mouse models of AD [ 41 ]. GAS attenuated vascular dementia in a rat model by moderating the expressions of Aβ and p-tau in the brain [ 42 , 43 ]. It is worth noting that GAS treatment reduced the generation of Aβ and p-tau in the brain of mice compared with the Pb group ( Figure 7 ).…”

Section: Discussionmentioning

confidence: 99%

Effects of Gastrodin against Lead-Induced Brain Injury in Mice Associated with the Wnt/Nrf2 Pathway

et al. 2020

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Gastrodin (GAS), the main phenolic glycoside extracted from Gastrodia elata Blume, exhibited potential neuroprotective properties. Here we examined the protective effects of GAS against lead(Pb)-induced nerve injury in mice, and explores its underlying mechanisms. Our research findings revealed that GAS improved behavioral deficits in Pb-exposed mice. GAS reduced the accumulation of p-tau and amyloid-beta (Aβ). GAS inhibited Pb-induced inflammation in the brain, as indicated by the decreased levels of pro-inflammatory cytokines, including tumor necrosis factor-a (TNF-α), cyclooxygenase-2 (COX-2). GAS increased the expression levels of NR2A and neurotrophin brain-derived neurotrophic factor (BDNF). GAS inhibited Pb-induced apoptosis of neurons in hippocampus tissue, as indicated by the decreased levels of pro-apoptotic proteins Bax and cleaved caspase-3. Furthermore, the neuroprotective effects of GAS were associated with inhibiting oxidative stress by modulating nuclear factor-erythroid 2-related factor 2 (Nrf2)-mediated antioxidant signaling. GAS supplement activated the Wnt/β-catenin signaling pathway and reduced the expression of Wnt inhibitor Dickkopf-1 (Dkk-1). Collectively, this study clarified that GAS exhibited neuroprotective property by anti-oxidant, anti-inflammatory and anti-apoptosis effects and its ability to regulate the Wnt/Nrf2 pathway.

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Section: Discussionmentioning

confidence: 99%

Effects of Gastrodin against Lead-Induced Brain Injury in Mice Associated with the Wnt/Nrf2 Pathway

et al. 2020

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“…Furthermore, CIG was reported to inhibit microglia activation through suppression of the JAK/STAT signaling pathway in vitro and in an experimental autoimmune encephalomyelitis animal model ( Yin et al, 2014 ; Qu et al, 2019 ). Tau pathology was reported to be involved in several central nervous system (CNS) diseases, including AD, vascular dementia, traumatic brain injury, and multiple sclerosis ( Hu et al, 2018 ; Chidambaram et al, 2020 ; Mirzaii-Dizgah et al, 2020 ; Shi et al, 2020 ). We inferred that the inhibition of tau accumulation and JAK2/STAT1 pathway activation might underlie the common mechanism of CIG’s pharmacological effects on NMDAR expression and synaptic dysfunction in CNS disorders.…”

Section: Discussionmentioning

confidence: 99%

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

Huang

Guo

et al. 2021

Front. Aging Neurosci.

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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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“…The BCCAO model in rats was established as previously reported 35 . Rats were randomly divided into the following groups: sham (n = 11), BCCAO (n = 8) and BCCAO + donepezil (1 mg/kg, n = 9), respectively.…”

Section: Methodsmentioning

confidence: 99%

Donepezil down‐regulates propionylation, 2‐hydroxyisobutyrylation, butyrylation, succinylation, and crotonylation in the brain of bilateral common carotid artery occlusion‐induced vascular dementia rats

Wang

Lü

Gao

et al. 2020

Clin Exp Pharma Physio

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Vascular dementia (VaD), caused by stroke or small vessel disease, is the second‐most common type of dementia after Alzheimer's disease (AD). Donepezil is an acetylcholinesterase inhibitor that is currently used in patients with mild to moderate AD, and has recently been shown to improve cognitive performance in patients with VaD. In this study, we evaluated the effects of donepezil on VaD, and investigated the underlying molecular mechanisms of action. VaD was established by ligation of the bilateral common carotid artery occlusion (BCCAO). Executive function was tested by the Morris water maze (MWM) test and the attentional set shifting task (ASST). Our results showed that donepezil improved executive dysfunction and cognitive flexibility in BCCAO rats. In addition, we showed that donepezil treatment decreased the level of Aβ1‐42 in BCCAO rats by enzyme‐linked immunosorbent assay. Post‐translational modifications (PTMs) are known to be critical mechanisms in the regulation of various cellular processes. Furthermore, PTMs have been linked to the central nervous system, which highlights the importance of PTMs in neurodegenerative diseases. In this study, we used western blot analysis to identify several novel PTMs in the hippocampus of BCCAO rats that were treated with or without donepezil. The data revealed that lysine propionylation, 2‐hydroxyisobutyrylation, butyrylation, succinylation, and crotonylation were elevated in the hippocampus of BCCAO rats when compared to sham rats. This increase was abolished by donepezil treatment. Taken together, we speculate that donepezil treatment improves cognitive function in our animal model of VaD, possibly by reducing aberrant acyl‐PTMs.

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Gastrodin Alleviates Vascular Dementia in a 2-VO-Vascular Dementia Rat Model by Altering Amyloid and Tau Levels

Cited by 32 publications

References 39 publications

Effects of Gastrodin against Lead-Induced Brain Injury in Mice Associated with the Wnt/Nrf2 Pathway

Effects of Gastrodin against Lead-Induced Brain Injury in Mice Associated with the Wnt/Nrf2 Pathway

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

Donepezil down‐regulates propionylation, 2‐hydroxyisobutyrylation, butyrylation, succinylation, and crotonylation in the brain of bilateral common carotid artery occlusion‐induced vascular dementia rats

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