Osthole ameliorates cognitive impairments via augmenting neuronal population in APP / PS1 transgenic mice

Xiao, Honghe; Wang, Yuying; Wu, Yutong; Li, Hongyan; Liang, Xicai; Lin, Yin Liang; Kong, Liang; Ni, Yingnan; Deng, Yan; Li, Yan; Li, Wanyi; Yang, Jingxian

doi:10.1016/j.neures.2020.04.001

Cited by 15 publications

(4 citation statements)

References 48 publications

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“…Osthole may improve learning and memory functions, inhibit neuronal apoptosis, and elevate the expression of glial cell line derived neurotrophic factor (GDNF), synaptophysin (SYP), and postsynaptic density protein 95 (PSD95). In addition, osthole could remarkably enhance the proliferation of neural stem cells (NSCs) and increase the amount of mature neurons in amyloid precursor protein/presenilin 1 (APP/ PS1) transgenic mice [80]. Chu et al promulgated that osthole exhibited a neuroprotection effect on glutamateinduced apoptotic cells and an AD mouse model via modulating oxidative stress; especially Nrf2 signaling [81].…”

Section: Neuroprotective Activitymentioning

confidence: 99%

Osthole: an overview of its sources, biological activities, and modification development

Sun

Zhang

2021

Med Chem Res

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Osthole, also known as osthol, is a coumarin derivative found in several medicinal plants such as Cnidium monnieri and Angelica pubescens. It can be obtained via extraction and separation from plants or total synthesis. Plenty of experiments have suggested that osthole exhibited multiple biological activities covering antitumor, anti-inflammatory, neuroprotective, osteogenic, cardiovascular protective, antimicrobial, and antiparasitic activities. In addition, there has been some research done on the optimization and modification of osthole. This article summarizes the comprehensive information regarding the sources and modification progress of osthole. It also introduces the up-to-date biological activities of osthole, which could be of great value for its use in future research.

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Section: Neuroprotective Activitymentioning

confidence: 99%

Osthole: an overview of its sources, biological activities, and modification development

Sun

Zhang

2021

Med Chem Res

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“…H&E and Nissl staining was used to determine pathological changes and neuron loss, respectively, as reports previously (Liu et al, 2020; Xiao et al, 2021). In brief, after perfused with 0.1 M PBS (pH 7.4), the rat brain tissues were rapidly fixed with 4% formalin at 4°C for 48 h. Thereafter, the brain sections (thickness of 3.5 μm) were dehydrated and embedded in paraffin.…”

Section: Methodsmentioning

confidence: 99%

Trilobatin attenuates cerebral ischaemia/reperfusion‐induced blood–brain barrier dysfunction by targeting matrix metalloproteinase 9: The legend of a food additive

Feng,

Li,

Lin

et al. 2023

British J Pharmacology

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Background and PurposeBlood‐brain barrier (BBB) breakdown is one of the most crucial pathological changes of cerebral ischemia‐reperfusion (I/R) injury. Trilobatin (TLB), a naturally occurring food additive, exerts neuroprotective effect against cerebral I/R injury as demonstrated in our previous study. This study was designed to investigate the effect of TLB on BBB disruption after cerebral I/R injury.Experimental ApproachRats with focal cerebral ischemia caused by transient middle cerebral artery occlusion (MCAO) and brain microvascular endothelial cells along with human astrocytes to mimic BBB injury caused by oxygen and glucose deprivation (OGD)/reoxygenation (OGD/R).Key resultsThe results showed that TLB effectively maintained BBB integrity and inhibited neuronal loss following cerebral I/R challenge. Furthermore, TLB increased tight junction proteins including ZO‐1, Occludin and Claudin 5, decreased the levels of apolipoprotein E (APOE) 4, cyclophilin A (CypA), and phosphorylated nuclear factor kappa B (NF‐κB), thereby reduced proinflammatory cytokines. Additionally, TLB also decreased Bax/Bcl‐2 ratio and cleaved‐caspase 3 level along with reduced the number of apoptotic neurons. Intriguingly, molecular docking and transcriptomics predicted MMP9 was a prominent gene evoked by TLB treatment. Furthermore, the protective effect of TLB on cerebral I/R‐induced BBB breakdown was largely abolished by overexpression of MMP9, and the beneficial effect of TLB on OGD/R‐induced the loss of BBB integrity in human brain microvascular endothelial cell and astrocyte co‐cultures was markedly reinforced by knockdown of MMP9.Conclusions and implicationsOur findings reveal a novel property of TLB: saving BBB disruption following cerebral I/R via targeting MMP9 and inhibiting APOE4/CypA/NF‐κB axis.

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“…After washing with PBS, add an anti-fluorescence quencher to mount the slides, observe and take pictures under a fluorescence microscope. As it does in the previous reports ( Li H. et al, 2021 ; Xiao et al, 2021 ), we use ImageJ software to scan the fluorescence intensity of each field to measure the expression level.…”

Section: Methodsmentioning

confidence: 99%

“…After being washed until the color returned blue, the sections incubated with 0.5% ammonia hydroxide and followed by dying with eosin for 5 s, permeabilized with dimethylbenzene after dehydration, and then sealed with neutral gum. For Nissl staining, the brain sections were stained with Cresyl violet after being degreased with different concentrations of alcohol solution ( Xiao et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

Effects of Broussonetia papyrifera (L.) L'Hér. ex Vent. fruits water extract on hippocampal neurogenesis in the treatment of APP/PS1 transgenic mice

et al. 2022

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Background: Adult neurogenesis plays an important role in repairing damaged neurons and improving cognitive impairment in Alzheimer’s disease (AD). B. Papyrifera (L.) L'Hér. ex Vent. fruits (BL), a traditional Chinese medicine for tonifying the kidney, has been reported to improve cognitive function in AD mice, but the underlying mechanisms have not been clearly illuminated. This study aimed to provide an overview of the differential compounds in the brain of APP/PS1 mice after BL water extract (BLWE) treatment through metabolomics technology and to elucidate whether the therapeutic effect and mechanism are through the enhancement of neurogenesis.Methods: APP/PS1 transgenic mice were treated with different doses of BLWE. After 6 weeks of intragastric injection, the therapeutic effects of BLWE on APP/PS1 transgenic mice were determined by the Morris water maze test, immunohistochemistry, hematoxylin & eosin and Nissl staining, enzyme-linked immunosorbent assay and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Subsequently, metabolomics technology was used to analyze the regulatory effect of BLWE on differential compounds in the brain of APP/PS1 mice, and on this basis, its molecular mechanism of BLWE was screened. Finally, the protein expression of the Wnt/β-catenin signaling pathway was detected by Western blotting.Results: After BLWE treatment, the learning and memory function of APP/PS1 mice were significantly improved, which was related to the increase in the number of Nestin+/BrdU+ and NeuN+/BrdU+ cells, and the decrease in the number of apoptotic cells in the hippocampus. BLWE treatment could also up-regulate the expression of synapse-associated proteins. Moreover, BLWE could modulate endogenous metabolic compounds in the brains of AD mice, including N-acetyl-aspartate, glutamine, etc. Furthermore, BLWE inhibited the phosphorylation of Tyr216-GSK-3β and β-catenin protein while increased CyclinD1 protein expression.Conclusion: We demonstrated that BLWE can enhance neural stem cells proliferation and improve neurogenesis, thereby efficiently repairing damaged neurons in the hippocampus and ameliorating cognitive impairment in APP/PS1 transgenic mice. The mechanism is at least partly through activating the Wnt/β-catenin signaling pathway.

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Osthole ameliorates cognitive impairments via augmenting neuronal population in APP / PS1 transgenic mice

Cited by 15 publications

References 48 publications

Osthole: an overview of its sources, biological activities, and modification development

Osthole: an overview of its sources, biological activities, and modification development

Trilobatin attenuates cerebral ischaemia/reperfusion‐induced blood–brain barrier dysfunction by targeting matrix metalloproteinase 9: The legend of a food additive

Effects of Broussonetia papyrifera (L.) L'Hér. ex Vent. fruits water extract on hippocampal neurogenesis in the treatment of APP/PS1 transgenic mice

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