scholarly journals Gastrodia-Uncaria Water Extract Inhibits Endoplasmic Reticulum Stress and Matrix Metalloproteinase in Protecting against Cerebral Ischemia

2021 ◽  
Author(s):  
Angus Y Choi ◽  
Jia Wen Xian ◽  
Sum Yi Ma ◽  
Zhixiu Lin ◽  
Chun Wai Chan
Keyword(s):  
Endoplasmic Reticulum ◽  
Cerebral Ischemia ◽  
Endoplasmic Reticulum Stress ◽  
Blood Brain Barrier ◽  
Neuroprotective Effect ◽  
Water Extract ◽  
Neuronal Cell ◽  
Brain Barrier ◽  
Brain Diseases ◽  
Blood Brain

Stroke is the second leading cause of death in worldwide, in which cerebral ischemia accounts for 87% of all cases. The building up of endoplasmic reticulum stress in cerebral ischemia contributes to the disruption of blood brain barrier and neuronal cell death. The only FDA-approved drug, recombinant tissue plasminogen activator, is still of limited use due to the narrow window period and lack of neuroprotective effect. Therefore, it is necessary to explore alternative treatment on cerebral ischemia. Tianma-Gouteng decoction is a traditional Chinese Medicine prescription used to treat brain diseases in China. In this study, we investigated the neuroprotective effect of a water extract consisting of Gastrodia elata and Uncaria rhynchophylla, which are the two main herbs in the decoction. Cerebral ischemia was induced in rats using middle cerebral artery occlusion. GUW-treated rats have significantly reduced infarction volume and recovered neurological functions. The number of protein aggregates and caspase-12 positive cells were significantly inhibited. In vitro oxygen-glucose deprivation / reoxygenation stroke model demonstrated that the unfolded protein response proteins GRP78 and PDI were upregulated by GUW. Less ubiquitin puncta and normalized ubiquitin distribution indicated the reduction in endoplasmic reticulum stress. Furthermore, a lower Evan blue signal and MMPsense signal was observed, suggesting that GUW may preserve the blood brain barrier integrity through inhibiting MMP activity. Taken together, this suggested that GUW protected ischemic neurons and the blood brain barrier through inhibiting endoplasmic reticulum stress.

scholarly journals Neuroprotective Effect of Activated Protein C on Blood–Brain Barrier Injury During Focal Cerebral Ischemia/Reperfusion

Dose-Response ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 155932582091728
Author(s):  
Jinqiao Wang ◽  
Gaofeng Rao ◽  
Yifan Ma ◽  
Jingjing Zhang ◽  
Jingjing Shen ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Blood Brain Barrier ◽  
Protein C ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Activated Protein C ◽  
Brain Barrier ◽  
Cerebral Ischemia Reperfusion ◽  
Blood Brain

Although the effect of activated protein C (APC) on neuronal injury and neuroinflammatory responses has been extensively studied, the detailed mechanism underlying APC-protective effect in the blood–brain barrier (BBB) injury during ischemia is still not clear. In this study, the APC effect against neuroinflammatory responses was evaluated in the model of right middle cerebral artery occlusion in male Sprague-Dawley rats with 2 hours of ischemia and 22 hours of reperfusion. The results showed that APC can significantly improve the neurological function scoring and reduce the infarct volume and BBB permeability. Moreover, the expression of protein nuclear factor-kappa B (NF-κB), both in cytoplasm and nuclei, was reduced. The downstream of NF-κB activation, including tumor necrosis factor-α and interleukin-1β secretion, was inhibited. In all, APC exerts a neuroprotective effect in focal cerebral ischemia–reperfusion in rats by inhibiting the activation and nuclear translocation of NF-κB. It may indicate a therapeutic approach for ischemic brain injury.

scholarly journals Astragaloside IV Reduces Cerebral Ischemia/Reperfusion-Induced Blood-Brain Barrier Permeability in Rats by Inhibiting ER Stress-Mediated Apoptosis

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Bonan Hou ◽  
Rui Liu ◽  
You Wu ◽  
Shuiqing Huang
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Western Blot ◽  
Blood Brain Barrier ◽  
Ischemia Reperfusion ◽  
Brain Barrier ◽  
Related Protein ◽  
Astragaloside Iv ◽  
Protein Levels ◽  
Blood Brain

Background. Previous studies proved that AS-IV could prevent blood-brain barrier (BBB) against an increase in permeability. However, its underlying molecular mechanism has not been enlightened yet. The aim of the study is to reveal the potential protective mechanism of astragaloside IV (AS-IV) on the blood-brain barrier after ischemia-reperfusion. Methods. In vivo, AS-IV neurological protection was measured by Long’s five-point scale and 2,3,5-triphenyltetrazolium chloride staining. AS-IV protection for BBB was observed by Evans blue extravasation technique. Endoplasmic reticulum stress and apoptosis-related protein levels were measured by western blot with AS-IV intervention. In vitro, cell apoptosis was analyzed by western blot and flow cytometry.Endoplasmic reticulum stress-related protein levels were quantified through western blot. Results. AS-IV treatment could decrease the infarct size in rats’ brain and protect the BBB against Evans blue permeating through brain, after ischemia/reperfusion, significantly. Further, ischemia/reperfusion or oxygen‐glucose deprivation/reperfusion was found to have an increase in endothelial cell apoptosis proteins, such as Bax, Bcl-2, and caspase-3, and endoplasmic reticulum stress-associated proteins, such as phosphorylated PERK and eIF2α, Bip, and CHOP, which were attenuated by AS-IV treatment. Conclusions. AS-IV can effectively protect the blood-brain barrier and reduce the area of cerebral infarction via inhibiting endoplasmic reticulum stress-mediated apoptosis in endothelial cells.

Microbubbles in combination with focused ultrasound for the delivery of quercetin-modified sulfur nanoparticles through the blood brain barrier into the brain parenchyma and relief of endoplasmic reticulum stress to treat Alzheimer's disease

Nanoscale ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 6498-6511 ◽  
Author(s):  
Yanan Liu ◽  
Youcong Gong ◽  
Wenjie Xie ◽  
Anlian Huang ◽  
Xiaoyu Yuan ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Neurodegenerative Diseases ◽  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Brain Parenchyma ◽  
Brain Barrier ◽  
Blood Brain ◽  
The Brain ◽  
Sulfur Nanoparticles

The delivery of drugs across the blood–brain barrier (BBB) effectively and safely is one of the major challenges in the treatment of neurodegenerative diseases.

scholarly journals Can Natural Products Exert Neuroprotection without Crossing the Blood–Brain Barrier?

2021 ◽  
Vol 22 (7) ◽  
pp. 3356
Author(s):  
Manon Leclerc ◽  
Stéphanie Dudonné ◽  
Frédéric Calon
Keyword(s):  
Natural Products ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Diseases ◽  
Omega 3 ◽  
Indirect Pathway ◽  
Brain Functions ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Peripheral Metabolism

The scope of evidence on the neuroprotective impact of natural products has been greatly extended in recent years. However, a key question that remains to be answered is whether natural products act directly on targets located in the central nervous system (CNS), or whether they act indirectly through other mechanisms in the periphery. While molecules utilized for brain diseases are typically bestowed with a capacity to cross the blood–brain barrier, it has been recently uncovered that peripheral metabolism impacts brain functions, including cognition. The gut–microbiota–brain axis is receiving increasing attention as another indirect pathway for orally administered compounds to act on the CNS. In this review, we will briefly explore these possibilities focusing on two classes of natural products: omega-3 polyunsaturated fatty acids (n-3 PUFAs) from marine sources and polyphenols from plants. The former will be used as an example of a natural product with relatively high brain bioavailability but with tightly regulated transport and metabolism, and the latter as an example of natural compounds with low brain bioavailability, yet with a growing amount of preclinical and clinical evidence of efficacy. In conclusion, it is proposed that bioavailability data should be sought early in the development of natural products to help identifying relevant mechanisms and potential impact on prevalent CNS disorders, such as Alzheimer’s disease.

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