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The Role of Astragaloside IV against Cerebral Ischemia/Reperfusion Injury: Suppression of Apoptosis via Promotion of P62-LC3-Autophagy

Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Hebei University of Chinese Medicine, Shijiazhuang 050200, China
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Molecules 2019, 24(9), 1838; https://doi.org/10.3390/molecules24091838
Received: 2 April 2019 / Revised: 4 May 2019 / Accepted: 8 May 2019 / Published: 13 May 2019
(This article belongs to the Special Issue Discovery of Active Ingredients from Natural Products)
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Abstract

Background: Ischemia/reperfusion (I/R) caused by ischemic stroke treatments leads to brain injury, and autophagy plays a role in the pathology. Astragaloside IV is a potential neuroprotectant, but its underlying mechanism on cerebral I/R injury needs to be explored. The objective of this study is to investigate the neuroprotective mechanism of Astragaloside IV against cerebral I/R injury. Methods: Middle cerebral artery occlusion method (MCAO) and oxygen and glucose deprivation/reoxygenation (OGD/R) method were used to simulate cerebral I/R injury in Sprague-Dawley (SD) rats and HT22 cells, respectively. The neurological score, 2,3,5-Triphe-nyltetrazolium chloride (TTC) staining, and transmission electron microscope were used to detect cerebral damage in SD rats. Cell viability and cytotoxicity assay were tested in vitro. Fluorescent staining and flow cytometry were applied to detect the level of apoptosis. Western blotting was conducted to examine the expression of proteins associated with autophagy. Results: This study found that Astragaloside IV could decrease the neurological score, reduce the infarct volume in the brain, and alleviate cerebral I/R injury in MCAO rats. Astragaloside IV promoted cell viability and balanced Bcl-2 and Bax expression in vitro, reduced the rate of apoptosis, decreased the expression of P62, and increased the expression of LC3II/LC3I in HT22 cells after OGD/R. Conclusions: These data suggested that Astragaloside IV plays a neuroprotective role by down-regulating apoptosis by promoting the degree of autophagy. View Full-Text
Keywords: Astragaloside IV; cerebral ischemia/reperfusion injury; autophagy; apoptosis; mechanism Astragaloside IV; cerebral ischemia/reperfusion injury; autophagy; apoptosis; mechanism
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Zhang, Y.; Zhang, Y.; Jin, X.-F.; Zhou, X.-H.; Dong, X.-H.; Yu, W.-T.; Gao, W.-J. The Role of Astragaloside IV against Cerebral Ischemia/Reperfusion Injury: Suppression of Apoptosis via Promotion of P62-LC3-Autophagy. Molecules 2019, 24, 1838.

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