Astragaloside IV alleviates ischemia reperfusion-induced apoptosis by inhibiting the activation of key factors in death receptor pathway and mitochondrial pathway

Yin, Fei; Zhou, Huifen; Fang, Yu-Chen; Li, Chang; He, Yu; Yu, Li; Wan, Haitong; Yang, Jiehong

doi:10.1016/j.jep.2019.112319

Cited by 79 publications

(46 citation statements)

References 34 publications

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“…A. membranaceus is the major component of XSEC. Many active compounds, such as astragaloside IV and calycosin-7-O-β-D-glucoside, derived from A. membranaceus possess a variety of biological activities, such as antioxidant, antiapoptosis, and anti-inflammatory activities, that reverse ischemic injury (Fu et al, 2014;Li et al, 2017;Yin et al, 2019). In particular, astragaloside IV promotes hippocampal neurogenesis in the intact brain, and astragaloside VI induces proliferation of neural stem cells (NSCs) in the subventricular zone (SVZ) and peri-infarct cortex via activating the epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) pathway after a stroke (Huang et al, 2018;Chen et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

MRI Evaluation of Axonal Remodeling After Combination Treatment With Xiaoshuan Enteric-Coated Capsule and Enriched Environment in Rats After Ischemic Stroke

Zhan

Yang

et al. 2019

Front. Physiol.

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Xiaoshuan enteric-coated capsule (XSEC) is a compound Chinese medicine widely used for the treatment of ischemic stroke. Enriched environment (EE) is a rehabilitative intervention designed to facilitate physical, cognitive, and social activity after brain injury. This study aimed to assess whether the XSEC and EE combination could provide synergistic efficacy in axonal remodeling compared to that with a single treatment after ischemic stroke using magnetic resonance imaging (MRI) followed by histological analysis. Rats were subjected to permanent middle cerebral artery occlusion and treated with XSEC and EE alone or in combination for 30 days. T2weighted imaging and diffusion tensor imaging (DTI) were performed to examine the infarct volume and axonal remodeling, respectively. The co-localization of Ki67 with NG2 or CNPase was examined by immunofluorescence staining to assess oligodendrogenesis. The expressions of growth associated protein-43 (GAP-43) and growth inhibitors NogoA/Nogo receptor (NgR)/RhoA/Rho-associated kinase2 (ROCK2) were measured using western blot and qRT-PCR. The Morris water maze (MWM) was performed to evaluate the cognitive function. MRI and histological measurements indicated XSEC and EE individually benefited axonal reorganization after stroke. Notably, XSEC + EE decreased infarct volume compared with XSEC or EE monotherapy and increased ipsilateral residual volume compared with vehicle group. DTI showed XSEC + EE robustly increased fractional anisotropy while decreased axial diffusivity and radial diffusivity in the injured cortex, striatum, and external capsule. Meanwhile, diffusion tensor tractography revealed XSEC + EE elevated fiber density in the cortex and external capsule and increased fiber length in the striatum and external capsule compared with the monotherapies. These MRI measurements, confirmed by histology, showed that XSEC + EE promoted axonal restoration. Additionally, XSEC + EE amplified oligodendrogenesis, decreased the expressions

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Section: Discussionmentioning

confidence: 99%

MRI Evaluation of Axonal Remodeling After Combination Treatment With Xiaoshuan Enteric-Coated Capsule and Enriched Environment in Rats After Ischemic Stroke

Zhan

Yang

et al. 2019

Front. Physiol.

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“…Astragaloside IV (c 14 H 68 O 14 ) is one of the main active chemicals and the quality-control marker of the traditional chinese medicine Astragalus membranaceus, which is the main ingredient of Buyang Huanwu decoction, as recorded in the book 'correction on the Errors of Medical Works' written by Qingren Wang in the Qing dynasty (31,32). Numerous studies have demonstrated that Astragaloside IV has anti-inflammatory and antiapoptotic properties, is involved in the regulation of vascular remodeling and energy metabolism, and exerts a neuroprotective effect on cIRI (16,18,27,(33)(34)(35)(36)(37). Our previous study has demonstrated that Astragaloside IV alleviates CIRI by inhibiting neuronal apoptosis and confirmed that it exerts its role by regulating autophagy (9).…”

Section: Astragaloside IV Attenuates Cerebral Ischemia-reperfusion Inmentioning

confidence: 99%

“…calcium overload is an important link between apoptosis and neuronal necrosis (16,17). A number of studies have demonstrated that extracellular calcium can be absorbed and transported into the mitochondria during ischemia-reperfusion (I/R) injury, leading to increased mitochondrial membrane permeability and promoting oxidative reaction and apoptosis (18)(19)(20). calcium-sensing receptor (caSR) is a member of the G-protein coupled receptor superfamily and is sensitive to the extracellular application of ca 2+ , Gd 3+…”

Section: Introductionmentioning

confidence: 99%

Astragaloside IV attenuates cerebral ischemia‑reperfusion injury in rats through the inhibition of calcium‑sensing receptor‑mediated apoptosis

Zhang

Zhao

et al. 2020

Int J Mol Med

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cerebral ischemia-reperfusion injury (cIRI), caused by the reperfusion of blocked vessels following ischemic stroke, can lead to secondary brain injury. Throughout cIRI, apoptosis serves an important role. Astragaloside IV is a potential neuroprotectant that alleviates cIRI by inhibiting apoptosis. The calcium-sensing receptor (caSR) is a G-protein-coupled receptor, the activation of which aggravates ischemia-reperfusion injury. The aim of the present study was to investigate whether the protective effect of Astragaloside IV on cIRI may be associated with the regulation of caSR. A rat middle cerebral artery occlusion/reperfusion (McAO/R) model and an oxygen and glucose deprivation/reoxygenation (OGd/R) model of pheochromocytoma (Pc12) cells were used to study the neuronal injury induced by cIRI. Neurological function scores (NFS), 2,3,5-triphe-nylterazolium chloride and hematoxylin and eosin staining were used to determine brain damage in rats. cell viability was measured to evaluate the injury of OGd/R Pc12 cells. Western blotting was used to examine the expression of proteins associated with apoptosis and caSR. The caSR antagonist NPS-2143 and agonist Gdcl 3 were used to further confirm the effects of caSR during the process of apoptosis. The results demonstrated that Astragaloside IV alleviated cIRI by decreasing the NFS of rats, reducing the infarction volume of the brain and promoting the viability of Pc12 cells, as well as inhibiting the expression of cleaved caspase-3 and caSR, which was induced by cIRI. The results of the present study suggested that the activation of caSR may be involved in cIRI-induced brain damage in rats, and that Astragaloside IV may alleviate cIRI by inhibiting caSR activation-induced apoptosis.

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“…All identi ed compounds were subjected to ADME screening, among compounds below these requirements, six (Hydroxysa or yellow A, AstragalosideIV, Ferulic acid, Ligustrazine, Z-ligustilide, Linoleic acid) were considered bioactive compounds. These compounds are the major components of BYHWD, and their effects on cerebral ischemia is have been investigated previously [11][12][13][14][15][16]. Remove duplicate components and remove components with ambiguous targets.…”

Section: Compounds In Herbal Medicinesmentioning

confidence: 99%

Study on the Mechanism of Buyang Huanwu Decoction for the treatment of Ischemic Stroke Based on Network Pharmacology

Wang¹,

Lü²,

Cao³

et al. 2020

Preprint

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Background: Buyang Huanwu Decoction (BYHWD) is one of the representative prescriptions for tonifying qi and promoting blood circulation. This formula has been widely used in Chinese clinical practice for treatment and prevention of ischemic cerebral vascular diseases. However, the mechanism and active compounds of BYHWD used in clinical practice for ischemic stroke are not well understood. The purpose of this study was to understand the potential active components of BYHWD and further explore its mechanism of improving ischemic stroke. Methods: This study was based on network pharmacology and bioinformatics analysis. The compounds of BYHWD were obtained from public databases. Oral bioavailability as well as drug-likeness were screened by using absorption, distribution, metabolism, and excretion (ADME) criteria. Then, components of BYHWD, candidate targets of each component and known therapeutic targets of ischemic cerebral were collected. A network of compound-target genes and compound-ischemic cerebral was established by means of network pharmacology data sources. The enrichment of key targets and pathways was analyzed by using string database and DAVID database. In addition, we verified three key targets predicted by western blot analysis (IL6, VEGFA and HIF1A). Results: Network pharmacology analysis results of BYHWD identified 7 herbs, 42 compounds and 79 target genes associated to cerebral ischemia. The 10 key compounds were baicalein, beta-carotene, Baicalin, kaempferol, luteolin, quercetin, hydroxysafflor yellow A, isorhamnetin, Bifendate, formononetin,Calycosin, AstragalosideIV, Stigmasterol, sitosterol, Z-ligustilide, Dihydrocapsaicin. Core genes in this network were IL6, TNF, VEGFA, HIF1A, MAPK1, MAPK3, JUN, STAT3, IL1B and IL10. And pathways TNF, IL-17, Apoptosis, PI3K-Akt, Toll-like receptor, MAPK, NF-kappa B and HIF-1 signaling pathway, etc. related to ischemic stroke were identified. In vitro experiments, The results showed that compared with the control group (no treatment), BYHWD could significantly inhibit the expression of IL6 and increased the expression of HIF1A and VEGFA. Conclusions: Network pharmacology analysis can reveal close interactions between multi-components and multi-targets, and enhance our understanding of the potential effects of BYHWD in cerebral ischemia.

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Astragaloside IV alleviates ischemia reperfusion-induced apoptosis by inhibiting the activation of key factors in death receptor pathway and mitochondrial pathway

Cited by 79 publications

References 34 publications

MRI Evaluation of Axonal Remodeling After Combination Treatment With Xiaoshuan Enteric-Coated Capsule and Enriched Environment in Rats After Ischemic Stroke

MRI Evaluation of Axonal Remodeling After Combination Treatment With Xiaoshuan Enteric-Coated Capsule and Enriched Environment in Rats After Ischemic Stroke

Astragaloside IV attenuates cerebral ischemia‑reperfusion injury in rats through the inhibition of calcium‑sensing receptor‑mediated apoptosis

Study on the Mechanism of Buyang Huanwu Decoction for the treatment of Ischemic Stroke Based on Network Pharmacology

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