Astragaloside IV reduces neuronal apoptosis and parthanatos in ischemic injury by preserving mitochondrial hexokinase-II

Liu, Ying; Yang, Yilin; Zhao, Yunpeng; Zhang, Jingmin; Liu, Baolin; Jiao, Shujie; Zhang, Xiaojian

doi:10.1016/j.freeradbiomed.2018.11.033

Cited by 53 publications

(50 citation statements)

References 38 publications

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“…5f-i). Besides, As-IV reduces the release of pro-apoptotic proteins and resultantly protects neurons from apoptosis and parthanatos 23 . In this study, at 3 dpi, there were significantly less infarction area, numbers of TUNEL and NeuN double positive cells, and level of Caspase 3 protein expression in the cortex of As-IV treated mice (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…As-IV is a primary bioactive compound of Radix Astragali (Fig. 6b), which exerts beneficial effect on cognitive recovery after stroke 23 . Further analysis in our study showed that, at 3 dpi, there was significantly less infraction area and less double positive TUNEL and NeuN cells numbers/NeuN positive cells numbers percentage in the cortex of As-IV treated mice (n = 5, Fig.…”

Section: Neural Apoptosis In Ischemic Cortex Is Ameliorated By Adminimentioning

confidence: 99%

“…Astragaloside IV (As-IV), a primary bioactive compound of Radix Astragali, Astragalus mongholicus Bunge (Fabaceae), has been described as potential neuroprotective effect in experimental models of Alzheimer’s disease and cerebral ischemia 22 . It has been found As-IV protected neurons from apoptosis and autophagy 23 , 24 , some by regulating Akt/GSK-3β/ β-catenin pathway 25 – 27 . As-IV could be a new therapeutic drug candidate for post-stroke treatment and effectively promote neural stem cells (NSCs) proliferation and neurogenesis in transient cerebral ischemic brains 28 .…”

Section: Introductionmentioning

confidence: 99%

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Antagonistic effects of IL-17 and Astragaloside IV on cortical neurogenesis and cognitive behavior after stroke in adult mice through Akt/GSK-3β pathway

et al. 2020

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We aimed to investigate the exact effect of IL-17 on regulating neural stem cells (NSCs) stemness and adult neurogenesis in ischemic cortex after stroke, how Astragaloside IV(As-IV) regulated IL-17 expression and the underlying mechanism. Photochemical brain ischemia model was established and IL-17 protein expression was observed at different time after stroke in WT mice. At 3 days after stroke, when IL-17 expression peaked, IL-17 knock out (KO) mice were used to observe cell proliferation and neurogenesis in ischemic cortex. Then, As-IV was administered intravenously to assess cell apoptosis, proliferation, neurogenesis, and cognitive deficits by immunochemistry staining, western blots, and animal behavior tests in WT mice. Furthermore, IL-17 KO mice and As-IV were used simultaneously to evaluate the mechanism of cell apoptosis and proliferation after stroke in vivo. Besides, in vitro, As-IV and recombinant mouse IL-17A was administered, respectively, into NSCs culture, and then their diameters, viable cell proliferation and pathway relevant protein was assessed. The results showed knocking out IL-17 contributed to regulating PI3K/Akt pathway, promoting NSCs proliferation, and neurogenesis after ischemic stroke. Moreover, As-IV treatment helped inhibit neural apoptosis, promote the neurogenesis and eventually relieve mice anxiety after stroke. Unsurprisingly, IL-17 protein expression could be downregulated by As-IV in vivo and in vitro and they exerted antagonistic effect on neurogenesis by regulating Akt/GSK-3β pathway, with significant regulation for apoptosis. In conclusion, IL-17 exerts negative effect on promoting NSCs proliferation, neurogenesis and cognitive deficits after ischemic stroke, which could be reversed by As-IV.

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Section: Discussionmentioning

confidence: 99%

Section: Neural Apoptosis In Ischemic Cortex Is Ameliorated By Adminimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Antagonistic effects of IL-17 and Astragaloside IV on cortical neurogenesis and cognitive behavior after stroke in adult mice through Akt/GSK-3β pathway

et al. 2020

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“…In the former studies, not much can be found about the actual isolation of astragaloside IV. The majority of manuscripts describe the results of the pharmacological activity that astragaloside IV has exhibited in a living organism, where astragaloside IV was obtained from a purchased standard compound [79]. The previous report of Lee and co-investigators confirmed the possibility to isolate astragaloside II from Astragalus membranaceus using a flash chromatograph, which certainly shortened the time of separation; however, astragaloside IV was not within the obtained compounds [80], contrary to Lai and colleagues who isolated this saponin in a bioactivity guided fractionation model [81].…”

Section: Recovery Of Astragaloside IV From Plant Materialsmentioning

confidence: 99%

In Silico Studies on Triterpenoid Saponins Permeation through the Blood–Brain Barrier Combined with Postmortem Research on the Brain Tissues of Mice Affected by Astragaloside IV Administration

Stępnik

Kukuła-Koch

2020

IJMS

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As the number of central nervous system (CNS) drug candidates is constantly growing, there is a strong need for precise a priori prediction of whether an administered compound is able to cross the blood–brain barrier (BBB). The aim of this study was to evaluate the ability to cross the BBB of triterpenoid saponins occurring in Astragalus mongholicus roots. The research was carried out using in silico methods combined with postmortem studies on the brain tissues of mice treated with isolated astragaloside IV (AIV). Firstly, to estimate the ability to cross the BBB by the tested saponins, new quantitative structure–activity relationship (QSAR) models were established. The reliability and predictability of the model based on the values of the blood–brain barrier penetration descriptor (logBB), the difference between the n-octanol/water and cyclohexane/water logP (ΔlogP), the logarithm of n-octanol/water partition coefficient (logPow), and the excess molar refraction (E) were both confirmed using the applicability domain (AD). The critical leverage value h* was found to be 0.128. The relationships between the standardized residuals and the leverages were investigated here. The application of an in vitro acetylcholinesterase-inhibition test showed that AIV can be recognized as the strongest inhibitor among the tested compounds. Therefore, it was isolated for the postmortem studies on brain tissues and blood using semi-preparative HPLC with the mobile phase composed of water, methanol, and ethyl acetate (1.7:2.1:16.2 v/v/v). The results of the postmortem studies on the brain tissues show a regular dependence of the final concentration of AIV in the analyzed brain samples of animals treated with 12.5 and 25 mg/kg b.w. of AIV (0.00012299 and 0.0002306 mg, respectively, per one brain). Moreover, the AIV logBB value was experimentally determined and found to be equal to 0.49 ± 0.03.

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“…Astragaloside IV (As IV), a primary bioactive compound of Radix Astragali: Astragalus mongholicus Bunge (Fabaceae), has beneficial effect on ameliorating cognitive deficits after stroke through its anti-oxidant, anti-inflammatory, and anti-apoptosis properties (Li et al, 2019;Xue et al, 2019;. Furthermore, it has been found that As IV could enhance adult hippocampal neurogenesis (Yang et al, 2017;Huang et al, 2018) and promote neural stem cells (NSCs) proliferation in transiently ischemic cerebral brains (Chen X. et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Astragaloside IV Exerts Cognitive Benefits and Promotes Hippocampal Neurogenesis in Stroke Mice by Downregulating Interleukin-17 Expression via Wnt Pathway

et al. 2020

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Background: Stroke remains a leading cause of adult disability and the demand for stroke rehabilitation services is growing, and Astragaloside IV (As IV), a primary bioactive compound of Radix Astragali: Astragalus mongholicus Bunge (Fabaceae), may be a promising stroke therapy. Methods: To access the effect of As IV on adult mice after ischemic stroke, a photochemical ischemia model was established on C57BL/6 mice, which were intravenously administered As IV for three consecutive days later. And then the cognitive benefits and hippocampal neurogenesis were evaluated by Morris Water Maze (MWM) test, Golgi staining, and immunohistochemical staining in vivo and in vitro. Furthermore, to find out the underlying mechanism, interleukin-17 (IL-17) knockout (KO) mice were used, through RNA sequence (RNA-seq) analysis and immunohistochemistry. Then the mechanism of neurogenesis promoted by As IV was observed by western blot both in vivo and in vitro. Specifically, As IV, recombinant mouse IL-17A and IL-17F, and Wingless/integrated (Wnt)-expressing virus was administered respectively in neural stem cells (NSCs), and then their diameters and protein expression of Nestin, IL-17, and Wnt pathway relevant protein, were measured in vitro. Results: Administering As IV resulted in significant amelioration of stroke-induced cognitive deficits. And more hippocampal neurons with normal morphology, significant increments in the length of the apical dendrites, and the density of their spines were observed in As IV-treated mice. Furthermore, the immunohistochemistry staining of DCX/ BrdU and Sox2/Nestin showed As IV could promote hippocampal neurogenesis and NSC proliferation after ischemic stroke, as well as in vitro. For the mechanism underlying, IL-17 expression was downregulated significantly by As IV treatment and knocking out IL-17 was associated with nervous regeneration and synapse repair according to the analysis of RNA-seq. Consistent to As IV treatment, knocking out IL-17 showed some promotion on hippocampal neurogenesis and proliferation of NSCs, with activating Wnt pathway after

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Astragaloside IV reduces neuronal apoptosis and parthanatos in ischemic injury by preserving mitochondrial hexokinase-II

Cited by 53 publications

References 38 publications

Antagonistic effects of IL-17 and Astragaloside IV on cortical neurogenesis and cognitive behavior after stroke in adult mice through Akt/GSK-3β pathway

Antagonistic effects of IL-17 and Astragaloside IV on cortical neurogenesis and cognitive behavior after stroke in adult mice through Akt/GSK-3β pathway

In Silico Studies on Triterpenoid Saponins Permeation through the Blood–Brain Barrier Combined with Postmortem Research on the Brain Tissues of Mice Affected by Astragaloside IV Administration

Astragaloside IV Exerts Cognitive Benefits and Promotes Hippocampal Neurogenesis in Stroke Mice by Downregulating Interleukin-17 Expression via Wnt Pathway

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