Objectives Ageing is a universal and gradual process of organ deterioration. Radiation induces oxidative stress in cells, which leads to genetic damage and affects cell growth, differentiation and senescence. Astragaloside (AS)-IV has antioxidative, anti-apoptotic and anti-inflammatory properties. Methods To study the protective mechanism of AS-IV on radiation-induced brain cell senescence, we constructed a radiation-induced brain cell ageing model, using biochemical indicators, senescence-associated galactosidase (SA-β-gal) senescence staining, flow cytometry and Western blotting to analyse the AS-IV resistance mechanism to radiation-induced brain cell senescence. Key findings Radiation reduced superoxide dismutase (SOD) activity and expressions of cyclin-dependent kinase (CDK2), CDK4, cyclin E and transcription factor E2F1 proteins, and increased expressions of p21, p16, cyclin D and retinoblastoma (RB) proteins, malondialdehyde (MDA) activity, SA-β-gal–positive cells and cells stagnating in G1 phase. After treatment with AS-IV, the level of oxidative stress in cells significantly decreased and expression of proteins related to the cell cycle and ageing significantly changed. In addition, SA-β-gal–positive cells and cells arrested in G1 phase were significantly reduced. Conclusions These data suggest that AS-IV can antagonize radiation-induced brain cells senescence; and its mechanism may be related to p53-p21 and p16-RB signalling pathways of ageing regulation.
With multiple targets and low cytotoxicity, natural medicines can be used as potential neuroprotective agents. The increase in oxidative stress levels and inflammatory responses in the brain caused by radiation affects cognitive function and neuronal structure, and ultimately leads to abnormal changes in neurogenesis, differentiation, and apoptosis. Astragaloside Ⅳ (AS-Ⅳ), one of the main active constituents of astragalus, is known for its antioxidant, antihypertensive, antidiabetic, anti-infarction, anti-inflammatory, anti-apoptotic and wound healing, angiogenesis, and other protective effects. In this study, the mechanism of AS-IV against radiation-induced apoptosis of brain cells in vitro and in vivo was explored by radiation modeling, which provided a theoretical basis for the development of anti-radiation Chinese herbal active molecules and brain health products. In order to study the protective mechanism of AS-IV on radiation-induced brain cell apoptosis in mice, the paper constructed a radiation-induced brain cell apoptosis model, using TUNEL staining, flow cytometry, Western blotting to analyze AS-IV resistance mechanism to radiation-induced brain cell apoptosis. The results of TUNEL staining and flow cytometry showed that the apoptosis rate of radiation group was significantly increased. The results of Western blotting indicated that the expression levels of p-JNK, p-p38, p53, Caspase-9 and Caspase-3 protein, and the ratio of Bax to Bcl-2 in radiation group were significantly increased. There was no significant difference in the expression levels of JNK and p38. After AS-IV treatment, the apoptosis was reduced and the expression of apoptosis related proteins was changed. These data suggested that AS-IV can effectively reduce radiation-induced apoptosis of brain cells, and its mechanism may be related to the phosphorylation regulation of JNK-p38.
Radiation can induce nerve cell damage. Synapse connectivity and functionality are thought to be the essential foundation of all cognitive functions. Therefore, treating and preventing damage to synaptic structure and function is an urgent challenge. Astragaloside IV (AS‐IV) is a glycoside extracted from Astragalus membranaceus (Fisch.). Bunge is a widely used traditional Chinese medicine in China with various pharmacological properties, including protective effects on the central nervous system (CNS). In this study, the effect of AS‐IV on synapse damage and BDNF/TrkB signaling pathway in radiated C57BL/6 mice with X‐rays was investigated. PC12 cells and primary cortical neurons were exposed to UVA in vitro. Open field test and rotarod test were used to observe the effects of AS‐IV on the motor and explore the abilities of radiated mice. The pathological changes in the brain were observed by hematoxylin and eosin and Nissl staining. Immunofluorescence analysis was used to detect the synapse damage. The expressions of the BDNF/TrkB pathway and neuroprotection‐related molecules were detected by Western blotting and Quantitative‐RTPCR, respectively. The results showed that AS‐IV could improve the motor and explore abilities of radiated mice, reduce pathological damage to the cortex, enhance neuroprotection functions, and activate BDNF/TrkB pathway. In conclusion, AS‐IV could relieve radiation‐induced synapse damage, at least partly through the BDNF/TrkB pathway.
Background and Purpose:Alzheimer’s disease (AD) is a neurodegenerative disease whose main clinical symptoms are cognitive impairment. Synaptic dysfunction is currently a widely accepted pathogenic factor for AD, and this process is closely related to abnormalities in the glutamate receptor /cyclic adenosine monophosphate response element binding protein (NMDAR/CREB) signaling pathway is closely related. The purpose of this study was to identify a new drug for AD treatment. Experimental Approach: PC12 cells, primary neuron model and APPswe/PSEN1dE9(APP/PS1) transgenic mouse model were studied using Aβ1-42 oligomer intervention. Combined with the treatment of AS-IV and NMDAR inhibitors, RT-qPCR, Western-blotting, immunofluorescence and behavioral analysis were performed to explore the pharmacological action and possible mechanism of AS-IV. Key Results: AS-IV significantly improved synaptic damage in AD models and up-regulated the expression of NMDAR (NR1, NR2A, NR2B), CaMKs (CaMKII, CaMKIV), CREB and BDNF. Ultimately, learning, memory, and cognitive impairments in APP/PS1 mice were improved. Inhibition of NMDAR expression significantly attenuated the related protective function of AS-IV. Conclusion and Implications: AS-IV effectively exerts its anti-AD function by activating the NMDAR /CREB signaling pathway. This could help in the development of drugs to treat AD.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.