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Notoginsenoside R1 Decreases Cell Apoptosis in the Brains of Rats with Cerebral Infarction by Activating Notch1 Signaling Pathway
Vol 38, Issue 3, 2024
Abstract
Background: Cerebral infarction (CI) often leads to disability or cognitive deficits with limited effective therapeutic options. This study investigated the effect and mechanism of Notoginsenoside R1 (NGR1) on protecting cells from apoptosis in rat CI models. Methods: Sprague Dawley (SD) rats were used to establish CI models through middle cerebral artery occlusion (MCAO) treatment. Hematoxylin-eosin (H&E) staining was used to observe pathological changes. Cell apoptosis was assessed by Bcl-2 apoptosis regulator (Bcl-2)/Bcl-2 associated X (Bax), cleaved caspase-3, and cleaved caspase-9 levels determined by western blot and enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry (IHC) was used to evaluate levels of hes family bHLH transcription factor 1 (Hes1) and Notch receptor 1 (Notch1). Additionally, Notch1 pathway activation was regulated by the Notch inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) and Notch 1 activator valproic acid (VPA), and the consequent effect on brain cell apoptosis was determined. Results: In CI rat brains, the levels of cleaved caspase-3 and cleaved caspase-9 were elevated (p < 0.001), while Bcl-2/Bax was decreased (p < 0.001). NGR1 reversed these changes (p < 0.01). Hes1 and Notch1 levels were reduced in CI rat brains (p < 0.001) and were reversed by NGR1 (p < 0.001). Furthermore, compared to NGR1-treated CI rats, additional DAPT/VPA decreased/increased levels of Hes1, Notch1, Bcl-2/Bax (p < 0.001), and increased/decreased cleaved caspase-3 and cleaved caspase-9 levels (p < 0.001). Conclusion: NGR1 can decrease cell apoptosis in the brains of CI rats by activating the Notch1 signaling, presenting a novel therapeutic strategy with potential therapeutic targets for treating CI.
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Copyright (c) 2024 Jiankun Wang, Fen Zhang
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Medical Genetics, University of Torino Medical School, Italy

Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy