Abstract
In recent years, more attention has been given to novel patterns of cell death observed during ischemia/reperfusion (I/R). Necroptosis is a regulable secondary cell death pathway; necroptosis is different from traditional forms of cell death, and it is regulated by the RIPK1-RIPK3-MLKL signaling pathway. JLX001 is the double hydrochloride of the natural compound cyclovirobuxine D (CVB-D). Previous studies have confirmed that CVB-D exerts a significant effect on cardiovascular and cerebrovascular diseases and that JLX001 can reduce ischemic brain injury by inhibiting cell apoptosis. For the first time, this project explored the in vivo and in vitro inhibitory effects of the therapeutic administration of JLX001 on the neuronal necroptosis caused by cerebral ischemia–reperfusion injury (CIRI). The middle cerebral artery occlusion reperfusion (MCAO/R) model was used to simulate I/R injury in rats in vivo, and oxygen-glucose deprivation and reperfusion (OGD/R) was used to simulate I/R injury in vitro. After the administration of JLX001, the relative expression of necroptosis-related molecules was measured by ELISA, RT–PCR, HE staining, immunofluorescence and Western blotting. The results showed that JLX001 significantly reduced pathological damage and the cerebral infarction rate in rat brain tissues, and the expression of neuronal necroptosis-related molecules was reduced, suggesting that JLX001 may regulate CIRI through the classic RIPK1-RIPK3-MLKL necroptosis pathway.
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Acknowledgements
This project was supported by the National Science and Technology Major Project of the Ministry of Science and Technology of China [2016ZX09101031] and [2019ZX09301-134], the China Pharmaceutical University “Double First-Class” Construction Technology Innovation Team Project [CPU2018GY23] and [CPU2018GY24] and the National Natural Science Foundation of China [82073845].
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WL and XG: were involved in collecting information and writing a draft of the manuscript. DX, LZ, FL and AY: consolidated information and were involved in modifying the article. YL and YH were involved in selecting the theme. All the authors read and approved the final manuscript. The authors declare that all the data were generated in-house and that no paper mill was used.
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Li, W., Gou, X., Xu, D. et al. Therapeutic effects of JLX001 on neuronal necroptosis after cerebral ischemia–reperfusion in rats. Exp Brain Res 240, 3167–3182 (2022). https://doi.org/10.1007/s00221-022-06474-9
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DOI: https://doi.org/10.1007/s00221-022-06474-9