Ilexgenin A Alleviates Myocardial Ferroptosis in Response to Ischemia Reperfusion Injury via the SIRT1 Pathway.

Autor: Yang B; Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Jue XY; Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Luo SF; The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China., Tan ZB; Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Yang LN; Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Feng YT; Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Tan YZ; Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Liu B; Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Zhang JZ; Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Deng B; Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Wu WW; Department of Rehabilitation, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Zhang SW; Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Jazyk: angličtina
Zdroj: Phytotherapy research : PTR [Phytother Res] 2024 Dec 19. Date of Electronic Publication: 2024 Dec 19.
DOI: 10.1002/ptr.8414
Abstrakt: Myocardial ischemia-reperfusion (I/R) injury has emerged as an increasingly serious cardiovascular health concern worldwide, with ferroptosis playing a pivotal role as the underlying pathogenic process. This study aimed to investigate the pharmacological effect and mechanism of Ilexgenin A on cardiomyocyte ferroptosis induced by myocardial I/R injury. In vivo, we established a murine anterior descending artery ligation/recanalization model to evaluate the cardioprotective effect of Ilexgenin A. Bioinformatics analysis, molecular docking, and Surface Plasmon Resonance imaging were conducted to predict the pharmacological targets of Ilexgenin A. In vitro experiments, the neonatal rat cardiomyocytes (NRCMs) were utilized to further explore the mechanism of Ilexgenin A in inhibiting ferroptosis using chemiluminescence and immunofluorescence staining, electron microscopy, biochemical assay, RT-qPCR, western blotting, and so on. The results showed that Ilexgenin A protected against cardiac dysfunction, ameliorated myocardial ferroptosis and mitochondrial damage induced by murine myocardial I/R injury via the silence information regulator 1 (SIRT1) pathway, the trend was consistently observed in NRCMs. Additionally, the SIRT1 knockdown by siRNA delivery partially abrogated the beneficial effects of Ilexgenin A on ameliorating mitochondrial damage, and then aggravated erastin-induced ferroptosis in NRCMs. Overall, Our research demonstrated that the inhibition of ferroptosis via the SIRT1 pathway was one of the mechanisms by which Ilexgenin A exerted cardioprotective effect.
(© 2024 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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