Research progress on the effects of novel hypoglycemic drugs in diabetes combined with myocardial ischemia/reperfusion injury

Yang, Tiangui; Zhang, Daqing

doi:10.1016/j.arr.2023.101884

Cited by 4 publications

(2 citation statements)

References 119 publications

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“…MIRI is a pathological process that occurs when blood ow is restored to the ischaemic myocardial tissue while causing stress injury. Myocardial I/R injury is associated with severe clinical manifestations leading to a high incidence of cardiac insu ciency and heart failure [11]. There are no effective methods to reduce MI/RI, so early intervention is particularly important, and TCM has unique advantages in this regard [12].…”

Section: Discussionmentioning

confidence: 99%

Shuangshen Ningxin Capsule alleviates myocardial ischemia-reperfusion injury in miniature pigs by modulating mitophagy:network pharmacology and experiments in vivo

Jia

Chen

Xin

et al. 2023

Preprint

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Background:Myocardial ischemia/reperfusion injury (MI/RI) is a common pathological basis for several cardiovascular diseases, for which no effective treatment exists. Shuangshen Ningxin (SSNX) capsule which is developed by Xiyuan Hospital, Chinese Academy of Traditional Chinese Medicine has been demonstrated to alleviate MI/RI, but its mechanism remains to be further elucidated. Methods: The MI/RI miniature pigs model was constructed to evaluate the pharmacodynamics of SSNX by blocking the proximal blood flow of the left anterior descending branch of the cardiac coronary artery through an interventional balloon. The major chemical compounds and potential targets of SSNX were screened by HPLC-MS and SwissTargetPrediction. The targets of MI/RI were identified based on Online Mendelian Inheritance in Man(OMIM) and GeneCards. Cytoscape 3.9.0 was applied to construct a protein-protein interaction (PPI) network, and Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using metascape. To further validate the mechanism of SSNX, Molecular docking, Transmission electron microscopy, and Western blot analysis were used to test the effectiveness of targets in related pathways. Results:The result of experiment in vivo confirmed that SSNX significantly improved cardiac function, attenuated myocardial I/R injury. Through network analysis, a total of 15 active components and 201 targets were obtained from SSNX, 75 of which are potential targets for the treatment of MI/RI. KEGG and MCODE analysis showed that SSNX is involved in the mitophagy signaling pathway, and ginsenoside Rg1, ginsenoside Rb1 and ginsenoside Rb2 are key components associated with the mitophagy. Further experimental results proved that SSNX protected mitochondrial structure and function, and significantly reduced the expression of mitophagy-related proteins PINK1, Parkin, FUNDC1 and BNIP3 in MI/RI miniature pigs. Conclusion:In this study, the integration of network pharmacology and experiments in vivo demonstrated that SSNX interfered with MI/RI by inhibiting mitophagy.

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Section: Discussionmentioning

confidence: 99%

Shuangshen Ningxin Capsule alleviates myocardial ischemia-reperfusion injury in miniature pigs by modulating mitophagy:network pharmacology and experiments in vivo

Jia

Chen

Xin

et al. 2023

Preprint

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“…It is caused by ectopic thrombosis or the rupture of lipid plaques at the site of coronary artery lesions, leading to acute occlusion of the coronary artery and subsequent acute ischemia and hypoxia in the cardiomyocyte (Han et al, 2023). Currently, timely and effective reperfusion treatments, such as thrombolysis, percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG) can be used to restore blood flow (Yang & Zhang, 2023). However, a substantial amount of clinical evidence and experimental research has shown that myocardial ischemia‐reperfusion injury (MIRI) can counteract the effects of reperfusion therapy to some extent (Ye et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

cFLIP_L alleviates myocardial ischemia‐reperfusion injury by regulating pyroptosis

Zhang,

Wu,

Liu

et al. 2023

Cell Biology International

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Alleviating myocardial ischemia‐reperfusion injury (MIRI) plays a critical role in the prognosis and improvement of cardiac function following acute myocardial infarction. Pyroptosis is a newly identified form of cell death that has been implicated in the regulation of MIRI. In our study, H9c2 cells and SD rats were transfected using a recombinant adenovirus vector carrying cFLIPL, and the transfection was conducted for 3 days. Subsequently, H9c2 cells were subjected to 4 h of hypoxia followed by 12 h of reoxygenation to simulate an in vitro ischemia‐reperfusion model. SD rats underwent 30 min of ischemia followed by 2 h of reperfusion to establish an MIRI model. Our findings revealed a notable decrease in cFLIPL expression in response to ischemia/reperfusion (I/R) and hypoxia/reoxygenation (H/R) injuries. Overexpression of cFLIPL can inhibit pyroptosis, reducing myocardial infarction area in vivo, and enhancing H9c2 cell viability in vitro. I/R and H/R injuries induced the upregulation of ASC, cleaved Caspase 1, NLRP3, GSDMD‐N, IL‐1β, and IL‐18 proteins, promoting cell apoptosis. Our research indicates that cFLIPL may suppress pyroptosis by strategically binding with Caspase 1, inhibiting the release of inflammatory cytokines and preventing cell membrane rupture. Therefore, cFLIPL could potentially serve as a promising target for alleviating MIRI by suppressing the pyroptotic pathway.

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Shuangshen Ningxin capsule alleviates myocardial ischemia–reperfusion injury in miniature pigs by modulating mitophagy: network pharmacology and experiments in vivo

Jia,

Chen,

Xin

et al. 2023

Chin Med

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Background Myocardial ischemia/reperfusion injury (MI/RI) is involved in a variety of pathological states for which there is no effective treatment exists. Shuangshen Ningxin (SSNX) capsule which is developed by Xiyuan Hospital, Chinese Academy of Traditional Chinese Medicine has been demonstrated to alleviate MI/RI, but its mechanism remains to be further elucidated. Methods The MI/RI miniature pigs model was constructed to assess the pharmacodynamics of SSNX by blocking the proximal blood flow of the left anterior descending branch of the cardiac coronary artery through an interventional balloon. The principal chemical compounds and potential targets of SSNX were screened by HPLC–MS and SwissTargetPrediction. The targets of MI/RI were identified based on Online Mendelian Inheritance in Man (OMIM) and GeneCards. Cytoscape 3.9.0 was applied to construct a protein–protein interaction (PPI) network, and Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using metascape. To further validate the mechanism of SSNX, Molecular docking, Transmission electron microscopy, and Western blot analysis were used to test the effectiveness of targets in related pathways. Results Our results indicated that SSNX significantly improved cardiac function, attenuated myocardial I/R injury. Through network analysis, a total of 15 active components and 201 targets were obtained from SSNX, 75 of which are potential targets for the treatment of MI/RI. KEGG and MCODE analysis showed that SSNX is involved in the mitophagy signaling pathway, and ginsenoside Rg1, ginsenoside Rb1 and ginsenoside Rb2 are key components associated with the mitophagy. Further experimental results proved that SSNX protected mitochondrial structure and function, and significantly reduced the expression of mitophagy-related proteins PTEN-induced putative kinase 1 (PINK1), Parkin, FUN14 domain containing 1 (FUNDC1) and Bcl-2/E1B-19 kDa interacting protein 3 (BNIP3) in MI/RI miniature pigs. Conclusion In our study, the integration of network pharmacology and experiments in vivo demonstrated that SSNX interfered with MI/RI by inhibiting mitophagy.

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Research progress on the effects of novel hypoglycemic drugs in diabetes combined with myocardial ischemia/reperfusion injury

Cited by 4 publications

References 119 publications

Shuangshen Ningxin Capsule alleviates myocardial ischemia-reperfusion injury in miniature pigs by modulating mitophagy:network pharmacology and experiments in vivo

Shuangshen Ningxin Capsule alleviates myocardial ischemia-reperfusion injury in miniature pigs by modulating mitophagy:network pharmacology and experiments in vivo

cFLIP_L alleviates myocardial ischemia‐reperfusion injury by regulating pyroptosis

Shuangshen Ningxin capsule alleviates myocardial ischemia–reperfusion injury in miniature pigs by modulating mitophagy: network pharmacology and experiments in vivo

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Research progress on the effects of novel hypoglycemic drugs in diabetes combined with myocardial ischemia/reperfusion injury

Cited by 4 publications

References 119 publications

Shuangshen Ningxin Capsule alleviates myocardial ischemia-reperfusion injury in miniature pigs by modulating mitophagy:network pharmacology and experiments in vivo

Shuangshen Ningxin Capsule alleviates myocardial ischemia-reperfusion injury in miniature pigs by modulating mitophagy:network pharmacology and experiments in vivo

cFLIPL alleviates myocardial ischemia‐reperfusion injury by regulating pyroptosis

Shuangshen Ningxin capsule alleviates myocardial ischemia–reperfusion injury in miniature pigs by modulating mitophagy: network pharmacology and experiments in vivo

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cFLIP_L alleviates myocardial ischemia‐reperfusion injury by regulating pyroptosis