Panax Notoginseng Saponins Protect H9c2 Cells From Hypoxia-reoxygenation Injury Through the Forkhead Box O3a Hypoxia-inducible Factor-1 Alpha Cell Signaling Pathway

Liu, Xinwen; Lu, Meng-Kai; Zhong, Huiting; Liu, Jingjing; Fu, Yongping

doi:10.1097/fjc.0000000000001120

Cited by 10 publications

(5 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, certain medications such as ryanodine, JNK inhibitors, berberine, and trimetazidine have shown potential in heart protection by either inhibiting autophagy or enhancing mitochondrial repair. Additionally, distinct non-coding RNAs that target autophagy have emerged as pivotal players in MIRI [44,71]. Consequently, the ongoing quest to pinpoint precise cellular mechanisms, sustain optimal autophagic processes, and curtail excessive autophagy represents a central therapeutic endeavor, offering a promising outlook for future strategies in addressing MIRI and enhancing cardiac protection.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Integrated bioinformatics identify the critical genes of mitophagy in myocardial ischemia- reperfusion injury

Chen,

Liu,

Yuan

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: Myocardial ischemia is a prevalent cardiovascular disease with a high incidence and mortality rate. Restoring blood flow to the ischemic myocardium as soon as possible is crucial for improving patients' prognosis, but this process can lead to myocardial ischemia-reperfusion injury (MIRI). Mitophagy is a specific cellular autophagic process that has been consistently linked to various cardiovascular disorders.Nevertheless, the connection between ischemia-reperfusion and mitophagy remains unclear. This study's objective is to discern and substantiate central mitophagy-related genes associated with MIRI through bioinformatics analysis. Methods: The microarray expression profile dataset (GSE108940) was obtained from the Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) were identified using GEO2R. These DEGs were then cross-referenced with genes in the mitophagy database. Differential nucleotide sequence analysis used enrichment analysis.The DEGs were obtained through protein-protein interaction (PPI)network analysis. And the hub genes were clustered by cytoHubba and MCODE of Cytoscape software. GSEA analysis was conducted on central genes. Finally, we conducted Western blotting, immunofluorescence, and quantitative polymerase chain reaction (qPCR) analyses to corroborate the expression patterns of pivotal genes in MIRI-afflicted rats. Results: 2719 DEGs and 61 mitophagy-DEGs were obtained,followed by enrichment analyses and construction of PPI network. HSP90AA1, RPS27A, EEF2, EIF4A1, EIF2S1,HIF-1α and BNIP3 were the 7 hub genes identified by cytoHubba and MCODE of Cytoscape software. The functional clustering score of HIF-1α and BNIP3 was 9.647 by analysis of Cytoscape (MCODE). In our constructed MIRI rat model, western blot and immunofluorescence confirmed a significant elevation in the expression of HIF-1α and BNIP3, along with a significant increase in the ratio of LC3II to LC3I. Finally,qPCR confirmed that expression of HIF-1α, BNIP3 and LC3 mRNA in MIRI group was elevated significantly. Conclusions: Seven central genes among the mitophagy-related DEGs have been pinpointed, potentially holding pivotal significance in MIRI, which indicated that HIF-1α/BNIP3 pathway of mitophag was correlated with pathogenesis of MIRI. Mitophagy may play an important role in MIRI.This research will offer valuable insights into the underlying mechanisms and potential therapeutic targets, which can be explored in future studies.

show abstract

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Integrated bioinformatics identify the critical genes of mitophagy in myocardial ischemia- reperfusion injury

Chen,

Liu,

Yuan

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Furthermore, certain medications such as ryanodine, JNK inhibitors, berberine, and trimetazidine have shown potential in heart protection by either inhibiting autophagy or enhancing mitochondrial repair. Additionally, distinct non-coding RNAs that target autophagy have emerged as pivotal players in MIRI [ 72 ]. Consequently, the ongoing quest to pinpoint precise cellular mechanisms, sustain optimal autophagic processes, and curtail excessive autophagy represents a central therapeutic endeavor, offering a promising outlook for future strategies in addressing MIRI and enhancing cardiac protection.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics integration reveals key genes associated with mitophagy in myocardial ischemia-reperfusion injury

Chen,

Liu,

Yuan

et al. 2024

BMC Cardiovasc Disord

View full text Add to dashboard Cite

Background Myocardial ischemia is a prevalent cardiovascular disorder associated with significant morbidity and mortality. While prompt restoration of blood flow is essential for improving patient outcomes, the subsequent reperfusion process can result in myocardial ischemia–reperfusion injury (MIRI). Mitophagy, a specialized autophagic mechanism, has consistently been implicated in various cardiovascular disorders. However, the specific connection between ischemia–reperfusion and mitophagy remains elusive. This study aims to elucidate and validate central mitophagy-related genes associated with MIRI through comprehensive bioinformatics analysis. Methods We acquired the microarray expression profile dataset (GSE108940) from the Gene Expression Omnibus (GEO) and identified differentially expressed genes (DEGs) using GEO2R. Subsequently, these DEGs were cross-referenced with the mitophagy database, and differential nucleotide sequence analysis was performed through enrichment analysis. Protein–protein interaction (PPI) network analysis was employed to identify hub genes, followed by clustering of these hub genes using cytoHubba and MCODE within Cytoscape software. Gene set enrichment analysis (GSEA) was conducted on central genes. Additionally, Western blotting, immunofluorescence, and quantitative polymerase chain reaction (qPCR) analyses were conducted to validate the expression patterns of pivotal genes in MIRI rat model and H9C2 cardiomyocytes. Results A total of 2719 DEGs and 61 mitophagy-DEGs were identified, followed by enrichment analyses and the construction of a PPI network. HSP90AA1, RPS27A, EEF2, EIF4A1, EIF2S1, HIF-1α, and BNIP3 emerged as the seven hub genes identified by cytoHubba and MCODE of Cytoscape software. Functional clustering analysis of HIF-1α and BNIP3 yielded a score of 9.647, as determined by Cytoscape (MCODE). In our MIRI rat model, Western blot and immunofluorescence analyses confirmed a significant elevation in the expression of HIF-1α and BNIP3, accompanied by a notable increase in the ratio of LC3II to LC3I. Subsequently, qPCR confirmed a significant upregulation of HIF-1α, BNIP3, and LC3 mRNA in the MIRI group. Activation of the HIF-1α/BNIP3 pathway mediates the regulation of the degree of Mitophagy, thereby effectively reducing apoptosis in rat H9C2 cardiomyocytes. Conclusions This study has identified seven central genes among mitophagy-related DEGs that may play a pivotal role in MIRI, suggesting a correlation between the HIF-1α/BNIP3 pathway of mitophagy and the pathogenesis of MIRI. The findings highlight the potential importance of mitophagy in MIRI and provide valuable insights into underlying mechanisms and potential therapeutic targets for further exploration in future studies.

show abstract

“…Na + -K + -ATPase activity decreased significantly after MIRI ( 48 ). This situation increases intracellular Na + , and more Ca 2+ enters the cell through Na + -Ca 2+ exchange, resulting in calcium overload ( 49 – 51 ). Total saponins of A. Elata (aralosides, AS) can significantly increase the activity of Na + -K + -ATPase and Ca 2+ -Mg 2+ -ATPase ( 17 ).…”

Section: Discussionmentioning

confidence: 99%

Effect and possible mechanisms of saponins in Chinese herbal medicine exerts for the treatment of myocardial ischemia-reperfusion injury in experimental animal: a systematic review and meta-analysis

Sun¹,

Fan²,

Yang³

et al. 2023

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

IntroductionPreventing ischemia-reperfusion injury is the main direction of myocardial infarction treatment in the convalescent stage. Some studies have suggested that saponins in Traditional Chinese medicine (TCM) preparations can protect the myocardium by various mechanisms. Our meta-analysis aims to evaluate the efficacy of TCM saponins in treating myocardial ischemia-reperfusion injury (MIRI) and to summarize the potential molecular mechanisms further.MethodsWe conducted a literature search in six electronic databases [Web of Science, PubMed, Embase, Cochrane Library, Sinomed, China National Knowledge Infrastructure (CNKI)] until October 2022.ResultsSeventeen eligible studies included 386 animals (254 received saponins and 132 received vehicles). The random effect model is used to calculate the combined effect. The effect size is expressed as the weighted average difference (WMD) and 95% confidence interval (CI). Compared with placebo, saponins preconditioning reduced infarct size after MIRI significantly (WMD: −3.60,95% CI: −4.45 to −2.74, P < 0.01, I2: 84.7%, P < 0.001), and significantly increased EF (WMD: 3.119, 95% CI: 2.165 to 4.082, P < 0.01, I2: 82.9%, P < 0.0 L) and FS (WMD: 3.157, 95% CI: 2.218 to 4.097, P < 0.001, I2: 81.3%, P < 0.001).DiscussionThe results show that the pre-administration of saponins from TCM has a significant protective effect on MIRI in preclinical studies, which provides an application prospect for developing anti-MIRI drugs with high efficiency and low toxicity.

show abstract

Panax Notoginseng Saponins Protect H9c2 Cells From Hypoxia-reoxygenation Injury Through the Forkhead Box O3a Hypoxia-inducible Factor-1 Alpha Cell Signaling Pathway

Cited by 10 publications

References 36 publications

WITHDRAWN: Integrated bioinformatics identify the critical genes of mitophagy in myocardial ischemia- reperfusion injury

WITHDRAWN: Integrated bioinformatics identify the critical genes of mitophagy in myocardial ischemia- reperfusion injury

Bioinformatics integration reveals key genes associated with mitophagy in myocardial ischemia-reperfusion injury

Effect and possible mechanisms of saponins in Chinese herbal medicine exerts for the treatment of myocardial ischemia-reperfusion injury in experimental animal: a systematic review and meta-analysis

Contact Info

Product

Resources

About