Dataset Information

Atractylenolide I alleviates ischemia/reperfusion injury by preserving mitochondrial function and inhibiting caspase-3 activity.

ABSTRACT:

Objective

Myocardial ischemia/reperfusion (I/R) injury causes various severe heart diseases, including myocardial infarction. This study aimed to determine the therapeutic effect of atractylenolide I (ATR-I), which is an active ingredient isolated from Atractylodes macrocephala, on myocardial I/R injury.

Methods

Male Sprague-Dawley rats were randomly allocated to the five following groups (nine rats/group): control, I/R, and I/R?+?ATR-I preconditioning (10, 50, and 250 µg). The effects of ATR-I on rats with I/R injury were verified in cardiomyocytes with hypoxia/reoxygenation. Production of reactive oxygen species was determined. The proliferative ability of cardiomyocytes was detected using the bromodeoxyuridine assay. Mitochondrial membrane potential was measured using flow cytometry. Cellular apoptosis was assessed by flow cytometry and the terminal dUTP-digoxigenin nick end labeling assay.

Results

I/R and hypoxia/reoxygenation injury increased mitochondrial dysfunction and activated caspase-3 and Bax/B cell lymphoma 2 expression in vitro and in vivo. ATR-I pretreatment dose-dependently significantly attenuated myocardial apoptosis and suppressed oxidative stress as reflected by increased mitochondrial DNA copy number and superoxide dismutase activity, and decreased reactive oxygen species and Ca²⁺ content.

Conclusion

ATR-I protects against I/R injury by protecting mitochondrial function and inhibiting activation of caspase-3.

SUBMITTER: Sun C

PROVIDER: S-EPMC7923999 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Atractylenolide I alleviates ischemia/reperfusion injury by preserving mitochondrial function and inhibiting caspase-3 activity.

Sun Caiqin C Zhang Xuesong X Yu Fei F Liu Chen C Hu Fangbin F Liu Li L Chen Jing J Wang Jue J

The Journal of international medical research 20210201 2

<h4>Objective</h4>Myocardial ischemia/reperfusion (I/R) injury causes various severe heart diseases, including myocardial infarction. This study aimed to determine the therapeutic effect of atractylenolide I (ATR-I), which is an active ingredient isolated from <i>Atractylodes macrocephala</i>, on myocardial I/R injury.<h4>Methods</h4>Male Sprague-Dawley rats were randomly allocated to the five following groups (nine rats/group): control, I/R, and I/R + ATR-I preconditioning (10, 50, and 250 µg). ...[more]

PMID: 33641489

Similar Datasets

Project description:Mitochondrial dysfunction is a salient feature of myocardial ischemia/reperfusion injury (MIRI), while the potential mechanism of mitochondrial dynamics disorder remains unclear. This study sought to explore whether activation of Adenosine monophosphate-activated protein kinase (AMPK) could alleviate MIRI by regulating GTPase dynamin-related protein 1 (Drp1)-mediated mitochondrial dynamics. Isolated mouse hearts in a Langendorff perfusion system were subjected to ischemia/reperfusion (I/R) treatment, and H9C2 cells were subjected to hypoxia /reoxygenation (H/R) treatment in vitro. The results showed that AICAR, the AMPK activator, could significantly improve the function of left ventricular, decrease arrhythmia incidence and myocardial infarction area of isolated hearts. Meanwhile, AICAR increased superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) content in myocardial homogenate. Mechanistically, AICAR inhibited the phosphorylation of Drp1 at Ser 616 while enhanced phosphorylation of Drp1 at Ser 637. In addition, AICAR reduced the expression of inflammatory cytokines including TNF-ɑ, IL-6, and IL-1β, as well as mitochondrial fission genes Mff and Fis1, while improved the expression of mitochondrial fusion genes Mfn1 and Mfn2. Similar results were also observed in H9C2 cells. AICAR improved mitochondrial membrane potential (MMP), reduced reactive oxygen species (ROS) production, and inhibited mitochondrial damage. To further prove if Drp1 regulated mitochondrial dynamics mediated AMPK protection effect, the mitochondrial fission inhibitor Mdivi-1 was utilized. We found that Mdivi-1 significantly improved MMP, inhibited ROS production, reduced the expression of TNF-a, IL-6, IL-1β, Fis1, and Mff, and improved the expression of Mfn1 and Mfn2. However, the protection effect of Mdivi-1 was not reversed by AMPK inhibitor Compound C. In conclusion, this study confirmed that activation of AMPK exerted the protective effects on MIRI, which were largely dependent on the inhibition of Drp1-mediated mitochondrial fission.

Dataset Information

Atractylenolide I alleviates ischemia/reperfusion injury by preserving mitochondrial function and inhibiting caspase-3 activity.

Objective

Methods

Results

Conclusion

Publications

Atractylenolide I alleviates ischemia/reperfusion injury by preserving mitochondrial function and inhibiting caspase-3 activity.

Similar Datasets

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