Calenduloside E Ameliorates Myocardial Ischemia-Reperfusion Injury through Regulation of AMPK and Mitochondrial OPA1

Wang, Min; Wang, Ruiying; Zhou, Jiahui; Xie, Xueheng; Sun, Guibo; Sun, Xiaobo

doi:10.1155/2020/2415269

Cited by 23 publications

(28 citation statements)

References 30 publications

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“…4c). Consistent with our findings, Wang et al found that CE can ameliorate myocardial I/R injury by reversing I/R-induced cardiac dysfunction and inhibiting infarct size (Wang et al 2020a). Interestingly, our results also showed that CE treatment at doses of ≥ 16 µg/mL inhibited cell viability in HT22 cells (Fig.…”

Section: Ce Treatment Ameliorated Neurological Deficits and Brain Inj...supporting

confidence: 92%

Calenduloside E alleviates cerebral ischemia/reperfusion injury by preserving mitochondrial function

et al. 2022

J Mol Histol

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Calenduloside E (CE) isolated from Aralia elata (Miq.) Seem. is a natural triterpenoid saponin that can reportedly ameliorate myocardial ischemia/reperfusion injury. However, its potential roles and mechanism in cerebral ischemia/reperfusion injury are barely understood. In this study, we established an oxygen-glucose deprivation/reoxygenation (OGD/R) model in HT22 cells. We found that CE significantly attenuated the OGD/R-induced inhibition of cell viability and apoptotic cell death in HT22 cells. Moreover, CE treatment significantly ameliorated OGD/R-induced mitochondrial fission by inhibiting mitochondrial dynamin-related protein 1 (Drp1) recruitment and increasing Drp1 phosphorylation at Ser637. CE treatment significantly ameliorated OGD/R-induced mitochondrial dysfunction by increasing the mitochondrial membrane potential and reducing the mitochondrial ROS and cellular calcium accumulation. Moreover, CE treatment significantly inhibited the OGD/R-induced release of mitochondrial Cytochrome C and increase in Bax, Cleaved-caspase3 and Cleaved-caspase9 protein levels, whereas CE treatment significantly reversed the OGD/R-induced decrease in Bcl-2 and full length of caspase3 and caspase9 protein levels. In vivo, we found that CE treatment significantly ameliorated ischemic/hypoxic-induced brain infarct volume, neurological deficits, and neuronal apoptosis in mice after middle cerebral artery occlusion and reperfusion. CE treatment also significantly ameliorated the mitochondrial transmembrane potential, decreased Cytochrome C release, and reversed the increase in Bax, Cleaved-caspase3 and Cleaved-caspase9 protein levels and the decrease in Bcl-2 and full length of caspase3 and caspase9 protein levels induced by cerebral ischemia/reperfusion (I/R). All these results indicated that CE treatment exerted a neuroprotective effect by ameliorating mitochondrial dysfunction during cerebral I/R injury.

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Section: Ce Treatment Ameliorated Neurological Deficits and Brain Inj...supporting

confidence: 92%

Calenduloside E alleviates cerebral ischemia/reperfusion injury by preserving mitochondrial function

et al. 2022

J Mol Histol

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“…Recently, sappanone A (SA) postconditioning was demonstrated to ameliorate MIRI by regulating mitochondrial quality control via activating AMPK ( Shi et al, 2021 ). Calenduloside E (CE) is effective in mitigating MIRI by modulating AMPK-mediated OPA1-related mitochondrial fusion ( Wang et al, 2020 ). These studies strongly suggest that the activation of AMPK plays a crucial role in the prevention of MIRI by regulating the mitochondrial function.…”

Section: Introductionmentioning

confidence: 99%

AMPK Activation Alleviates Myocardial Ischemia-Reperfusion Injury by Regulating Drp1-Mediated Mitochondrial Dynamics

Li²,

Jin³

et al. 2022

Front. Pharmacol.

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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.

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“…Coenzyme Q10 can induce the AMPK-YAP-OPA1 cell signal transduction pathway, thus, improving mitochondrial function and reducing the degree of arteriosclerosis ( 114 ). Calenduloside E can reduce cardiac ischemia-reperfusion injury by regulating OPA1-related mitochondrial fusion mediated by AMPK activation ( 115 ). In the cardiomyocyte model of ischemia-reperfusion injury, increased expression of OPA1 can reduce the oxidative stress of cells through the Ca +2 /calmodulin-dependent protein kinase II (CaMKII signaling) pathway ( 116 ).…”

Section: Role Of Gtpase-dependent Fusion Proteins In Heart Diseasesmentioning

confidence: 99%

Role of GTPase-Dependent Mitochondrial Dynamins in Heart Diseases

Liu

Song

Yan

et al. 2021

Front. Cardiovasc. Med.

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Heart function maintenance requires a large amount of energy, which is supplied by the mitochondria. In addition to providing energy to cardiomyocytes, mitochondria also play an important role in maintaining cell function and homeostasis. Although adult cardiomyocyte mitochondria appear as independent, low-static organelles, morphological changes have been observed in cardiomyocyte mitochondria under stress or pathological conditions. Indeed, cardiac mitochondrial fission and fusion are involved in the occurrence and development of heart diseases. As mitochondrial fission and fusion are primarily regulated by mitochondrial dynamins in a GTPase-dependent manner, GTPase-dependent mitochondrial fusion (MFN1, MFN2, and OPA1) and fission (DRP1) proteins, which are abundant in the adult heart, can also be regulated in heart diseases. In fact, these dynamic proteins have been shown to play important roles in specific diseases, including ischemia-reperfusion injury, heart failure, and metabolic cardiomyopathy. This article reviews the role of GTPase-dependent mitochondrial fusion and fission protein-mediated mitochondrial dynamics in the occurrence and development of heart diseases.

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Calenduloside E Ameliorates Myocardial Ischemia-Reperfusion Injury through Regulation of AMPK and Mitochondrial OPA1

Cited by 23 publications

References 30 publications

Calenduloside E alleviates cerebral ischemia/reperfusion injury by preserving mitochondrial function

Calenduloside E alleviates cerebral ischemia/reperfusion injury by preserving mitochondrial function

AMPK Activation Alleviates Myocardial Ischemia-Reperfusion Injury by Regulating Drp1-Mediated Mitochondrial Dynamics

Role of GTPase-Dependent Mitochondrial Dynamins in Heart Diseases

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