Naringenin improves mitochondrial function and reduces cardiac damage following ischemia-reperfusion injury: the role of the AMPK-SIRT3 signaling pathway

Yu, Liming; Dong, Xue; Xue, Xiaodong; Zhang, Jian; Li, Zhi; Wu, Hongjiang; Yang, Zhaohui; Yang, Yang; Wang, Huishan

doi:10.1039/c9fo00001a

Cited by 82 publications

(53 citation statements)

References 57 publications

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“…Yu, et al found that naringenin ameliorated ischaemia-reperfusion injury mainly by activation of AMPK-SIRT3 signalling pathway. 25 In their study, inhibition of AMPK by AMPK1α siRNA or Compound C (AMPK inhibitor) markedly suppressed SIRT3 levels, and however, SIRT3 siRNA could not significantly change AMPK phosphorylation, showing that SIRT3 was the down-stream target of AMPK. Therefore, the above studies hinted that a crosstalk may exist between AMPK and SIRT3 signalling.…”

Section: Discussionmentioning

confidence: 94%

“…23 Interestingly, SIRT3 has been reported as a downstream effector of AMPK in several disease models, and activation of AMPK-SIRT3 signalling contributes to the improvement of mitochondrial function, thus alleviating the progress of diseases. 24,25 However, in liver fibrosis, whether celastrol regulate AMPK-SIRT3 signalling remains poorly understood. Moreover, whether activation of AMPK-SIRT3 signalling contributes to the anti-inflammatory effect of celastrol remains to be determined.…”

Section: The Active Ingredients Extracted From Traditional Chinesementioning

confidence: 99%

“…AMPK has been proved involved in the pathophysiology of liver fibrosis, and up‐regulation of AMPK phosphorylation facilitated to the attenuation of liver fibrosis . Interestingly, SIRT3 has been reported as a downstream effector of AMPK in several disease models, and activation of AMPK‐SIRT3 signalling contributes to the improvement of mitochondrial function, thus alleviating the progress of diseases …”

Section: Introductionmentioning

confidence: 99%

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Celastrol exerts anti‐inflammatory effect in liver fibrosis via activation of AMPK‐SIRT3 signalling

Wang

et al. 2019

J Cellular Molecular Medi

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Celastrol, a pentacyclic tritepene extracted from Tripterygium Wilfordi plant, showing potent liver protection effects on several liver‐related diseases. However, the anti‐inflammatory potential of celastrol in liver fibrosis and the detailed mechanisms remain uncovered. This study was to investigate the anti‐inflammatory effect of celastrol in liver fibrosis and to further reveal mechanisms of celastrol‐induced anti‐inflammatory effects with a focus on AMPK‐SIRT3 signalling. Celastrol showed potent ameliorative effects on liver fibrosis both in activated hepatic stellate cells (HSCs) and in fibrotic liver. Celastrol remarkably suppressed inflammation in vivo and inhibited the secretion of inflammatory factors in vitro. Interestingly, celastrol increased SIRT3 promoter activity and SIRT3 expression both in fibrotic liver and in activated HSCs. Furthermore, SIRT3 silencing evidently ameliorated the anti‐inflammatory potential of celastrol. Besides, we found that celastrol could increase the AMPK phosphorylation. Further investigation showed that SIRT3 siRNA decreased SIRT3 expression but had no obvious effect on phosphorylation of AMPK. In addition, inhibition of AMPK by employing compound C (an AMPK inhibitor) or AMPK1α siRNA significantly suppressed SIRT3 expression, suggesting that AMPK was an up‐stream protein of SIRT3 in liver fibrosis. We further found that depletion of AMPK significantly attenuated the inhibitory effect of celastrol on inflammation. Collectively, celastrol attenuated liver fibrosis mainly through inhibition of inflammation by activating AMPK‐SIRT3 signalling, which makes celastrol be a potential candidate compound in treating or protecting against liver fibrosis.

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Section: Discussionmentioning

confidence: 94%

Section: The Active Ingredients Extracted From Traditional Chinesementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Celastrol exerts anti‐inflammatory effect in liver fibrosis via activation of AMPK‐SIRT3 signalling

Wang

et al. 2019

J Cellular Molecular Medi

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“…Previous studies have demonstrated that phosphorytion of AMPK could up-regulate LXRα expression (38). Flavonoids, such as naringenin and quercetin, were considered as the effective therapeutic approaches that appear to influence AMPK (39,40). Recently, Hajar Furthermore specific AMPKα1/α2 siRNA transfection was performed to validate the role of AMPK in LXRα and its target genes.…”

Section: Discussionmentioning

confidence: 99%

Hesperetin inhibits foam cell formation in macrophages via activating LXRα signal in an AMPK dependent manner

Chen

Zou

Chen

et al. 2020

Preprint

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Abbreviations:ABCA1: ATP-binding cassette subfamily A member 1 ABCG1: ATP-binding cassette subfamily G member 1 ABCG5: ATP-binding cassette subfamily G member 5 AMPK: adenosine monophosphate activated protein kinases CE: cholesterol ester CER: Cholesterol esterification rate LXRα: liver X receptor alpha pAMPK: phosphorylated-AMPK RCT: cholesterol reverse transport SR-BI: scavenger receptor class B type I TC: total cholesterol Abstract Cholesterol efflux from macrophages is the first step of cholesterol reverse transport (RCT), whose increase inhibits cholesterol accumulation and foam cell formation to suppress atherogenesis. Liver X receptor alpha (LXRα) and adenosine monophosphate activated protein kinases (AMPK) both have the pivotal role in cholesterol homeostasis. However the association between these two molecules in cell model of atherosclerosis is poorly understood.Hesperetin has been reported to possess several protective effects for cardiovascular diseases, while little is known about the role of hesperetin and its underlying mechanism on macrophage foam cell formation. In this study, we sought to investigate the potential effects of hesperetin in cholesterol efflux by using human macrophage derived foam cells, focusing on liver X receptor alpha (LXRα) and adenosine monophosphate activated protein kinases (AMPK) implication. Hesperetin treatment concentration-dependently reduced foam cell formation, intracellular cholesterol level and cholesterol esterification rate, and enhanced cholesterol efflux in THP-1 macrophages. Hesperetin upregulated the protein levels of LXRα and its targets including ABCA1, ABCG1 as well as SR-BI, and phosphorylated-AMPK.Meanwhile, hesperetin-induced upregulation of LXRα expression was enhanced by AMPK agonist and inhibited by AMPK inhibitor. Furthermore, hesperetin increased mRNA level of LXRα and its target genes, all which were depressed by AMPKα1/α2 small interfering RNA (siRNA) transfection. In conclusion, we founded for the first time that hesperetin could active AMPK. And this activation upregulated LXRα and its targets including ABCA1, ABCG1 and SR-BI, which significantly inhibited foam cell formation and promoted cholesterol efflux in THP-1 macrophages. Our results highlight the therapeutic potential of hespretin for the possible reduction in foam cell formation. This new mechanism could contribute the anti-atherogenic effects of hesperetin.

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“…It ameliorates hypoxia/reoxygenation-induced ER stress-mediated apoptosis in H9c2 cells via activating transcription factor 6 (ATF6), inositol-requiring enzyme1α (IRE1α) and ERK signaling activation [ 200 ]. A previous report has shown that naringin improves mitochondrial function and reduces cardiac damage following I-R injury via the AMP-activated protein kinase (AMPK)-sirtuin 3 signaling pathway [ 201 ].…”

Section: Exogenous Natural Antioxidants To Protect Cardiac Muscle From Oxidative Stressmentioning

confidence: 99%

Modulations of Cardiac Functions and Pathogenesis by Reactive Oxygen Species and Natural Antioxidants

et al. 2021

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Homeostasis in the level of reactive oxygen species (ROS) in cardiac myocytes plays a critical role in regulating their physiological functions. Disturbance of balance between generation and removal of ROS is a major cause of cardiac myocyte remodeling, dysfunction, and failure. Cardiac myocytes possess several ROS-producing pathways, such as mitochondrial electron transport chain, NADPH oxidases, and nitric oxide synthases, and have endogenous antioxidation mechanisms. Cardiac Ca2+-signaling toolkit proteins, as well as mitochondrial functions, are largely modulated by ROS under physiological and pathological conditions, thereby producing alterations in contraction, membrane conductivity, cell metabolism and cell growth and death. Mechanical stresses under hypertension, post-myocardial infarction, heart failure, and valve diseases are the main causes for stress-induced cardiac remodeling and functional failure, which are associated with ROS-induced pathogenesis. Experimental evidence demonstrates that many cardioprotective natural antioxidants, enriched in foods or herbs, exert beneficial effects on cardiac functions (Ca2+ signal, contractility and rhythm), myocytes remodeling, inflammation and death in pathological hearts. The review may provide knowledge and insight into the modulation of cardiac pathogenesis by ROS and natural antioxidants.

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Naringenin improves mitochondrial function and reduces cardiac damage following ischemia-reperfusion injury: the role of the AMPK-SIRT3 signaling pathway

Abstract: Naringenin directly inhibits mitochondrial oxidative stress damage and preserves mitochondrial biogenesis via AMPK-SIRT3 signaling, thus attenuating MI/R injury.

Cited by 82 publications

References 57 publications

Celastrol exerts anti‐inflammatory effect in liver fibrosis via activation of AMPK‐SIRT3 signalling

Celastrol exerts anti‐inflammatory effect in liver fibrosis via activation of AMPK‐SIRT3 signalling

Hesperetin inhibits foam cell formation in macrophages via activating LXRα signal in an AMPK dependent manner

Modulations of Cardiac Functions and Pathogenesis by Reactive Oxygen Species and Natural Antioxidants

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