Icariin protects cardiomyocytes against ischaemia/reperfusion injury by attenuating sirtuin 1‐dependent mitochondrial oxidative damage

Wu, Bing; Feng, Jianyu; Yu, Liming; Wang, Yanchun; Chen, Yongqing; Yan, Wei; Han, Jaeseok; Xiao, Feng; Zhang, Yu; Di, Shouyin; Ma, Zhiqiang; Fan, Chongxi; Ha, Xiaoqin

doi:10.1111/bph.14457

Cited by 77 publications

(55 citation statements)

References 84 publications

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“…Cardiac Myocyte Apoptosis. Previous studies confirmed that oxidative stress and subsequent cardiac myocyte apoptosis play central roles in the initiation and progression of myocardial I/R injury [9,35]. We then assessed the role of Hotair in I/R-induced oxidative stress and cardiac myocyte apoptosis.…”

Section: Hotair Protects Against I/r-induced Oxidative Stress Andmentioning

confidence: 89%

“…H9c2 cells were purchased from ATCC (Manassas, VA, USA) and cultured in Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal bovine serum (FBS). To imitate the I/R injury in vitro, H9c2 cells were preincubated in Krebs buffer with pyruvate (5 μM) and sodium sulfite (50 μM) in the humidified incubator (5% CO 2 /95% N 2 , 37°C) for 2 hours, which were then replaced with fresh DMEM containing 10% FBS under normoxic conditions (5% CO 2 /95% air, 37°C) for additional 24 hours to generate hypoxia/reoxygenation (H/R) cell model according to previous studies with a little modifications [34,35]. To notify the role of BRD4 in vitro, H9c2 cells were incubated with small interfering RNA against BRD4 (siBrd4, 50 nM; #RSS338226, Thermo Fisher Scientific) using Lipofectamine RNAiMAX (Invitrogen) for 24 hours before H/R stimulation [32].…”

Section: Measurement Of Cardiac Troponin I (Ctni) N-terminal B-type mentioning

confidence: 99%

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The Long Noncoding RNA Hotair Regulates Oxidative Stress and Cardiac Myocyte Apoptosis during Ischemia-Reperfusion Injury

Meng

Jiao

Zhu

et al. 2020

Oxidative Medicine and Cellular Longevity

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Oxidative stress and subsequent cardiac myocyte apoptosis play central roles in the initiation and progression of myocardial ischemia-reperfusion (I/R) injury. Homeobox transcript antisense intergenic RNA (Hotair) was previously implicated in various heart diseases, yet its role in myocardial I/R injury has not been clearly demonstrated. Mice with cardiac-restricted knockdown or overexpression of Hotair were exposed to I/R surgery. H9c2 cells were cultured and subjected to hypoxia/reoxygenation (H/R) stimulation to further verify the role and underlying mechanisms of Hotair in vitro. Histological examination, molecular detection, and functional parameters were determined in vivo and in vitro. In response to I/R or H/R treatment, Hotair expression was increased in a bromodomain-containing protein 4-dependent manner. Cardiac-restricted knockdown of Hotair exacerbated, whereas Hotair overexpression prevented I/R-induced oxidative stress, cardiac myocyte apoptosis, and cardiac dysfunction. Mechanistically, we observed that Hotair exerted its beneficial effects via activating AMP-activated protein kinase alpha (AMPKα). Further detection revealed that Hotair activated AMPKα through regulating the enhancer of zeste homolog 2/microRNA-451/calcium-binding protein 39 (EZH2/miR-451/Cab39) axis. We provide the evidence that endogenous lncRNA Hotair is an essential negative regulator for oxidative stress and cardiac myocyte apoptosis in myocardial I/R injury, which is dependent on AMPKα activation via the EZH2/miR-451/Cab39 axis.

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Section: Hotair Protects Against I/r-induced Oxidative Stress Andmentioning

confidence: 89%

Section: Measurement Of Cardiac Troponin I (Ctni) N-terminal B-type mentioning

confidence: 99%

The Long Noncoding RNA Hotair Regulates Oxidative Stress and Cardiac Myocyte Apoptosis during Ischemia-Reperfusion Injury

Meng

Jiao

Zhu

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Results of the MTT assay and LDH release demonstrated that mPEG-ICA could decrease cell damage induced by OGD and that mPEG-ICA NPs could release ICA completely from particles. Previous studies have demonstrated that cardiomyocyte ischaemia leads to cytochrome C release from dysfunctional mitochondrial into the cytosol, then cytochrome C initiates apoptosis, which results in functional cell loss and decreased heart function [45,46].Therefore, anti-apoptosis is a new strategy for treating ischaemic cardiomyopathy. Traditional Chinese medicine, such as berberine, tetrandrine and resveratrol, can improve heart function and reverse cardiac remodelling by reducing apoptosis [47,48].…”

Section: Discussionmentioning

confidence: 99%

mPEG-icariin nanoparticles for treating myocardial ischaemia

Zheng

Yan

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Icariin (ICA), a major active ingredient from Chinese medicine, has unique pharmacological effects on ischaemic heart disease. However, its hydrophobic property limits its administration and leads to poor efficacy. This work aimed to change its hydrophobic property and improve the treatment efficacy. We designed a new nano-drug to increase the ICA delivery. ICA was modified with hydrophilic polyethylene glycol monomethyl ether (mPEG) by a succinic anhydride linker to form a polyethylene glycol-icariin (mPEG-ICA) polymer. The structure of this polymer was identified by Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The content of ICA in the polymer was 32% as detected by ultraviolet spectrophotometry. mPEG-ICA nanoparticles, of 143.3 nm, were prepared by the dialysis method, and zeta potential was 0.439 mV by dynamic light scattering. The nanoparticles had a spherical shape on transmission electron microscopy. In media with pH 7.4 and 6.8, ICA release from mPEG-ICA nanoparticles after 72 h was about 0.78% and 64.05%, respectively, so the ICA release depended on the release media pH. On MTT and lactate dehydrogenase activity assay, mPEG-ICA nanoparticles could reduce cell damage induced by oxgen-glucose deprivation. Hoechst 33258 staining and TUNEL and AnnexinV-FITC/PI double staining showed that ICA nanoparticles could increase the activity of H9c2 cardiomyocytes under oxgen-glucose deprivation conditions by decreasing apoptosis. ICA modified by hydrophilic mPEG could improve its efficacy.

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“…Icariin (C 33 H 40 O 15 , ICA) is a flavonoid monomer isolated from the herb Epimedium, and it has garnered attention for its prospects in pharmacology, including its cardioprotective functions (Zhou et al, 2014;Meng et al, 2015). Icariin protects cardiomyocytes against oxidative stress by activating sirtuin-1 (Wu et al, 2018), thereby alleviating oxidative stress-induced cardiac apoptosis via mitochondrial protection (Song et al, 2016), and protects cardiomyocytes from apoptosis induced by hypertrophy via inhibition of ROS-dependent JNK (Zhou et al, 2014). However, the protective effect of icariin against DCM has not yet been reported.…”

Section: Introductionmentioning

confidence: 99%

Icariin Ameliorates Diabetic Cardiomyopathy Through Apelin/Sirt3 Signalling to Improve Mitochondrial Dysfunction

Lin

Huang

et al. 2020

Front. Pharmacol.

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Myocardial contractile dysfunction in diabetic cardiomyocytes is a significant promoter of heart failure. Herein, we investigated the effect of icariin, a flavonoid monomer isolated from Epimedium, on diabetic cardiomyopathy (DCM) and explored the mechanisms underlying its unique pharmacological cardioprotective functions. High glucose (HG) conditions were simulated in vitro using cardiomyocytes isolated from neonatal C57 mice, while DCM was stimulated in vivo in db/db mice. Mice and cardiomyocytes were treated with icariin, with or without overexpression or silencing of Apelin and Sirt3 via transfection with adenoviral vectors (Ad-RNA) and specific small hairpin RNAs (Ad-sh-RNA), respectively. Icariin markedly improved mitochondrial function both in vivo and in vitro, as evidenced by an increased level of mitochondrial-related proteins via western blot analysis (PGC-1a, Mfn2, and Cyt-b) and an increased mitochondrial membrane potential, as observed via JC-1 staining. Further, icariin treatment decreased cardiac fibrogenesis (Masson staining), and inhibited apoptosis (TUNEL staining). Together, these changes improved cardiac function, according to multiple transthoracic echocardiography parameters, including LVEF, LVSF, LVESD, and LVEDD. Moreover, icariin significantly activated Apelin and Sirt3, which were inhibited by HG and DCM. Importantly, when Ad-sh-Apelin and Ad-sh-Sirt3 were transfected in cardiomyocytes or injected into the heart of db/db mice, the cardioprotective effects of icariin were abolished and mitochondrial homeostasis was disrupted. Further, it was postulated that since Ad-Apelin

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Icariin protects cardiomyocytes against ischaemia/reperfusion injury by attenuating sirtuin 1‐dependent mitochondrial oxidative damage

Abstract: Pretreatment with icariin protected cardiomyocytes from I/R-induced oxidative stress through activation of sirtuin-1 /FOXO1 signalling.

Cited by 77 publications

References 84 publications

The Long Noncoding RNA Hotair Regulates Oxidative Stress and Cardiac Myocyte Apoptosis during Ischemia-Reperfusion Injury

The Long Noncoding RNA Hotair Regulates Oxidative Stress and Cardiac Myocyte Apoptosis during Ischemia-Reperfusion Injury

mPEG-icariin nanoparticles for treating myocardial ischaemia

Icariin Ameliorates Diabetic Cardiomyopathy Through Apelin/Sirt3 Signalling to Improve Mitochondrial Dysfunction

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