Astragaloside IV Inhibits Doxorubicin-Induced Cardiomyocyte Apoptosis Mediated by Mitochondrial Apoptotic Pathway &lt;i&gt;via&lt;/i&gt; Activating the PI3K/Akt Pathway

Jia, Yuanyuan; Zuo, Daiying; Li, Zengqiang; Liu, Hanmo; Dai, Zhengning; Cai, Jiayi; Lili, Pang; Wu, Yingliang

doi:10.1248/cpb.c13-00556

Cited by 69 publications

(49 citation statements)

References 30 publications

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“…Tu et al, revealed that AS-IV prevented ischemia/reperfusion-induced cardiac malfunction, maintained the integrity of myocardial structure through regulating energy metabolism [16]. In addition, the cardioprotective effects of AS-IV against LPS [26], isoproterenol [27] and doxorubicin [28] via diverse effects upon a variety of intracellular signaling pathways have been previously described, including the activation of TLR4/NF-кB and PI3K/AKT pathways. Consistent with the findings of these previous studies, our study showed that AS-IV significantly increased H9c2 cells viability, and decreased apoptotic cell rate in vitro, and significantly reduced infarct volume and improved outcome in vivo.…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV Protects Rat Cardiomyocytes from Hypoxia-Induced Injury by Down-Regulation of miR-23a and miR-92a

Gong

Chang

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Astragaloside IV (AS-IV), a traditional Chinese medicine isolated from Astragalus membranaceus, has been shown to exert cardioprotective effect previously. This study aimed to reveal the effects of AS-IV on hypoxia-injured cardiomyocyte. Methods: H9c2 cells were treated with various doses of AS-IV for 24 h upon hypoxia. CCK-8 assay, flow cytometry/Western blot, and qRT-PCR were respectively conducted to measure the changes in cell viability, apoptosis, and the expression of miR-23a and miR-92a. Sprague–Dawley rats were received coronary ligation, and were administrated by various doses of AS-IV for 14 days. The infarct volume and outcome of rats followed by ligation were tested by ultrasound, arteriopuncture and nitrotetrazolium blue chloride (NBT) staining. Results: We found that 10 μg/ml of AS-IV exerted myocardioprotective effects against hypoxia-induced cell damage, as AS-IV significantly increased H9c2 cells viability and decreased apoptosis. Interestingly, the myocardioprotective effects of AS-IV were alleviated by miR-23a and/or miR-92a overexpression. Knockdown of miR-23a and miR-92a activated PI3K/AKT and MAPK/ ERK signaling pathways. Bcl-2 was a target gene for miR-23a, and BCL2L2 was a target gene for miR-92a. In the animal model of myocardial infarction (MI), AS-IV significantly reduced the infarct volume, ejection fraction (EF), shortening fraction (FS) and LV systolic pressure (LVSP), and significantly increased left ventricular end-diastolic internal diameter (LVEDd). And also, the elevated expression of miR-23a and miR-92a in MI rat was reduced by AS-IV. Conclusion: AS-IV protected cardiomyocytes against hypoxia-induced injury possibly via down-regulation of miR-23a and miR-92a, and via activation of PI3K/AKT and MAPK/ERK signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Astragaloside IV Protects Rat Cardiomyocytes from Hypoxia-Induced Injury by Down-Regulation of miR-23a and miR-92a

Gong

Chang

Zhang

et al. 2018

Cell Physiol Biochem

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“…AGIV eliminates reactive oxygen species and protects cardiomyocytes after oxidative stress-mediated injury under hypoxic conditions [52]. The activation of the PI3K/Akt pathway caused by AGIV is a pivotal event in suppressing cardiomyocyte apoptosis [53]. AGIV Color version available online treatment significantly stimulates angiogenesis via the PI3K/Akt signaling pathway [41].…”

Section: The Importance Of Agivmentioning

confidence: 99%

Astragaloside IV Improves Vasodilatation Function by Regulating the PI3K/Akt/eNOS Signaling Pathway in Rat Aorta Endothelial Cells

et al. 2018

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Coronary heart disease (CHD) remains a major public health burden. Endothelial-dependent coronary artery vasoreactivity is a significant indicator of vascular function. Endothelial dysfunction is characterized by decreased nitric oxide (NO) bioavailability and predicts late cardiovascular events. Astragaloside IV (AGIV) is the main active component of the herb Astragalus membranaceus. Although it shows a significant protective effect against vascular endothelial dysfunction, the mechanisms of AGIV promoting the vascular dilation have not been elucidated. This study investigated the vasodilator effect of AGIV on rat aortic rings and the underlying effect of AGIV via the PI3K/Akt/eNOS signaling pathway. We measured the relaxation of isolated RARs after different concentrations of AGIV treatment. Rat aorta endothelial cells were cultured with different doses of AGIV, dimethylsulfoxide, and NG-nitro L-arginine methyl ester. The expression of phosphorylated (p)-Akt and -endothelial nitric oxide synthase (p-eNOS) were tested by Western blot analysis. The messenger (m)RNA expression of eNOS was quantified by real-time polymerase chain reaction. AGIV exerted a vasodilator effect on the aortic rings and increased the NO content in a concentration-dependent manner. The vasorelaxation was suppressed by an eNOS inhibitor. AGIV regulated the PI3K/Akt/eNOS signaling pathway via phosphorylation of Akt at Ser⁴⁷³ and dephosphorylation of eNOS at Thr⁴⁹⁵. The mRNA expression of eNOS was remarkably upregulated by AGIV. AGIV significantly induced the dilation of the aortic rings, leading to the vasodilator response by enhancing the eNOS release via the PI3K/Akt/eNOS signaling pathway.

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“…AST-IV strongly blocked Rheb/mTORC1 signaling pathway and reduced its downstream phospho-S6K levels in myocardial infarction (MI) and transverse aortic constriction (TAC) mice model [30]. AST-IV has shown the ability to attenuate oxidative stress and suppress the activation of the mitochondrial apoptosis via PI3K/Akt signaling pathway [32]. More and more studies showed that AST-IV exerted its cardioprotective function through a number of signaling pathways and multiple target molecules.…”

Section: Discussionmentioning

confidence: 99%

“…The transcriptional changes of p53-apoptotic pathway in hypercholesterolemia were also reversed after AST-IV treatment. Previous studies reported that AST-IV exerted anti-apoptosis effect on cardiomyocyte by attenuating oxidative stress and calpain-1 activation [31], inhibiting the activation of mitochondrial apoptotic pathway via PI3K/Akt pathway [32]. Whether p53-dependent apoptosis pathway is another target pathway for the anti-apoptosis effect of AST-IV needs to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV Prevents Cardiac Remodeling in the Apolipoprotein E-Deficient Mice by Regulating Cardiac Homeostasis and Oxidative Stress

Ding²,

et al. 2017

Cell Physiol Biochem

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Background: Hypercholesterolemia is a risk factor for the development of cardiac hypertrophy. Astragaloside IV (AST-IV) possesses cardiovascular protective properties. We hypothesize that AST-IV prevents cardiac remodeling with hypercholesterolemia via modulating tissue homeostasis and alleviating oxidative stress. Methods: The ApoE^-/- mice were treated with AST-IV at 1 or 10 mg/kg for 8 weeks. The blood lipids tests, echocardiography, and TUNEL were performed. The mRNA expression profile was detected by real-time PCR. The myocytes size and number, and the expressions of proliferation (ki67), senescence (p16^INK4a), oxidant (NADPH oxidase 4, NOX4) and antioxidant (superoxide dismutase, SOD) were observed by immunofluorescence staining. Results: Neither 1 mg/kg nor 10 mg/kg AST-IV treatment could decrease blood lipids in ApoE^-/- mice. However, the decreased left ventricular ejection fraction (LVEF) and fractional shortening (FS) in ApoE^–/– mice were significantly improved after AST-IV treatment. The cardiac collagen volume fraction declined nearly in half after AST-IV treatment. The enlarged myocyte size was suppressed, and myocyte number was recovered, and the alterations of genes expressions linked to cell cycle, proliferation, senescence, p53-apoptosis pathway and oxidant-antioxidants in the hearts of ApoE^-/- mice were reversed after AST-IV treatment. The decreased ki67 and increased p16^INK4a in the hearts of ApoE^-/- mice were recovered after AST-IV treatment. The percentages of apoptotic myocytes and NOX4-positive cells in AST-IV treated mice were decreased, which were consistent with the gene expressions. Conclusion: AST-IV treatment could prevent cardiac remodeling and recover the impaired ventricular function induced by hypercholesterolemia. The beneficial effect of AST-IV might partly be through regulating cardiac homeostasis and anti-oxidative stress.

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Astragaloside IV Inhibits Doxorubicin-Induced Cardiomyocyte Apoptosis Mediated by Mitochondrial Apoptotic Pathway <i>via</i> Activating the PI3K/Akt Pathway

Cited by 69 publications

References 30 publications

Astragaloside IV Protects Rat Cardiomyocytes from Hypoxia-Induced Injury by Down-Regulation of miR-23a and miR-92a

Astragaloside IV Protects Rat Cardiomyocytes from Hypoxia-Induced Injury by Down-Regulation of miR-23a and miR-92a

Astragaloside IV Improves Vasodilatation Function by Regulating the PI3K/Akt/eNOS Signaling Pathway in Rat Aorta Endothelial Cells

Astragaloside IV Prevents Cardiac Remodeling in the Apolipoprotein E-Deficient Mice by Regulating Cardiac Homeostasis and Oxidative Stress

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