Astragaloside IV Protects against Isoproterenol-Induced Cardiac Hypertrophy by Regulating NF-κB/PGC-1α Signaling Mediated Energy Biosynthesis

Zhang, Suping; Tang, Futian; Yang, Yuhong; Lü, Meili; Luan, Aina; Zhang, Jing; Yang, Juan; Wang, Hongxin

doi:10.1371/journal.pone.0118759

Cited by 48 publications

(53 citation statements)

References 34 publications

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“…Our previous studies confirmed that AsIV can suppressmyocardial hypertrophy and attenuate apoptosis of hypertrophic cardiomyocyte Yang et al 2013;Zhang et al 2015), which may be partially due to its anti-oxidative, anti-inflammatory and anti-apoptotic activities that might be endothelium-protective under pathophysiological conditions. Previous study has been demonstrated that AsIV inhibits H 2 O 2 -induced HUVECs apoptosis by suppressing Nox4 expression (Ma et al 2015).…”

supporting

confidence: 73%

Pretreatment with Astragaloside IV protects human umbilical vein endothelial cells from hydrogen peroxide induced oxidative stress and cell dysfunction via inhibiting eNOS uncoupling and NADPH oxidase – ROS – NF-κB pathway

Che

Tang

Lü

et al. 2016

Can. J. Physiol. Pharmacol.

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Keyword:Astragaloside IV, hydrogen peroxide, eNOS uncoupling, NF-κB, NADPH oxidase https://mc06.manuscriptcentral.com/cjpp-pubs production and decrease in intracellular superoxide anion production. Furthermore, pretreatment with AsIV increased endothelial nitric oxide synthase (eNOS) dimer/monomer ratio and its critical cofactor tetrahydrobiopterin (BH 4 ) content, decreased Nox4 protein expression, the most abundant Nox isoform in HUVECs, inhibited translocation of NF-κB p65 subunit into nuclear fraction while enhanced the protein expression of IκB-α, the inhibitor of NF-κB p65, reduced the levels of IL-1β, IL-6 and TNF-α in HUVECs medium, and decreased iNOS protein expression,. These results suggest that AsIV may protect HUVECs from H 2 O 2 induced oxidative stress via inhibiting NADPH oxidase-ROS-NF-κB pathway and eNOS uncoupling.

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supporting

confidence: 73%

Pretreatment with Astragaloside IV protects human umbilical vein endothelial cells from hydrogen peroxide induced oxidative stress and cell dysfunction via inhibiting eNOS uncoupling and NADPH oxidase – ROS – NF-κB pathway

Che

Tang

Lü

et al. 2016

Can. J. Physiol. Pharmacol.

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“…Previous studies have confirmed that AST-IV could reverse or delay cardiac remodeling caused by various reasons, such as viral infection [35], isoproterenol (ISO) [26, 31, 53] and lipopolysaccharide (LPS) [27]. AST-IV protected against ISO-induced cardiac hypertrophy via inhibiting p65 translocation and increasing PPARγ coactivator 1α (PGC-1α) [28]. TLR4/NF-small ka and Cyrillic B signaling pathways were the other targets for the effects of AST-IV against ISO-induced cardiac hypertrophy [26].…”

Section: Discussionmentioning

confidence: 99%

“…Over-stimulation of mTORC1 pathway through growth factors promoted cardiac senescence. Previous studies proved that AST-IV could resist the cardiac adrenergic [28] and angiotensin stimulation [56], inhibit mTORC1 [30], and thus protect against cardiac remodeling. In this study, we found that the hypercholesterolemic heart presented high expressions of p16 and p53, which could be reversed after AST-IV treatment.…”

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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“…Bunge, is one of the most widely used plant-derived drugs in traditional Chinese medicine for diabetes therapy (10). The saponin astragaloside IV has been reported to exert various pharmacological effects; astragaloside IV inhibited hepatic glycogen phosphorylase (GP) and glucose-6-phosphatase (G6P) activities thereby decreasing serum glucose levels in diabetic mice (12), attenuated lipolysis and reduced insulin resistance induced by tumor necrosis factor α (TNFα) in 3T3-L1 adipocytes (13), improved the symptoms of metabolic syndrome in fructose-fed rats (14), prevented human cardio vascular pathological changes and protected against cardiovascular injury in rats (15)(16)(17)(18) improved renal function (19)(20)(21)(22), reduced the progression of peripheral neuropathy (23), and attenuated inflammatory responses by suppressing the nuclear factor-κB (NF-κB) pathway (24)(25)(26). Xu et al (27) reported that other astragalosides, astragaloside II and isoastragaloside I, elevated serum levels of adiponectin and alleviated insulin resistance and glucose intolerance in obese mice.…”

Section: Introductionmentioning

confidence: 99%

Astragaloside IV facilitates glucose transport in C2C12 myotubes through the IRS1/AKT pathway and suppresses the palmitate-induced activation of the IKK/IκBα pathway

Zhu

Zheng

Chen

et al. 2016

International Journal of Molecular Medicine

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Abstract. Astragaloside IV is a monomer isolated from Astragalus membranaceus (Fisch.) Bunge, which is one of the most widely used plant-derived drugs in traditional Chinese medicine for diabetes therapy. In the present study, we aimed to examine the effects of astragaloside IV on glucose in C2C12 myotubes and the underlying molecular mechanisms responsible for these effects. Four-day differentiated C2C12 myotubes were exposed to palmitate for 16 h in order to establish a model of insulin resistance and 3 H glucose uptake, using 2-Deoxy-D-[1,2-3 H(N)]-glucose (radiolabeled 2-DG), was detected. Astragaloside IV was added 2 h prior to palmitate exposure. The translocation of glucose transporter 4 (GLUT4) was evaluated by subcellular fractionation, and the expression of insulin signaling molecules such as insulin receptor β (IRβ), insulin receptor substrate (IRS)1/protein kinase B (AKT) and inhibitory κB kinase (IKK)/inhibitor-κBα (IκBα), which are associated with insulin signal transduction, were assessed in the basal or the insulin-stimulated state using western blot analysis or RT-PCR. We also examined the mRNA expression of monocyte chemotactic protein 1 (MCP-1), intermonocyte chemotactic protein 1 (MCP-1), inter-, interleukin 6 (IL-6), tumor necrosis factor α (TNFα) and Toll-like receptor 4 (TLR4). Taken together, these findings demon-. Taken together, these findings demonstrated that astragaloside IV facilitates glucose transport in C2C12 myotubes through a mechanism involving the IRS1/ AKT pathway, and suppresses the palmitate-induced activathe palmitate-induced activation of the IKK/IκBα pathway. IntroductionSkeletal muscle accounts for 40% of body weight in humans, and 75% of infused glucose is cleared by skeletal muscle (1,2); thus, skeletal muscle serves as the major site of insulin-dependent glucose uptake. Due to the key role played by skeletal muscle in glucose homeostasis, deleterious factors which provoke reductions in glucose uptake by skeletal muscle, described as skeletal muscle insulin resistance, may lead to decreases in the disposal rate of serum glucose (3).The etiology of impaired insulin signaling in obese individuals is multifactorial and appears to be associated with at least two major events: a state of chronic, low-grade inflammation and the accumulation of intramyocellular lipids (4). Under physiological conditions, serum free fatty acids (FFAs) are an important fuel source for skeletal muscle, and 98-99% of FFAs bind to bovine serum albumin (5). Therefore, physiological concentrations of FFAs are in the µmol/l range (5). Constantly elevated serum levels of FFAs result in the transportation of FFAs into skeletal muscle cells, and subsequently stored as triglyceride. Whenever the accumulation of triglycerides and/or hydrolysis of triglycerides exceeds the oxidation capacity, incomplete lipid metabolic products, such as acyl-CoA, diacylglycerol and ceramide, are generated. These products inhibit the activation of critical molecules involved in insulin signaling, such as protein kinase B ...

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Astragaloside IV Protects against Isoproterenol-Induced Cardiac Hypertrophy by Regulating NF-κB/PGC-1α Signaling Mediated Energy Biosynthesis

Cited by 48 publications

References 34 publications

Pretreatment with Astragaloside IV protects human umbilical vein endothelial cells from hydrogen peroxide induced oxidative stress and cell dysfunction via inhibiting eNOS uncoupling and NADPH oxidase – ROS – NF-κB pathway

Pretreatment with Astragaloside IV protects human umbilical vein endothelial cells from hydrogen peroxide induced oxidative stress and cell dysfunction via inhibiting eNOS uncoupling and NADPH oxidase – ROS – NF-κB pathway

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

Astragaloside IV facilitates glucose transport in C2C12 myotubes through the IRS1/AKT pathway and suppresses the palmitate-induced activation of the IKK/IκBα pathway

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