Astragaloside IV as Potential Antioxidant Against Diabetic Ketoacidosis in Juvenile Mice Through Activating JNK/Nrf2 Signaling Pathway

Deng, Lili

doi:10.1016/j.arcmed.2020.06.013

Cited by 11 publications

(7 citation statements)

References 25 publications

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“…Astragaloside exhibits strong antiapoptotic, anti-inflammatory, and antioxidant effects in many cell types, 28,29 suggesting that astragaloside may exert these effects in AFLD. As expected, we found that astragaloside administration could significantly inhibit alcohol-induced lipid accumulation, cell apoptosis, oxidative stress and inflammation.…”

Section: Discussionmentioning

confidence: 99%

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Astragaloside alleviates alcoholic fatty liver disease by suppressing oxidative stress

Jiang

Gao

Chai

et al. 2021

The Kaohsiung J of Med Scie

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Alcoholic fatty liver disease (AFLD) is the most common liver disease and can progress to fatal liver cirrhosis and carcinoma, affecting millions of patients worldwide.The functions of astragaloside on the cardiovascular system have been elucidated.However, its role in AFLD is unclear. Ethanol-treated AML-12 cells were used as a cell model of alcoholic fatty liver. Real-time quantitative reverse transcription-PCR and Western blotting detected genes and proteins expressions. Reactive oxygen species (ROS), triglyceride, total cholesterol, low-density lipoprotein, albumin, ferritin, bilirubin, superoxide dismutase, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were examined using commercial kits. Lipid accumulation was assessed by Oil red O staining. MTT and flow cytometry measured cell viability and apoptosis. JC-1 was used to analyze mitochondrial membrane potential. A rat model of AFLD was established by treating rats with ethanol. Astragaloside suppressed ethanol-induced lipid accumulation, oxidative stress, and the production of AST and ALT in AML-12 cells. Ethanol induced TNF-α and reduced IL-10 expression, which were reversed by astragaloside. Ethanol promoted Bax expression and cytochrome C release and inhibited Bcl-2 and ATP expression. Astragaloside hampered these apoptosis effects in AML-12 cells. Impaired mitochondrial membrane potential was recovered by astragaloside. However, all these astragaloside-mediated beneficial effects were abolished by the ROS inducer pyocyanin. Ethanol-induced activation of NF-κB signaling was suppressed by astragaloside in vitro and in vivo, suggesting that astragaloside inhibited oxidative stress by suppressing the activation of NF-κB signaling, thus improving liver function and alleviating AFLD in rats. Our study elucidates the pharmacological mechanism of astragaloside and provides potential therapeutic strategies for AFLD.

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Section: Discussionmentioning

confidence: 99%

“…It has been reported that astragaloside potentially suppresses oxidative stress by regulating the JNK/Nrf2 signaling pathway 28 or Nrf2/ Keap1 pathway 37 ; however, the molecular mechanism by which astragaloside regulates oxidative stress in AFLD is unknown. NF-κB signaling is involved in the regulation of ROS and oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Astragaloside alleviates alcoholic fatty liver disease by suppressing oxidative stress

Jiang

Gao

Chai

et al. 2021

The Kaohsiung J of Med Scie

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“…Additionally, this study also analyzed the phosphorylation level of JNK and the expression level of Nrf2 protein in pancreatic tissue after administration and pointed out that its potential mechanism of action may involve the regulation of JNK/Nrf2 signal pathway by AS-IV. 28 SMSO's treatment of type 2 diabetes also seems to involve the Nrf2 antioxidant pathway. In a rat model of type 2 diabetes induced by a high-fat and high-sugar diet and STZ, SMSO induces Nrf2 expression and Akt and GSK3β phosphorylation in a dose-dependent manner to exert a protective effect on pancreatic β cells.…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV Ameliorates Streptozotocin Induced Pancreatic β-Cell Apoptosis and Dysfunction Through SIRT1/P53 and Akt/GSK3β/Nrf2 Signaling Pathways

Lin¹,

Xu²,

Zheng³

et al. 2022

DMSO

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Background: Absolute or relative lack of insulin secretion caused by pancreatic β-cell dysfunction can lead to diabetes. Astragaloside IV (AS-IV), the main components of the traditional Chinese medicine Astragalus, has anti-oxidant, anti-inflammatory and antiapoptotic properties, and exerts anti-diabetic pharmacological effects. Purpose: To explore whether AS-IV can protect the apoptosis and dysfunction of pancreatic β-cells induced by streptozotocin (STZ) and its underlying molecular mechanism. Methods: STZ-induced pancreatic β-cell line INS-1 was treated with different concentrations of AS-IV, then cell viability, apoptosis, oxidative stress and insulin secretion was assessed by CCK-8, TUNEL staining, Western blot, commercial kits and qRT-PCR, respectively. The expression of proteins involved in Sirtuin 1 (SIRT1)/p53 and Akt/glycogen synthase kinase-3 β (GSK3β)/nuclear factor E2-related factor 2 (Nrf2) signaling was measured by Western blot assay. Besides, Akt inhibitor MK-2206 and SIRT1 inhibitor EX-527 were used to co-treat STZ-induced INS-1 cells in the presence of AS-IV, and the above experiments were repeated. Results: AS-IV increased the cell viability of INS-1 cells induced by STZ. AS-IV also reduced the increase in apoptosis rate and reversed STZ-induced down-regulation of Bcl-2 and upregulation of Bax and Cleaved caspase 3. In addition, AS-IV significantly reduced STZinduced malondialdehyde upregulation and reduced superoxide dismutase and glutathione peroxidase levels. Furthermore, the use of AS-IV was found to increase the insulin secretion capacity of INS-1 cells with impaired function, along with the increase of the mRNA levels of insulin 1 and insulin 2. Mechanism studies further showed that MK-2206 and EX-527 reversed the protective effect of AS-IV against STZ-induced injury on INS-1 cells. Conclusion: AS-IV exerted cytoprotective effect on STZ-induced INS-1 cells through regulating SIRT1/p53 and Akt/GSK3β/Nrf2 signaling pathways. These findings are expected to provide new supplements to the molecular mechanism of AS-IV in the treatment of diabetes.

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“…The active substances of AM have been confirmed to play positive roles in the regulation of the oxidative/antioxidant balance and inflammatory response [ 19 ]. Among them, AS-IV, as the primary active ingredient of AM, has antiviral, metabolic regulation, antioxidant, tumor inhibition, and other biological functions [ 29 , 30 ]. With the deepening of AS-IV researches, AS-IV has vital pharmacological effects in the remedy of CVDs, anti-hyperglycemia, anti-aging, and other aspects [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV alleviates senescence of vascular smooth muscle cells through activating Parkin-mediated mitophagy

Zhang

et al. 2022

Human Cell

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Astragaloside IV (AS-IV), as one of the main active components of Astragalus membranaceus, has been reported to have cardiovascular protective effects. However, the role and molecular mechanism of AS-IV in vascular senescence have not been clearly stated. The in vitro aging model was constructed using bleomycin (BLM) in vascular smooth muscle cells (VSMCs). Cell senescence were assessed through Western blotting analysis of aging markers, flow cytometry, and the β-galactosidase (SA-β-Gal) kit. Mitophagy was determined through transmission electron microscopy, TMRM staining, and Western blotting analysis of p62. A model of aging blood vessels was induced by d-gal. The vascular wall thickness of mice was also evaluated by H&E staining. Our data proved that AS-IV plays an anti-senescent role in vitro and in vivo. Results showed that AS-IV effectively improved mitochondrial injury, raised MMP, and mediated mitophagy in BLM-induced senescent VSMCs and d-gal induced aging mice. Parkin expression strengthened AS-IV’s anti-senescent function. In conclusions, AS-IV attenuated BLM-induced VSMC senescence via Parkin to regulate mitophagy. Therefore, AS-IV-mediated Parkin might be a latent therapeutic agent and target for VSMC senescence.

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Astragaloside IV as Potential Antioxidant Against Diabetic Ketoacidosis in Juvenile Mice Through Activating JNK/Nrf2 Signaling Pathway

Cited by 11 publications

References 25 publications

Astragaloside alleviates alcoholic fatty liver disease by suppressing oxidative stress

Astragaloside alleviates alcoholic fatty liver disease by suppressing oxidative stress

Astragaloside IV Ameliorates Streptozotocin Induced Pancreatic β-Cell Apoptosis and Dysfunction Through SIRT1/P53 and Akt/GSK3β/Nrf2 Signaling Pathways

Astragaloside IV alleviates senescence of vascular smooth muscle cells through activating Parkin-mediated mitophagy

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