Astragalosides IV protected the renal tubular epithelial cells from free fatty acids-induced injury by reducing oxidative stress and apoptosis

Chen, Qingqing; Su, Yong; Ju, Yinghui; Ma, Keke; Li, Weizu

doi:10.1016/j.biopha.2018.09.049

Cited by 57 publications

(46 citation statements)

References 44 publications

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“…Recent studies have shown that AS-IV has potent antidiabetes, anti-inflammatory, antioxidative, antifibrotic, antihypertensive, and myocardial protective activities [13][14][15][16][17]. Furthermore, AS-IV treatment can inhibit the pathogenic process of DN in rodents [17][18][19][20][21][22][23][24]. In addition, AS-IV treatment ameliorates endoplasmic reticulum stress in renal tubular epithelial cells and improves renal function and fibrosis in animal models of DN [22,[25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic Analysis Reveals the Protection of Astragaloside IV against Diabetic Nephropathy by Modulating Inflammation

Zhang

Tao

Chen

et al. 2020

Oxidative Medicine and Cellular Longevity

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Background. Diabetic nephropathy (DN) is one of the leading causes of end-stage kidney disease. Recently, there is no specific drug available to block the kidney damage. Astragaloside IV (AS-IV) is a major active component of Astragalus membranaceus (Fisch) Bge and has been demonstrated to benefit the kidney functions. This study explores the potential pharmacological action of AS-IV in DN of rats. Methods. Male Sprague-Dawley rats were fed with high-fat diet and injected with streptozotocin to induce diabetes. The diabetic rats were randomized and treated with vehicle or AS-IV (80 mg/kg) daily by gavage for 12 weeks as the DN or AS-IV group, respectively. The normal control rats were fed with normal chow and injected with vehicles (n=8 per group). These rats were monitored for diabetes- and kidney function-related measures. The expression profiles of gene mRNA transcripts in the kidney tissues were analyzed by RNA-seq and quantitative RT-PCR. The levels of advanced glycation end products (AGEs), IL-1β, and IL-18 in the serum samples and kidney tissues were quantified by ELISA. The levels of collagen IV (COL-4) and fibronectin (FN) expression in kidney tissues were examined by immunohistochemistry and Western blot. Results. In comparison with the DN group, AS-IV treatment significantly reduced blood glucose levels, food and water consumption, 24 h urine, renal index values, 24 h urine total proteins, blood urea nitrogen (BUN) levels, and creatinine clearance rates (CCR), accompanied by minimizing the DN-induced early kidney damages, fibrosis, and microstructural changes. Furthermore, AS-IV treatment significantly modulated the DN-altered gene transcription profiles in the kidney of rats, particularly for inflammation-related genes, including the nucleotide-binding oligomerization domain-like receptor signaling, which was validated by quantitative RT-PCR. AS-IV treatment significantly decreased the levels of serum and kidney AGEs, IL-1β, and IL-18 expression and fibrosis indexes in the kidney of rats. Conclusion. AS-IV treatment ameliorated the severity of DN by inhibiting inflammation-related gene expression in the kidney of rats.

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Section: Introductionmentioning

confidence: 99%

Transcriptomic Analysis Reveals the Protection of Astragaloside IV against Diabetic Nephropathy by Modulating Inflammation

Zhang

Tao

Chen

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Studies have shown that renal fibrosis could be ameliorated by blunting EMT in a variety of kidney diseases ( Yang and Liu, 2002 ; Grande et al., 2015 ). In diabetes, high fat and high glucose (HFG) led to elevated levels of reactive oxygen species (ROS), transforming growth factor-β1 (TGFβ1), and other factors, thereby inducing EMT in TECs ( Ha and Lee, 2003 ; Hills and Squires, 2011 ; Chen et al., 2018 ). And inhibition of EMT could alleviate renal dysfunction and the progression of tubulointerstitial fibrosis in DN ( Shi et al., 2017 ; Zhao et al., 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Trimetazidine Inhibits Renal Tubular Epithelial Cells to Mesenchymal Transition in Diabetic Rats via Upregulation of Sirt1

Yang

Wang

et al. 2020

Front. Pharmacol.

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Trimetazidine (TMZ), as a metabolic regulator, is effective in treatment of coronary atherosclerotic heart disease with rare side effects in the clinic for long years. Interestingly, studies have shown that TMZ protects against several acute kidney injuries (AKI). However, the effect of TMZ on chronic kidney diseases (CKD) remains unknown. This study aimed to investigate the role of TMZ in diabetic nephropathy (DN) and its potential mechanisms. A rat model of DN was established in male Sprague-Dawley rats by streptozotocin (STZ) intraperitoneal injection. Experimental rats were separated into three groups: control, DN and DN + TMZ treatment. Metabolic parameters, pathological features and renal function markers were evaluated after 20 weeks of diabetes induction. In vitro experiments, the effect of TMZ on high fat and high glucose (HFG) induced or TGFb1-induced epithelial-to-mesenchymal transition (EMT) was examined in HK-2 cells. Our results showed that TMZ could maintain renal function without affecting hemodynamic and plasma metabolic levels in diabetic rats. The effect was associated with a reversion of pathological progression of DN, especially for tubulointerstitial fibrosis. EMT is an important contributor to renal fibrosis. In this study, we investigated the role of TMZ in the process of EMT in DN. Mechanistically; TMZ attenuated HFG-induced EMT by relieving oxidative stress via deacetylation forkhead box O1 (FoxO1) in a Sirt1-dependent pathway. And it suppressed TGFb1-induced EMT by deacetylating Smd4 in a Sirt1-dependent manner. Moreover, our study found that TMZ upregulated Sirt1 expression by increasing the expression of nicotinamide phosphoribosyl transferase (Nampt), which is a rate limiting enzyme for nicotinamide adenine dinucleotide (NAD +) generation by salvage pathway. And the increased NAD + promoted Sirt1 expression. In conclusion, TMZ can prevent renal dysfunction and pathogenesis of tubulointerstitial fibrosis in DN, partly by inhibition of EMT via FoxO1/ROS pathway and TGFb/Smad pathway in a Nampt/NAD + /Sirt1 dependent manner.

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“…Activation of the antioxidant system is crucial to preventing oxidative damage. NFE2L2 is a target of exogenous toxic substances and oxidative stress, and it plays a vital role in the presence of these insults [37]. Normally, NFE2L2 binds to KEAP1 in the cytoplasm, which prevents its translocation to the nucleus and inhibits the transcription of a series of cytoprotective genes [38].…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV Protects Against Oxidative Stress in Calf Small Intestine Epithelial Cells via NFE2L2-Antioxidant Response Element Signaling

Wang

Jiang

Cheng

et al. 2019

IJMS

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Oxidative stress can damage intestinal epithelial cell integrity and function, causing gastrointestinal disorders. Astragaloside IV (ASIV) exhibits a variety of biological and pharmacological properties, including anti-inflammatory and antioxidant effects. The purpose of this research was to investigate the cytoprotective action of ASIV and its mechanisms in calf small intestine epithelial cells with hydrogen peroxide (H2O2)-induced oxidative stress. ASIV pretreatment not only increased cell survival, but it also decreased reactive oxygen species generation and apoptosis, enhanced superoxide dismutase, catalase, and glutathione peroxidase levels, and it reduced malondialdehyde formation. Furthermore, pretreatment with ASIV elevated the mRNA and protein levels of nuclear factor erythroid 2-related factor 2 (NFE2L2), heme oxygenase-1 (HMOX1), and NAD(P)H quinone dehydrogenase 1 (NQO1). The NFE2L2 inhibitor ML385 inhibited NFE2L2 expression and then blocked HMOX1 and NQO1 expression. These results demonstrate that ASIV treatment effectively protects against H2O2-induced oxidative damage in calf small intestine epithelial cells through the activation of the NFE2L2-antioxidant response element signaling pathway.

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Astragalosides IV protected the renal tubular epithelial cells from free fatty acids-induced injury by reducing oxidative stress and apoptosis

Cited by 57 publications

References 44 publications

Transcriptomic Analysis Reveals the Protection of Astragaloside IV against Diabetic Nephropathy by Modulating Inflammation

Transcriptomic Analysis Reveals the Protection of Astragaloside IV against Diabetic Nephropathy by Modulating Inflammation

Trimetazidine Inhibits Renal Tubular Epithelial Cells to Mesenchymal Transition in Diabetic Rats via Upregulation of Sirt1

Astragaloside IV Protects Against Oxidative Stress in Calf Small Intestine Epithelial Cells via NFE2L2-Antioxidant Response Element Signaling

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