Astragaloside suppresses apoptosis of the podocytes in rats with diabetic nephropathy via miR-378/TRAF5 signaling pathway

Xiao, Lei; Zhang, Boda; Ren, Ji-Gang; Luo, Fangli

doi:10.1016/j.lfs.2018.05.037

Cited by 31 publications

(18 citation statements)

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“…Detailed inspection was performed for remaining 61 full-text studies; 37 of these were not considered because they presented at least one of the excluding criteria. Finally, 24 eligible studies were identified: 13 in English ( Gui et al., 2012 ; Chen et al., 2014 ; Lu et al., 2015 ; Wang et al., 2015 ; Guo et al., 2016 ; Sun et al., 2016 ; Guo et al., 2017 ; Liu et al., 2017 ; Du et al., 2018 ; Lei et al., 2018a ; Lei et al., 2018b ; Fan et al., 2019 ; Ju et al., 2019 ) and 11 in Chinese ( Chen and Chen, 2016 ; Huang et al., 2016 ; Li and Zhang, 2016 ; Ran and Ma, 2016 ; Wang et al., 2017 ; Han et al., 2018 ; He et al., 2018 ; Li, 2018 ; Liu et al., 2019 ; Ma et al., 2019 ; Song et al., 2020 ) ( Figure 2 ).…”

Section: Resultsmentioning

confidence: 99%

Protective Effect and Possible Mechanisms of Astragaloside IV in Animal Models of Diabetic Nephropathy: A Preclinical Systematic Review and Meta-Analysis

et al. 2020

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Astragaloside IV (AS-IV) has a variety of biological activities and is widely used to treat kidney diseases. We conducted a systematic review of 24 animal studies including 424 animals to evaluate the efficacy of AS-IV for diabetic nephropathy (DN); all current possible mechanisms were summarized. A search strategy was applied to eight databases from inception to June 2020. The CAMARADES 10-item quality checklist and Rev-Man 5.3 software were used to analyze the risks of bias of each study and data regarding outcome measures, respectively. The mean study quality score was 5.4 points (range 3-8 points). Meta-analyses data and comparisons between groups showed that AS-IV significantly slowed the progression of pathological signs in the kidney including glomeruli and tubules, increasing creatinine clearance rate, decreasing blood urea nitrogen, serum creatinine, 24-h urinary neutrophil gelatinase-associated lipocalin and N-acetyl-b-Dglucosaminidase, 24-h urinary albumin, 24-h urinary microalbumin and HbA1c. There were no significant differences between experimental and control groups with respect to mortality or levels of alanine aminotransferase and aspartate aminotransferase. In terms of the possible mechanisms of treatment of DN, AS-IV acts through antifibrotic, antioxidant, and antiapoptotic mechanisms, thereby alleviating endoplasmic reticulum stress, inhibiting mitochondrial fission, and increasing autophagic activity. Taken together, our findings suggest that AS-IV is a multifaceted renoprotective candidate drug for DN.

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Section: Resultsmentioning

confidence: 99%

Protective Effect and Possible Mechanisms of Astragaloside IV in Animal Models of Diabetic Nephropathy: A Preclinical Systematic Review and Meta-Analysis

et al. 2020

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“…AS-IV is a small molecular saponin and has diverse pharmacological activities, which has widely used in traditional medicine in China. AS-IV suppressed podocytes apoptosis through miR-378/TRAF5 signaling pathway, thereby inhibiting the development of DN [27]. In diabetic rats, AS-IV ameliorates DN by inhibiting ILK expression and restoring integrin α3β1 expression [28].…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV protects against diabetic nephropathy via activating eNOS in streptozotocin diabetes-induced rats

Fan

Fan²,

Zhu

et al. 2019

BMC Complement Altern Med

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BackgroundAstragaloside IV (AS-IV) was reported to play a role in improving diabetic nephropathy (DN), however, the underlying mechanisms still remain unclear. The aim of the present study is to investigate whether AS-IV ameliorates DN via the regulation of endothelial nitric oxide synthase (eNOS).MethodsDN model was induced in Sprague-Dawley (SD) male rats by intraperitoneal injection of 65 mg/kg streptozotocin (STZ). Rats in the AS-IV treatment group were orally gavaged with 5 mg/kg/day or 10 mg/kg/day AS-IV for eight consecutive weeks. Body weight, blood glucose, blood urea nitrogen (BUN), Serum creatinine (Scr), proteinuria and Glycosylated hemoglobin (HbA1c) levels were measured. Hematoxylin-Eosin (HE) and Periodic Acid-Schiff (PAS) staining were used to detect the renal pathology. The apoptosis status of glomerular cells was measured by TUNEL assay. The phosphorylation and acetylation of eNOS were detected by western blot. The effects of AS-IV on high-glucose (HG)-induced apoptosis and eNOS activity were also investigated in human renal glomerular endothelial cells (HRGECs) in vitro.ResultsTreatment with AS-IV apparently reduced DN symptoms in diabetic rats, as evidenced by reduced BUN, Scr, proteinuria, HbA1c levels and expanding mesangial matrix. AS-IV treatment also promoted the synthesis of nitric oxide (NO) in serum and renal tissues and ameliorated the phosphorylation of eNOS at Ser 1177 with decreased eNOS acetylation. Moreover, HG-induced dysfunction of HRGECs including increased cell permeability and apoptosis, impaired eNOS phosphorylation at Ser 1177, and decreased NO production, were all reversed by AS-IV treatment.ConclusionsThese novel findings suggest that AS-IV ameliorates functional abnormalities of DN through inhibiting acetylation of eNOS and activating its phosphorylation at Ser 1177. AS-IV could be served as a potential therapeutic drug for DN.

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“…Lei et al found that miR-378 was also downregulated in DKD. Astragaloside ( AS-IV ) could regulate the miR-378/TNF receptor-associated factor5 (TRAF5) signaling pathway and suppressed subsequently podocyte apoptosis [108]. miR-21 and TGF- β 1/Smad existed in a complex regulation relationship to enhance renal tubular EMT by inhibiting target Smad7.…”

Section: The Action Mechanisms Of Chm On Dkdmentioning

confidence: 99%

The Efficacy and Mechanism of Chinese Herbal Medicine on Diabetic Kidney Disease

Zhong

Liu

et al. 2019

Journal of Diabetes Research

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Diabetic kidney disease (DKD) is the most common microvascular complication of diabetes and is one of the main causes of end-stage renal disease (ESRD) in many countries. The pathological features of DKD are the hypertrophy of mesangial cells, apoptosis of podocytes, glomerular basement membrane (GBM) thickening, accumulation of extracellular matrix (ECM), glomerular sclerosis, and tubulointerstitial fibrosis. The etiology of DKD is very complicated and many factors are involved, such as genetic factors, hyperglycemia, hypertension, hyperlipidemia, abnormalities of renal hemodynamics, and metabolism of vasoactive substances. Although some achievements have been made in the exploration of the pathogenesis of DKD, the currently available clinical treatment methods are still not completely effective in preventing the progress of DKD to ESRD. CHM composed of natural products has traditionally been used for symptom relief, which may offer new insights into therapeutic development of DKD. We will summarize the progress of Chinese herbal medicine (CHM) in the treatment of DKD from two aspects. In clinical trials, the Chinese herbal formulas were efficacy and safety confirmed by the randomized controlled trials. In terms of experimental research, studies provided evidence for the efficacy of CHM from the perspectives of balancing metabolic disorders, reducing inflammatory response and oxidative stress, antifibrosis, protecting renal innate cells, and regulating microRNA and metabolism. CHM consisting of different ingredients may play a role in synergistic interactions and multiple target points in the treatment of DKD.

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Astragaloside suppresses apoptosis of the podocytes in rats with diabetic nephropathy via miR-378/TRAF5 signaling pathway

Cited by 31 publications

References 20 publications

Protective Effect and Possible Mechanisms of Astragaloside IV in Animal Models of Diabetic Nephropathy: A Preclinical Systematic Review and Meta-Analysis

Protective Effect and Possible Mechanisms of Astragaloside IV in Animal Models of Diabetic Nephropathy: A Preclinical Systematic Review and Meta-Analysis

Astragaloside IV protects against diabetic nephropathy via activating eNOS in streptozotocin diabetes-induced rats

The Efficacy and Mechanism of Chinese Herbal Medicine on Diabetic Kidney Disease

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