Protective effects of Astragaloside IV on endoplasmic reticulum stress-induced renal tubular epithelial cells apoptosis in type 2 diabetic nephropathy rats

Ju, Yinghui; Su, Yong; Chen, Qingqing; Ma, Keke; Ji, Tianjiao; Wang, Zhongyuan; Li, Weizu

doi:10.1016/j.biopha.2018.10.041

Cited by 78 publications

(62 citation statements)

References 38 publications

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“…The levels of kidney function and pathological changes suggest that our experimental protocol induced the early stage of DN in rats. These findings extended previous observations [26,43] and support the notion that AS-IV treatment ameliorates the progression of DN and improves the kidney function.…”

Section: Discussionsupporting

confidence: 91%

“…As a result, AS-IV treatment significantly improved the kidney function by reducing BUN levels, 24 h urine creatinine, and proteinuria in early DN rats. Furthermore, we did not detect significantly higher SCR in the DN group of rats, inconsistent with previous observations [26]. However, we detected significantly higher CCR in the DN group, which was reduced in the AS-IV group.…”

Section: Discussioncontrasting

confidence: 78%

“…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]. However, the molecular mechanisms underlying the pharmacological action of AS-IV remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionsupporting

confidence: 91%

Section: Discussioncontrasting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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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“…Fortunately, some of the compounds purified from the six herbs of GSJD have been used to treat DN and gained satisfactory results. For instance, astragaloside IV 26,[40][41][42][43][44][45][46] , berberine 39,[47][48][49][50][51] , emodin 38,52 and rhein 53,54 could ameliorate DN by modulating multiple signalling pathways. Therefore, further investigation of the active compounds in GSJD is worthwhile.…”

Section: Discussionmentioning

confidence: 99%

Renoprotective effects of Gushen Jiedu capsule on diabetic nephropathy in rats

Zhang

Yang

Zhao

et al. 2020

Sci Rep

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Gushen Jiedu capsule (GSJD) is a formula that has been widely used in traditional Chinese medicine for the prevention and treatment of diabetic nephropathy (DN). However, the mechanism underlying the protective effects of GSJD on DN is still unclear. This study was performed to clarify the therapeutic effects of GSJD on DN and its underlying mechanisms. High-fat diet-and streptozotocin-induced DN rats were treated with or without GSJD suspension by gavage for 8 weeks, and biochemical changes in blood and urine were analysed. Kidneys were isolated for histological, TUNEL and Western blot analysis. Compared to the DN group, the GSJD-treated groups exhibited decreased urinary albumin, ameliorated renal dysfunction, including serum creatinine and blood urea nitrogen, and attenuated total cholesterol, triglyceride and total protein levels. However, there were no significant effects of GSJD on body weight, fasting blood glucose or albuminuria. Histology showed that GSJD could retard the progression of DN and decrease the apoptosis rate from 52% to less than 20%. Western blot analysis showed that GSJD could regulate the mitochondrial apoptotic pathway by downregulating the expression of Bax and upregulating the expression of BCL-2 in the kidneys of DN rats. Moreover, the Akt pathway, an upstream signalling pathway of the BCL-2 family, was also ameliorated by GSJD. Further, the podocyte foot process markers podocin and nephrin were upregulated by GSJD in DN rats. This study demonstrated that GSJD might play a renoprotective role by inhibiting apoptosis and regulating the mitochondrial apoptotic and Akt pathways during pathological changes in DN. Diabetic nephropathy (DN) is a diabetes-induced microvascular complication that is responsible for 50% of all cases of end-stage renal disease (ESRD) and is characterized by hyperglycaemia, continuous albuminuria, high blood pressure and impaired renal function 1-3. Additionally, DN is a major risk factor for mortality in patients with diabetic complications worldwide 4,5. Hence, the prevention and treatment of DN have become a serious health issue, and the development of DN medications would be beneficial. Traditional Chinese medicine (TCM) has been used in the treatment of diabetes and related complications for thousands of years in China, which emphasizes the whole regulatory action on the human body 6,7. Thus, TCM formulae have become an important source for the discovery of new medications to prevent and treat DN 8,9. For instance, the NaoXinTong capsule 10 improves glomerular function, inhibits extracellular matrix accumulation, activates the insulin signalling pathway and improves glucose metabolism in db/db mice, suggesting a favourable effect on kidney function. The Gushen Jiedu capsule (GSJD) originated from the classic kidney-tonifying prescription of "Shuilu Erxian Dan" in the Song Dynasty (1170 AD) in China (Supplementary Fig. S1), containing Semen Euryales, Fructus Rosa laevigata, Rhizome Coptis chinensis, Rhizome Rheum tanguticum, Radix Astragalus membranaceus and ...

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“…Extensive research has shown that endoplasmic reticulum (ER) stress‐induced apoptotic pathways are frequently described in many diseases. ER stress plays a critical role in the progress of diabetes and DN [3,4]. It is a series of pipeline systems composed of membranes in the cytosol and is a critical cell organelle with multiple functions.…”

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confidence: 99%

Pyruvate alleviates high glucose‐induced endoplasmic reticulum stress and apoptosis in HK‐2 cells

et al. 2020

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Endoplasmic reticulum (ER) stress plays a critical role in the development of diabetic nephropathy (DN). We previously demonstrated that pyruvate (Pyr)‐enriched oral rehydration solution improved glucometabolic disorders and ameliorated DN outcome in db/db mice. Here, we investigated the effects of Pyr on high glucose‐induced ER stress and apoptosis in HK‐2 cells. Our results suggest that high glucose can induce reactive oxygen species production, apoptosis and ER stress in HK‐2 cells, and that Pyr treatment can ameliorate these effects and restore the expression of key proteins involved in ER stress. Thus, Pyr may have potential for the development of novel strategies for the prevention and treatment of clinical DN.

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Protective effects of Astragaloside IV on endoplasmic reticulum stress-induced renal tubular epithelial cells apoptosis in type 2 diabetic nephropathy rats

Cited by 78 publications

References 38 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

Renoprotective effects of Gushen Jiedu capsule on diabetic nephropathy in rats

Pyruvate alleviates high glucose‐induced endoplasmic reticulum stress and apoptosis in HK‐2 cells

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