scholarly journals Renoprotective Effect of Danhong Injection on Streptozotocin-Induced Diabetic Rats through a Peroxisome Proliferator-Activated ReceptorγMediated Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Xue Yang ◽  
Xiang Xiao ◽  
Hailian Wang ◽  
Yi Li ◽  
Li Wang ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Elevated Serum ◽  
Enrichment Analysis ◽  
Diabetic Rats ◽  
Pathway Enrichment Analysis ◽  
Peroxisome Proliferator ◽  
Diabetic Kidney ◽  
Danhong Injection ◽  
Total Urine

The aim of the study was to investigate the protective effect of Danhong injection (DHI) on diabetic kidney disease and explore the potential mechanisms. Diabetic kidney disease was induced by unilateral nephrectomy, high-fat diet, and streptozotocin. After DHI administration, the renal function deterioration, 24-hour total urine protein excretion, and elevated serum lipid levels were reversed to some extent, and the renal pathological damage was also ameliorated. The KEGG pathway enrichment analysis demonstrated that the PPARγsignal pathway was significantly upregulated in DH group. And the increased expressions of PPARγand UCP-1 were confirmed by immunohistochemistry, whereas the p38MAPK was significantly decreased. These data show that DHI could delay the progress of DKD, and the effect might be achieved in part by activating the PPARγsignaling pathway.

scholarly journals Gynostemma Pentaphyllum Ameliorates Lipid Metabolic Abnormalities in Diabetic Kidney Disease

2022 ◽  
Author(s):  
Pengrui Wang ◽  
Shouhai Jiao ◽  
Li Sun ◽  
Helin Sun ◽  
Cunzhi Wang ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Enrichment Analysis ◽  
Underlying Mechanism ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Protective Mechanisms ◽  
Diabetic Kidney ◽  
Gynostemma Pentaphyllum ◽  
Protein Protein Interaction

Abstract Background: Patients with diabetic kidney disease (DKD) were often accompanied with dislipidemia. Gynostemma pentaphyllum can ameliorate insulin resistance and reduce the synthesis of triglycerides and cholesterol, but the underlying mechanism is still unclear. Therefore, we used the network pharmacologic strategies to evaluate potential therapeutic effects and protective mechanisms of gynostemma pentaphyllum on diabetic kidney disease. Methods: Gynostemma pentaphyllum's potential targets were predicted using the TCMSP databases. The pathogenic factors involved in DKD and dislipidemia were screened by the OMIM and Gene Cards databases. The common targets of gynostemma pentaphyllum, DKD and dislipidemia were used to establish a protein-protein interaction (PPI) network. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to explore the potential molecular pathways. Results: The key targets for the therapeutic effects of gynostemma pentaphyllum included IL-6, AKT1, VEGFA, PTGS2, CCL2 and CASP3. Enrichment analysis showed that the underlying mechanism were mainly the involved in inhibition of inflammatory response, negative regulation of apoptotic process and angiogenesis. TNF, PI3K-Akt, and HIF-1 signaling pathways were considered as the key pathways. Conclusion: Gynostemma pentaphyllum played a therapeutic role in DKD complicated with dislipidemia, mainly through influencing inflammation response, apoptosis and angiogenesis.

scholarly journals A Network Pharmacology Approach to Understanding the Mechanisms of Action of Traditional Medicine: Rheum L. for Diabetic Kidney Disease

2020 ◽  
Author(s):  
Jinli Luo ◽  
Chunli Piao ◽  
De Jin ◽  
Li Wang ◽  
Xiaohua Zhao ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Molecular Mechanisms ◽  
Chinese Herb ◽  
Enrichment Analysis ◽  
Peripheral Circulation ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Diabetic Kidney ◽  
Underlying Mechanisms

Abstract BackgroundRheum L. (Da-huang in pinyin, Radix Rhei Et Rhizome in pharmaceutical name), a classic Chinese herb, has been extensively used to treat diabetic kidney disease in clinical practice in China for many years. However, the pharmacological mechanisms of Rheum L. remain elusive. To decrypt the underlying mechanisms of Rheum L. in the treatment of diabetic kidney disease using a systems pharmacology approach. MethodsA network pharmacology-based strategy was proposed to elucidate the underlying multi-component, multi-target, and multi-pathway mode of action of Rheum L. against diabetic kidney disease. We collected putative targets of Rheum L. and a network of the interactions among the putative targets of Rheum L. and known therapeutic targets of diabetic kidney disease was built. The major hubs were imported to the Database to perform a pathway enrichment analysis. ResultsA total of 6 active ingredients and 271 targets of Rheum L. were picked out. 11 cellular biological processes and 18 pathways of Rheum L. mostly associated with inflammatory response, apoptosis, fibrosis, and peripheral circulation. ConclusionsRheum L. could alleviate diabetic kidney disease via the molecular mechanisms predicted by network pharmacology.

scholarly journals Network Pharmacology-Based Investigation into the Mechanisms of Qibangyishen Formula for the Treatment of Diabetic Kidney Disease

2021 ◽  
Author(s):  
Zhi Wang ◽  
Guihua Jian
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Osteoclast Differentiation ◽  
Treatment Strategies ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Disease Genes ◽  
Active Ingredients ◽  
Diabetic Kidney

Abstract Background Diabetic kidney disease is the main microvascular complication of diabetes, and new treatment strategies are needed. We investigated the multi-component, multi-target, and multi-path mechanism of Qibangyishen formula for the treatment of diabetic kidney disease by network pharmacology methods. Methods We collected the active ingredients and targets of Qibangyishen formula and examined diabetic kidney disease-related genes by searching the ETCM, TCMID, and DisGeNet databases. We constructed and analyzed the genetic network through Cytoscape software and used the STRING platform for pathway enrichment analysis. Results We uncovered 421 active ingredients of Qibangyishen formula, corresponding to 748 targets. A network analysis screen revealed 47 hub-node targets, and 13 of these targets were diabetic kidney disease-related disease genes. Further functional analysis identified 26 targets acting on 11 pathways related to the development of diabetic kidney disease, including PI3K-Akt, thyroid hormone, neurotrophin, Wnt, chemokine, and osteoclast differentiation signaling pathways. Conclusions This study suggests that Qibangyishen formula regulates multiple genes and biological processes related to diabetic kidney disease and provides a foundation for further research and clinical applications.

scholarly journals Gynostemma Pentaphyllum Ameliorates Lipid Metabolic Abnormalities in Diabetic Kidney Disease

2021 ◽  
Author(s):  
Pengrui Wang ◽  
Shouhai Jiao ◽  
Li Sun ◽  
Helin Sun ◽  
Cunzhi Wang ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Enrichment Analysis ◽  
Underlying Mechanism ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Protective Mechanisms ◽  
Diabetic Kidney ◽  
Gynostemma Pentaphyllum ◽  
Protein Protein Interaction

Abstract Background: Patients with diabetic kidney disease (DKD) were often accompanied with dislipidemia. Gynostemma pentaphyllum can ameliorate insulin resistance and reduce the synthesis of triglycerides and cholesterol, but the underlying mechanism is still unclear. Therefore, we used the network pharmacologic strategies to evaluate potential therapeutic effects and protective mechanisms of gynostemma pentaphyllum on diabetic kidney disease. Methods: Gynostemma pentaphyllum's potential targets were predicted using the TCMSP databases. The pathogenic factors involved in DKD and dislipidemia were screened by the OMIM and Gene Cards databases. The common targets of gynostemma pentaphyllum, DKD and dislipidemia were used to establish a protein-protein interaction (PPI) network. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to explore the potential molecular pathways. Results: The key targets for the therapeutic effects of gynostemma pentaphyllum included IL-6, AKT1, VEGFA, PTGS2, CCL2 and CASP3. Enrichment analysis showed that the underlying mechanism were mainly the involved in inhibition of inflammatory response, negative regulation of apoptotic process and angiogenesis. TNF, PI3K-Akt, and HIF-1 signaling pathways were considered as the key pathways. Conclusion: Gynostemma pentaphyllum played a therapeutic role in DKD complicated with dislipidemia, mainly through influencing inflammation response, apoptosis and angiogenesis.

scholarly journals CFAP45 is a Potential Predictor of Mitochondrial Dysfunction in Diabetic Kidney Disease

2021 ◽  
Author(s):  
Yang Chen ◽  
Min Shen ◽  
Yun Shi ◽  
Li Ji ◽  
Yong Gu ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Signaling Pathways ◽  
Diabetic Kidney Disease ◽  
Tricarboxylic Acid Cycle ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Diabetic Kidney ◽  
Expression Levels ◽  
Potential Biomarker

Abstract Background: Cilia and Flagella Associated Protein 45 (CFAP45) is known to be involved in the regulation of ciliary motility. However, its potential role in diabetic kidney disease (DKD) remains unknown. This study demonstrated the role of CFAP45 in the development of DKD based on the Gene Expression Omnibus database.Methods: First, we investigated the expression of CFAP45 in a whole-genome expression microarray (GSE30122). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as Gene Set Enrichment Analysis (GSEA), were then conducted to identify the key signaling pathways associated with CFAP45. The networks between transcript factors and hub genes were then constructed by Cytoscape software.Findings: The expression levels of CFAP45 mRNA were reduced in DKD samples as compared to normal samples. Receiver operating characteristic (ROC) curve analysis suggested the significant discriminatory power (area under curve [AUC] = 0.811) of CFAP45 between DKD and normal tissues. Low expression levels of CFAP45 were correlated with apoptosis, senescence and the induction of mast cell infiltration. Function enrichment analysis indicated that CFAP45 is involved in the most significant hallmarks of mitochondrial metabolism dysfunction, including glycolysis and gluconeogenesis, fatty acid metabolism and degradation, ubiquitin-dependent protein catabolic processes, the tricarboxylic acid cycle (TCA) cycle, the action of oxidoreductase on Nicotinamide adenine dinucleotide (NADH), and the peroxisome proliferator-activated receptor (PPAR) signaling pathways located in the mitochondrial matrix and the lysosomal membrane. The transcription factor SMAD4 was found to negatively regulate the PPAR γ coactivator 1α (PGC1α). Interpretation: CFAP45 may regulate mitochondrial metabolic activity by affecting the function of the primary cilium on the kidney epithelial cells. CFAP45 may serve as a potential biomarker for the diagnosis and treatment of DKD.

scholarly journals 20(S)-Ginsenoside Rg3 Protects Kidney from Diabetic Kidney Disease via Renal Inflammation Depression in Diabetic Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Tong Zhou ◽  
Lin Sun ◽  
Shuo Yang ◽  
You Lv ◽  
Yue Cao ◽  
...  
Keyword(s):  
Treatment Group ◽  
Kidney Disease ◽  
Cell Apoptosis ◽  
Diabetic Kidney Disease ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Renal Tubular Cell ◽  
Ginsenoside Rg3 ◽  
Diabetic Kidney ◽  
Renal Tubular

20(S)-Ginsenoside Rg3 (20(S)-Rg3) has been shown to induce apoptosis by interfering with several signaling pathways. Furthermore, it has been reported to have anticancer and antidiabetic effects. In order to detect the protective effect of 20(S)-Rg3 on diabetic kidney disease (DKD), diabetic rat models which were established by administering high-sugar, high-fat diet combined with intraperitoneal injection of streptozotocin (STZ), and age-matched wild-type (WT) rat were given 20(S)-Rg3 for 12 weeks, with three groups: control group (normal adult rats with saline), diabetic group (diabetic rats with saline), and 20(S)-Rg3 treatment group (diabetic rats with 20(S)-Rg3 (10 mg/kg body weight/day)). The biochemical indicators and the changes in glomerular basement membrane and mesangial matrix were detected. TUNEL staining was used to detect glomerular and renal tubular cell apoptosis. Immunohistochemical staining was used to detect the expression of fibrosis factors and inflammation factors in rat kidney tissues. Through periodic acid-Schiff staining, we observed that the change in renal histology was improved and renal tubular epithelial cell apoptosis decreased significantly by treatment with 20(S)-Rg3. Plus, the urine protein decreased in the rats with the 20(S)-Rg3 treatment. Fasting blood glucose, creatinine, total cholesterol, and triglyceride levels in the 20(S)-Rg3 treatment group were all lower than those in the diabetic group. Mechanistically, 20(S)-Rg3 dramatically downregulated the expression of TGF-β1, NF-κB65, and TNF-α in the kidney. These resulted in a significant prevention of renal damage from the inflammation. The results of the current study suggest that 20(S)-Rg3 could potentially be used as a novel treatment against DKD.

Renal type I inositol 1,4,5-trisphosphate receptor is reduced in streptozotocin-induced diabetic rats and mice

1999 ◽  
Vol 276 (1) ◽  
pp. F54-F61 ◽  
Author(s):  
Kumar Sharma ◽  
Lewei Wang ◽  
Yanqing Zhu ◽  
Aurora DeGuzman ◽  
Gao-Yuan Cao ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Diabetic Rats ◽  
Type I ◽  
Renal Hypertrophy ◽  
Diabetic Kidney ◽  
Inositol 1,4,5 Trisphosphate ◽  
Rats And Mice ◽  
Tgf Β1

The mechanisms underlying glomerular hypertrophy and hyperfiltration in diabetes remain unclear. We have previously demonstrated that the cytokine transforming growth factor-β1 (TGF-β1) is increased in early diabetic kidney disease and TGF-β1 inhibits the expression of the inositol 1,4,5-trisphosphate (IP3)-gated calcium channel, the type I IP3 receptor (IP3R), in mesangial cells. To test the hypothesis that reduced type I IP3R may be important in diabetic kidney disease, we evaluated type I IP3R expression in the kidney of streptozotocin-induced diabetic rats and mice. Two-week-old diabetic rats have decreased renal type I IP3R protein and mRNA levels. Immunostaining of normal rat kidney demonstrated presence of type I IP3R in glomerular and vascular smooth muscle cells, whereas diabetic rats had reduced staining in both compartments. Reduction of type I IP3R also occurred in parallel with renal hypertrophy, increased creatinine clearance, and increased renal TGF-β1 expression in the diabetic rats. Two-week-old diabetic mice also had reduced renal type I IP3R protein and mRNA expression in association with renal hypertrophy and increased TGF-β1 mRNA expression. These findings demonstrate that there is reduced type I IP3R in glomerular and vascular smooth muscle cells in the diabetic kidney, which may contribute to the altered renal vasoregulation and renal hypertrophy of diabetes.

Elevated Serum Levels of Carbohydrate Antigen 72–4 in Diabetic Kidney Disease

2021 ◽  
Author(s):  
Lei Shi ◽  
Jiali Meng ◽  
Bin Zhang ◽  
Jiandong Chen ◽  
Jianzhong Chen ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Elevated Serum ◽  
Serum Levels ◽  
Carbohydrate Antigen ◽  
Urinary Albumin ◽  
Renal Diseases ◽  
Diabetic Patients ◽  
Healthy Controls ◽  
Diabetic Kidney

AbstractThe aim of this study was to determine whether carbohydrate antigen 72–4 (CA72–4) is elevated in diabetic kidney disease (DKD), and examine the association between urinary albumin-to-creatinine ratio (UACR) and CA72–4 in patients with type 2 diabetes mellitus (T2DM). Non-dialysis patients with T2DM (n=296) and 90 healthy controls were recruited in this study. CA72–4 level was measured by electrochemiluminescence immunoassay. DKD was defined as UACR≥ 30 mg/g in the absence of a urinary infection or other renal diseases. We found that patients with DKD had significantly higher serum CA72–4 levels compared to those with normoalbuminuria and healthy controls. Positive rates of CA72–4 increased gradually and markedly from normoalbuminuria to microalbuminuria and to macroalbuminuria in diabetic patients (7.5, 11.2, and 17.4%, respectively; P for trend< 0.05). CA72–4 also showed a positive correlation with UACR (r=0.288, P< 0.01). Logistic regression analysis revealed the association of increased UACR with an increased odds ratio of elevation of CA72–4 levels (P for trend< 0.05) after multivariable adjustment. In conclusion, serum levels of CA72–4 increase abnormally with the increase in urinary albumin excretion, which affects the specificity of diagnosis of malignancies. An appropriate interpretation of CA72–4 is essential to prevent unnecessary and even hazardous diagnostic procedures in patients with T2DM.

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