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 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 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 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 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 Administration of mesenchymal stem cells in diabetic kidney disease: a systematic review and meta-analysis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wenshan Lin ◽  
Hong-Yan Li ◽  
Qian Yang ◽  
Guangyong Chen ◽  
Shujun Lin ◽  
...  
Keyword(s):  
Systematic Review ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Meta Analysis ◽  
Treated Group ◽  
Hypoglycemic Effect ◽  
Cochrane Library ◽  
Great Promise ◽  
Therapeutic Effects ◽  
Diabetic Kidney

Abstract Background Mesenchymal stem cell (MSC) therapy shows great promise for diabetic kidney disease (DKD) patients. Research has been carried out on this topic in recent years. The main goals of this paper are to evaluate the therapeutic effects of MSCs on DKD through a meta-analysis and address the mechanism through a systematic review of the literature. Method An electronic search of the Embase, Cochrane Library, ISI Web of Science, PubMed, and US National Library of Medicine (NLM) databases was performed for all articles about MSC therapy for DKD, without species limitations, up to January 2020. Data were pooled for analysis with Stata SE 12. Result The MSC-treated group showed a large and statistically significant hypoglycemic effect at 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, and 6 months. Total hypoglycemic effect was observed (SMD = − 1.954, 95%CI − 2.389 to − 1.519, p < 0.001; I2 = 85.1%). The overall effects on serum creatinine (SCr) and blood urea nitrogen (BUN) were analyzed, suggesting that MSC decreased SCr and BUN and mitigated the impairment of renal function (SCr: SMD = − 4.838, 95%CI − 6.789 to − 2.887, p < 0.001; I2 = 90.8%; BUN: SMD = − 4.912, 95%CI − 6.402 to − 3.422, p < 0.001; I2 = 89.3%). Furthermore, MSC therapy decreased the excretion of urinary albumin. Fibrosis indicators were assessed, and the results showed that transforming growth factor-β, collagen I, fibronectin, and α-smooth muscle actin were significantly decreased in the MSC-treated group compared to the control group. Conclusion MSCs might improve glycemic control and reduce SCr, BUN, and urinary protein. MSCs can also alleviate renal fibrosis. MSC therapy might be a potential treatment for DKD.

scholarly journals Administration of Mesenchymal Stem Cells in Diabetic Kidney Disease: A Systematic Review and Meta-analysis

2020 ◽  
Author(s):  
Wenshan Lin ◽  
Qian Yang ◽  
Guangyong Chen ◽  
Shujun Lin ◽  
Chunling Liao ◽  
...  
Keyword(s):  
Systematic Review ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Meta Analysis ◽  
Treated Group ◽  
Hypoglycemic Effect ◽  
Cochrane Library ◽  
Great Promise ◽  
Therapeutic Effects ◽  
Diabetic Kidney

Abstract Background: Mesenchymal stem cell (MSC) therapy shows great promise for diabetic kidney disease (DKD) patients. Research has been carried out on this topic in recent years. The main goal of this paper is to evaluate the therapeutic effects of MSCs on DKD through a meta-analysis and address the mechanism through a systematic review of the literature.Method: An electronic search of the Embase, Cochrane Library, ISI Web of Science, PubMed and U.S National Library of Medicine (NLM) databases was performed for all articles about MSC therapy for DKD, without species limitations, up to January 2020. Data were pooled for analysis with Stata SE 12.Result: The MSC-treated group showed a large and statistically significant hypoglycemic effect at 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months and 6 months. Total hypoglycemic effect was observed (SMD=-1.954, 95%CI: -2.389 to -1.519, p＜0.001). The overall effects on serum creatinine (SCr) and blood urea nitrogen (BUN) were analyzed, suggesting that MSC decreased SCr and BUN and mitigated the impairment of renal function (SCr: SMD= -4.838, 95%CI: -6.789 to -2.887, p＜0.001; BUN: SMD= -4.912, 95%CI: -6.402 to -3.422, p＜0.001). Furthermore, MSC therapy decreased the excretion of urinary albumin. Fibrosis indicators were assessed, and the results showed that transforming growth factor-β, collagen-I, fibronectin and α-smooth muscle actin were significantly decreased in the MSC-treated group compared to the control group.Conclusion: MSCs may improve glycemic control and reduce SCr, BUN, and urinary protein. MSCs can also alleviate renal fibrosis. MSC therapy is a potential treatment for DKD.

Therapeutic effects of lisinopril and empagliflozin in a mouse model of hypertension-accelerated diabetic kidney disease

2021 ◽  
Author(s):  
Mette Viberg Østergaard ◽  
Thomas Secher ◽  
Michael Christensen ◽  
Casper Gravesen Salinas ◽  
Urmas Roostalu ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Mouse Model ◽  
Diabetic Kidney Disease ◽  
Synergistic Effects ◽  
Standard Of Care ◽  
Therapeutic Interventions ◽  
Therapeutic Effects ◽  
Tubulointerstitial Injury ◽  
Diabetic Kidney ◽  
Control Disease

Hypertension is a critical comorbidity for progression of diabetic kidney disease (DKD). To facilitate development of novel therapeutic interventions with the potential to control disease progression, there is a need to establish translational animal models that predict treatment effects in human DKD. The present study aimed to characterize renal disease and outcomes of standard of medical care in a mouse model of advanced DKD facilitated by adeno-associated virus (AAV)-mediated renin overexpression in uninephrectomized (UNx) db/db mice. Five weeks after single AAV administration and four weeks after UNx, female db/db UNx-ReninAAV mice received (PO, QD) vehicle, lisinopril (40 mg/kg), empagliflozin (20 mg/kg) or combination treatment for 12 weeks (n=17 per group). Untreated db/+ mice (n=8) and vehicle-dosed db/db UNx-LacZAAV mice (n=17) served as controls. Endpoints included plasma, urine and histomorphometric markers of kidney disease. Total glomerular numbers and individual glomerular volume was evaluated by whole-kidney 3D imaging analysis. db/db UNx-ReninAAV mice developed hallmarks of progressive DKD characterized by severe albuminuria, advanced glomerulosclerosis and glomerular hypertrophy. Lisinopril significantly improved albuminuria, glomerulosclerosis, tubulointerstitial injury and inflammation. While empagliflozin alone had no therapeutic effect on renal endpoints, lisinopril and empagliflozin exerted synergistic effects on renal outcomes. In conclusion, the db/db UNx-ReninAAV mouse demonstrates good clinical translatability with respect to the physiological and histological hallmarks of progressive DKD. Efficacy of standard of care to control hypertension and hyperglycemia provides proof-of-concept for testing novel drug therapies in the model.

scholarly journals Tongxinluo preserves the renal function in diabetic kidney disease via protecting the HK-2 cells from the patterns of programmed cell death

2021 ◽  
Vol 16 (2) ◽  
pp. 52-64
Author(s):  
Shuang Shen ◽  
Yunlong Hou ◽  
Yiling Wu
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Caspase 3 ◽  
Excretion Rate ◽  
Underlying Mechanism ◽  
Diabetic Kidney ◽  
Caspase 1 ◽  
Urine Albumin ◽  
Proximal Tubular ◽  
Cells Cultured

This study was explored the renoprotective effect of Tongxinluo (a Traditional Chinese Medicine) on diabetic kidney disease and its underlying mechanism. The results revealed significant (p<0.05) up-regulation of the expression of Bcl-2 and down-regulation of NF-κB p-p65, ASC, NLRP3, caspase-1, cleaved GSDMD, IL-1β, caspase-3, Bax and the ratio of Bcl-2 and Bax in immortalized proximal tubular HK-2 cells cultured by hyperglycemia combined with hyperlipidemia. In db/db mice, Tongxinluo treatment substantially decreased the 24 hours albuminuria excretion rate and the urine albumin-creatinine ratios and renal morphologic abnormalities. Similarly, the levels of NF-κB p-p65, NLRP3, caspase-1, cleaved GSDMD, IL-1β, caspase-3, and the ratio of Bcl-2 and Bax were down-regulated by Tongxinluo treatment in the kidney samples of db/db mice (p<0.05). Taken together, according to the anti-pyroptosis and anti-apoptosis effect of Tongxinluo, it shows the potential to be effective for the treatment of diabetic kidney disease.

scholarly journals Administration of Mesenchymal Stem Cells in Diabetic Kidney Disease: A Systematic Review and Meta-analysis

2020 ◽  
Author(s):  
Wenshan Lin ◽  
Hong-Yan Li ◽  
Qian Yang ◽  
Guangyong Chen ◽  
Shujun Lin ◽  
...  
Keyword(s):  
Systematic Review ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Meta Analysis ◽  
Treated Group ◽  
Hypoglycemic Effect ◽  
Cochrane Library ◽  
Great Promise ◽  
Therapeutic Effects ◽  
Diabetic Kidney

Abstract Background: Mesenchymal stem cell (MSC) therapy shows great promise for diabetic kidney disease (DKD) patients. Research has been carried out on this topic in recent years. The main goal of this paper is to evaluate the therapeutic effects of MSCs on DKD through a meta-analysis and address the mechanism through a systematic review of the literature. Method: An electronic search of the Embase, Cochrane Library, ISI Web of Science, PubMed and U.S National Library of Medicine (NLM) databases was performed for all articles about MSC therapy for DKD, without species limitations, up to January 2020. Data were pooled for analysis with Stata SE 12. Result: The MSC-treated group showed a large and statistically significant hypoglycemic effect at 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months and 6 months. Total hypoglycemic effect was observed (SMD=-1.954, 95%CI: -2.389 to -1.519, p＜0.001; I²= 85.1%). The overall effects on serum creatinine (SCr) and blood urea nitrogen (BUN) were analyzed, suggesting that MSC decreased SCr and BUN and mitigated the impairment of renal function (SCr: SMD= -4.838, 95%CI: -6.789 to -2.887, p＜0.001; I²= 90.8%; BUN: SMD= -4.912, 95%CI: -6.402 to -3.422, p＜0.001; I²= 89.3 %). Furthermore, MSC therapy decreased the excretion of urinary albumin. Fibrosis indicators were assessed, and the results showed that transforming growth factor-β, collagen-I, fibronectin and α-smooth muscle actin were significantly decreased in the MSC-treated group compared to the control group. Conclusion: MSCs might improve glycemic control and reduce SCr, BUN, and urinary protein. MSCs can also alleviate renal fibrosis. MSC therapy might be a potential treatment for DKD.

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