<p>BCc1 Nanomedicine Therapeutic Effects in Streptozotocin and High-Fat Diet Induced Diabetic Kidney Disease</p>

Abstract Background Growing clinical evidences show the potentials of Colquhounia root tablet (CRT) in alleviating diabetic kidney disease (DKD). However, its pharmacological properties and underlying mechanisms remain unclear. Methods ‘Drug target-Disease gene’ interaction network was constructed and the candidate network targets were screened through evaluating node genes' topological importance. Then, a DKD rat model induced by high-fat diet/streptozotocin was established and used to determine pharmacological effects and network regulatory mechanisms of CRT against DKD, which were also verified using HK2 cell model induced by high glucose. Results The candidate network targets of CRT against DKD were involved into various type II diabetes-related and nephropathy-related pathways. Due to the topological importance of the candidate network targets and the important role of the imbalance between immunity and inflammation in the pathogenesis of DKD, PI3K/AKT/NF-кB signaling-mediated immune-modulatory and anti-inflammatory actions of CRT were selected to be experimentally verified. On the basis of high-fat diet (HFD) / streptozotocin (STZ)-induced DKD rat model, CRT effectively reduced the elevated level of blood glucose, decreased the accumulation of renal lipid, suppressed inflammation and the generation of ECM proteins, and ameliorated kidney function and the renal histopathology through inhibiting the activation of PI3K, AKT and NF-кB proteins, reducing the nuclear accumulation of NF-кB protein and the serum levels of downstream cytokines, which were in line with the in vitro findings. Conclusions Our data suggest that CRT may be the promising candidate drug for treating DKD via reversing the imbalance of immune-inflammation system mediated by the PI3K/AKT/NF-кB/IL-1β/TNF-α signaling.

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The effects of compound centella formula on OxInflammation and silent information regulator 1 in a high‑fat diet/streptozotocin‑induced diabetic kidney disease rat model

Experimental and Therapeutic Medicine ◽

10.3892/etm.2021.10394 ◽

2021 ◽

Vol 22 (3) ◽

Author(s):

Qin Zhu ◽

Xiao-Hong Li ◽

Hong-Yu Chen ◽

Qin-Yang Jin

Keyword(s):

Kidney Disease ◽

Rat Model ◽

High Fat Diet ◽

Diabetic Kidney Disease ◽

High Fat ◽

Diabetic Kidney ◽

Silent Information Regulator 1

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Codonopsis tangshen Oliv. Amelioration Effect on Diabetic Kidney Disease Rats Induced by High Fat Diet Feeding Combined with Streptozotocin

Natural Products and Bioprospecting ◽

10.1007/s13659-018-0187-5 ◽

2018 ◽

Vol 8 (6) ◽

pp. 441-451 ◽

Cited By ~ 1

Author(s):

Xian-Yuan Lu ◽

Feng-Hua Zhou ◽

Ya-Qian Dong ◽

Lin-Na Gong ◽

Qing-Yun Li ◽

...

Keyword(s):

Kidney Disease ◽

High Fat Diet ◽

Diabetic Kidney Disease ◽

High Fat ◽

Diabetic Kidney

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Gynostemma Pentaphyllum Ameliorates Lipid Metabolic Abnormalities in Diabetic Kidney Disease

10.21203/rs.3.rs-1149570/v2 ◽

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.

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

Stem Cell Research & Therapy ◽

10.1186/s13287-020-02108-5 ◽

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.

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

10.21203/rs.3.rs-70844/v2 ◽

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.

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

AJP Renal Physiology ◽

10.1152/ajprenal.00154.2021 ◽

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.

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

10.21203/rs.3.rs-70844/v3 ◽

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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