scholarly journals Radix Rehmanniae and Corni Fructus against Diabetic Nephropathy via AGE-RAGE Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Jing Chen ◽  
Yuping Chen ◽  
Anmei Shu ◽  
Jinfu Lu ◽  
Qiu Du ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Animal Experiments ◽  
Structure And Function ◽  
Metabolic Parameters ◽  
Network Pharmacology ◽  
Active Compounds ◽  
Renal Structure ◽  
Corni Fructus ◽  
And Function

Background and Aims. Radix Rehmanniae and Corni Fructus (RC) have been widely applied to treat diabetic nephropathy (DN) for centuries. But the mechanism of how RC plays the therapeutic role against DN is unclear as yet. Methods. The information about RC was obtained from a public database. The active compounds of RC were screened by oral bioavailability (OB) and drug-likeness (DL). Gene ontology (GO) analysis was performed to realize the key targets of RC, and an active compound-potential target network was created. The therapeutic effects of RC active compounds and their key signal pathways were preliminarily probed via network pharmacology analysis and animal experiments. Results. In this study, 29 active compounds from RC and 64 key targets related to DN were collected using the network pharmacology method. The pathway enrichment analysis showed that RC regulated advanced glycosylation end product (AGE-) RAGE and IL-17 signaling pathways to treat DN. The animal experiments revealed that RC significantly improved metabolic parameters, inflammation renal structure, and function to protect the kidney against DN. Conclusions. The results revealed the relationship between multicomponents and multitargets of RC. The administratiom of RC might remit the DM-induced renal damage through the AGE-RAGE signaling pathway to improve metabolic parameters and protect renal structure and function.

scholarly journals A Network Pharmacology-Based Approach for Exploring Key Active Compounds and Pharmacological Mechanisms of Tangshen Formula for Treatment of Diabetic Nephropathy

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Weie Zhou ◽  
Xuefeng Zhou ◽  
Yuan Zhang ◽  
Yuyang Wang ◽  
Wenjie Wu ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Synergistic Effects ◽  
Mapk Signaling ◽  
Network Pharmacology ◽  
Active Compounds ◽  
Promising Source ◽  
Tangshen Formula ◽  
Compound Target

Diabetic nephropathy (DN) is one of the common and severe microvascular complications of diabetes mellitus (DM). The occurrence and development of DN are related to multiple factors in the human body, which makes DN a complex disease, and the pathogeneses of DN have not yet been fully illustrated. Furthermore, DN lacks effective drugs for treatment nowadays. Chinese herbal medicine (CHM) often shows the feature of multicomponents, multitargets, multipathways, and synergistic effects and shows a promising source of new therapeutic drugs for DN. As a CHM, Tangshen Formula (TSF) was used to treat DN patients in China. However, its bioactive compounds and holistic pharmacological mechanisms on DN are both unclear. A network pharmacology approach was firstly applied to explore multiple active compounds and multiple key pharmacological mechanisms for TSF treating DN by drug-targeted interaction databases, herb-compound-target network, protein-protein interaction network, compound-target-pathway network, and analysis methods. And the results showed that TSF have the characteristic of multicomponents, multitargets, multipathways, and synergistic effects for treating DN. The quercetin, naringenin, kaempferol, and isorhamnetin as key active compounds and the PI3K-Akt signaling pathway, TNF signaling pathway, nonalcoholic fatty liver disease (NAFLD), focal adhesion, rap1 signaling pathway, T cell receptor signaling pathway, MAPK signaling pathway, and insulin resistance as the key molecular mechanisms play important roles in TSF treating DN. Moreover, quercetin, naringenin, kaempferol, and isorhamnetin were successfully detected in TSF by the UHPLC-MS/MS analysis method. And their concentrations were 0.224, 8.295, 0.0564, and 0.0879 mg·kg-1, respectively. The present findings not only provide new insights for a deeper understanding of the constituent basis and pharmacology of TSF but also provide guidance for further pharmacological studies on TSF.

Tongxinluo ameliorates renal structure and function by regulating miR-21-induced epithelial-to-mesenchymal transition in diabetic nephropathy

2014 ◽  
Vol 306 (5) ◽  
pp. F486-F495 ◽  
Author(s):  
Jin-yang Wang ◽  
Yan-bin Gao ◽  
Na Zhang ◽  
Da-wei Zou ◽  
Li-ping Xu ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Epithelial To Mesenchymal Transition ◽  
Smooth Muscle Actin ◽  
Physiological Role ◽  
Structure And Function ◽  
Clearance Ratio ◽  
Mesenchymal Transition ◽  
Renal Structure ◽  
And Function ◽  
E Cadherin

Diabetic nephropathy (DN) is one of the most important diabetic microangiopathies. The epithelial-to-mesenchymal transition (EMT) plays an important role in DN. The physiological role of microRNA-21 (miR-21) was closely linked to EMT. However, it remained elusive whether tongxinluo (TXL) ameliorated renal structure and function by regulating miR-21-induced EMT in DN. This study aimed to determine the effect of TXL on miR-21-induced renal tubular EMT and to explore the relationship between miR-21 and TGF-β1/smads signals. Real-time RT-PCR, cell transfection, in situ hybridization (ISH), and laser confocal microscopy were used, respectively. Here, we revealed that TXL dose dependently lowered miR-21 expression in tissue, serum, and cells. Overexpression of miR-21 can enhance α-smooth muscle actin (SMA) expression and decrease E-cadherin expression by upregulating smad3/p-smad3 expression and downregulating smad7 expression. Interestingly, TXL also increased E-cadherin expression and decreased α-SMA expression by regulating miR-21 expression. More importantly, TXL decreased collagen IV, fibronectin, glomerular basement membrane, glomerular area, and the albumin/creatinine ratio, whereas it increased the creatinine clearance ratio. The results demonstrated that TXL ameliorated renal structure and function by regulating miR-21-induced EMT, which was one of the mechanisms to protect against DN, and that miR-21 may be one of the therapeutic targets for TXL in DN.

Discordant effects of guanidines on renal structure and function and on regional vascular dysfunction and collagen changes in diabetic rats

Diabetes ◽  
1997 ◽  
Vol 46 (1) ◽  
pp. 94-106 ◽  
Author(s):  
J. R. Nyengaard ◽  
K. Chang ◽  
S. Berhorst ◽  
K. M. Reiser ◽  
J. R. Williamson ◽  
...  
Keyword(s):  
Vascular Dysfunction ◽  
Diabetic Rats ◽  
Structure And Function ◽  
Renal Structure ◽  
And Function

scholarly journals Differences between diabetic and non-diabetic nephropathy patients in cardiac structure and function at the beginning of hemodialysis and their impact on the prediction of mortality

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199758
Author(s):  
Chao Tang ◽  
Han Ouyang ◽  
Jian Huang ◽  
Jing Zhu ◽  
Xiaosong Gu
Keyword(s):  
Diabetic Nephropathy ◽  
Diastolic Dysfunction ◽  
Peak Velocity ◽  
Structure And Function ◽  
Cardiac Valve ◽  
Cardiac Structure ◽  
Prediction Of Mortality ◽  
Cardiac Structure And Function ◽  
Lv Diastolic Dysfunction ◽  
And Function

Objectives To characterize differences in cardiac structure and function in hemodialysis (HD) patients with diabetic nephropathy (DN) and in those without using echocardiography and to determine their impact on the prediction of mortality using echocardiographic parameters. Methods Clinical, laboratory, and echocardiographic data were collected from patients commencing HD. Results Compared with those without DN, patients with DN had lower peak velocity of the early diastolic wave (e′), larger left atria, and higher peak early diastolic velocity (E)/e′ and peak velocity of tricuspid regurgitation (TR). In addition, a larger proportion of DN patients had a combination of left ventricular (LV) diastolic dysfunction, cardiac valve calcification, moderate-to-severe cardiac valve regurgitation (CVR), and at least moderate pericardial effusion (PE). After accounting for age, sex, smoking, hypertension, hemoglobin, and albumin, DN was responsible for e′  < 10 cm/s, E/e′ >13 m/s, TR >2.8 m/s, LV diastolic dysfunction, CVR, and PE. LV diastolic dysfunction and E/e′ >13 were the most useful predictors of mortality in patients with DN. Conclusions Patients with DN who undergo HD tend to have worse LV diastolic function and are more likely to have heart valve problems. LV diastolic dysfunction and E/e′ are predictors of death in DN patients.

scholarly journals Potential mechanisms of Guizhi decoction against hypertension based on network pharmacology and Dahl salt-sensitive rat model

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jiye Chen ◽  
Yongjian Zhang ◽  
Yongcheng Wang ◽  
Ping Jiang ◽  
Guofeng Zhou ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Rat Model ◽  
Experimental Studies ◽  
Matrix Metalloproteinase 2 ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Active Ingredients ◽  
Active Compounds ◽  
Guizhi Decoction

Abstract Background Guizhi decoction (GZD), a classical Chinese herbal formula, has been widely used to treat hypertension, but its underlying mechanisms remain elusive. The present study aimed to explore the potential mechanisms and therapeutic effects of GZD on hypertension by integrating network pharmacology and experimental validation. Methods The active ingredients and corresponding targets were collected from the Traditional Chinese Medicine Systems Pharmacology database and Analysis Platform (TCMSP). The targets related to hypertension were identified from the CTD, GeneCards, OMIM and Drugbank databases. Multiple networks were constructed to identify the key compounds, hub targets, and main biological processes and pathways of GZD against hypertension. The Surflex-Dock software was used to validate the binding affinity between key targets and their corresponding active compounds. The Dahl salt-sensitive rat model was used to evaluate the therapeutic effects of GZD against hypertension. Results A total of 112 active ingredients, 222 targets of GZD and 341 hypertension-related targets were obtained. Furthermore, 56 overlapping targets were identified, five of which were determined as the hub targets for experimental verification, including interleukin 6 (IL-6), C–C motif chemokine 2 (CCL2), IL-1β, matrix metalloproteinase 2 (MMP-2), and MMP-9. Pathway enrichment analysis results indicated that 56 overlapping targets were mainly enriched in several inflammation pathways such as the tumor necrosis factor (TNF) signaling pathway, Toll-like receptor (TLR) signaling pathway and nuclear factor kappa-B (NF-κB) signaling pathway. Molecular docking confirmed that most active compounds of GZD could bind tightly to the key targets. Experimental studies revealed that the administration of GZD improved blood pressure, reduced the area of cardiac fibrosis, and inhibited the expression of IL-6, CCL2, IL-1β, MMP-2 and MMP-9 in rats. Conclusion The potential mechanisms and therapeutic effects of GZD on hypertension may be attributed to the regulation of cardiac inflammation and fibrosis.

scholarly journals A Network Pharmacology Approach to Uncover the Mechanisms of Shen-Qi-Di-Huang Decoction against Diabetic Nephropathy

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Sha Di ◽  
Lin Han ◽  
Qing Wang ◽  
Xinkui Liu ◽  
Yingying Yang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Protein Protein Interaction ◽  
Regulation Of Blood Pressure ◽  
Protein Protein Interaction Network

Shen-Qi-Di-Huang decoction (SQDHD), a well-known herbal formula from China, has been widely used in the treatment of diabetic nephropathy (DN). However, the pharmacological mechanisms of SQDHD have not been entirely elucidated. At first, we conducted a comprehensive literature search to identify the active constituents of SQDHD, determined their corresponding targets, and obtained known DN targets from several databases. A protein-protein interaction network was then built to explore the complex relations between SQDHD targets and those known to treat DN. Following the topological feature screening of each node in the network, 400 major targets of SQDHD were obtained. The pathway enrichment analysis results acquired from DAVID showed that the significant bioprocesses and pathways include oxidative stress, response to glucose, regulation of blood pressure, regulation of cell proliferation, cytokine-mediated signaling pathway, and the apoptotic signaling pathway. More interestingly, five key targets of SQDHD, named AKT1, AR, CTNNB1, EGFR, and ESR1, were significant in the regulation of the above bioprocesses and pathways. This study partially verified and predicted the pharmacological and molecular mechanisms of SQDHD on DN from a holistic perspective. This has laid the foundation for further experimental research and has expanded the rational application of SQDHD in clinical practice.

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