A Nucleoside/Nucleobase-Rich Extract from Cordyceps Sinensis Inhibits the Epithelial–Mesenchymal Transition and Protects against Renal Fibrosis in Diabetic Nephropathy

Dong, Zhen; Sun, Yehuan; Wei, Guangwei; Li, Siying; Zhao, Zhongxi

doi:10.3390/molecules24224119

Cited by 26 publications

(23 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is accumulating evidence indicating that the RAF/MEK/ERK signaling pathway plays an important role in EMT during DKD. 35 , 36 It has been demonstrated that the response of ERK/MAPK signaling cascades activation to growth factors or mutant RAS could up-regulate TGF-β-induced EMT. 37 A previous study revealed that the RAF signaling pathway increases the expression of SNAIL1 and/or SNAIL2, thereby promoting cancer-associated EMT manifested as cell motility and invasive behavior upregulation.…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV Alleviates Renal Tubular Epithelial-Mesenchymal Transition via CX3CL1-RAF/MEK/ERK Signaling Pathway in Diabetic Kidney Disease

Hu¹,

Tang²,

Liu³

et al. 2022

DDDT

View full text Add to dashboard Cite

Background Epithelial–mesenchymal transition (EMT) plays an important role in interstitial matrix deposition and renal fibrosis in diabetic kidney disease (DKD). It has been verified that Astragaloside IV (AS-IV) is beneficial for ameliorating DKD. However, the underlying mechanisms of AS-IV on regulating EMT in DKD are yet to be established. Accumulated evidence has suggested that C-X3-C motif ligand 1 (CX3CL1) plays a significant role in the progression of EMT. Purpose We aimed to investigate whether AS-IV could alleviate EMT by regulating CX3CL1 in DKD and reveal its underlying mechanisms. Methods For the in vivo study, mice were divided into the following five groups (n=10): db/m+vehicle, db/db+vehicle, db/db+AS-IV-L (10mg/kg/d), db/db+AS-IV-M (20mg/kg/d), db/db+AS-IV-H (40mg/kg/d). After 12 weeks of treatment, the renal injuries were assessed based on the related parameters of urine, blood and histopathological examination. Immunohistochemistry and Western blotting were used to detect relative proteins levels. Then in HK-2 cells, the molecular mechanism of AS-IV attenuating the EMT in mice with DKD through the CX3CL1-RAF/MEK/ERK pathway was studied. Results In the present study, we found that AS-IV reduced urinary protein levels and improved renal pathological damage in DKD mice. Moreover, AS-IV ameliorated the renal tubular EMT induced by hyperglycemia or high glucose (HG), and decreased the expression of CX3CL1 and inhibited the activation of the RAF/MEK/ERK pathway in vivo and in vitro. In HK-2 cells, downregulation of CX3CL1 suppressed the stimulation of the RAF/MEK/ERK pathway and EMT induced by HG. However, CX3CL1 overexpression eliminated the benefits of AS-IV on the RAF/MEK/ERK pathway and EMT. Conclusion In summary, we indicated that AS-IV alleviates renal tubular EMT through the CX3CL1-RAF/MEK/ERK signaling pathway, indicating that CX3CL1 could be a potential therapeutic target of AS-IV in DKD.

show abstract

Section: Discussionmentioning

confidence: 99%

Astragaloside IV Alleviates Renal Tubular Epithelial-Mesenchymal Transition via CX3CL1-RAF/MEK/ERK Signaling Pathway in Diabetic Kidney Disease

Hu¹,

Tang²,

Liu³

et al. 2022

DDDT

View full text Add to dashboard Cite

show abstract

“…Some relevant studies highlight new perspectives of TCM for delaying DN progression and strengthen the therapeutic rationale for TCM on the treatment of DN [ 23 , 24 ]. Cordyceps contains several active ingredients which affect multiple targets and pathways in the progression of DN and has been used as an adjuvant on the treatment of DN in China for a long time [ 7 , 25 ]. In this study, we selected 7 active ingredients from Cordyceps based on the OB and DL, including linoleyl acetate, arachidonic acid, cholesteryl palmitate, CLR, beta-sitosterol, cerevisterol, and peroxyergosterol.…”

Section: Discussionmentioning

confidence: 99%

Based on Network Pharmacology Tools to Investigate the Molecular Mechanism of Cordyceps sinensis on the Treatment of Diabetic Nephropathy

Wang

et al. 2021

Journal of Diabetes Research

View full text Add to dashboard Cite

Background. Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus and is a major cause of end-stage kidney disease. Cordyceps sinensis (Cordyceps, Dong Chong Xia Cao) is a widely applied ingredient for treating patients with DN in China, while the molecular mechanisms remain unclear. This study is aimed at revealing the therapeutic mechanisms of Cordyceps in DN by undertaking a network pharmacology analysis. Materials and Methods. In this study, active ingredients and associated target proteins of Cordyceps sinensis were obtained via Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Swiss Target Prediction platform, then reconfirmed by using PubChem databases. The collection of DN-related target genes was based on DisGeNET and GeneCards databases. A DN-Cordyceps common target interaction network was carried out via the STRING database, and the results were integrated and visualized by utilizing Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to determine the molecular mechanisms and therapeutic effects of Cordyceps on the treatment of DN. Results. Seven active ingredients were screened from Cordyceps, 293 putative target genes were identified, and 85 overlapping targets matched with DN were considered potential therapeutic targets, such as TNF, MAPK1, EGFR, ACE, and CASP3. The results of GO and KEGG analyses revealed that hub targets mainly participated in the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, PI3K-Akt signaling pathway, and IL-17 signaling pathway. These targets were correlated with inflammatory response, apoptosis, oxidative stress, insulin resistance, and other biological processes. Conclusions. Our study showed that Cordyceps is characterized as multicomponent, multitarget, and multichannel. Cordyceps may play a crucial role in the treatment of DN by targeting TNF, MAPK1, EGFR, ACE, and CASP3 signaling and involved in the inflammatory response, apoptosis, oxidative stress, and insulin resistance.

show abstract

“…In vivo studies, renal brosis can be improved by blocking MAPK signaling pathway [41]. In vitro studies shown that, under high glucose, p38MAPK activation promotes renal tubular epithelial cell EMT progress [42], and p38 inhibitor SB203580 signi cantly reverses the EMT progress by downregulated the expression of E-Cadherin and type 1 collagen in HK-2 cells [43,44]. mTOR is a serine/threonine kinase, which belongs to the family of phosphatidylinositol kinase-related kinases.…”

Section: Discussionmentioning

confidence: 99%

Protective Mechanism of Qi-Dan-Dihuang Decoction in Diabetic Kidney Disease Based on Network pharmacology

Kuang¹,

You²,

Qi³

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Qi-Dan-Dihuang Decoction (QDD) has been used for treating diabetic kidney disease (DKD), but the mechanisms are poorly understood. The aim of this study is to reveal the therapeutic effects and the mechanism of QDD in ameliorating DKD by network pharmacology, in vivo, and in vitro studies.Methods: The effect of QDD on body weight, fast blood glucose, oral glucose tolerance test (OGTT), 24 h urinary protein (24hU-Pro), serum creatinine (Scr), blood urea nitrogen (BUN), and pathological evaluation in kidney were investigated in vivo using C57BLKS/J db/db mice. The main active compounds of QDD, compound-disease interaction targets, and related processes and pathways were discerned by network pharmacology analysis through Chinese Medicine Systems Pharmacology Database (TCMSP) and TCM Database@Taiwan. The protein-protein interaction (PPI) network were established through STRING database. GO and KEGG pathway were used for analysis processes and pathways. Then Western blot was used to verified the predicted results. Finally, cell viability, wound healing and mainly pathway protein expression were detected in vitro using renal tubular epithelial cells HK-2 and NRK-52E cells.Results: Although QDD treatment showed no significant difference in FBG and AUC of OGTT, but had significant reduction in Scr level in C57BLKS/J db/db mice. Histopathologic results showed that QDD ameliorated the expansion of mesangial area, thickened membranes of Bowman’s capsules and basement membrane of glomerular capillaries, renal tubular epithelial cells vacuolar degeneration and reversed the glomerular and tubulointerstitial in C57BLKS/J db/db mice. For network pharmacology analysis of QDD, 143 active compounds related to 274 possible targets in QDD obtained and 117 compound-disease interaction targets were screened out combining with Genecards database. 18 key targets was excavated through network topological analysis. GO and KEGG pathway enrichment analysis showed that compound-disease interaction targets were significantly enriched in processes and pathways that are closely related to DKD. Western blot results showed that QDD significantly attenuated EMT-related proteins, p-NF-κb, IL-1β, IL-18, p-p38MAPK/p38MAPK, p-AKT/AKT, and p-mTOR/ mTOR protein expressions. Treatment with QDD could alleviate cell viability damaged, EMT process, p-NF-κb, IL-1β, IL-18, p-p38MAPK/p38MAPK, p-AKT/AKT and p-mTOR/ mTOR protein expressions by high D-gulcose.Conclusions: This study provides convincing evidence suggest that QDD protects renal fibrosis of DKD, by regulating EMT in RTECs and inflammatory response through p38MAPK and AKT/mTOR signaling pathways.

show abstract

A Nucleoside/Nucleobase-Rich Extract from Cordyceps Sinensis Inhibits the Epithelial–Mesenchymal Transition and Protects against Renal Fibrosis in Diabetic Nephropathy

Cited by 26 publications

References 49 publications

Astragaloside IV Alleviates Renal Tubular Epithelial-Mesenchymal Transition via CX3CL1-RAF/MEK/ERK Signaling Pathway in Diabetic Kidney Disease

Astragaloside IV Alleviates Renal Tubular Epithelial-Mesenchymal Transition via CX3CL1-RAF/MEK/ERK Signaling Pathway in Diabetic Kidney Disease

Based on Network Pharmacology Tools to Investigate the Molecular Mechanism of Cordyceps sinensis on the Treatment of Diabetic Nephropathy

Protective Mechanism of Qi-Dan-Dihuang Decoction in Diabetic Kidney Disease Based on Network pharmacology

Contact Info

Product

Resources

About