Emodin protects against oxidative stress and apoptosis in HK-2 renal tubular epithelial cells after hypoxia/reoxygenation

Chen, Hui; Huang, Risheng; Xiang, Yu; Ye, Qiong; Pan, Lulu; Shao, Guojian; Pan, Jing

doi:10.3892/etm.2017.4473

Cited by 36 publications

(32 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, eight compounds were found to inhibit the expression of α -SMA and collagen III. Among these compounds were curcumin and emodin, which have been described in previous studies [ 5 , 22 ]. Here, we described six potent renal fibrosis inhibitors, including Ligustrazine, Glycyrrhizic acid, Astragaloside iv, Hydroxysafflor Yellow A, Crocin, and Gypenosides, that can block the differentiation of NRK49F cells in vitro towards fibrosis.…”

Section: Discussionmentioning

confidence: 99%

“…The results show that several identified compounds were less potent than TGF- β 1 receptor blocker SB525334. However, in consideration of the strongly bifunctional role of TGF- β (profibrotic, but anti-inflammatory), it requires great care for the application of TGF- β -directed treatments [ 5 , 22 ]. Thus, high inhibitory rate of TGF- β and high anti-renal fibrosis effects are primary but not unanimous corresponding.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Establishing a Cell‐Based High‐Content Screening Assay for TCM Compounds with Anti‐Renal Fibrosis Effects

Wang

Sun

et al. 2018

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Renal fibrosis is thought to be the final common pathway leading to chronic kidney disease (CKD) and end-stage renal failure. Except for renal replacement therapy, no adequate treatment regimen is available; therefore studies on the treatment of renal fibrosis have attracted significant interest. In recent years, studies have shown that traditional Chinese medicine (TCM) may represent an attractive source to produce drugs with antifibrosis effects. The aim of this study was to establish a robust cell-based high-content screening (HCS) approach to identify TCM compounds with antifibrosis effects in NRK49F cells following TGF-β1 exposure. When designing the model, one of the most important steps involved the stability and reproducibility of this cell-based model. Therefore, we initially optimized the experimental parameters. Then, our HCS model was validated using SB525334, an inhibitor of the TGF-β1 receptor, and curcumin and emodin, two TCM compounds with well-documented anti-renal fibrosis activity. Subsequently, the proven reliable HCS model was used to screen a standard TCM compound library, which included 344 TCM molecules. Based on our HCS algorithm, a total of 16 compounds were identified to have prospective inhibitory activity. These compounds were further validated by verification experiments. Strikingly, eight compounds have been shown to inhibit renal fibrosis; six of them had rarely been described in the literature, namely, Ligustrazine, Glycyrrhizic acid, Astragaloside iv, Hydroxysafflor Yellow A, Crocin, and Gypenosides. To the best of our knowledge, this is the first study in which a HCS assay was performed to identify TCM compounds with anti-renal fibrosis effects. The HCS approach was successfully applied to screen active compounds and will be propitious to further anti-renal fibrosis drugs discovery research. Meanwhile, it may offer possibilities for identifying lead compounds for treating other diseases from registered Chinese herbal medicines.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Establishing a Cell‐Based High‐Content Screening Assay for TCM Compounds with Anti‐Renal Fibrosis Effects

Wang

Sun

et al. 2018

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

show abstract

“…The cells with traces TAK1 overexpression plasmid or vehicle plasmid treatment were divided into four groups: Vehicle plasmid sham group, Vehicle plasmid H/R group, TAK1 overexpression plasmid sham group and TAK1 overexpression plasmid H/R group. The HR trial was performed as described previously, hypoxia 3 h or sham control for 72 h in each group [35]. The cells with trail of p38 specific inhibitor (SB203580) and TAK1 overexpression plasmid treatment were divided into four groups: TAK1 overexpression plasmid sham group and TAK1 overexpression plasmid H/R group, TAK1 overexpression plasmid plus SB203580 sham group and TAK1 overexpression plasmid plus SB203580 H/R group.…”

Section: Cell Culture and Experimental Groupingmentioning

confidence: 99%

TAK1 mediates apoptosis via p38 involve in ischemia-induced renal fibrosis

Zhou

Zhong

Huang

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

View full text Add to dashboard Cite

Renal fibrosis is a common and characteristic symptom of chronic kidney disease (CKD). However, the molecular mechanisms of renal fibrosis remain elusive. Ischemia injury, as a major cause of AKI, deserves more attention in order to improve the knowledge of AKI-induced fibrosis. Transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) interacts directly with TGF-β, which play a critical role in the progression of fibrosis. Therefore, the present study aimed to investigate the role of TAK1 in the pathogenesis of ischemia-induced renal fibrosis. Compared with mice in the vehicle group, mice intraperitoneally injected with TAK1 inhibitor were found to have lower serum creatinine, less tubular damage and more mild fibrosis following ischemia-induced AKI. Furthermore, inhibition of TAK1 reduced p38 phosphorylation, decreased expression of Bax and caspase 3 and apoptosis cells in kidneys of mice treated with IR-induced AKI. Compared with vehicle-treated renal tubular epithelial cells, TAK1 overexpression cells were found to have a higher apoptosis and fibrosis index level and p38 phosphorylation following hypoxia/reoxygenation (H/R) treatment. Furthermore, the p38 inhibitor combined with TAK1 overexpression verified the role of TAK1/p38 signaling pathway in apoptosis and fibrosis index level of renal tubular epithelial cells treated with H/R. Thus, our results show that TAK1 plays an important role in the pathogenesis of ischemia-induced renal fibrosis and may mediate p38-regulated cell apoptosis.

show abstract

“…Network pharmacology is a powerful tool that can explain the function of a complicated biological system [9]. Recently, it has been widely used to explore the pharmacological mechanisms of Chinese herbs, which has enabled it to be * * * *…”

Section: Discussionmentioning

confidence: 99%

The Mechanisms of the Herbal Components of CRSAS on HK‐2 Cells in a Hypoxia/Reoxygenation Model Based on Network Pharmacology

Xie

Yang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Background. Acute kidney injury is a global problem, which brings a great burden to the society and family. The component of rhubarb, Salvia miltiorrhiza, Astragalus membranaceus, and safflower (CRSAS) has been proved as an useful agent to treat acute kidney injury (AKI) patients in China. Objective. To assess the effect of CRSAS on human renal tubular epithelial cells (HK-2) after the hypoxia/reoxygenation (H/R) and investigate the potential mechanisms. Methods. Network pharmacology was used to predict the potential pathways shared by CRSAS and AKI. Cell counting kit-8 (CCK-8) was used to assess the HK-2 vitality. Apoptosis of HK-2 cells was detected by carboxyfluorescein succinimidyl ester/propidium iodide (CFSF/PI) staining. Expression of GRP78, CHOP, caspase-3, and Bax was detected by western blot and quantitative real-time RT-PCR. Result. CRSAS and AKI shared the endoplasmic reticulum stress (ERS) pathway based on network pharmacology analysis. CRSAS increases the vitality of HK-2 cells and reduces the apoptosis of HK-2 cells induced by H/R injury. The expression of GRP78 and CHOP in CRSAS groups was lower than that of control groups. Conclusions. H/R can induce HK-2 cell apoptosis and ERS. CRSAS can reduce HK-2 cell apoptosis by inhibiting the ERS. Therefore, CRSAS might be able to treat kidney disease due to I/R injury. Animal experiment should be done to further prove our finding.

show abstract

Emodin protects against oxidative stress and apoptosis in HK-2 renal tubular epithelial cells after hypoxia/reoxygenation

Cited by 36 publications

References 21 publications

Establishing a Cell‐Based High‐Content Screening Assay for TCM Compounds with Anti‐Renal Fibrosis Effects

Establishing a Cell‐Based High‐Content Screening Assay for TCM Compounds with Anti‐Renal Fibrosis Effects

TAK1 mediates apoptosis via p38 involve in ischemia-induced renal fibrosis

The Mechanisms of the Herbal Components of CRSAS on HK‐2 Cells in a Hypoxia/Reoxygenation Model Based on Network Pharmacology

Contact Info

Product

Resources

About