Discovery of polypodiside as a Keap1-dependent Nrf2 activator attenuating oxidative stress and accumulation of extracellular matrix in glomerular mesangial cells under high glucose

Yao, Huankai; Zhang, Nan; Zhang, Wenting; Li, Jindong; Hua, Huilian; Li, Yan

doi:10.1016/j.bmc.2020.115833

Cited by 9 publications

(8 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A two‐dimensional interaction image (Figure 5c) also indicates that the driving forces for the formation of Keap1‐Corylin complexes are Pi‐cation and Pi‐alkyl as well as the formation of hydrogen and Pi‐Pi bonds. These findings indicated that corylin can interact with Keap1 to disrupt the formation of Keap1‐Nrf2 complexes (Yao et al, 2020).…”

Section: Resultsmentioning

confidence: 98%

“…Corylin activated and translocated Nrf2 to the nucleus where it increased ARE transcriptional regulation. This stems from the destruction of the Keap1‐Nrf2 complex (Yao et al, 2020). Therefore, we also explored whether corylin could competitively combine with Keap1 to exert antioxidant effects based on this indication.…”

Section: Discussionmentioning

confidence: 99%

“…After three washes with lysis buffer, pellets were resuspended and boiled in SDS loading buffer for 5 min. The precipitated protein was resolved by 10% SDS-PAGE and detected by western blotting using corresponding antibodies (Yao et al, 2020).…”

Section: Co-immunoprecipitation Assaymentioning

confidence: 99%

See 2 more Smart Citations

Corylin from Psoralea fructus (Psoralea corylifolia L.) protects against UV‐induced skin aging by activating Nrf2 defense mechanisms

Liu

Zhu

et al. 2022

Phytotherapy Research

View full text Add to dashboard Cite

Oxidative stress damage can lead to premature skin aging or age‐related skin disorders. Therefore, strategies to improve oxidative stress‐induced aging are needed to protect the skin and to treat skin diseases. This study aimed to determine whether the flavonoid corylin derived from Psoralea corylifolia can prevent UV‐induced skin aging and if so, to explore the potential molecular mechanisms. We found that corylin potently blocked UV‐induced skin photoaging in mice by reducing oxidative stress and increasing the nuclear expression of nuclear factor‐erythroid factor 2‐related factor 2 Nrf2. We also found that corylin stimulated Nrf2 translocation into the nucleus and increased the delivery of its target antioxidant genes together with Kelch‐like ECH‐associated protein 1 (Keap1) to dissociate Nrf2. These findings indicate that corylin could prevent skin aging by inhibiting oxidative stress via Keap1‐Nrf2 in mouse cells. Thus, Nrf2 activation might be a therapeutic target for preventing skin aging or skin diseases caused by aging. Our findings also provided evidence that warrants the further investigation of plant ingredients to facilitate the discovery of novel therapies targeting skin aging.

show abstract

Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Corylin from Psoralea fructus (Psoralea corylifolia L.) protects against UV‐induced skin aging by activating Nrf2 defense mechanisms

Liu

Zhu

et al. 2022

Phytotherapy Research

View full text Add to dashboard Cite

show abstract

“…Experiments using Nrf2 knockout ( KO ) mice have shown that a deficiency in Nrf2 signaling results in greater inflammation and associated ECM degradation in mice exposed to UVB, likely due to the reduced expression of cytoprotective enzymes such as heme oxygenase 1 [ 90 ]. Other studies have used specific activators of Nrf2 to reduce the oxidative burden in the cell and reduce ECM production [ 91 , 92 ]. Multiple studies have observed that bleomycin-induced lung fibrosis is more severe in Nrf2 KO mice, and Nrf2 deficiency also promoted epithelial-mesenchymal transition (EMT) in vitro [ 87 , [93] , [94] , [95] ].…”

Section: Nrf2-mediated Regulation Of Ecmmentioning

confidence: 99%

The Nrf2 transcription factor: A multifaceted regulator of the extracellular matrix

Hiebert

2021

Matrix Biology Plus

View full text Add to dashboard Cite

The transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) is widely recognized as a master regulator of the cellular stress response by facilitating the transcription of cytoprotective genes. As such, the Nrf2 pathway is critical in guarding the cell from the harmful effects of excessive reactive oxygen species/reactive nitrogen species (ROS/RNS) and in maintaining cellular redox balance. While excessive ROS/RNS are harmful to the cell, physiological levels of ROS/RNS play important roles in regulating numerous signaling pathways important for normal cellular function, including the synthesis of extracellular matrix (ECM). Recent advances have underscored the importance of ROS/RNS, and by extension, factors that influence redox-balance such as Nrf2, in regulating ECM production and deposition. In addition to reducing the oxidative burden in the cell, the discovery that Nrf2 can also directly target genes that regulate and form the ECM has cemented it as a multifaceted player in the regulation of ECM proteins, and provides new insight into its potential usefulness as a target for treating ECM-related pathologies.

show abstract

“…In searching for Nrf2 activators 3-phenylpropanoic acid is an important fragment 26 , the moieties derived from which can also be found in many natural compounds ( Figure 1 ). Our previous investigations have revealed polypodiside and daphnoretin-7-O-β-D-glucopyranoside as Nrf2 activators attenuated oxidative stress and accumulation of ECM mesangial cells under high glucose 27 , 28 , and both of them possess cinnamoyl group which is analogue of 3-phenylpropanoic acid. However, these compounds are dimers with glucose moiety, which results in the complex structures.…”

Section: Introductionmentioning

confidence: 99%

Discovery of caffeoylisocitric acid as a Keap1-dependent Nrf2 activator and its effects in mesangial cells under high glucose

Yao

Zhang²,

Yang

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

Diabetic nephropathy (DN) is one of the severe microvascular complications of diabetes mellitus. Oxidative stress resulting from aberrant metabolism of glucose mediates renal inflammation and fibrosis in the progression of DN. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor regulating the expression of antioxidant enzymes. Activating Nrf2 will give a promising therapy for DN. To discover novel Nrf2 activators, we have investigated caffeoylisocitric acid using mesangial cells under high glucose. The results showed at 10 μM, caffeoylisocitric acid significantly inhibited the self-limited proliferation of mesangial cells induced by high glucose. Further assessments have disclosed caffeoylisocitric acid mitigated oxidative stress, inflammation and accumulation of extracellular matrix resulting from high glucose via inactivating MAPK signalling. Meanwhile activation of Nrf2 was observed and involved in these effects through the interaction between Keap1 and caffeoylisocitric acid to disrupt Keap1-Nrf2 complex. Therefore, caffeoylisocitric acid is a promising Nrf2 activator targeting DN.

show abstract

Discovery of polypodiside as a Keap1-dependent Nrf2 activator attenuating oxidative stress and accumulation of extracellular matrix in glomerular mesangial cells under high glucose

Cited by 9 publications

References 48 publications

Corylin from Psoralea fructus (Psoralea corylifolia L.) protects against UV‐induced skin aging by activating Nrf2 defense mechanisms

Corylin from Psoralea fructus (Psoralea corylifolia L.) protects against UV‐induced skin aging by activating Nrf2 defense mechanisms

The Nrf2 transcription factor: A multifaceted regulator of the extracellular matrix

Discovery of caffeoylisocitric acid as a Keap1-dependent Nrf2 activator and its effects in mesangial cells under high glucose

Contact Info

Product

Resources

About