Obacunone attenuates high glucose-induced oxidative damage in NRK-52E cells by inhibiting the activity of GSK-3β

2019 ◽  
Vol 513 (1) ◽  
pp. 226-233 ◽  
Author(s):  
Jie Zhou ◽  
Tianyang Wang ◽  
Haoze Wang ◽  
Yinjie Jiang ◽  
Shaojun Peng
Author(s):  
Saad Alkahtani ◽  
Saud Alarifi ◽  
Abdullah A. Alkahtane ◽  
Gadah Albasher ◽  
Mohammed AL-Zharani ◽  
...  

2017 ◽  
Vol 42 (5) ◽  
pp. 1897-1906 ◽  
Author(s):  
Kai Dong ◽  
Pengjie Hao ◽  
Sheng Xu ◽  
Shutai Liu ◽  
Wenjuan Zhou ◽  
...  

Background/Aims: Patients with diabetes mellitus have a higher risk of dental implant failure. One major cause is high-glucose induced oxidative stress. Alpha-lipoic acid (ALA), a naturally occurring compound and dietary supplement, has been established as a potent antioxidant that is a strong scavenger of free radicals. However, few studies have yet investigated the effect of ALA on osteogenic differentiation of osteoblasts cultured with high glucose medium. The aim of this study is to investigate the effects of ALA on the osteoblastic differentiation in MC3T3-E1 cells under high glucose condition. Methods: MC3T3-E1 cells were divided into 4 groups including normal glucose (5.5 mM) group (control), high glucose (25.5 mM) group, high glucose + 0.1 mM ALA group, and high glucose + 0.2 mM ALA group. The proliferation, osteogenic differentiation and mineralization of cells were evaluated by MTT assay, alkaline phosphatase (ALP) activity assay, alizarin red staining and real time-polymerase chain reaction. High-glucose induced oxidative damage was also assessed by the production of reactive oxygen species (ROS) and superoxide dismutase (SOD). Western blots were performed to examine the role of PI3K/Akt pathway. Results: The proliferation, osteogenic differentiation and mineralization of MC3T3-E1 cells were significantly decreased by the ROS induced by high-glucose. All observed oxidative damage and osteogenic dysfunction induced were inhibited by ALA. Moreover, the PI3K/Akt pathway was activated by ALA. Conclusions: We demonstrate that ALA may attenuate high-glucose mediated MC3T3-E1 cells dysfunction through antioxidant effect and modulation of PI3K/Akt pathway.


Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1449 ◽  
Author(s):  
Chi-Rei Wu ◽  
Hung-Chi Chang ◽  
Yih-Dih Cheng ◽  
Wan-Cheng Lan ◽  
Shu-Er Yang ◽  
...  

The medicinal ferns of Polydiaceae and Davalliaceae species are called “Gusuibu” by Chinese physicians and used as antiaging dietary medicines. Our previous report revealed that Drynaria fortunei (Polydiaceae) protected against 6-hydroxydopamine (6-OHDA)-induced oxidative damage via the PI3K/AKT pathway in B35 neuroblastoma cells. The present study compares the antioxidant phytoconstituent contents and radical scavenging capacities of five Davalliaceae species. The further aim was to clarify the protective mechanism of Davallia mariesii (DM) against 6-OHDA-induced oxidative damage and apoptosis in B35 cells. The results show that Araiostegia perdurans (AP) and DM extracts have better radical scavenging capacities against 1,1-diphenyl-2-picryhydrazyl (DPPH) and reactive oxygen species (ROS) than other Davalliaceae species. However, only DM extract inhibited 6-OHDA autoxidation under cell-free systems and increased cell viability, compared to B35 cells solely exposed to 6-OHDA. DM extract decreased apoptosis and restored mitochondrial expression in 6-OHDA-treated B35 cells. Additional data indicated that DM extract decreased intracellular ROS and nitric oxide levels generated by 6-OHDA exposure. DM extract also restored glutathione (GSH) levels and the activities of glutathione peroxidase and reductase, and then decreased the elevated malondialdehyde (MDA) levels. Finally, DM extract regulated the protein expression of the caspase cascade and PI3K/AKT/GSK-3β pathways. These results suggest that the protective mechanism of DM extract against 6-OHDA-induced oxidative damage and apoptosis might be related to its radical scavenging capacity, maintaining the mitochondrial function to inhibit the Bcl-2/caspase cascade pathway and activating intracellular antioxidant defenses (GSH recycling, HO-1 and NQO-1) by modulating the activation of the PI3K/AKT/GSK-3β pathway.


The Analyst ◽  
2017 ◽  
Vol 142 (2) ◽  
pp. 284-291 ◽  
Author(s):  
Andrew Schmudlach ◽  
Jeremy Felton ◽  
Robert T. Kennedy ◽  
Norman J. Dovichi

Glucotoxicity is a causative agent of type-2 diabetes, where high glucose levels damage the islets of Langerhans resulting in oxidative damage and endoplasmic reticulum stress.


2011 ◽  
Vol 409 (2) ◽  
pp. 350-355 ◽  
Author(s):  
Pan Yu ◽  
Zhenxiang Wang ◽  
Xuejun Sun ◽  
Xiaohua Chen ◽  
Suyun Zeng ◽  
...  

2020 ◽  
Vol 98 (4) ◽  
pp. 458-465 ◽  
Author(s):  
Xuehan Wu ◽  
Weilu Huang ◽  
Minxue Quan ◽  
Yongqi Chen ◽  
Jiaxin Tu ◽  
...  

Brain-type glycogen phosphorylase (pygb) is one of the rate-limiting enzymes in glycogenolysis that plays a crucial role in the pathogenesis of type 2 diabetes mellitus. Here we investigated the role of pygb in high-glucose (HG)-induced cardiomyocyte apoptosis and explored the underlying mechanisms, by using the specific pygb inhibitors or pygb siRNA. Our results show that inhibition of pygb significantly attenuates cell apoptosis and oxidative stress induced by HG in H9c2 cardiomyocytes. Inhibition of pygb improved glucose metabolism in cardiacmyocytes, as evidenced by increased glycogen content, glucose consumption, and glucose transport. Mechanistically, pygb inhibition activates the Akt–GSK-3β signaling pathway and suppresses the activation of NF-κB in H9c2 cells exposed to HG. Additionally, pygb inhibition promotes the expression and the translocation of hypoxia-inducible factor-1α (HIF-1α) after HG stimulation. However, the changes in glucose metabolism and HIF-1α activation mediated by pygb inhibition are significantly reversed in the presence of the Akt inhibitor MK2206. In conclusion, this study found that inhibition of pygb prevents HG-induced cardiomyocyte apoptosis via activation of Akt–HIF-α.


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