Abstract:
:Chalcone is a plant metabolite widely found in fruits, vegetables, spices and tea, and has anti-tumor, anti-inflammation, immunomodulation, antibacterial and anti-oxidation activities, as well as many other pharmacological and biological effects. Our team has shown that its analogs have antioxidant activity, and oxidative stress is a pathological hallmark of retinal ischemia/reperfusion injury that can lead to retinal damage and visual loss. This investigation aims to identify a chalcone that protects retinal ganglion cells in vitro from the effects of oxidative stress and examine its mechanism. Rat retinal ganglion cell-5 cells were pretreated with chalcones and then exposed to tert-butyl hydroperoxide that causes oxidative damage. Controls received dimethyl sulfoxide only or tert-butyl hydroperoxide in dimethyl sulfoxide. Only (E)-3,4-dihydroxy-2'-methylether ketone (L2H17), of the five chalcone analogs, markedly increased the survival rate of oxidatively injured RGC-5 cells. Thus, subsequent experiments only analyzed the results of the L2H17 intervention. Cell viability and apoptosis were measured. Intracellular superoxide dismutase and reactive oxygen species levels were used to assess induced oxidative stress. The mechanism of action by L2H17 was explored by measuring the ER stress/UPR pathway and the expression and localization of Nrf2. All results demonstrated that L2H17 could reduce the apoptosis of oxidatively injured cells, inhibit caspase-3 activity, increase Bcl-2 expression, decrease Bad expression, increase the activity of superoxide dismutase, inhibit the production of reactive oxygen species, increase Nrf2 immunoreactivity, and reduce the activating transcription factor 4, phospho-eukaryotic initiation factor 2 and CHOP expression. L2H17 protects retinal ganglion cells induced by oxidative stress by regulating Nrf2, which indicates that it has the potential to become a drug for retinal ischemia/reperfusion.
journal_name
Neural Regen Resjournal_title
Neural regeneration researchauthors
Wang L,Chen HC,Yang X,Tao JJ,Liang G,Wu JZ,Wu WC,Wang Y,Song ZM,Zhang Xdoi
10.4103/1673-5374.237140subject
Has Abstractpub_date
2018-09-01 00:00:00pages
1665-1672issue
9eissn
1673-5374issn
1876-7958pii
NeuralRegenRes_2018_13_9_1665_237140journal_volume
13pub_type
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