|
| Name | Experimental subjects | Functions and mechanisms |
|
| Edaravone | CECs | Augments the expression of Nrf2 and its target genes, such as HO-1, GPX-1, and GCLC [23] |
| SERPINA3K (SA3K) | CECs | Protects against oxidative stress by targeting the ROS generation/degradation system and modulating the Keap1-Nrf2 signaling pathway [189] |
| Cultured pterygial epithelial cells (PECs) | Inhibits NADPH oxidase 4 (NOX4) and elevates Nrf2, NQO1, and SOD2 [190] |
| Rosmarinic acid (RA) | PECs | Reduces the cell viability of PECs. Increases Nrf2, HO-1, and NQO1 expression and activates SOD and CAT [191] |
| Chondrocyte-derived extracellular matrix (CDECM) | Human conjunctival epithelial cells (ConECs) and PECs | Inhibits NF-κB activation and improves Nrf2 induction by blocking the p38 MAPK and PKC signaling pathways [192] |
| 4-HNE | CECs | Elevates the ROS generation enzyme NOX4 and induces Nrf2 and its downstream effectors [193] |
| RPEs | Increases Nrf2 activity and GSH synthesis in a dose-dependent manner [194] |
| Trichostatin A (TSA) | Corneal fibroblasts | Inhibits TGF-β-induced ROS accumulation and myofibroblast differentiation via enhanced Nrf2-ARE signaling [195] |
| DL-3-n-butylphthalide (NBP) | Rat diabetic cataract model | Delays the onset and progression of diabetic cataract by enhancing the expressions of Nrf2, TRX, and CAT [95] |
| Acetyl-L-carnitine | LECs | Prevents homocysteine-induced suppression of Nrf2/Keap1-mediated antioxidation [91] |
| Puerarin | Rat diabetic cataract model | Prevents cataract development and progression in diabetic rats through Nrf2/HO-1 signaling [88] |
| RPEs | Activates Nrf2/HO-1 antioxidant signaling pathway [196] |
| Rosmarinic acid | Sprague-Dawley rat pup selenite-inducedcataractogenesis model | Increases the protein expressions of filensin, calpain 2, Nrf2, SOD, HO-1, and NQO1; the antioxidant enzyme activities; and the GSH level [94] |
| Morin | LECs | Induces HO-1 via the ERK-Nrf2 signaling pathway [92] |
| Calcium dobesilate | Rat D-galactose-induced cataract model | Increases Nrf2 and HO-1 levels and inhibits the Keap1 level [197] |
| Rosa laevigata Michx. | LECs | Inhibits ROS production and elevates mitochondrial membrane potential, through the induction of HO-1 expression mediated by the PI3K/Akt and Nrf2/ARE pathways [89] |
| Hyperoside | LECs | Increased Nrf2 level and the binding activity of its antioxidant components, increased the expression of HO-1, and restored cell vitality through ERK [90] |
| Quercetin | TMCs | Upregulates antioxidant peroxiredoxins through the activation of the Nrf2/Nrf1 transcription pathway [198] |
| RPEs | Protects RPEs from H2O2-induced cytotoxicity by activating the Nrf2 pathway [199] |
| Sodium butyrate | Mouse experimental autoimmune uveitis (EAU) model | Regulates Th17/Treg cell balance to ameliorate uveitis via the Nrf2/HO-1 pathway [122] |
| Lutein | RPEs | Reverses hyperglycemia-mediated blockage of Nrf2 translocation by modulating the activation of intracellular protein kinases [200] |
| Dh404 | Müller cells | Reduces Müller cell gliosis and vascular leakage as well as the hypoxia-induced increase in ROS and angiogenic factors with a concomitant increase in Nrf2-responsive antioxidants [134, 201] |
| Myricetin derivatives (F2) | RPEs | Protects RPE cells against OS by the activation of Nrf2 and SOD2 [202] |
| Fenofibrate | Mice diabetic retinas | Increases the expression of Nrf2, NQO1, and HO-1 [203] |
| Probucol | Müller cells | Activates the Keap1/Nrf2/ARE pathway [204] |
| Homocysteine | Müller cells | Increases the expression of Nrf2, NQO1, and HO-1 [205] |
| Ebselen | Müller cells | Reduces the ROS levels and increases the expression of Nrf2, HO-1, glutathione peroxidase-1, NQO1, and glutamate-cysteine ligase [206] |
| DL-3-n-butylphthalide | Müller cells | Increases the expression level of HO-1 in a time-dependent manner [207] |
| 3H-1,2-dithiole-3-thione | RPEs | Induces Nrf2 phosphorylation, causing Nrf2 disassociation with Keap1 and its subsequent nuclear accumulation [208] |
| Curcumin | RPEs | Prevents high glucose damage through ERK1/2-mediated activation of the Nrf2/HO-1 pathway [135] |
| Glycyrrhizin | RPEs | Protects against sodium iodate-induced RPE and retinal injury through activation of the Akt and Nrf2/HO-1 pathway [209] |
| Escin | RPEs | Activates Akt-Nrf2 signaling [210] |
| Ginsenoside Rh3 | RPEs and mice retinas | Rh3 induces miRNA-141 expression causing the downregulation of Keap1 and activating Nrf2 [211] |
| Hesperetin | RPEs | Upregulates the Keap1-Nrf2/HO-1 signal pathway [212] |
| Lycopene | RPEs | Inhibits ICAM-1 expression and NF-κB activation by Nrf2-regulated cell redox state [213] |
| 4-Acetoxyphenol | RPEs | Blocks the increase of cellular ROS and upregulates NQO1 and HO-1 genes by stabilizing and inducing the nuclear translocation of Nrf2 [214] |
| Taxifolin | RPEs | Enhances the nuclear accumulation of Nrf2 and increases the expression of HO-1, GCLC, GCLM, and NQO1 [215] |
| Genipin | RPEs | Reverses the inhibitory effects of H2O2 by promoting cell viability, attenuating ROS accumulation and cell apoptosis, and increasing the expression of Nrf2, HO-1, and NQO1 [216] |
| α-Tocopherol | RPEs | Activates the Keap1/Nrf2 pathway by increasing Nrf2 expression and inducing its translocation to the nucleus, and increases HO-1 as well as NQO1 [217] |
| Astaxanthin | RPEs | Activates the Nrf2-ARE pathway by inducing Nrf2 nuclear localization and increasing NQO1, HO-1, GCLM, and GCLC [218] |
| Salvianolic acid A | RPEs | Causes Nrf2 phosphorylation, accumulation, and nuclear translocation and increases the expression of HO-1 [219] |
| Salvianolic acid B | RPEs | Protects cells from OS-induced cell death by activating glutaredoxin 1 [220] |
| Lipoamide | RPEs | Induces the expression of Nrf2 and its translocation to the nucleus, leading to an increase in the expression or activity of NQO1, GST, GCL, catalase, and Cu/Zn SOD [221] |
| Thymoquinone | RPEs | Enhances the activation of the Nrf2/HO-1 signaling pathway [222] |
| Blueberry anthocyanins | Diabetes rat retinas | Increases the mRNA levels of Nrf2 and HO-1, and the nuclear location of Nrf2 and protein levels of HO-1 [223] |
| Grape seed proanthocyanidin extract | Diabetes rat retinas | Increases the expression of Nrf2 and HO-1 [224] |
| Carbamyl erythropoietin | Diabetes rat retinas | Increases the expression of Nrf2, HO-1, and NQO1 [225] |
| Ginsenoside Rb1 | Diabetes rat retinas | Increases the expression of Nrf2, GCLC, and GCLM [226] |
| Pyridoxamine | Retinal photoreceptor cells | Partly protects cells against light damage by Nrf2 expression [227] |
| Scutellarin (SC) | RECs and RPEs | Enhances nuclear Nrf2 accumulation and the SC-provided alleviation on BRB breakdown in STZ-induced diabetic mice was diminished in Nrf2 knockout mice [228] |
| Delphinidin (2-(3,4,5-trihydroxyphenyl) chromenylium-3,5,7-triol) | RPEs | Reverses the decreased activities of SOD, CAT, and GSH-PX and the elevated MDA level via increasing nuclear Nrf2 protein expression [229] |
| 4-Hydroxy-7-oxo-5-heptanoate (HOHA) lactone | RPEs | Induces upregulation of Nrf2, GCLM, HO-1, and NQO1 [230] |
| Melatonin | The retina of diabetic rats | Significantly upregulates glutamate-cysteine ligase by retaining Nrf2 in the nucleus and stimulating Akt phosphorylation [231] |
| Galangin | RECs and RPEs | Alleviates DR by reversing TNFα-induced blood-retinal barrier dysfunction by abrogating oxidative stress injury via activating Nrf2 [232] |
| Nonsteroidal anti-inflammatory drugs (NSAIDs) | Laser-induced CNV model in rat; RPEs | Inhibits neovascularization of choroid through the HO-1-dependent pathway [233] |
| RS9 | Retinal microvascular endothelial cells (RMECs) | Decreases retinal neovascularization through suppressing VEGF expression and increasing Nrf2, HO-1, and NQO1 [234] |
| 661W cells and Müller glia cells | Enhances the expression of Nrf2 and increases the expression of HO-1, GCLC, GCLM, and NQO1 [235] |
| Acetaldehyde dehydrogenase 2 (ALDH2) | Diabetic rats’ retinas | Increases the expression of Nrf2 [236] |
| Lipoic acid | RGCs | Induces the expression of HO-1 by promoting the translocation of Nrf2 to the nucleus [237, 238] |
| Sulforaphane | FECD corneal specimens | Enhances cell viability by decreasing ROS. Enhances nuclear translocation of Nrf2, DJ-1, HO-1, and NQO1 and decreases p53 [52] |
| Müller cells | Enhances the nuclear accumulation of Nrf2 and increases the expression of HO-1 and NQO1 [136] |
| Rabbit KC corneas | Protects corneas against oxidative stress injury through activation of the Nrf2/HO-1 antioxidant pathway [37] |
| LECs | Includes the expression of NQO1 and TXNRD1 and the Nrf2 translocation to the nucleus [87, 239] |
TMCs
RGCs | Attenuates H2O2-induced oxidative stress via PI3K/Akt-mediated Nrf2 signaling activation [240, 241] |
| CDDO-Im | 661W | Inhibits ROS, increases OS, and increases neuronal cell survival after I/R injury [107] |
| Nrf2 KO mice | Increases expressions of Nrf2, HO-1, NQO1, and GCLM in the retina, reduces inflammatory mediator expression, and reduces leukocyte adherence to retinal vasculature [121] |
| RTA 408 | RPEs | Activates Nrf2 and increases the expression of its downstream genes, such as HO-1, NQO1, SOD2, catalase, Grx1, and Trx1 [242] |
| Soluble P-selectin | RGCs | Increases NQO1 and HO-1 expression levels, along with increased transcription factor Nrf2 [243] |
| Eriodictyol | RGCs | Enhances the nuclear translocation of Nrf2 and elevates the expression of HO-1 [244] |
| RPEs | Induces the nuclear translocation of Nrf2, enhances the expression of HO-1 and NQO1, and increases the levels of intracellular glutathione [245] |
| Neuroligin-3 | RGCs and RPEs | Activates Nrf2 signaling and enables Nrf2 protein stabilization, nuclear translocation, and expression of HO-1, NOQ1, and GCLC [246] |
| Long-acting (1R)-isopropyloxygenipin (IPRG001) | RGCs | The protective action depends on NO induction and the Nrf2/HO-1 antioxidant response element pathway by S-nitrosylation [247] |
| Resveratrol | RGCs | Upregulates the expression of Nrf2, HO-1, and NQO1 [248, 249] |
| L-carnitine (LC) | RGCs | Increases levels of Nrf2, HO-1, and γ-GCS and decreases expression of Keap1 protein [3] |
| SNJ-1945 (an exogenous calpain inhibitor) | RGCs | Protects RGCs against OS induced by high glucose [250] |
| Monomethyl fumarate | Ganglion cell layer | Fumaric acid esters exert a neuronal protective function in the retinal I/R model via Nrf2 modulation [251] |
| Trimetazidine | RGCs | Confers protection against RGC apoptosis via Nrf2/HO-1 signaling [252] |
| LECs | Reduces ROS production, inhibits Keap1 demethylation, and rescues Nrf2 expression level [93] |
| Hydrogen sulfide gas (H2S) donor drugs | RGCs | Increases the levels of Nrf2 and HO-1 and inhibits OS-induced cell death [253] |
| 5α-Androst-3β, 5α, 6β-triol (TRIOL) | RGCs | Activates and upregulates Nrf2 and HO-1 by negative regulation of Keap1 [254] |
| Nipradilol | RGCs | Protects RGCs through S-nitrosylation of Keap1 and HO-1 induction [255] |
| Flavonoids | RGCs | Induces Nrf2 and HO-1 [256] |
| RPEs | Induces the expression of Nrf2 and HO-1 [257] |
| Sulbutiamine | RGCs | Stimulates CAT and significantly increased Nrf2 and HO-1 levels [258] |
| Chalcone analog L2H17 | RGCs | Exhibits its antioxidative effects by activating the Nrf2 pathway [259] |
| Chlorogenic acid | RGCs | Relieves oxidative stress injury in retinal ganglion cells through lncRNA-TUG1/Nrf2 [260] |
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