{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:52:32Z","timestamp":1787730752765,"version":"build-2784847793"},"reference-count":184,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T00:00:00Z","timestamp":1646179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>Thymoquinone is a naturally occurring compound and is the major component of <jats:italic>Nigella sativa<\/jats:italic>, also known as black seed or black cumin. For centuries thymoquinone has been used especially in the Middle East traditionally to treat wounds, asthma, allergies, fever, headache, cough, hypertension, and diabetes. Studies have suggested beneficial effects of thymoquinone to be attributed to its antioxidant, antibacterial, anti-oxidative stress, anti-inflammatory, and neuroprotective properties. Recently, there has been a surge of interest in thymoquinone as a treatment for neurodegeneration in the brain, such as that seen in Alzheimer\u2019s (AD) and Parkinson\u2019s diseases (PD). <jats:italic>In vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> studies on animal models of AD and PD suggest the main neuroprotective mechanisms are based on the anti-inflammatory and anti-oxidative properties of thymoquinone. Neurodegenerative conditions of the eye, such as Age-related Macular Degeneration (AMD) and glaucoma share at least in part similar mechanisms of neuronal cell death with those occurring in AD and PD. This review aims to summarize and critically analyze the evidence to date of the effects and potential neuroprotective actions of thymoquinone in the eye and ocular neurodegenerations.<\/jats:p>","DOI":"10.3389\/fncel.2022.786926","type":"journal-article","created":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T04:52:45Z","timestamp":1646196765000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Thymoquinone in Ocular Neurodegeneration: Modulation of Pathological Mechanisms via Multiple Pathways"],"prefix":"10.3389","volume":"16","author":[{"given":"Nur Musfirah","family":"Mahmud","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luminita","family":"Paraoan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurliza","family":"Khaliddin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengku Ain","family":"Kamalden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,2]]},"reference":[{"key":"B1","first-page":"296","article-title":"Thymoquinone triggers anti-apoptotic signaling targeting death ligand and apoptotic regulators in a model of hepatic ischemia reperfusion injury.","volume":"3","author":"Abd El-Ghany","year":"2009","journal-title":"Drug Discov. Ther."},{"key":"B2","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1080\/01616412.2018.1441776","article-title":"Protective effects of thymoquinone on D-galactose and aluminum chloride induced neurotoxicity in rats: biochemical, histological and behavioral changes.","volume":"40","author":"Abulfadl","year":"","journal-title":"Neurol. Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1177\/0960327118755256","article-title":"Thymoquinone alleviates the experimentally induced Alzheimer\u2019s disease inflammation by modulation of TLRs signaling.","volume":"37","author":"Abulfadl","year":"","journal-title":"Hum. Exp. Toxicol."},{"key":"B4","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1177\/0960327118755256","article-title":"Thymoquinone alleviates the experimentally induced Alzheimer\u2019s disease inflammation by modulation of TLRs signaling.","volume":"37","author":"Abulfadl","year":"","journal-title":"Hum. Exp. Toxicol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1080\/01902148.2020.1726529","article-title":"Thymoquinone treatment modulates the Nrf2\/HO-1 signaling pathway and abrogates the inflammatory response in an animal model of lung fibrosis.","volume":"46","author":"Ahmad","year":"2020","journal-title":"Exp. Lung Res."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1186\/s40942-019-0179-6","article-title":"Serum vascular endothelial growth factor is a biomolecular biomarker of severity of diabetic retinopathy.","volume":"5","author":"Ahuja","year":"2019","journal-title":"Int. J. Retina Vitreous"},{"key":"B7","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1080\/1061186x.2020.1722136","article-title":"Thymoquinone and curcumin combination protects cisplatin-induced kidney injury, nephrotoxicity by attenuating NF\u03baB, KIM-1 and ameliorating Nrf2\/HO-1 signalling.","volume":"28","author":"Al Fayi","year":"2020","journal-title":"J. Drug Target"},{"key":"B8","doi-asserted-by":"crossref","first-page":"20","DOI":"10.34154\/2020-EJCS-0201-20-26\/euraass","article-title":"Targeting Itch\/p73 pathway by thymoquinone as a novel therapeutic strategy for cancers with p53 mutation.","volume":"2","author":"Alghamdi","year":"2020","journal-title":"Eur. J. Cell Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.bbrc.2012.11.139","article-title":"Thymoquinone protects cultured rat primary neurons against amyloid \u03b2-induced neurotoxicity.","volume":"433","author":"Alhebshi","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B10","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.neulet.2013.09.049","article-title":"Thymoquinone protects cultured hippocampal and human induced pluripotent stem cells-derived neurons against \u03b1-synuclein-induced synapse damage.","volume":"570","author":"Alhebshi","year":"2014","journal-title":"Neurosci. Lett."},{"key":"B11","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.bbrep.2018.12.005","article-title":"Neuroprotective efficacy of thymoquinone against amyloid beta-induced neurotoxicity in human induced pluripotent stem cell-derived cholinergic neurons.","volume":"17","author":"Alhibshi","year":"2019","journal-title":"Biochem. Biophys. Rep."},{"key":"B12","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.ejphar.2006.05.046","article-title":"Neuroprotective effects of thymoquinone against transient forebrain ischemia in the rat hippocampus.","volume":"543","author":"Al-Majed","year":"2006","journal-title":"Eur. J. Pharmacol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2232","DOI":"10.1016\/j.intimp.2011.10.013","article-title":"Comparative evaluation of anti-inflammatory properties of thymoquinone and curcumin using an asthmatic murine model.","volume":"11","author":"Ammar el","year":"2011","journal-title":"Int. Immunopharmacol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1002\/acn3.282","article-title":"Antioxidants inhibit neuronal toxicity in Parkinson\u2019s disease-linked LRRK2.","volume":"3","author":"Angeles","year":"2016","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1016\/j.ijbiomac.2014.06.003","article-title":"A structural study on the protection of glycation of superoxide dismutase by thymoquinone.","volume":"69","author":"Anwar","year":"2014","journal-title":"Int. J. Biol. Macromol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"8742","DOI":"10.3390\/molecules20058742","article-title":"Glutathione in Cellular Redox Homeostasis: association with the Excitatory Amino Acid Carrier 1 (EAAC1).","volume":"20","author":"Aoyama","year":"2015","journal-title":"Molecules"},{"key":"B17","doi-asserted-by":"crossref","first-page":"10211","DOI":"10.1016\/S0021-9258(19)50004-7","article-title":"Immunochemical evidence for the presence of advanced glycation end products in human lens proteins and its positive correlation with aging.","volume":"267","author":"Araki","year":"1992","journal-title":"J. Biol. Chem."},{"key":"B18","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.neuint.2019.04.014","article-title":"Thymoquinone prevents neurodegeneration against MPTP in vivo and modulates \u03b1-synuclein aggregation in vitro.","volume":"128","author":"Ardah","year":"2019","journal-title":"Neurochem. Int."},{"key":"B19","first-page":"1","article-title":"The interaction of glutathione and thymoquinone and their antioxidant properties.","volume":"15","author":"Armutcu","year":"2018","journal-title":"Electr. J. Gener. Med."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/432685","article-title":"The Role of Inflammation in THE Pathogenesis of Macular Edema Secondary to Retinal Vascular Diseases.","volume":"2014","author":"Ascaso","year":"2014","journal-title":"Mediat. inflammat."},{"key":"B21","doi-asserted-by":"publisher","first-page":"773","DOI":"10.5603\/FM.a2019.0027","article-title":"Thymoquinone and curcumin modify inducible nitric oxide synthase, caspase 3, and thioredoxin immunohistochemical expression in acetaminophen hepatotoxicity.","volume":"78","author":"Atteya","year":"2019","journal-title":"Folia Morphol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1081\/DCT-120020404","article-title":"Thymoquinone Is a Potent Superoxide Anion Scavenger.","volume":"26","author":"Badary","year":"2003","journal-title":"Drug Chem. Toxicol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1016\/j.jmb.2008.12.081","article-title":"Proteasomes Can Degrade a Significant Proportion of Cellular Proteins Independent of Ubiquitination.","volume":"386","author":"Baugh","year":"2009","journal-title":"J. Mol. Biol."},{"key":"B24","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0039-6257(00)00140-5","article-title":"The role of oxidative stress in the pathogenesis of age-related macular degeneration.","volume":"45","author":"Beatty","year":"2000","journal-title":"Survey Ophthalmol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"2465","DOI":"10.1016\/j.ijbiomac.2017.10.135","article-title":"Monitoring the protective ability of thymoquinone mixture with p-cymene against bovine serum albumin (BSA) glycation: mCR-ALS analysis based on combined spectroscopic and electrochemical methods.","volume":"107","author":"Benvidi","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1215\/S1152851705000232","article-title":"The role of pericytes in blood-vessel formation and maintenance.","volume":"7","author":"Bergers","year":"2005","journal-title":"Neuro Oncol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"5512","DOI":"10.1111\/j.1742-4658.2008.06696.x","article-title":"Natural polyphenols as proteasome modulators and their role as anti-cancer compounds.","volume":"275","author":"Bonfili","year":"2008","journal-title":"Febs J."},{"key":"B28","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.bcp.2016.01.006","article-title":"Thymoquinone strongly inhibits fMLF-induced neutrophil functions and exhibits anti-inflammatory properties in vivo.","volume":"104","author":"Boudiaf","year":"2016","journal-title":"Biochem. Pharmacol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1111\/1440-1681.12961","article-title":"Thymoquinone protects rat liver after partial hepatectomy under ischaemia\/reperfusion through oxidative stress and endoplasmic reticulum stress prevention.","volume":"45","author":"Bouhlel","year":"2018","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1016\/j.biopha.2017.08.018","article-title":"Thymoquinone prevents endoplasmic reticulum stress and mitochondria-induced apoptosis in a rat model of partial hepatic warm ischemia reperfusion.","volume":"94","author":"Bouhlel","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"B31","article-title":"Global Prevalence of Blindness and Distance and Near Vision Impairment in 2020: progress towards the Vision 2020 targets and what the future holds.","volume":"61","author":"Bourne","year":"2020","journal-title":"Investig. Ophthalmol. Visual Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"e130","DOI":"10.1016\/S2214-109X(20)30425-3","article-title":"Trends in prevalence of blindness and distance and near vision impairment over 30 years: an analysis for the Global Burden of Disease Study.","volume":"9","author":"Bourne","year":"2021","journal-title":"Lancet Global Health"},{"key":"B33","doi-asserted-by":"crossref","DOI":"10.3390\/nu11030504","article-title":"Cytoplasmic and Mitochondrial NADPH-Coupled Redox Systems in the Regulation of Aging.","volume":"11","author":"Bradshaw","year":"2019","journal-title":"Nutrients"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019194","article-title":"Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in wistar rats.","volume":"6","author":"Braidy","year":"2011","journal-title":"PLoS One"},{"key":"B35","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.bpobgyn.2010.10.016","article-title":"Oxidative stress.","volume":"25","author":"Burton","year":"2011","journal-title":"Best Pract. Res. Clin. Obstetr. Gynaecol."},{"key":"B36","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1089\/ars.2006.8.1975","article-title":"Nitrosative stress, cellular stress response, and thiol homeostasis in patients with Alzheimer\u2019s disease.","volume":"8","author":"Calabrese","year":"2006","journal-title":"Antioxid. Redox Signal."},{"key":"B37","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2020.00844","article-title":"Eye-light on age-related macular degeneration: targeting nrf2-pathway as a novel therapeutic strategy for retinal pigment epithelium.","volume":"11","author":"Catanzaro","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"2128","DOI":"10.1111\/j.1742-4658.2010.07629.x","article-title":"Effects of thymoquinone on isolated and cellular proteasomes.","volume":"277","author":"Cecarini","year":"2010","journal-title":"Febs J."},{"key":"B39","first-page":"237","article-title":"Inhibition of histamine release from mast cells by nigellone.","volume":"70","author":"Chakravarty","year":"1993","journal-title":"Ann. Allergy"},{"key":"B40","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1177\/112067210501500206","article-title":"Lens Epithelial Apoptosis and Cell Proliferation in Human Age-Related Cortical Cataract.","volume":"15","author":"Charakidas","year":"2005","journal-title":"Eur. J. Ophthalmol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"7204","DOI":"10.18632\/oncotarget.23208","article-title":"Inflammatory responses and inflammation-associated diseases in organs.","volume":"9","author":"Chen","year":"2017","journal-title":"Oncotarget"},{"key":"B42","doi-asserted-by":"publisher","first-page":"4987","DOI":"10.3892\/etm.2018.6072","article-title":"Thymoquinone reduces spinal cord injury by inhibiting inflammatory response, oxidative stress and apoptosis via PPAR-\u03b3 and PI3K\/Akt pathways.","volume":"15","author":"Chen","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"B43","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.jneuroim.2018.04.018","article-title":"Thymoquinone increases the expression of neuroprotective proteins while decreasing the expression of pro-inflammatory cytokines and the gene expression NF\u03baB pathway signaling targets in LPS\/IFN\u03b3-activated BV-2 microglia cells.","volume":"320","author":"Cobourne-Duval","year":"2018","journal-title":"J. Neuroimmunol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"3227","DOI":"10.1007\/s11064-016-2047-1","article-title":"The Antioxidant Effects of Thymoquinone in Activated BV-2 Murine Microglial Cells.","volume":"41","author":"Cobourne-Duval","year":"2016","journal-title":"Neurochem. Res."},{"key":"B45","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1111\/j.1600-0536.1975.tb05478.x","article-title":"Susceptibility to primary irritants: age dependence and relation to contact allergic reactions.","volume":"1","author":"Coenraads","year":"1975","journal-title":"Contact Dermat."},{"key":"B46","doi-asserted-by":"publisher","first-page":"3555","DOI":"10.1167\/iovs.14-13917","article-title":"Activation of Bax in Three Models of Retinitis Pigmentosa.","volume":"55","author":"Comitato","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"B47","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.exer.2013.08.017","article-title":"Autophagy and mitophagy participate in ocular lens organelle degradation.","volume":"116","author":"Costello","year":"2013","journal-title":"Exp. Eye Res."},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/646354","article-title":"Oxidative stress, mitochondrial dysfunction, and aging.","volume":"2012","author":"Cui","year":"2012","journal-title":"J. Signal Transd."},{"key":"B49","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/j.biopha.2018.01.047","article-title":"Thymoquinone activates MAPK pathway in hippocampus of streptozotocin-treated rat model.","volume":"99","author":"Dalli","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.5114\/aoms.2016.61918","article-title":"Diabetic macular edema, retinopathy and age-related macular degeneration as inflammatory conditions.","volume":"12","author":"Das","year":"2016","journal-title":"Arch. Med. Sci."},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1111\/jfbc.13366","article-title":"Thymoquinone (Tq) protects necroptosis induced by autophagy\/mitophagy-dependent oxidative stress in human bronchial epithelial cells exposed to cigarette smoke extract (CSE).","volume":"44","author":"Dera","year":"","journal-title":"J. Food Biochem."},{"key":"B52","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1002\/biof.1590","article-title":"Thymoquinone attenuates oxidative stress of kidney mitochondria and exerts nephroprotective effects in oxonic acid-induced hyperuricemia rats.","volume":"46","author":"Dera","year":"","journal-title":"Biofactors"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1111\/jfbc.13216","article-title":"Thymoquinone attenuates IgE-mediated allergic response via pi3k-Akt-NF\u03baB pathway and upregulation of the Nrf2-HO1 axis.","volume":"44","author":"Dera","year":"","journal-title":"J. Food Biochem."},{"key":"B54","article-title":"Effect of thymoquinone on MDA and SOD levels in sterptozotocine induced diabetic albino rats.","volume":"7","author":"Desai","year":"2015","journal-title":"J. Pharmaceut. Sci. Res."},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9040347","article-title":"The Relevance of Oxidative Stress in the Pathogenesis and Therapy of Retinal Dystrophies.","volume":"9","author":"Dom\u00e8nech","year":"2020","journal-title":"Antioxidants"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.615598","article-title":"Thymoquinone Prevents Dopaminergic Neurodegeneration by Attenuating Oxidative Stress Via the Nrf2\/ARE Pathway.","volume":"11","author":"Dong","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1435","DOI":"10.1001\/archopht.120.11.1435","article-title":"The role of apoptosis in age-related macular degeneration.","volume":"120","author":"Dunaief","year":"2002","journal-title":"Arch. Ophthalmol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.toxlet.2017.05.018","article-title":"Thymoquinone exerts neuroprotective effect in animal model of Parkinson\u2019s disease.","volume":"276","author":"Ebrahimi","year":"2017","journal-title":"Toxicol. Lett."},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01738-3","article-title":"Pericytes regulate VEGF-induced endothelial sprouting through VEGFR1.","volume":"8","author":"Eilken","year":"2017","journal-title":"Nat. Commun."},{"key":"B60","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.bbagen.2007.01.002","article-title":"Thymoquinone attenuates proinflammatory responses in lipopolysaccharide-activated mast cells by modulating NF-kappaB nuclear transactivation.","volume":"1770","author":"El Gazzar","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2020.153324","article-title":"Thymoquinone administration ameliorates Alzheimer\u2019s disease-like phenotype by promoting cell survival in the hippocampus of amyloid beta(1-42) infused rat model.","volume":"79","author":"Elibol","year":"2020","journal-title":"Phytomedicine"},{"key":"B62","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1080\/24750573.2019.1673945","article-title":"Thymoquinone (TQ) demonstrates its neuroprotective effect via an anti-inflammatory action on the A\u03b2(1\u201342)-infused rat model of Alzheimer\u2019s disease.","volume":"29","author":"Elibol","year":"2019","journal-title":"Psychiatry Clin. Psychopharmacol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1159\/000480018","article-title":"Pharmacotherapy with Thymoquinone Improved Pancreatic \u03b2-Cell Integrity and Functional Activity, Enhanced Islets Revascularization, and Alleviated Metabolic and Hepato-Renal Disturbances in Streptozotocin-Induced Diabetes in Rats.","volume":"101","author":"El-Shemi","year":"2018","journal-title":"Pharmacology"},{"key":"B64","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/j.ijpharm.2018.07.012","article-title":"Treatment merits of Latanoprost\/Thymoquinone - Encapsulated liposome for glaucomatus rabbits.","volume":"548","author":"Fahmy","year":"2018","journal-title":"Int. J. Pharm."},{"key":"B65","doi-asserted-by":"publisher","first-page":"298","DOI":"10.4172\/2155-9570.1000298","article-title":"Modes of Retinal Cell Death in Diabetic Retinopathy.","volume":"4","author":"Feenstra","year":"2013","journal-title":"J. Clin. Exp. Ophthalmol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.redox.2017.05.015","article-title":"Altered bioenergetics and enhanced resistance to oxidative stress in human retinal pigment epithelial cells from donors with age-related macular degeneration.","volume":"13","author":"Ferrington","year":"2017","journal-title":"Redox Biol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1016\/j.biopha.2018.03.159","article-title":"Thymoquinone alleviates arsenic induced hippocampal toxicity and mitochondrial dysfunction by modulating mPTP in Wistar rats.","volume":"102","author":"Firdaus","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.583687","article-title":"The Role of Inflammation in Diabetic Retinopathy.","volume":"11","author":"Forrester","year":"2020","journal-title":"Front. Immunol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1016\/j.etap.2015.09.010","article-title":"Ameliorative effects of thymoquinone against eye lens changes in streptozotocin diabetic rats.","volume":"40","author":"Fouad","year":"2015","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"B70","doi-asserted-by":"crossref","first-page":"5944","DOI":"10.1021\/acs.jafc.7b01929","article-title":"Lutein activates the transcription factor Nrf2 in human retinal pigment epithelial cells.","volume":"65","author":"Frede","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"B71","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.exer.2014.04.010","article-title":"Autophagy in the eye: implications for ocular cell health.","volume":"124","author":"Frost","year":"2014","journal-title":"Exp. Eye Res."},{"key":"B72","doi-asserted-by":"publisher","first-page":"10446","DOI":"10.1073\/pnas.0403886101","article-title":"Induction of phase 2 genes by sulforaphane protects retinal pigment epithelial cells against photooxidative damage.","volume":"101","author":"Gao","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B73","doi-asserted-by":"publisher","first-page":"4145","DOI":"10.1074\/jbc.M210285200","article-title":"Leber\u2019s Hereditary Optic Neuropathy (LHON) Pathogenic Mutations Induce Mitochondrial-dependent Apoptotic Death in Transmitochondrial Cells Incubated with Galactose Medium*.","volume":"278","author":"Ghelli","year":"2003","journal-title":"J. Biol. Chem."},{"key":"B74","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1161\/CIRCRESAHA.110.223545","article-title":"Oxidative stress and diabetic complications.","volume":"107","author":"Giacco","year":"2010","journal-title":"Circ. Res."},{"key":"B75","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1161\/circulationaha.106.621854","article-title":"Advanced Glycation End Products: Sparking the Development of Diabetic Vascular Injury.","volume":"114","author":"Goldin","year":"2006","journal-title":"Circulation"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.453","article-title":"Dysfunctional autophagy in RPE, a contributing factor in age-related macular degeneration.","volume":"8","author":"Golestaneh","year":"2017","journal-title":"Cell Death Dis."},{"key":"B77","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2017.00656","article-title":"Therapeutic potential and pharmaceutical development of thymoquinone: a multitargeted molecule of natural origin.","volume":"8","author":"Goyal","year":"2017","journal-title":"Front. Pharmacol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"E394","DOI":"10.1152\/ajpendo.00250.2015","article-title":"Thymoquinone, a bioactive component of Nigella sativa, normalizes insulin secretion from pancreatic \u03b2-cells under glucose overload via regulation of malonyl-CoA.","volume":"310","author":"Gray","year":"2016","journal-title":"Am. J. Physiol. Endocrinol. Metabol."},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012124","article-title":"Thymoquinone induces telomere shortening. DNA damage and apoptosis in human glioblastoma cells.","volume":"5","author":"Gurung","year":"2010","journal-title":"PLoS One"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-43568-x","article-title":"Thymoquinone therapy remediates elevated brain tissue inflammatory mediators induced by chronic administration of food preservatives.","volume":"9","author":"Hamdan","year":"2019","journal-title":"Sci. Rep."},{"key":"B81","doi-asserted-by":"publisher","first-page":"591","DOI":"10.3109\/02713683.2011.573898","article-title":"Ameliorative effect of thymoquinone on ovalbumin-induced allergic conjunctivitis in Balb\/c mice.","volume":"36","author":"Hayat","year":"2011","journal-title":"Curr. Eye Res."},{"key":"B82","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1167\/iovs.07-1361","article-title":"Mitochondrial Complex I Defect Induces ROS Release and Degeneration in Trabecular Meshwork Cells of POAG Patients: protection by Antioxidants.","volume":"49","author":"He","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"B83","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.jcgg.2010.10.006","article-title":"Senile cataracts and oxidative stress.","volume":"1","author":"Ho","year":"2010","journal-title":"J. Clin. Gerontol. Geriatr."},{"key":"B84","first-page":"105","article-title":"Vascular endothelial growth factors and their inhibitors in ocular neovascular disorders.","volume":"4","author":"Homayouni","year":"2009","journal-title":"J. Ophthalm. Vision Res."},{"key":"B85","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1016\/j.pharep.2017.03.002","article-title":"Thymoquinone ameliorates renal damage in unilateral ureteral obstruction in rats.","volume":"69","author":"Hosseinian","year":"2017","journal-title":"Pharmacol. Rep."},{"key":"B86","doi-asserted-by":"crossref","first-page":"3713","DOI":"10.1167\/iovs.04-0404","article-title":"Receptor for advanced glycation end products and age-related macular degeneration.","volume":"45","author":"Howes","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"B87","doi-asserted-by":"publisher","first-page":"4514","DOI":"10.1002\/jcb.27739","article-title":"Thymoquinone protects human retinal pigment epithelial cells against hydrogen peroxide induced oxidative stress and apoptosis.","volume":"120","author":"Hu","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/7432797","article-title":"Oxidative Stress and Inflammation: what Polyphenols Can Do for Us?","volume":"2016","author":"Hussain","year":"2016","journal-title":"Oxidat. Med. Cell. Longev."},{"key":"B89","doi-asserted-by":"publisher","first-page":"230","DOI":"10.15283\/ijsc16021","article-title":"The Effect of Thymoquinone, \u03b17 Receptor Agonist and \u03b17 Receptor Allosteric Modulator on the Cerebral Cortex in Experimentally Induced Alzheimer\u2019s Disease in Relation to MSCs Activation.","volume":"9","author":"Ibrahim AbdEl Fattah","year":"2016","journal-title":"Int. J. Stem Cells"},{"key":"B90","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1001\/archopht.116.12.1629","article-title":"Advanced glycation end products in age-related macular degeneration.","volume":"116","author":"Ishibashi","year":"1998","journal-title":"Arch. Ophthalmol."},{"key":"B91","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1016\/j.biopha.2017.08.074","article-title":"Thymoquinone-rich fraction nanoemulsion (TQRFNE) decreases A\u03b240 and A\u03b242 levels by modulating APP processing, up-regulating IDE and LRP1, and down-regulating BACE1 and RAGE in response to high fat\/cholesterol diet-induced rats.","volume":"95","author":"Ismail","year":"","journal-title":"Biomed. Pharmacother."},{"key":"B92","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.cbi.2017.07.014","article-title":"Beneficial effects of TQRF and TQ nano- and conventional emulsions on memory deficit, lipid peroxidation, total antioxidant status, antioxidants genes expression and soluble A\u03b2 levels in high fat-cholesterol diet-induced rats.","volume":"275","author":"Ismail","year":"","journal-title":"Chem. Biol. Interact."},{"key":"B93","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1007\/s10571-013-9982-z","article-title":"Thymoquinone prevents \u03b2-amyloid neurotoxicity in primary cultured cerebellar granule neurons.","volume":"33","author":"Ismail","year":"2013","journal-title":"Cell Mol. Neurobiol."},{"key":"B94","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.mrrev.2005.11.001","article-title":"The role of oxidative stress in glaucoma.","volume":"612","author":"Izzotti","year":"2006","journal-title":"Mutat. Res."},{"key":"B95","author":"Jadeja","year":"2021","journal-title":"Oxidative Stress and Inflammation in Retinal Degeneration."},{"key":"B96","doi-asserted-by":"crossref","first-page":"615","DOI":"10.3233\/JAD-2011-101908","article-title":"Age-related macular degeneration (AMD): Alzheimer\u2019s disease in the eye?","volume":"24","author":"Kaarniranta","year":"2011","journal-title":"J. Alzheimers Dis."},{"key":"B97","doi-asserted-by":"publisher","first-page":"e155","DOI":"10.7417\/ct.2013.1559","article-title":"Effectiveness of thymoquinone in the treatment of experimental asthma.","volume":"164","author":"Kalemci","year":"2013","journal-title":"Clin. Ter."},{"key":"B98","doi-asserted-by":"publisher","first-page":"3805","DOI":"10.1167\/iovs.06-1280","article-title":"Oxidative damage in the retinal mitochondria of diabetic mice: possible protection by superoxide dismutase.","volume":"48","author":"Kanwar","year":"2007","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B99","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.ejbas.2017.07.002","article-title":"The role of thymoquinone as a potent antioxidant in ameliorating the neurotoxic effect of sodium arsenate in female rat.","volume":"4","author":"Kassab","year":"2017","journal-title":"Egypt. J. Basic Appl. Sci."},{"key":"B100","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1007\/s00018-016-2147-8","article-title":"Inflammation and its role in age-related macular degeneration.","volume":"73","author":"Kauppinen","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"B101","doi-asserted-by":"publisher","first-page":"75","DOI":"10.5681\/bi.2014.006","article-title":"The effect of single dose of thymoquinone, the main constituents of Nigella sativa, in guinea pig model of asthma.","volume":"4","author":"Keyhanmanesh","year":"2014","journal-title":"Bioimpacts"},{"key":"B102","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/s10735-010-9271-9","article-title":"Apoptotic factors (Bcl-2 and Bax) and diabetic retinopathy in type 2 diabetes.","volume":"41","author":"Khalfaoui","year":"2010","journal-title":"J. Mol. Histol."},{"key":"B103","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1080\/10715760600978815","article-title":"Nonenzymatic reduction of thymoquinone in physiological conditions.","volume":"41","author":"Khalife","year":"2007","journal-title":"Free Radic. Res."},{"key":"B104","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/s11010-012-1368-x","article-title":"Attenuation of A\u03b2-induced neurotoxicity by thymoquinone via inhibition of mitochondrial dysfunction and oxidative stress.","volume":"369","author":"Khan","year":"2012","journal-title":"Mol. Cell Biochem."},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.180","article-title":"DRP1 inhibition rescues retinal ganglion cells and their axons by preserving mitochondrial integrity in a mouse model of glaucoma.","volume":"6","author":"Kim","year":"2015","journal-title":"Cell Death Dis."},{"key":"B106","doi-asserted-by":"publisher","first-page":"281","DOI":"10.4274\/tjo.50146","article-title":"Effects of Topical Thymoquinone in an Experimental Dry Eye Model.","volume":"48","author":"Kocat\u00fcrk","year":"2018","journal-title":"Turk. J. Ophthalmol."},{"key":"B107","doi-asserted-by":"publisher","first-page":"5327","DOI":"10.1167\/iovs.03-0353","article-title":"Diabetes-induced mitochondrial dysfunction in the retina.","volume":"44","author":"Kowluru","year":"2003","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B108","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.cotox.2017.11.002","article-title":"NF-\u03baB in Oxidative Stress.","volume":"7","author":"Lingappan","year":"2018","journal-title":"Curr. Opin. Toxicol."},{"key":"B109","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.foodchem.2011.02.076","article-title":"Inhibition of the formation of advanced glycation end products by thymoquinone.","volume":"128","author":"Losso","year":"2011","journal-title":"Food Chem."},{"key":"B110","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.3390\/nu2121247","article-title":"Dietary advanced glycation end products and aging.","volume":"2","author":"Luevano-Contreras","year":"2010","journal-title":"Nutrients"},{"key":"B111","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1556\/018.68.2017.3.2","article-title":"Protective effect of thymoquinone against lead-induced antioxidant defense system alteration in rat liver.","volume":"68","author":"Mabrouk","year":"2017","journal-title":"Acta Biol. Hung"},{"key":"B112","first-page":"25","article-title":"Nigella sativa as an antiglycating agent for human serum albumin.","volume":"2","author":"Mahmood","year":"2013","journal-title":"Med. Sci."},{"key":"B113","doi-asserted-by":"publisher","first-page":"156","DOI":"10.2174\/187152710791012071","article-title":"Microglia and inflammation in Alzheimer\u2019s disease.","volume":"9","author":"Mandrekar-Colucci","year":"2010","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"B114","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1080\/01902148.2020.1801895","article-title":"Thymoquinone ameliorates the PM2.5-induced lung injury in rats.","volume":"46","author":"Mao","year":"2020","journal-title":"Exp. Lung Res."},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/9409363","article-title":"Glutathione as a Biomarker in Parkinson\u2019s Disease: associations with Aging and Disease Severity.","volume":"2016","author":"Mischley","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"B116","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1038\/cr.2010.178","article-title":"Crosstalk of reactive oxygen species and NF-\u03baB signaling.","volume":"21","author":"Morgan","year":"2011","journal-title":"Cell Res."},{"key":"B117","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1080\/15216549900201153","article-title":"Thymoquinone protects against carbon tetrachloride hetatotoxicity in mice via an antioxidant mechanism.","volume":"47","author":"Nagi","year":"1999","journal-title":"IUBMB Life"},{"key":"B118","doi-asserted-by":"publisher","first-page":"13291","DOI":"10.1074\/jbc.R900010200","article-title":"The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress.","volume":"284","author":"Nguyen","year":"2009","journal-title":"J. Biol. Chem."},{"key":"B119","doi-asserted-by":"publisher","first-page":"145","DOI":"10.3109\/13816819609057889","article-title":"Apoptosis in ocular disease: a molecular overview.","volume":"17","author":"Nickells","year":"1996","journal-title":"Ophthalm. Genet."},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/3164734","article-title":"The Role of the Reactive Oxygen Species and Oxidative Stress in the Pathomechanism of the Age-Related Ocular Diseases and Other Pathologies of the Anterior and Posterior Eye Segments in Adults.","volume":"2016","author":"Nita","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"B121","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/s0168-8227(98)00074-6","article-title":"Increased serum levels of advanced glycation end-products and diabetic complications.","volume":"41","author":"Ono","year":"1998","journal-title":"Diabetes Res. Clin. Pract."},{"key":"B122","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1111\/aos.13009","article-title":"Cell death pattern in lens epithelium of cataract patients.","volume":"94","author":"Osnes-Ringen","year":"2016","journal-title":"Acta Ophthalmol."},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-01765-3","article-title":"Photoreceptor metabolic reprogramming: current understanding and therapeutic implications.","volume":"4","author":"Pan","year":"2021","journal-title":"Commun. Biol."},{"key":"B124","first-page":"1","article-title":"Nigella sativa seed extracts prevent the glycation of protein and DNA.","volume":"1","author":"Pandey","year":"2018","journal-title":"Curr. Perspect. Med. Aromat. Plants"},{"key":"B125","doi-asserted-by":"publisher","first-page":"96","DOI":"10.5578\/turkjsurg.4583","article-title":"Thymoquinone reduces ischemia and reperfusion-induced intestinal injury in rats, through anti-oxidative and anti-inflammatory effects.","volume":"36","author":"Parlar","year":"2020","journal-title":"Turk. J. Surg."},{"key":"B126","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1136\/bjophthalmol-2011-300539","article-title":"Global estimates of visual impairment: 2010.","volume":"96","author":"Pascolini","year":"2012","journal-title":"Br. J. Ophthalmol."},{"key":"B127","doi-asserted-by":"publisher","first-page":"1865","DOI":"10.3390\/ijms15021865","article-title":"Antioxidant drug therapy approaches for neuroprotection in chronic diseases of the retina.","volume":"15","author":"Payne","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/780179","article-title":"Mitochondrial dysfunction: different routes to Alzheimer\u2019s disease therapy.","volume":"2014","author":"Picone","year":"2014","journal-title":"Oxid. Med. Cell. Longev."},{"key":"B129","first-page":"188","article-title":"Thymoquinone recovers learning function in a rat model of Alzheimer\u2019s disease.","volume":"8","author":"Poorgholam","year":"2018","journal-title":"Avicenna J. Phytomed."},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9100921","article-title":"Nigella sativa\u2019s Anti-Inflammatory and Antioxidative Effects in Experimental Inflammation.","volume":"9","author":"Pop","year":"2020","journal-title":"Antioxidants"},{"key":"B131","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1007\/s12026-008-8018-0","article-title":"Microglial cells and Parkinson\u2019s disease.","volume":"41","author":"Qian","year":"2008","journal-title":"Immunol. Res."},{"key":"B132","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1002\/ptr.2708","article-title":"Thymoquinone protects dopaminergic neurons against MPP+ and rotenone.","volume":"23","author":"Radad","year":"2009","journal-title":"Phytother. Res."},{"key":"B133","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.cbi.2018.02.006","article-title":"Improvement of antihyperglycemic activity of nano-thymoquinone in rat model of type-2 diabetes.","volume":"295","author":"Rani","year":"2018","journal-title":"Chem. Biol. Interact."},{"key":"B134","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1038\/nrm2468","article-title":"Diversity of degradation signals in the ubiquitin-proteasome system.","volume":"9","author":"Ravid","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B135","doi-asserted-by":"publisher","first-page":"38","DOI":"10.2174\/138920291501140306113344","article-title":"The Mechanistic Links Between Proteasome Activity. Aging and Age-related Diseases.","volume":"15","author":"Saez","year":"2014","journal-title":"Curr. Genomics"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26427-0","article-title":"The 20S as a stand-alone proteasome in cells can degrade the ubiquitin tag.","volume":"12","author":"Sahu","year":"2021","journal-title":"Nat. Commun."},{"key":"B137","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.cbi.2011.02.029","article-title":"Thymoquinone ameliorates chemical induced oxidative stress and \u03b2-cell damage in experimental hyperglycemic rats.","volume":"190","author":"Sankaranarayanan","year":"2011","journal-title":"Chem. Biol. Interact."},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1111\/and.13623","article-title":"Thymoquinone could be protective against valproic acid-induced testicular toxicity by antioxidant and anti-inflammatory mechanisms.","volume":"52","author":"Savran","year":"2020","journal-title":"Andrologia"},{"key":"B139","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1002\/ptr.2177","article-title":"Thymoquinone decreases AGE-induced NF-kappaB activation in proximal tubular epithelial cells.","volume":"21","author":"Sayed","year":"2007","journal-title":"Phytother. Res."},{"key":"B140","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1172\/jci119180","article-title":"Increased accumulation of the glycoxidation product N(epsilon)-(carboxymethyl)lysine in human tissues in diabetes and aging.","volume":"99","author":"Schleicher","year":"1997","journal-title":"J. Clin. Invest."},{"key":"B141","first-page":"227","article-title":"Neuroprotective effect of thymoquinone, the Nigella sativa bioactive compound, in 6-hydroxydopamine-induced hemi-parkinsonian rat model.","volume":"13","author":"Sedaghat","year":"2014","journal-title":"Iran J. Pharm. Res."},{"key":"B142","doi-asserted-by":"publisher","first-page":"e274","DOI":"10.1097\/BCR.0b013e31827a2be1","article-title":"Evaluation of the effect of thymoquinone treatment on wound healing in a rat burn model.","volume":"34","author":"Sel\u00e7uk","year":"2013","journal-title":"J. Burn Care Res."},{"key":"B143","doi-asserted-by":"publisher","first-page":"117","DOI":"10.3109\/0886022x.2015.1103601","article-title":"Protective effects of thymoquinone against apoptosis and oxidative stress by arsenic in rat kidney.","volume":"38","author":"Sener","year":"2016","journal-title":"Ren. Fail"},{"key":"B144","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1158\/1541-7786.mcr-07-2088","article-title":"Targeting nuclear factor-kappa B activation pathway by thymoquinone: role in suppression of antiapoptotic gene products and enhancement of apoptosis.","volume":"6","author":"Sethi","year":"2008","journal-title":"Mol. Cancer Res."},{"key":"B145","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1111\/jcmm.13944","article-title":"Advanced glycation end products-related modulation of cathepsin L and NF-\u03baB signalling effectors in retinal pigment epithelium lead to augmented response to TNF\u03b1.","volume":"23","author":"Sharif","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"B146","doi-asserted-by":"crossref","first-page":"14487","DOI":"10.3390\/molecules200814487","article-title":"Neuroprotective effects of mitochondria-targeted plastoquinone and thymoquinone in a rat model of brain ischemia\/reperfusion injury.","volume":"20","author":"Silachev","year":"2015","journal-title":"Molecules"},{"key":"B147","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/6795383","article-title":"In Vitro Wound Healing Activities of Three Most Commonly Used Thai Medicinal Plants and Their Three Markers.","volume":"2020","author":"Siriwattanasatorn","year":"2020","journal-title":"Evid Based Complement. Alternat. Med."},{"key":"B148","first-page":"523","article-title":"Advanced glycation end products (AGEs) co-localize with AGE receptors in the retinal vasculature of diabetic and of AGE-infused rats.","volume":"150","author":"Stitt","year":"1997","journal-title":"Am. J. Pathol."},{"key":"B149","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-14015-6","article-title":"Advanced glycation end products promote VEGF expression and thus choroidal neovascularization via Cyr61-PI3K\/AKT signaling pathway.","volume":"7","author":"Sun","year":"2017","journal-title":"Sci. Rep."},{"key":"B150","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1007\/s11064-019-02908-z","article-title":"Role of Oxidative Stress, MAPKinase and Apoptosis Pathways in the Protective Effects of Thymoquinone Against Acrylamide-Induced Central Nervous System Toxicity in Rat.","volume":"45","author":"Tabeshpour","year":"2020","journal-title":"Neurochem. Res."},{"key":"B151","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.jneuroim.2015.06.011","article-title":"Anti-inflammatory effects of thymoquinone in activated BV-2 microglial cells.","volume":"286","author":"Taka","year":"2015","journal-title":"J. Neuroimmunol."},{"key":"B152","doi-asserted-by":"publisher","first-page":"10515","DOI":"10.1073\/pnas.1509879112","article-title":"In vivo imaging of axonal transport of mitochondria in the diseased and aged mammalian CNS.","volume":"112","author":"Takihara","year":"2015","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B153","doi-asserted-by":"publisher","first-page":"2989","DOI":"10.7150\/ijbs.49890","article-title":"The Role of Inflammation in Age-Related Macular Degeneration.","volume":"16","author":"Tan","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"B154","doi-asserted-by":"publisher","first-page":"101","DOI":"10.3109\/15569527.2014.910802","article-title":"The radioprotective effect of Nigella sativa on nitrosative stress in lens tissue in radiation-induced cataract in rat.","volume":"34","author":"Taysi","year":"2015","journal-title":"Cutan Ocul. Toxicol."},{"key":"B155","doi-asserted-by":"publisher","DOI":"10.3390\/metabo10010027","article-title":"Effects of Thymoquinone on Small-Molecule Metabolites in a Rat Model of Cerebral Ischemia Reperfusion Injury Assessed using MALDI-MSI.","volume":"10","author":"Tian","year":"2020","journal-title":"Metabolites"},{"key":"B156","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1007\/s10522-013-9463-2","article-title":"Role of antioxidant enzymes and small molecular weight antioxidants in the pathogenesis of age-related macular degeneration (AMD).","volume":"14","author":"Tokarz","year":"2013","journal-title":"Biogerontology"},{"key":"B157","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/j.clinbiochem.2005.11.013","article-title":"Contribution of VEGF and PEDF to choroidal angiogenesis: a need for balanced expressions.","volume":"39","author":"Tong","year":"2006","journal-title":"Clin. Biochem."},{"key":"B158","doi-asserted-by":"publisher","first-page":"375","DOI":"10.3906\/sag-2006-147","article-title":"The stereological and histopathological evaluation of the effect of Thymoquinone on peridural fibrosis following laminectomy in rats.","volume":"51","author":"T\u00dcrk\u00d6z","year":"2020","journal-title":"Turk. J. Med. Sci."},{"key":"B159","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.redox.2016.01.010","article-title":"Redox homeostasis: the Golden Mean of healthy living.","volume":"8","author":"Ursini","year":"2016","journal-title":"Redox Biol."},{"key":"B160","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/s11010-017-3064-3","article-title":"AMPK and SIRT1 activation contribute to inhibition of neuroinflammation by thymoquinone in BV2 microglia.","volume":"435","author":"Velagapudi","year":"","journal-title":"Mol. Cell. Biochem."},{"key":"B161","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.intimp.2017.04.018","article-title":"Inhibition of neuroinflammation by thymoquinone requires activation of Nrf2\/ARE signalling.","volume":"48","author":"Velagapudi","year":"","journal-title":"Int. Immunopharmacol."},{"key":"B162","first-page":"138","article-title":"Pathogenic effects of advanced glycosylation: biochemical, biologic, and clinical implications for diabetes and aging.","volume":"70","author":"Vlassara","year":"1994","journal-title":"Lab. Invest."},{"key":"B163","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18122772","article-title":"Nrf2, the Master Regulator of Anti-Oxidative Responses.","volume":"18","author":"Vomund","year":"2017","journal-title":"Int. J. Mol. Sci."},{"key":"B164","first-page":"644","article-title":"Increased mitochondrial DNA damage and down-regulation of DNA repair enzymes in aged rodent retinal pigment epithelium and choroid.","volume":"14","author":"Wang","year":"2008","journal-title":"Mol. Vis."},{"key":"B165","doi-asserted-by":"publisher","first-page":"2235","DOI":"10.1007\/s10753-015-0206-1","article-title":"Thymoquinone Inhibits IL-1\u03b2-Induced Inflammation in Human Osteoarthritis Chondrocytes by Suppressing NF-\u03baB and MAPKs Signaling Pathway.","volume":"38","author":"Wang","year":"2015","journal-title":"Inflammation"},{"key":"B166","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.intimp.2015.03.013","article-title":"Thymoquinone inhibits lipopolysaccharide-induced inflammatory mediators in BV2 microglial cells.","volume":"26","author":"Wang","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"B167","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/eye.2010.196","article-title":"The role of anti-inflammatory agents in age-related macular degeneration (AMD) treatment.","volume":"25","author":"Wang","year":"2011","journal-title":"Eye"},{"key":"B168","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075356","article-title":"Thymoquinone Inhibits Tumor Growth and Induces Apoptosis in a Breast Cancer Xenograft Mouse Model: the Role of p38 MAPK and ROS.","volume":"8","author":"Woo","year":"2013","journal-title":"PLoS One"},{"key":"B169","first-page":"2834","article-title":"NF-\u03baB Activation in Light-Induced Retinal Degeneration in a Mouse Model.","volume":"43","author":"Wu","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"B170","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1089\/ars.2017.7216","article-title":"NAD (H) and NADP (H) redox couples and cellular energy metabolism.","volume":"28","author":"Xiao","year":"2018","journal-title":"Antioxid Redox Signal"},{"key":"B171","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/2571060","article-title":"Evaluation of Neuroprotective Effect of Thymoquinone Nanoformulation in the Rodent Cerebral Ischemia-Reperfusion Model.","volume":"2016","author":"Xiao","year":"2016","journal-title":"Biomed. Res. Int."},{"key":"B172","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-018-0829-y","article-title":"Thymoquinone reduces cardiac damage caused by hypercholesterolemia in apolipoprotein E-deficient mice.","volume":"17","author":"Xu","year":"2018","journal-title":"Lipids Health Dis."},{"key":"B173","doi-asserted-by":"publisher","first-page":"4766","DOI":"10.1167\/iovs.06-0871","article-title":"Role of NF-kappaB and MAPKs in light-induced photoreceptor apoptosis.","volume":"48","author":"Yang","year":"2007","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B174","doi-asserted-by":"publisher","DOI":"10.3390\/nu10070842","article-title":"Lutein and Zeaxanthin Isomers Protect against Light-Induced Retinopathy via Decreasing Oxidative and Endoplasmic Reticulum Stress in BALB\/cJ Mice.","volume":"10","author":"Yu","year":"2018","journal-title":"Nutrients"},{"key":"B175","first-page":"187","article-title":"Glycation inhibition by Nigella sativa (Linn)\u2013an in vitro model.","volume":"1","author":"Zafar","year":"2013","journal-title":"Asian J. Agric. Biol."},{"key":"B176","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s12603-012-0095-z","article-title":"Biomarkers of oxidative stress in patients with wet age related macular degeneration.","volume":"17","author":"Zafrilla","year":"2013","journal-title":"J. Nutr. Health Aging"},{"key":"B177","first-page":"1","article-title":"Potential Protective Role of Thymoquinone on Experimentally-induced Alzheimer Rats.","volume":"31","author":"Zaher","year":"2019","journal-title":"J. Pharmaceut. Res. Int."},{"key":"B178","doi-asserted-by":"publisher","first-page":"7703","DOI":"10.2147\/ijn.s262395","article-title":"Pharmacokinetics and Biodistribution of Thymoquinone-loaded Nanostructured Lipid Carrier After Oral and Intravenous Administration into Rats.","volume":"15","author":"Zakarial Ansar","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"B179","first-page":"155","article-title":"[The expression of Bcl-2, Bcl-xl, Bak and Bax proteins in axons of the optic nerve in closed-angle glaucoma].","volume":"106","author":"Zalewska","year":"2004","journal-title":"Klin Oczna"},{"key":"B180","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.pestbp.2018.03.006","article-title":"Protective role of thymoquinone against paraquat-induced hepatotoxicity in mice.","volume":"148","author":"Zeinvand-Lorestani","year":"2018","journal-title":"Pestic. Biochem. Physiol."},{"key":"B181","first-page":"1075","article-title":"Activation of nuclear factor-kappaB during retinal degeneration in rd mice.","volume":"14","author":"Zeng","year":"2008","journal-title":"Mol. Vis."},{"key":"B182","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/4350965","article-title":"ROS and ROS-Mediated Cellular Signaling.","volume":"2016","author":"Zhang","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"B183","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.cbi.2018.06.013","article-title":"Thymoquinone induces apoptosis in bladder cancer cell via endoplasmic reticulum stress-dependent mitochondrial pathway.","volume":"292","author":"Zhang","year":"2018","journal-title":"Chem. Biol. Interact."},{"key":"B184","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019456","article-title":"Age-related retinopathy in NRF2-deficient mice.","volume":"6","author":"Zhao","year":"2011","journal-title":"PLoS One"}],"container-title":["Frontiers in Cellular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2022.786926\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T04:53:20Z","timestamp":1646196800000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2022.786926\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,2]]},"references-count":184,"alternative-id":["10.3389\/fncel.2022.786926"],"URL":"https:\/\/doi.org\/10.3389\/fncel.2022.786926","relation":{},"ISSN":["1662-5102"],"issn-type":[{"value":"1662-5102","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,2]]},"article-number":"786926"}}