{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:41:35Z","timestamp":1790343695667,"version":"4.1.0"},"reference-count":104,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T00:00:00Z","timestamp":1641427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH grants","award":["RF1 AG057409, R01 AG056259, R01 DA048882, R01 NS086890 and DP1 DA041722"],"award-info":[{"award-number":["RF1 AG057409, R01 AG056259, R01 DA048882, R01 NS086890 and DP1 DA041722"]}]},{"name":"California Institute for Regenerative Medicine (CIRM) grant","award":["DISC2 COVID19-11811, and a COVID-19 award from Fast Grants"],"award-info":[{"award-number":["DISC2 COVID19-11811, and a COVID-19 award from Fast Grants"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Rosemary (Rosmarinus officinalis [family Lamiaceae]), an herb of economic and gustatory repute, is employed in traditional medicines in many countries. Rosemary contains carnosic acid (CA) and carnosol (CS), abietane-type phenolic diterpenes, which account for most of its biological and pharmacological actions, although claims have also been made for contributions of another constituent, rosmarinic acid. This review focuses on the potential applications of CA and CS for Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), and coronavirus disease 2019 (COVID-19), in part via inhibition of the NLRP3 inflammasome. CA exerts antioxidant, anti-inflammatory, and neuroprotective effects via phase 2 enzyme induction initiated by activation of the KEAP1\/NRF2 transcriptional pathway, which in turn attenuates NLRP3 activation. In addition, we propose that CA-related compounds may serve as therapeutics against the brain-related after-effects of SARS-CoV-2 infection, termed \u201clong-COVID.\u201d One factor that contributes to COVID-19 is cytokine storm emanating from macrophages as a result of unregulated inflammation in and around lung epithelial and endovascular cells. Additionally, neurological aftereffects such as anxiety and \u201cbrain fog\u201d are becoming a major issue for both the pandemic and post-pandemic period. Many reports hold that unregulated NLRP3 inflammasome activation may potentially contribute to the severity of COVID-19 and its aftermath. It is therefore possible that suppression of NLRP3 inflammasome activity may prove efficacious against both acute lung disease and chronic neurological after-effects. Because CA has been shown to not only act systemically but also to penetrate the blood\u2013brain barrier and reach the brain parenchyma to exert neuroprotective effects, we discuss the evidence that CA or rosemary extracts containing CA may represent an effective countermeasure against both acute and chronic pathological events initiated by SARS-CoV-2 infection as well as other chronic neurodegenerative diseases including AD and PD.<\/jats:p>","DOI":"10.3390\/antiox11010124","type":"journal-article","created":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T01:15:26Z","timestamp":1641518126000},"page":"124","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":110,"title":["Potential Therapeutic Use of the Rosemary Diterpene Carnosic Acid for Alzheimer\u2019s Disease, Parkinson\u2019s Disease, and Long-COVID through NRF2 Activation to Counteract the NLRP3 Inflammasome"],"prefix":"10.3390","volume":"11","author":[{"given":"Takumi","family":"Satoh","sequence":"first","affiliation":[{"name":"Department of Anti-Aging Food Research, School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1 Katakura, Hachioji 192-0982, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorit","family":"Trudler","sequence":"additional","affiliation":[{"name":"Departments of Molecular Medicine and Neuroscience and Neurodegeneration New Medicines Center, The Scripps Research Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Ki","family":"Oh","sequence":"additional","affiliation":[{"name":"Departments of Molecular Medicine and Neuroscience and Neurodegeneration New Medicines Center, The Scripps Research Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart A.","family":"Lipton","sequence":"additional","affiliation":[{"name":"Departments of Molecular Medicine and Neuroscience and Neurodegeneration New Medicines Center, The Scripps Research Institute, La Jolla, CA 92037, USA"},{"name":"Department of Neurosciences, University of California San Diego School of Medicine, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Nieto, G., Ros, G., and Castillo, J. (2018). Antioxidant and antimicrobial properties of rosemary (Rosmarinus officinalis, L.): A review. Medicines, 5.","DOI":"10.3390\/medicines5030098"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s12929-019-0499-8","article-title":"Rosmarinus officinalis L.(rosemary) as therapeutic and prophylactic agent","volume":"26","author":"Camargo","year":"2019","journal-title":"J. Biomed. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"731","DOI":"10.3390\/nu8110731","article-title":"Anticancer effects of rosemary (Rosmarinus officinalis L.) extract and rosemary extract polyphenols","volume":"8","author":"Moore","year":"2016","journal-title":"Nutrients"},{"key":"ref_4","unstructured":"(2021, November 19). Generally Recognized as Safe (GRAS) in USA, Available online: https:\/\/www.fda.gov\/food\/food-ingredients-packaging\/generally-recognized-safe-gras."},{"key":"ref_5","unstructured":"(2021, November 19). 5.\tCurrent EU Approval and Their E Number in EU. Available online: https:\/\/ec.europa.eu\/food\/safety\/food-improvement-agents\/additives\/database_en."},{"key":"ref_6","unstructured":"(2021, November 19). Approved Food Additives by Ministry of Health, Labor and Welfare of Japan. Available online: https:\/\/www.ffcr.or.jp\/tenka\/list\/post-12.html?OpenDocument."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"FSO283","DOI":"10.4155\/fsoa-2017-0124","article-title":"Rosmarinus officinalis L.: An update review of its phytochemistry and biological activity","volume":"4","author":"Andrade","year":"2018","journal-title":"Future Sci. OA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6155","DOI":"10.1007\/s12035-015-9519-1","article-title":"The dietary components carnosic acid and carnosol as neuroprotective agents: A mechanistic view","volume":"53","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1104\/pp.17.01183","article-title":"Carnosic acid and carnosol, two major antioxidants of rosemary, act through different mechanisms","volume":"175","author":"Loussouarn","year":"2017","journal-title":"Plant Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1089\/jmf.2012.2162","article-title":"Effect of Rosmarinus officinalis L. on MMP-9, MCP-1 levels, and cell migration in RAW 264.7 and smooth muscle cells","volume":"15","author":"Chae","year":"2012","journal-title":"J. Med. Food"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3674","DOI":"10.1021\/jf104837w","article-title":"Anti-inflammatory effects of supercritical carbon dioxide extract and its isolated carnosic acid from Rosmarinus officinalis leaves","volume":"59","author":"Kuo","year":"2011","journal-title":"J. Agric. Food Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5168","DOI":"10.1021\/jf0496705","article-title":"Analysis of volatiles in porcine liver p\u00e2t\u00e9s with added sage and rosemary essential oils by using SPME-GC-MS","volume":"52","author":"Ventanas","year":"2004","journal-title":"J. Agric. Food Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.phrs.2013.07.010","article-title":"Small molecule activators of the Nrf2-HO-1 antioxidant axis modulate heme metabolism and inflammation in BV2 microglia cells","volume":"76","author":"Foresti","year":"2013","journal-title":"Pharmacol. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"15","DOI":"10.4196\/kjpp.2016.20.1.15","article-title":"Carnosic acid protects against acetaminophen-induced hepatotoxicity by potentiating Nrf2-mediated antioxidant capacity in mice","volume":"20","author":"Guo","year":"2016","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.bbrc.2011.12.087","article-title":"Carnosic acid, a pro-electrophilic compound, inhibits LPS-induced activation of microglia","volume":"418","author":"Yanagitai","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1007\/s12017-017-8459-5","article-title":"Combination of EPA with carotenoids and polyphenol synergistically attenuated the transformation of microglia to M1 phenotype via inhibition of NF-\u03baB","volume":"19","author":"Hadad","year":"2017","journal-title":"Neuromol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.3389\/fimmu.2018.01807","article-title":"Carnosol modulates Th17 cell differentiation and microglial switch in experimental autoimmune encephalomyelitis","volume":"9","author":"Li","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1083\/jcb.201709069","article-title":"Microglia in Alzheimer\u2019s disease","volume":"217","author":"Hansen","year":"2018","journal-title":"J. Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/978-981-13-9913-8_13","article-title":"Microglia in Parkinson\u2019s Disease","volume":"1175","author":"Ho","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6709","DOI":"10.1007\/s12035-015-9593-4","article-title":"Microglia-Mediated Inflammation and Neurodegenerative Disease","volume":"53","author":"Xu","year":"2015","journal-title":"Mol. Neurobiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/j.cell.2020.02.002","article-title":"Structural mechanism for GSDMD targeting by autoprocessed caspases in pyroptosis","volume":"180","author":"Wang","year":"2020","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1038\/s41419-019-1761-4","article-title":"Propofol directly induces caspase-1-dependent macrophage pyroptosis through the NLRP3-ASC inflammasome","volume":"10","author":"Sun","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1111\/nyas.12458","article-title":"Mechanism of NLRP3 inflammasome activation","volume":"1319","author":"Sutterwala","year":"2014","journal-title":"Ann. N.Y. Acad. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kelley, N., Jeltema, D., Duan, Y., and He, Y. (2019). The NLRP3 inflammasome: An overview of mechanisms of activation and regulation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133328"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1189\/jlb.3MR0516-224R","article-title":"Caspase-1 as a multifunctional inflammatory mediator: Noncytokine maturation roles","volume":"100","author":"Sun","year":"2016","journal-title":"J. Leukoc. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nature09663","article-title":"A role for mitochondria in NLRP3 inflammasome activation","volume":"469","author":"Zhou","year":"2011","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2183026","DOI":"10.1155\/2016\/2183026","article-title":"ROS-mediated NLRP3 inflammasome activation in brain, heart, kidney, and testis ischemia\/reperfusion injury","volume":"2016","author":"Minutoli","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e2025847118","DOI":"10.1073\/pnas.2025847118","article-title":"Soluble \u03b1-synuclein-antibody complexes activate the NLRP3 inflammasome in hiPSC-derived microglia","volume":"118","author":"Trudler","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/s41586-019-1769-z","article-title":"NLRP3 inflammasome activation drives tau pathology","volume":"575","author":"Ising","year":"2019","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"135279","DOI":"10.1016\/j.neulet.2020.135279","article-title":"\u03b2-Amyloid activates NLRP3 inflammasome via TLR4 in mouse microglia","volume":"736","author":"Liu","year":"2020","journal-title":"Neurosci. Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/s41418-018-0124-5","article-title":"MPTP-driven NLRP3 inflammasome activation in microglia plays a central role in dopaminergic neurodegeneration","volume":"26","author":"Lee","year":"2019","journal-title":"Cell Death Differ."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"643254","DOI":"10.3389\/fphar.2021.643254","article-title":"Neurodegenerative disease and the NLRP3 inflammasome","volume":"12","author":"Holbrook","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"101202","DOI":"10.1016\/j.arr.2020.101202","article-title":"Targeting microglial autophagic degradation in NLRP3 inflammasome-mediated neurodegenerative diseases","volume":"65","author":"Wu","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4184","DOI":"10.1128\/MCB.15.8.4184","article-title":"Cloning and characterization of a novel erythroid cell-derived CNC family transcription factor heterodimerizing with the small Maf family proteins","volume":"15","author":"Itoh","year":"1995","journal-title":"Mol. Cell. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.freeradbiomed.2015.06.021","article-title":"Mechanisms of activation of the transcription factor Nrf2 by redox stressors, nutrient cues, and energy status and the pathways through which it attenuates degenerative disease","volume":"88 Pt B","author":"Tebay","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.tins.2006.11.004","article-title":"Redox regulation of neuronal survival mediated by electrophilic compounds","volume":"30","author":"Satoh","year":"2007","journal-title":"Trends Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.freeradbiomed.2013.07.022","article-title":"Nrf2\/ARE-mediated antioxidant actions of pro-electrophilic drugs","volume":"65","author":"Satoh","year":"2013","journal-title":"Free Radic. Biol Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.12688\/f1000research.12111.1","article-title":"Recent advances in understanding NRF2 as a druggable target: Development of pro-electrophilic and non-covalent NRF2 activators to overcome systemic side effects of electrophilic drugs like dimethyl fumarate","volume":"6","author":"Satoh","year":"2017","journal-title":"F1000Research"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1073\/pnas.0505723102","article-title":"Activation of the Keap1\/Nrf2 pathway for neuroprotection by electrophilic phase II inducers","volume":"103","author":"Satoh","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1007\/s12272-016-0827-4","article-title":"Mitochondria and the NLRP3 inflammasome: Physiological and pathological relevance","volume":"39","author":"Yu","year":"2016","journal-title":"Arch. Pharm. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1038\/ni.3704","article-title":"Mitochondria are the powerhouses of immunity","volume":"18","author":"Mills","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5963","DOI":"10.1111\/jcmm.16357","article-title":"Verapamil inhibits early acute liver failure through suppressing the NLRP3 inflammasome pathway","volume":"25","author":"Han","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.cell.2013.02.054","article-title":"The adaptor MAVS promotes NLRP3 mitochondriallLocalization and inflammasome activation","volume":"153","author":"Subramanian","year":"2013","journal-title":"Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4358","DOI":"10.4049\/jimmunol.1301170","article-title":"The mitochondrial antiviral protein MAVS associates with NLRP3 and regulates its inflammasome activity","volume":"191","author":"Park","year":"2013","journal-title":"J. Immunol."},{"key":"ref_45","first-page":"697","article-title":"Hydrogen attenuates sepsis-associated encephalopathy by NRF2 mediated NLRP3 pathway inactivation","volume":"69","author":"Xie","year":"2020","journal-title":"Agents Actions"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.freeradbiomed.2019.01.003","article-title":"5-(3,4-Difluorophenyl)-3-(6-methylpyridin-3-yl)-1,2,4-oxadiazole (DDO-7263), a novel Nrf2 activator targeting brain tissue, protects against MPTP-induced subacute Parkinson\u2019s disease in mice by inhibiting the NLRP3 inflammasome and protects PC12 cells against oxidative stress","volume":"134","author":"Xu","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.bbrc.2012.03.049","article-title":"Real-time monitoring of inflammation status in 3T3-L1 adipocytes possessing a secretory Gaussia luciferase gene under the control of nuclear factor-\u03baB response element","volume":"420","author":"Nagasaki","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1016\/j.immuni.2021.05.004","article-title":"Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation","volume":"54","author":"Xian","year":"2021","journal-title":"Immunity"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/nrd1175","article-title":"Anti-TNF-\u03b1 therapies: The next generation","volume":"2","author":"Palladino","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1055\/s-0029-1240622","article-title":"Activated glutathione metabolism participates in protective effects of carnosic acid against oxidative stress in neuronal HT22 cells","volume":"76","author":"Tamaki","year":"2009","journal-title":"Planta Medica."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.neulet.2008.01.079","article-title":"Carnosic acid protects neuronal HT22 cells through activation of the antioxidant-responsive element in free carboxylic acid- and catechol hydroxyl moieties-dependent manners","volume":"434","author":"Satoh","year":"2008","journal-title":"Neurosci. Lett."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1021\/ac960506t","article-title":"Supercritical fluid extraction of natural antioxidants from rosemary:\u2009 comparison with liquid solvent sonication","volume":"69","author":"Tena","year":"1997","journal-title":"Anal. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1759091415593294","DOI":"10.1177\/1759091415593294","article-title":"Nrf2 and HSF-1 pathway activation via hydroquinone-based proelectrophilic small molecules is regulated by electrochemical oxidation potential","volume":"7","author":"Satoh","year":"2015","journal-title":"ASN Neuro."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.bbrc.2008.12.106","article-title":"Simple ortho- and para-hydroquinones as compounds neuroprotective against oxidative stress in a manner associated with specific transcriptional activation","volume":"379","author":"Satoh","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1111\/j.1471-4159.2007.05039.x","article-title":"Carnosic acid, a catechol-type electrophilic compound, protects neurons both in vitro and in vivo through activation of the Keap1\/Nrf2 pathway via S-alkylation of targeted cysteines on Keap1","volume":"104","author":"Satoh","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1021\/tx700302s","article-title":"Covalent modification at Cys151 dissociates the electrophile sensor Keap1 from the ubiquitin ligase CUL3","volume":"21","author":"Rachakonda","year":"2008","journal-title":"Chem. Res. Toxicol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e00099-20","DOI":"10.1128\/MCB.00099-20","article-title":"The molecular mechanisms regulating the KEAP1-NRF2 pathway","volume":"40","author":"Baird","year":"2020","journal-title":"Mol. Cell. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.freeradbiomed.2020.03.023","article-title":"Beyond repression of Nrf2: An update on Keap1","volume":"157","author":"Kopacz","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"E4048","DOI":"10.1073\/pnas.1613067114","article-title":"MEF2D haploinsufficiency downregulates the NRF2 pathway and renders photoreceptors susceptible to light-induced oxidative stress","volume":"114","author":"Nagar","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1111\/j.1471-4159.2011.07449.x","article-title":"Dual neuroprotective pathways of a pro-electrophilic compound via HSF-1-activated heat-shock proteins and Nrf2-activated phase 2 antioxidant response enzymes","volume":"119","author":"Satoh","year":"2011","journal-title":"J. Neurochem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1089\/neu.2018.6155","article-title":"Carnosic acid improves outcome after repetitive mild traumatic brain injury","volume":"36","author":"Maynard","year":"2019","journal-title":"J. Neurotrauma."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"7847","DOI":"10.1167\/iovs.12-10793","article-title":"Protective effect of carnosic acid, a pro-electrophilic compound, in models of oxidative stress and light-induced retinal degeneration","volume":"53","author":"Rezaie","year":"2012","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Schwager, J., Richard, N., Fowler, A., Seifert, N., and Raederstorff, D. (2016). Carnosol and related substances modulate chemokine and cytokine production in macrophages and chondrocytes. Molecules, 21.","DOI":"10.3390\/molecules21040465"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2680409","DOI":"10.1155\/2016\/2680409","article-title":"The Therapeutic Potential of rosemary (Rosmarinus officinalis) diterpenes for Alzheimer\u2019s disease","volume":"2016","author":"Habtemariam","year":"2016","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.phymed.2017.08.015","article-title":"A randomised double-blind placebo-controlled pilot trial of a combined extract of sage, rosemary and melissa, traditional herbal medicines, on the enhancement of memory in normal healthy subjects, including influence of age","volume":"39","author":"Perry","year":"2018","journal-title":"Phytomedicine"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e2499","DOI":"10.1038\/cddis.2016.389","article-title":"Therapeutic advantage of pro-electrophilic drugs to activate the Nrf2\/ARE pathway in Alzheimer\u2019s disease models","volume":"7","author":"Lipton","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.cbi.2014.11.011","article-title":"Carnosic acid protects against 6-hydroxydopamine-induced neurotoxicity in in vivo and in vitro model of Parkinson\u2019s disease: Involvement of antioxidative enzymes induction","volume":"225","author":"Wu","year":"2015","journal-title":"Chem. Interact."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1097\/01.wnr.0000239951.14954.10","article-title":"Carnosol, a component of rosemary (Rosmarinus officinalis L.) protects nigral dopaminergic neuronal cells","volume":"17","author":"Kim","year":"2006","journal-title":"NeuroReport"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Esteras, N., and Abramov, A.Y. (2020). Mitochondrial calcium deregulation in the mechanism of \u03b2-amyloid and tau pathology. Cells, 9.","DOI":"10.3390\/cells9092135"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1007\/s12035-016-9743-3","article-title":"Oxidative modification and its implications for the neurodegeneration of Parkinson\u2019s disease","volume":"54","author":"Zhao","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.tjog.2011.10.004","article-title":"Management of moderate toa severe Alzheimer\u2019s disease: Focus on memantine","volume":"50","author":"Dominguez","year":"2011","journal-title":"Taiwan J. Obstet Gynecol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.2174\/09298673113209990112","article-title":"Rationally designed multi-targeted agents against neurodegenerative diseases","volume":"20","author":"Geldenhuys","year":"2013","journal-title":"Curr. Med. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.jhep.2020.09.031","article-title":"COVID-19: Discovery, diagnostics and drug development","volume":"74","author":"Asselah","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.it.2020.11.002","article-title":"T cells: Warriors of SARS-CoV-2 infection","volume":"42","author":"Prattichizzo","year":"2021","journal-title":"Trends Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"570122","DOI":"10.3389\/fimmu.2020.570122","article-title":"Immune-boosting, antioxidant and anti-inflammatory food supplements targeting pathogenesis of COVID-19","volume":"11","author":"Mrityunjaya","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Uddin, M., Mustafa, F., Rizvi, T.A., Loney, T., Suwaidi, H.A., Al-Marzouqi, A.H.H., Eldin, A.K., Alsabeeha, N., Adrian, T.E., and Stefanini, C. (2020). SARS-CoV-2\/COVID-19: Viral genomics, epidemiology, vaccines, and therapeutic interventions. Viruses, 12.","DOI":"10.20944\/preprints202004.0005.v1"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.3389\/fimmu.2020.01518","article-title":"Targeting the NLRP3 Inflammasome in severe COVID-19","volume":"11","author":"Freeman","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s00011-020-01413-2","article-title":"Inflammasome formation in the lungs of patients with fatal COVID-19","volume":"70","author":"Toldo","year":"2020","journal-title":"Inflamm. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1007\/s00011-020-01389-z","article-title":"Coronavirus (Covid-19) sepsis: Revisiting mitochondrial dysfunction in pathogenesis, aging, inflammation, and mortality","volume":"69","author":"Shenoy","year":"2020","journal-title":"Inflamm. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1177\/1074248420958973","article-title":"COVID-19 infection: Viral macro- and micro-vascular coagulopathy and thromboembolism\/prophylactic and therapeutic management","volume":"26","author":"Manolis","year":"2021","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e23618","DOI":"10.1002\/jcla.23618","article-title":"Ferritin in the coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis","volume":"34","author":"Cheng","year":"2020","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s12026-020-09145-5","article-title":"COVID-19 as part of the hyperferritinemic syndromes: The role of iron depletion therapy","volume":"68","author":"Perricone","year":"2020","journal-title":"Immunol. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"650","DOI":"10.2174\/1381612826666201221150857","article-title":"Hydrogen gas therapy: From preclinical studies to clinical trials","volume":"27","author":"Sano","year":"2021","journal-title":"Curr. Pharm. Des."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13613-020-00792-3","article-title":"Pilot trial of high-dose vitamin C in critically ill COVID-19 patients","volume":"11","author":"Zhang","year":"2021","journal-title":"Ann. Intensiv. Care"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"117842","DOI":"10.1016\/j.lfs.2020.117842","article-title":"Crosstalk between endoplasmic reticulum stress and anti-viral activities: A novel therapeutic target for COVID-19","volume":"255","author":"Banerjee","year":"2020","journal-title":"Life Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"173288","DOI":"10.1016\/j.ejphar.2020.173288","article-title":"Endoplasmic reticulum as a potential therapeutic target for COVID-19 infection management?","volume":"882","author":"Sureda","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1080\/15548627.2020.1817280","article-title":"Coronavirus interactions with the cellular autophagy machinery","volume":"16","author":"Miller","year":"2020","journal-title":"Autophagy"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Fakhri, S., Nouri, Z., Moradi, S.Z., Akkol, E.K., Piri, S., Sobarzo-S\u00e1nchez, E., Farzaei, M.H., and Echeverr\u00eda, J. (2021). Targeting multiple signal transduction pathways of SARS-CoV-2: Approaches to COVID-19 therapeutic candidates. Molecules, 26.","DOI":"10.3390\/molecules26102917"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.tips.2020.07.003","article-title":"Can activation of NRF2 be a strategy against COVID-19?","volume":"41","author":"Cuadrado","year":"2020","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s13601-020-00362-7","article-title":"Nrf2-interacting nutrients and COVID-19: Time for research to develop adaptation strategies","volume":"10","author":"Bousquet","year":"2020","journal-title":"Clin. Transl. Allergy"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.freeradbiomed.2015.06.014","article-title":"p62 links autophagy and Nrf2 signaling","volume":"88","author":"Jiang","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1093\/jb\/mvp149","article-title":"Role of Nrf2 and p62\/ZIP in the neurite outgrowth by carnosic acid in PC12h cells","volume":"147","author":"Kosaka","year":"2010","journal-title":"J. Biochem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1002\/biof.1726","article-title":"Long-COVID syndrome-associated brain fog and chemofog: Luteolin to the rescue","volume":"47","author":"Theoharides","year":"2021","journal-title":"BioFactors"},{"key":"ref_94","first-page":"1","article-title":"Long COVID: Cognitive complaints (brain fog) and dysfunction of the cingulate cortex","volume":"Jun 18","author":"Hugon","year":"2021","journal-title":"J. Neurol"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"670298","DOI":"10.3389\/fncel.2021.670298","article-title":"Microglial implications in SARS-CoV-2 infection and COVID-19: Lessons from viral RNA neurotropism and possible relevance to Parkinson\u2019s disease","volume":"15","author":"Awogbindin","year":"2021","journal-title":"Front. Cell Neurosci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"570251","DOI":"10.3389\/fimmu.2020.570251","article-title":"NLRP3 inflammasome: The stormy link between obesity and COVID-19","volume":"11","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Mccarty, M.F., Iloki Assanga, S.B., Luj\u00e1n, L.L., O\u2019Keefe, J.H., and DiNicolantonio, J.J. (2020). Nutraceutical strategies for suppressing NLRP3 inflammasome activation: Pertinence to the management of COVID-19 and beyond. Nutrients, 13.","DOI":"10.3390\/nu13010047"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Mccord, J.M., Hybertson, B.M., Cota-Gomez, A., Geraci, K.P., and Gao, B. (2020). Nrf2 activator PB125\u00ae as a potential therapeutic agent against COVID-19. Antioxidants, 9.","DOI":"10.1101\/2020.05.16.099788"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.freeradbiomed.2021.05.033","article-title":"Nrf2 activator PB125\u00ae as a carnosic acid-based therapeutic agent against respiratory viral diseases, including COVID-19","volume":"175","author":"McCord","year":"2021","journal-title":"Free Radic. Biol Med."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Hybertson, B.M., Gao, B., Bose, S., and McCord, J.M. (2019). Phytochemical combination PB125 activates the Nrf2 pathway and induces cellular protection against oxidative injury. Antioxidants, 8.","DOI":"10.3390\/antiox8050119"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e829","DOI":"10.1016\/S2665-9913(21)00321-0","article-title":"IL-1 and IL-6 inhibition affects the neutralising activity of anti-SARS-CoV-2 antibodies in patients with COVID-19","volume":"3","author":"Criscuolo","year":"2021","journal-title":"Lancet Rheumatol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1126\/science.abc7520","article-title":"Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model","volume":"369","author":"Rogers","year":"2020","journal-title":"Science"},{"key":"ref_103","first-page":"738","article-title":"Nutraceuticals of anti-inflammatory activity as complementary therapy for rheumatoid arthritis","volume":"30","year":"2012","journal-title":"Toxicol. Ind. Heal."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1002\/ptr.1709","article-title":"A Pilot trial evaluating meta050, a proprietary combination of reduced iso-alpha acids, rosemary extract and oleanolic acid in patients with arthritis and fibromyalgia","volume":"19","author":"Lukaczer","year":"2005","journal-title":"Phytother. Res."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/1\/124\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:26:57Z","timestamp":1760362017000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/1\/124"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,6]]},"references-count":104,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["antiox11010124"],"URL":"https:\/\/doi.org\/10.3390\/antiox11010124","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.741514899.793593101","asserted-by":"object"}]},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,6]]}}}