{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:23:54Z","timestamp":1792632234524,"version":"4.5.0"},"reference-count":50,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"6","license":[{"start":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T00:00:00Z","timestamp":1592956800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2020,6,24]]},"DOI":"10.1167\/iovs.61.6.51","type":"journal-article","created":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T13:32:04Z","timestamp":1593005524000},"page":"51","source":"Crossref","is-referenced-by-count":63,"title":["Perillaldehyde Ameliorates\n                    <i>Aspergillus fumigatus<\/i>\n                    Keratitis by Activating the Nrf2\/HO-1 Signaling Pathway and Inhibiting Dectin-1-Mediated Inflammation"],"prefix":"10.1167","volume":"61","author":[{"given":"Yiqun","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liting","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingwen","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqiang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiqiu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.intimp.2014.09.011","article-title":"Role of TREM-1 in response to Aspergillus fumigatus infection in corneal epithelial cells","volume":"23","author":"Hu","year":"2014","journal-title":"Int Immunopharmacol"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1038\/nrmicro.2017.90","article-title":"Aspergillus fumigatus morphology and dynamic host interactions","volume":"15","author":"van de Veerdonk","year":"2017","journal-title":"Nat Rev Microbiol"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1167\/iovs.17-21887","article-title":"Aspergillus fumigatus increased PAR-2 expression and elevated proinflammatory cytokines expression through the pathway of PAR-2\/ERK1\/2 in cornea","volume":"59","author":"Niu","year":"2018","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"3593","DOI":"10.1167\/iovs.14-15989","article-title":"The role of LOX-1 in innate immunity to Aspergillus fumigatus in corneal epithelial cells","volume":"56","author":"Li","year":"2015","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"1314","DOI":"10.1126\/science.1221789","article-title":"Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis","volume":"336","author":"Iliev","year":"2012","journal-title":"Science"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/ni1408","article-title":"Dectin-1 is required for beta-glucan recognition and control of fungal infection","volume":"8","author":"Taylor","year":"2007","journal-title":"Nat Immunol"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"2728","DOI":"10.1167\/iovs.14-15982","article-title":"Inhibition of corneal inflammation by the resolvin E1","volume":"56","author":"Lee","year":"2015","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"e0150114","DOI":"10.1371\/journal.pone.0150114","article-title":"Inhibition of TREM-1 and dectin-1 alleviates the severity of fungal keratitis by modulating innate immune responses","volume":"11","author":"Zhong","year":"2016","journal-title":"PLoS One"},{"key":"bib9","first-page":"409","article-title":"Preliminary analysis on essential oil composition of Perilla L. cultivated in Lithuania","volume":"66","author":"Bumblauskiene","year":"2009","journal-title":"Acta Pol Pharm"},{"key":"bib10","doi-asserted-by":"crossref","DOI":"10.3390\/molecules24010102","article-title":"Ethnomedicinal, phytochemical and pharmacological investigations of Perilla frutescens (L.) Britt","volume":"24","author":"Ahmed","year":"2018","journal-title":"Molecules"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.phymed.2003.08.004","article-title":"Vasodilative effect of perillaldehyde on isolated rat aorta","volume":"12","author":"Takagi","year":"2005","journal-title":"Phytomedicine"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pbb.2013.10.026","article-title":"Effects of perillaldehyde on alternations in serum cytokines and depressive-like behavior in mice after lipopolysaccharide administration","volume":"116","author":"Ji","year":"2014","journal-title":"Pharmacol Biochem Behav"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"1673","DOI":"10.1271\/bbb.65.1673","article-title":"Anti-inflammatory and anti-allergic actions by oral administration of a Perilla leaf extract in mice","volume":"65","author":"Ueda","year":"2001","journal-title":"Biosci Biotechnol Biochem"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.lfs.2018.05.038","article-title":"Perilla aldehyde attenuates CUMS-induced depressive-like behaviors via regulating TXNIP\/TRX\/NLRP3 pathway in rats","volume":"206","author":"Song","year":"2018","journal-title":"Life Sci"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"3335","DOI":"10.1007\/s00253-017-8146-3","article-title":"Calcium and oxidative stress mediate perillaldehyde-induced apoptosis in Candida albicans","volume":"101","author":"Tian","year":"2017","journal-title":"Appl Microbiol Biotechnol"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"7404","DOI":"10.1021\/acs.jafc.6b03546","article-title":"Perillaldehyde, a promising antifungal agent used in food preservation, triggers apoptosis through a metacaspase-dependent pathway in Aspergillus flavus","volume":"64","author":"Tian","year":"2016","journal-title":"J Agric Food Chem"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"3443","DOI":"10.1021\/acs.jafc.8b00353","article-title":"Intestinal anti-inflammatory activity of perillaldehyde","volume":"66","author":"Uemura","year":"2018","journal-title":"J Agric Food Chem"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"G32","DOI":"10.1152\/ajpgi.00294.2014","article-title":"Perilla frutescens extract ameliorates DSS-induced colitis by suppressing proinflammatory cytokines and inducing anti-inflammatory cytokines","volume":"308","author":"Urushima","year":"2015","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.ijfoodmicro.2015.02.022","article-title":"Efficacy and possible mechanisms of perillaldehyde in control of Aspergillus niger causing grape decay","volume":"202","author":"Tian","year":"2015","journal-title":"Int J Food Microbiol"},{"key":"bib20","doi-asserted-by":"crossref","first-page":"9524657","DOI":"10.1155\/2018\/9524657","article-title":"Perillaldehyde inhibits AHR signaling and activates NRF2 antioxidant pathway in human keratinocytes","volume":"2018","author":"Fuyuno","year":"2018","journal-title":"Oxid Med Cell Longev"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"11624","DOI":"10.1038\/ncomms11624","article-title":"Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription","volume":"7","author":"Kobayashi","year":"2016","journal-title":"Nat Commun"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"3467","DOI":"10.4049\/jimmunol.173.5.3467","article-title":"Nrf2 is a key transcription factor that regulates antioxidant defense in macrophages and epithelial cells: protecting against the proinflammatory and oxidizing effects of diesel exhaust chemicals","volume":"173","author":"Li","year":"2004","journal-title":"J Immunol"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.bcp.2015.04.007","article-title":"Ascorbic acid reduces HMGB1 secretion in lipopolysaccharide-activated RAW 264.7 cells and improves survival rate in septic mice by activation of Nrf2\/HO-1 signals","volume":"95","author":"Kim","year":"2015","journal-title":"Biochem Pharmacol"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.jaut.2015.04.005","article-title":"Prophylactic and therapeutic treatment with a synthetic analogue of a parasitic worm product prevents experimental arthritis and inhibits IL-1beta production via NRF2-mediated counter-regulation of the inflammasome","volume":"60","author":"Rzepecka","year":"2015","journal-title":"J Autoimmun"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.freeradbiomed.2013.04.008","article-title":"The role of the Nrf2-mediated defense system in corneal epithelial wound healing","volume":"61","author":"Hayashi","year":"2013","journal-title":"Free radical biology & medicine"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1007\/s00403-015-1554-2","article-title":"The role of transcription factor Nrf2 in skin cells metabolism","volume":"307","author":"Gegotek","year":"2015","journal-title":"Arch Dermatol Res"},{"key":"bib27","doi-asserted-by":"crossref","DOI":"10.3390\/nu9030223","article-title":"Antioxidants for healthy skin: the emerging role of aryl hydrocarbon receptors and nuclear factor-erythroid 2-related factor-2","volume":"9","author":"Furue","year":"2017","journal-title":"Nutrients"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/jid.2011.194","article-title":"Identification of ketoconazole as an AhR-Nrf2 activator in cultured human keratinocytes: the basis of its anti-inflammatory effect","volume":"132","author":"Tsuji","year":"2012","journal-title":"J Invest Dermatol"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.fct.2016.11.023","article-title":"Phytochemical and phytopharmacological review of Perilla frutescens L. (Labiatae), a traditional edible-medicinal herb in China","volume":"108","author":"Yu","year":"2017","journal-title":"Food Chem Toxicol"},{"issue":"8","key":"bib30","doi-asserted-by":"publisher","first-page":"3379","DOI":"10.1167\/iovs.07-1515","article-title":"Heme oxygenase-1 induction attenuates corneal inflammation and accelerates wound healing after epithelial injury","volume":"49","author":"Patil","year":"2008 Aug","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"e00686","DOI":"10.1128\/IAI.00575-17","article-title":"Candida albicans beta-glucan-containing particles increase HO-1 expression in oral keratinocytes via a reactive oxygen species\/p38 mitogen-activated protein kinase\/Nrf2 pathway","volume":"86","author":"Ishida","year":"2018","journal-title":"Infect Immun"},{"key":"bib32","first-page":"371","article-title":"Experimental model of Fusarium solani keratitis in rats","volume":"4","author":"Zhu","year":"2011","journal-title":"Int J Ophthalmol"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"89","DOI":"10.3855\/jidc.7570","article-title":"The role of Mincle in innate immune to fungal keratitis","volume":"11","author":"Zhao","year":"2017","journal-title":"J Infect Dev Ctries"},{"key":"bib34","first-page":"52","article-title":"Characterization of three ocular clinical isolates of P. aeruginosa: Viability, biofilm formation, adherence, infectivity, and effects of glycyrrhizin","volume":"6","author":"Peng","year":"2017","journal-title":"Pathogens (Basel, Switzerland)"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1167\/iovs.17-22585","article-title":"Atovaquone impairs growth of Aspergillus and fusarium keratitis isolates by modulating mitochondrial function and zinc homeostasis","volume":"59","author":"Clark","year":"2018","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1167\/iovs.02-0446","article-title":"Experimental keratomycosis in a mouse model","volume":"44","author":"Wu","year":"2003","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.fct.2016.08.029","article-title":"Genotoxicity assessment of the flavouring agent, perillaldehyde","volume":"97","author":"Hobbs","year":"2016","journal-title":"Food Chem Toxicol"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1186\/s12886-018-0847-6","article-title":"Phospholipase Cgamma2 is critical for Ca(2+) flux and cytokine production in anti-fungal innate immunity of human corneal epithelial cells","volume":"18","author":"Peng","year":"2018","journal-title":"BMC Ophthalmol"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1038\/nri1785","article-title":"Neutrophils and immunity: challenges and opportunities","volume":"6","author":"Nathan","year":"2006","journal-title":"Nat Rev Immunol"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"E9618","DOI":"10.1073\/pnas.1708247114","article-title":"Necroptosis controls NET generation and mediates complement activation, endothelial damage, and autoimmune vasculitis","volume":"114","author":"Schreiber","year":"2017","journal-title":"Proc Natl Acad Sci USA"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/j.cell.2019.02.028","article-title":"Resident macrophages cloak tissue microlesions to prevent neutrophil-driven inflammatory damage","volume":"177","author":"Uderhardt","year":"2019","journal-title":"Cell"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.3389\/fmicb.2019.01466","article-title":"Effect of perillaldehyde on prophylaxis and treatment of vaginal candidiasis in a murine model","volume":"10","author":"Qu","year":"2019","journal-title":"Front Microbiol"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1016\/j.cell.2016.09.034","article-title":"beta-Glucan reverses the epigenetic state of LPS-induced immunological tolerance","volume":"167","author":"Novakovic","year":"2016","journal-title":"Cell"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"1251086","DOI":"10.1126\/science.1251086","article-title":"Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity","volume":"345","author":"Saeed","year":"2014","journal-title":"Science"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1089\/ars.2008.2292","article-title":"Fragrant unsaturated aldehydes elicit activation of the Keap1\/Nrf2 system leading to the upregulation of thioredoxin expression and protection against oxidative stress","volume":"11","author":"Masutani","year":"2009","journal-title":"Antioxid Redox Signal"},{"key":"bib46","doi-asserted-by":"crossref","first-page":"380218","DOI":"10.1155\/2015\/380218","article-title":"Punicalagin induces Nrf2\/HO-1 expression via upregulation of PI3K\/AKT pathway and inhibits LPS-induced oxidative stress in RAW264.7 macrophages","volume":"2015","author":"Xu","year":"2015","journal-title":"Mediators Inflamm"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1196\/annals.1427.036","article-title":"The Nrf2-ARE pathway: an indicator and modulator of oxidative stress in neurodegeneration","volume":"1147","author":"Johnson","year":"2008","journal-title":"Ann NY Acad Sci"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1073\/pnas.1014275108","article-title":"Brusatol enhances the efficacy of chemotherapy by inhibiting the Nrf2-mediated defense mechanism","volume":"108","author":"Ren","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1186\/s12886-015-0112-1","article-title":"Role of Dectin-1 in the innate immune response of rat corneal epithelial cells to Aspergillus fumigatus","volume":"15","author":"Xu","year":"2015","journal-title":"BMC Ophthalmol"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1021\/np010621l","article-title":"Carvone and perillaldehyde interfere with the serum-induced formation of filamentous structures in Candida albicans at substantially lower concentrations than those causing significant inhibition of growth","volume":"65","author":"McGeady","year":"2002","journal-title":"J Nat Prod"}],"container-title":["Investigative Opthalmology &amp; Visual Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2770186","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:31:21Z","timestamp":1791927081000},"score":1,"resource":{"primary":{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2770186"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,24]]},"references-count":50,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,6,3]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.61.6.51","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2020,6,24]]}}}