{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T12:40:51Z","timestamp":1791376851625,"version":"4.3.2"},"reference-count":43,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2019,11,8]],"date-time":"2019-11-08T00:00:00Z","timestamp":1573171200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009108","name":"Shandong University","doi-asserted-by":"publisher","award":["2015WLJH50"],"award-info":[{"award-number":["2015WLJH50"]}],"id":[{"id":"10.13039\/100009108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81673558"],"award-info":[{"award-number":["81673558"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81874341"],"award-info":[{"award-number":["81874341"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","em-consulte.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biomedicine & Pharmacotherapy"],"published-print":{"date-parts":[[2020,1]]},"DOI":"10.1016\/j.biopha.2019.109669","type":"journal-article","created":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T06:23:59Z","timestamp":1574144639000},"page":"109669","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":14,"special_numbering":"C","title":["Naturally-derived diterpenoid sphaeropsidin C as an activator of Nrf2\/ARE pathway and its potential capability of relieving intracellular oxidative stress in human lung epithelial cells"],"prefix":"10.1016","volume":"121","author":[{"given":"Guo-Hui","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai-Ling","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Mei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling-Yi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Ning","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"9","key":"10.1016\/j.biopha.2019.109669_bib0005","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/j.rmed.2009.04.014","article-title":"Oxidative stress in the pathogenesis of diffuse lung diseases: a review","volume":"103","author":"Bargagli","year":"2009","journal-title":"Respir. Med."},{"issue":"5-6","key":"10.1016\/j.biopha.2019.109669_bib0010","doi-asserted-by":"crossref","first-page":"241","DOI":"10.3109\/10408360903142326","article-title":"Oxidative stress and human diseases: origin, link, measurement, mechanisms, and biomarkers","volume":"46","author":"Giustarini","year":"2009","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"issue":"5","key":"10.1016\/j.biopha.2019.109669_bib0015","first-page":"BE07","article-title":"Diabetes mellitus and oxidative stress: a Co-relative and therapeutic approach","volume":"13","author":"Chandra","year":"2019","journal-title":"J. Clin. Diagn. Res."},{"key":"10.1016\/j.biopha.2019.109669_bib0020","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.lfs.2018.08.067","article-title":"Oxidative stress - chronic kidney disease - cardiovascular disease: a vicious circle","volume":"210","author":"Ravarotto","year":"2018","journal-title":"Life Sci."},{"key":"10.1016\/j.biopha.2019.109669_bib0025","doi-asserted-by":"crossref","DOI":"10.1155\/2017\/2525967","article-title":"Oxidative stress in neurodegenerative diseases: from molecular mechanisms to clinical applications","volume":"2017","author":"Liu","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"issue":"2","key":"10.1016\/j.biopha.2019.109669_bib0030","doi-asserted-by":"crossref","first-page":"117","DOI":"10.2174\/138920106776597676","article-title":"Chronic obstructive pulmonary disease and oxidative stress","volume":"7","author":"Domej","year":"2006","journal-title":"Curr. Pharm. Biotechnol."},{"key":"10.1016\/j.biopha.2019.109669_bib0035","first-page":"702","article-title":"Redox regulation by NRF2 in aging and disease, Free Radic","volume":"134","author":"Schmidlin","year":"2019","journal-title":"Biol. Med."},{"issue":"1","key":"10.1016\/j.biopha.2019.109669_bib0040","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ccell.2018.03.022","article-title":"NRF2 and the hallmarks of Cancer","volume":"34","author":"de la Vega","year":"2018","journal-title":"Cancer Cell"},{"issue":"20","key":"10.1016\/j.biopha.2019.109669_bib0045","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1101\/gad.225680.113","article-title":"The emerging role of the Nrf2-Keap1 signaling pathway in cancer","volume":"27","author":"Jaramillo","year":"2013","journal-title":"Dev. Genes Evol."},{"issue":"3","key":"10.1016\/j.biopha.2019.109669_bib0050","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.taap.2012.08.028","article-title":"Sulforaphane prevents pulmonary damage in response to inhaled arsenic by activating the Nrf2-defense response","volume":"265","author":"Zheng","year":"2012","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.biopha.2019.109669_bib0055","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1016\/j.freeradbiomed.2017.04.365","article-title":"Epigallocatechin gallate upregulates NRF2 to prevent diabetic nephropathy via disabling KEAP1","volume":"108","author":"Sun","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.biopha.2019.109669_bib0060","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.taap.2018.08.019","article-title":"Nrf2 in alcoholic liver disease","volume":"357","author":"Sun","year":"2018","journal-title":"Toxicol. Appl. Pharmacol."},{"issue":"4","key":"10.1016\/j.biopha.2019.109669_bib0065","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/s41573-018-0008-x","article-title":"Therapeutic targeting of the NRF2 and KEAP 1 partnership in chronic diseases","volume":"18","author":"Cuadrado","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.biopha.2019.109669_bib0070","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.phytochem.2018.06.016","article-title":"Lycodine-type alkaloids and their glycosides from Lycopodiastrum casuarinoides","volume":"154","author":"Wang","year":"2018","journal-title":"Phytochemistry"},{"key":"10.1016\/j.biopha.2019.109669_bib0075","article-title":"Curcumin provides hepatoprotection against amoebic liver abscess induced by Entamoeba histolytica in Hamster: involvement of Nrf2\/HO-1 and NF-kappa B\/IL-1 beta signaling pathways","volume":"2019","author":"Roberto Macias-Perez","year":"2019","journal-title":"J. Immunol. Res."},{"issue":"5","key":"10.1016\/j.biopha.2019.109669_bib0080","doi-asserted-by":"crossref","DOI":"10.3390\/nu11051082","article-title":"Natural dietary supplementation of curcumin protects mice brains against ethanol-induced oxidative stress-mediated neurodegeneration and memory impairment via Nrf2\/TLR4\/RAGE signaling","volume":"11","author":"Ikram","year":"2019","journal-title":"Nutrients"},{"key":"10.1016\/j.biopha.2019.109669_bib0085","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.bcp.2018.07.006","article-title":"Resveratrol represses estrogen-induced mammary carcinogenesis through NRF2-UGT1A8-estrogen metabolic axis activation","volume":"155","author":"Zhou","year":"2018","journal-title":"Biochem. Pharmacol."},{"issue":"6","key":"10.1016\/j.biopha.2019.109669_bib0090","first-page":"4339","article-title":"Resveratrol protects against oxidative stress by activating the Keap-1\/Nrf2 antioxidant defense system in obese-asthmatic rats","volume":"16","author":"Li","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"10.1016\/j.biopha.2019.109669_bib0095","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.redox.2017.09.004","article-title":"Identification of novel Nrf2 activators from Cinnamomum chartophyllum HW Li and their potential application of preventing oxidative insults in human lung epithelial cells","volume":"14","author":"Zhou","year":"2018","journal-title":"Redox Biol."},{"key":"10.1016\/j.biopha.2019.109669_bib0100","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.phymed.2018.09.022","article-title":"Lignan and flavonoid support the prevention of cinnamon against oxidative stress related diseases","volume":"53","author":"Li","year":"2019","journal-title":"Phytomedicine"},{"issue":"3","key":"10.1016\/j.biopha.2019.109669_bib0105","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1080\/10715762.2019.1582769","article-title":"An isopentenyl-substituted flavonoid norartocarpin activates Nrf2 signalling pathway and prevents oxidative insults in human lung epithelial cells","volume":"53","author":"Yang","year":"2019","journal-title":"Free Radic. Res."},{"issue":"6","key":"10.1016\/j.biopha.2019.109669_bib0110","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.bcp.2012.11.016","article-title":"The Nrf2 cell defence pathway: Keap1-dependent and -independent mechanisms of regulation","volume":"85","author":"Bryan","year":"2013","journal-title":"Biochem. Pharmacol."},{"issue":"7","key":"10.1016\/j.biopha.2019.109669_bib0115","doi-asserted-by":"crossref","first-page":"3514","DOI":"10.1111\/jcmm.13628","article-title":"Nrf2 attenuates inflammatory response in COPD\/emphysema: crosstalk with Wnt3a\/-catenin and AMPK pathways","volume":"22","author":"Cui","year":"2018","journal-title":"J. Cell. Mol. Med."},{"issue":"19","key":"10.1016\/j.biopha.2019.109669_bib0120","doi-asserted-by":"crossref","first-page":"3576","DOI":"10.1111\/febs.14379","article-title":"The role of Nrf2 signaling in counteracting neurodegenerative diseases","volume":"285","author":"Dinkova-Kostova","year":"2018","journal-title":"FEBS J."},{"key":"10.1016\/j.biopha.2019.109669_bib0125","doi-asserted-by":"crossref","DOI":"10.1155\/2017\/9237263","article-title":"The role of Nrf2 in cardiovascular function and disease","volume":"2017","author":"Satta","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"10.1016\/j.biopha.2019.109669_bib0130","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.ejphar.2018.10.026","article-title":"Nrf2, a novel molecular target to reduce type 1 diabetes associated secondary complications: The basic considerations","volume":"843","author":"Negi","year":"2019","journal-title":"Eur. J. Pharmacol."},{"issue":"5","key":"10.1016\/j.biopha.2019.109669_bib0135","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1158\/0008-5472.CAN-18-2723","article-title":"NRF2 activation in Cancer: from DNA to protein","volume":"79","author":"Cloer","year":"2019","journal-title":"Cancer Res."},{"issue":"10","key":"10.1016\/j.biopha.2019.109669_bib0140","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1039\/C7NP00040E","article-title":"Diterpenoids of terrestrial origin","volume":"34","author":"Hanson","year":"2017","journal-title":"Nat. Prod. Rep."},{"issue":"7","key":"10.1016\/j.biopha.2019.109669_bib0145","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1111\/bph.12054","article-title":"Andrographolide protects against cigarette smoke-induced oxidative lung injury via augmentation of Nrf2 activity","volume":"168","author":"Guan","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.biopha.2019.109669_bib0150","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.neuroscience.2012.10.018","article-title":"Involvement of nrf2 signaling pathway in the neuroprotective activity of natural kaurane diterpenes","volume":"231","author":"Gonzalez-Burgos","year":"2013","journal-title":"Neurosci."},{"key":"10.1016\/j.biopha.2019.109669_bib0155","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."},{"issue":"12","key":"10.1016\/j.biopha.2019.109669_bib0160","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/j.jnutbio.2015.08.001","article-title":"The complexity of the Nrf2 pathway: beyond the antioxidant response","volume":"26","author":"Huang","year":"2015","journal-title":"J. Nutr. Biochem."},{"issue":"45","key":"10.1016\/j.biopha.2019.109669_bib0165","first-page":"42769","article-title":"Phosphorylation of Nrf2 at Ser-40 by protein kinase C regulates antioxidant response element-mediated transcription","volume":"277","author":"Huang","year":"2002","journal-title":"J. Biochem. Chem."},{"issue":"11","key":"10.1016\/j.biopha.2019.109669_bib0170","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1016\/j.bcp.2005.03.015","article-title":"Role of PI3K\/Akt and MEK\/ERK signaling pathways in sulforaphane- and erucin-induced phase II enzymes and MRP2 transcription, G(2)\/M arrest and cell death in Caco-2 cells","volume":"69","author":"Jakubikova","year":"2005","journal-title":"Biochem. Pharmacol."},{"issue":"46","key":"10.1016\/j.biopha.2019.109669_bib0175","first-page":"28962","article-title":"Butylated hydroxyanisole and its metabolite tert-butylhydroquinone differentially regulate mitogen-activated protein kinases - the role of oxidative stress in the activation of mitogen-activated protein kinases by phenolic antioxidants","volume":"272","author":"Yu","year":"1997","journal-title":"J. Biochem. Chem."},{"issue":"17","key":"10.1016\/j.biopha.2019.109669_bib0180","doi-asserted-by":"crossref","first-page":"8804","DOI":"10.1158\/0008-5472.CAN-05-3513","article-title":"Mechanism of action of sulforaphane: inhibition of p38 mitogen-activated protein kinase isoforms contributing to the induction of antioxidant response element-mediated heme oxygenase-1 in human hepatoma HepG2 cells","volume":"66","author":"Keum","year":"2006","journal-title":"Cancer Res."},{"key":"10.1016\/j.biopha.2019.109669_bib0185","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.freeradbiomed.2019.06.001","article-title":"Novel diterpenoid-type activators of the Keap1\/Nrf2\/ARE signaling pathway and their regulation of redox homeostasis","volume":"141","author":"Li","year":"2019","journal-title":"Free Radic. Biol. Med."},{"issue":"3","key":"10.1016\/j.biopha.2019.109669_bib0190","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1039\/C8TX00298C","article-title":"A review of arsenic exposure and lung cancer","volume":"8","author":"Wei","year":"2019","journal-title":"Toxicol. Res."},{"issue":"11","key":"10.1016\/j.biopha.2019.109669_bib0195","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1111\/1346-8138.14620","article-title":"Immunological dysfunction in chronic arsenic exposure: from subclinical condition to skin cancer","volume":"45","author":"Yu","year":"2018","journal-title":"J. Dermatol."},{"issue":"5","key":"10.1016\/j.biopha.2019.109669_bib0200","doi-asserted-by":"crossref","DOI":"10.3390\/ijerph15050929","article-title":"Inorganic arsenic in drinking water and bladder Cancer: a meta-analysis for dose-response assessment (vol 3, pg 316, 2006)","volume":"15","author":"Chu","year":"2018","journal-title":"Int. J. Environ. Res. Public Health"},{"issue":"3","key":"10.1016\/j.biopha.2019.109669_bib0205","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1093\/jnci\/djx201","article-title":"Lung, bladder, and kidney Cancer mortality 40Years after arsenic exposure reduction","volume":"110","author":"Smith","year":"2018","journal-title":"J. Natl. Cancer Inst."},{"issue":"1-2","key":"10.1016\/j.biopha.2019.109669_bib0210","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s11010-005-8227-y","article-title":"Inorganic arsenic compounds cause oxidative damage to DNA and protein by inducing ROS and RNS generation in human keratinocytes","volume":"279","author":"Ding","year":"2005","journal-title":"Mol. Cell. Biochem."},{"issue":"1-2","key":"10.1016\/j.biopha.2019.109669_bib0215","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1023\/B:MCBI.0000007262.26044.e8","article-title":"Oxidative mechanism of arsenic toxicity and carcinogenesis","volume":"255","author":"Shi","year":"2004","journal-title":"Mol. Cell. Biochem."}],"container-title":["Biomedicine & Pharmacotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0753332219352916?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0753332219352916?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T12:07:06Z","timestamp":1778242026000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0753332219352916"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1]]},"references-count":43,"alternative-id":["S0753332219352916"],"URL":"https:\/\/doi.org\/10.1016\/j.biopha.2019.109669","relation":{},"ISSN":["0753-3322"],"issn-type":[{"value":"0753-3322","type":"print"}],"subject":[],"published":{"date-parts":[[2020,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Naturally-derived diterpenoid sphaeropsidin C as an activator of Nrf2\/ARE pathway and its potential capability of relieving intracellular oxidative stress in human lung epithelial cells","name":"articletitle","label":"Article Title"},{"value":"Biomedicine & Pharmacotherapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.biopha.2019.109669","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 The Authors. Published by Elsevier Masson SAS.","name":"copyright","label":"Copyright"}],"article-number":"109669"}}