{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:57:09Z","timestamp":1791478629963,"version":"4.3.4"},"reference-count":43,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2013,5,1]],"date-time":"2013-05-01T00:00:00Z","timestamp":1367366400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"name":"Grant for Biological Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacological Research"],"published-print":{"date-parts":[[2013,5]]},"DOI":"10.1016\/j.phrs.2013.02.002","type":"journal-article","created":{"date-parts":[[2013,2,18]],"date-time":"2013-02-18T16:07:02Z","timestamp":1361203622000},"page":"34-43","source":"Crossref","is-referenced-by-count":39,"special_numbering":"C","title":["A kavalactone derivative inhibits lipopolysaccharide-stimulated iNOS induction and NO production through activation of Nrf2 signaling in BV2 microglial cells"],"prefix":"10.1016","volume":"71","author":[{"given":"Riyako","family":"Terazawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nozomi","family":"Akimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Itoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunori","family":"Fujita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanako","family":"Hamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Deguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munekazu","family":"Iinuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mami","family":"Noda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Nozawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.phrs.2013.02.002_bib0005","doi-asserted-by":"crossref","first-page":"2766","DOI":"10.2174\/138161210793176572","article-title":"Neuroinflammation, oxidative stress and the pathogenesis of Alzheimer's disease","volume":"16","author":"Agostinho","year":"2010","journal-title":"Current Pharmaceutical Design"},{"key":"10.1016\/j.phrs.2013.02.002_bib0010","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1006\/bbrc.1997.6943","article-title":"An nrf2\/small maf heterodimer mediates the induction of phase ii detoxifying enzyme genes through antioxidant response elements","volume":"236","author":"Itoh","year":"1997","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"10.1016\/j.phrs.2013.02.002_bib0015","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.freeradbiomed.2004.04.033","article-title":"The pathways and molecular mechanisms regulating nrf2 activation in response to chemical stress","volume":"37","author":"Nguyen","year":"2004","journal-title":"Free Radical Biology and Medicine"},{"key":"10.1016\/j.phrs.2013.02.002_bib0020","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0304-3835(01)00695-4","article-title":"Molecular basis for the contribution of the antioxidant responsive element to cancer chemoprevention","volume":"174","author":"Hayes","year":"2001","journal-title":"Cancer Letters"},{"key":"10.1016\/j.phrs.2013.02.002_bib0025","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1042\/bj20021619","article-title":"Curcumin activates the haem oxygenase-1 gene via regulation of nrf2 and the antioxidant-responsive element","volume":"371","author":"Balogun","year":"2003","journal-title":"Biochemical Journal"},{"key":"10.1016\/j.phrs.2013.02.002_bib0030","doi-asserted-by":"crossref","first-page":"11908","DOI":"10.1073\/pnas.172398899","article-title":"Direct evidence that sulfhydryl groups of keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants","volume":"99","author":"Dinkova-Kostova","year":"2002","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10.1016\/j.phrs.2013.02.002_bib0035","doi-asserted-by":"crossref","first-page":"267","DOI":"10.2174\/1568007054038238","article-title":"The nrf2-are signalling pathway: promising drug target to combat oxidative stress in neurodegenerative disorders","volume":"4","author":"van Muiswinkel","year":"2005","journal-title":"Current Drug Targets - CNS & Neurological Disorders"},{"key":"10.1016\/j.phrs.2013.02.002_bib0040","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1016\/j.bcp.2010.07.014","article-title":"Signaling to heme oxygenase-1 and its anti-inflammatory therapeutic potential","volume":"80","author":"Paine","year":"2010","journal-title":"Biochemical Pharmacology"},{"key":"10.1016\/j.phrs.2013.02.002_bib0045","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/sj.bjp.0706336","article-title":"Oregonin inhibits lipopolysaccharide-induced iNOS gene transcription and upregulates ho-1 expression in macrophages and microglia","volume":"146","author":"Lee","year":"2005","journal-title":"British Journal of Pharmacology"},{"key":"10.1016\/j.phrs.2013.02.002_bib0050","doi-asserted-by":"crossref","first-page":"3809","DOI":"10.4049\/jimmunol.0712437","article-title":"The heme oxygenase-1\/carbon monoxide pathway suppresses tlr4 signaling by regulating the interaction of tlr4 with caveolin-1","volume":"182","author":"Wang","year":"2009","journal-title":"Journal of Immunology"},{"key":"10.1016\/j.phrs.2013.02.002_bib0055","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.neuint.2010.11.008","article-title":"Anti-inflammatory activity of xanthohumol involves heme oxygenase-1 induction via nrf2-are signaling in microglial bv2 cells","volume":"58","author":"Lee","year":"2011","journal-title":"Neurochemistry International"},{"key":"10.1016\/j.phrs.2013.02.002_bib0060","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.ejphar.2011.11.016","article-title":"Involvement of heme oxygenase-1 induction in the cytoprotective and immunomodulatory activities of 6,4\u2032-dihydroxy-7-methoxyflavanone in murine hippocampal and microglia cells","volume":"674","author":"Li","year":"2012","journal-title":"European Journal of Pharmacology"},{"key":"10.1016\/j.phrs.2013.02.002_bib0065","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1111\/j.1471-4159.2010.07075.x","article-title":"Anti-inflammatory mechanism of ginsenoside rh1 in lipopolysaccharide-stimulated microglia: critical role of the protein kinase a pathway and hemeoxygenase-1 expression","volume":"115","author":"Jung","year":"2010","journal-title":"Journal of Neurochemistry"},{"key":"10.1016\/j.phrs.2013.02.002_bib0070","series-title":"Food and nutrition in Fiji","first-page":"554","author":"Aalbersberg","year":"1991"},{"key":"10.1016\/j.phrs.2013.02.002_bib0075","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1124\/dmd.105.004317","article-title":"Pharmacokinetics and disposition of the kavalactone kawain: interaction with kava extract and kavalactones in vivo and in vitro","volume":"33","author":"Mathews","year":"2005","journal-title":"Drug Metabolism and Disposition: The Biological Fate of Chemicals"},{"key":"10.1016\/j.phrs.2013.02.002_bib0080","doi-asserted-by":"crossref","first-page":"731","DOI":"10.2165\/00023210-200216110-00002","article-title":"Therapeutic potential of kava in the treatment of anxiety disorders","volume":"16","author":"Singh","year":"2002","journal-title":"CNS Drugs"},{"key":"10.1016\/j.phrs.2013.02.002_bib0085","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1055\/s-2004-815533","article-title":"Kava hepatotoxicity: are we any closer to the truth","volume":"70","author":"Anke","year":"2004","journal-title":"Planta Medica"},{"key":"10.1016\/j.phrs.2013.02.002_bib0090","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0031-9422(03)00111-0","article-title":"Piperidine alkaloids from Piper methysticum","volume":"63","author":"Dragull","year":"2003","journal-title":"Phytochemistry"},{"key":"10.1016\/j.phrs.2013.02.002_bib0095","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s00213-009-1549-9","article-title":"The kava anxiety depression spectrum study (kadss): a randomized, placebo-controlled crossover trial using an aqueous extract of Piper methysticum","volume":"205","author":"Sarris","year":"2009","journal-title":"Psychopharmacology"},{"key":"10.1016\/j.phrs.2013.02.002_bib0100","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/0014-2999(92)90037-5","article-title":"Extract of kava (Piper methysticum) and its methysticin constituents protect brain tissue against ischemic damage in rodents","volume":"215","author":"Backhauss","year":"1992","journal-title":"European Journal of Pharmacology"},{"key":"10.1016\/j.phrs.2013.02.002_bib0105","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1124\/mol.107.042499","article-title":"Kavalactones protect neural cells against amyloid beta peptide-induced neurotoxicity via extracellular signal-regulated kinase 1\/2-dependent nuclear factor erythroid 2-related factor 2 activation","volume":"73","author":"Wruck","year":"2008","journal-title":"Molecular Pharmacology"},{"key":"10.1016\/j.phrs.2013.02.002_bib0110","doi-asserted-by":"crossref","first-page":"3133","DOI":"10.1016\/j.bmc.2010.03.034","article-title":"A novel kavalactone derivative protects against h2o2-induced pc12 cell death via nrf2\/are activation","volume":"18","author":"Tanaka","year":"2010","journal-title":"Bioorganic and Medicinal Chemistry"},{"key":"10.1016\/j.phrs.2013.02.002_bib0115","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/ni1001-907","article-title":"Nitric oxide and the immune response","volume":"2","author":"Bogdan","year":"2001","journal-title":"Nature Immunology"},{"key":"10.1016\/j.phrs.2013.02.002_bib0120","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1053\/berh.2001.0196","article-title":"The role of nitric oxide in tissue destruction","volume":"15","author":"Abramson","year":"2001","journal-title":"Best Practice and Research. Clinical Rheumatology"},{"key":"10.1016\/j.phrs.2013.02.002_bib0125","doi-asserted-by":"crossref","first-page":"13725","DOI":"10.1016\/S0021-9258(17)36703-0","article-title":"Regulation of biosynthesis of nitric oxide","volume":"269","author":"Nathan","year":"1994","journal-title":"Journal of Biological Chemistry"},{"key":"10.1016\/j.phrs.2013.02.002_bib0130","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1046\/j.1471-4159.1999.0722215.x","article-title":"Murine microglial cells produce and respond to interleukin-18","volume":"72","author":"Prinz","year":"1999","journal-title":"Journal of Neurochemistry"},{"key":"10.1016\/j.phrs.2013.02.002_bib0135","doi-asserted-by":"crossref","first-page":"3456","DOI":"10.1074\/jbc.M110244200","article-title":"A sulforaphane analogue that potently activates the nrf2-dependent detoxification pathway","volume":"277","author":"Morimitsu","year":"2002","journal-title":"Journal of Biological Chemistry"},{"key":"10.1016\/j.phrs.2013.02.002_bib0140","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1016\/S0006-2952(03)00422-2","article-title":"Inhibition of lipopolysaccharide-induced nitric oxide production by flavonoids in raw264.7 macrophages involves heme oxygenase-1","volume":"66","author":"Lin","year":"2003","journal-title":"Biochemical Pharmacology"},{"key":"10.1016\/j.phrs.2013.02.002_bib0145","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1096\/fasebj.2.10.3290025","article-title":"Heme oxygenase: Function, multiplicity, regulatory mechanisms, and clinical applications","volume":"2","author":"Maines","year":"1988","journal-title":"FASEB Journal"},{"key":"10.1016\/j.phrs.2013.02.002_bib0150","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.niox.2011.06.001","article-title":"Nitric oxide activates nrf2 through s-nitrosylation of keap1 in pc12 cells","volume":"25","author":"Um","year":"2011","journal-title":"Nitric Oxide"},{"key":"10.1016\/j.phrs.2013.02.002_bib0155","doi-asserted-by":"crossref","first-page":"C441","DOI":"10.1152\/ajpcell.2001.280.3.C441","article-title":"Ifn-gamma+lps induction of iNOS is modulated by erk, jnk\/sapk, and p38(mapk) in a mouse macrophage cell line","volume":"280","author":"Chan","year":"2001","journal-title":"American Journal of Physiology: Cell Physiology"},{"key":"10.1016\/j.phrs.2013.02.002_bib0160","doi-asserted-by":"crossref","first-page":"47950","DOI":"10.1074\/jbc.M106639200","article-title":"Lipopolysaccharide-induced expression of interferon-beta mediates the timing of inducible nitric-oxide synthase induction in raw 264.7 macrophages","volume":"276","author":"Jacobs","year":"2001","journal-title":"Journal of Biological Chemistry"},{"key":"10.1016\/j.phrs.2013.02.002_bib0165","doi-asserted-by":"crossref","first-page":"2736","DOI":"10.4049\/jimmunol.149.8.2736","article-title":"Activated microglia mediate neuronal cell injury via a nitric oxide mechanism","volume":"149","author":"Chao","year":"1992","journal-title":"Journal of Immunology"},{"key":"10.1016\/j.phrs.2013.02.002_bib0170","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1016\/0028-3908(94)90045-0","article-title":"Expression of inducible nitric oxide synthase causes delayed neurotoxicity in primary mixed neuronal-glial cortical cultures","volume":"33","author":"Dawson","year":"1994","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.phrs.2013.02.002_bib0175","doi-asserted-by":"crossref","first-page":"92","DOI":"10.4049\/jimmunol.181.1.92","article-title":"Dual role of cd38 in microglial activation and activation-induced cell death","volume":"181","author":"Mayo","year":"2008","journal-title":"Journal of Immunology"},{"key":"10.1016\/j.phrs.2013.02.002_bib0180","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.febslet.2004.07.042","article-title":"Zerumbone, atropical ginger sesquiterpene, activates phase II drug metabolizing enzymes","volume":"572","author":"Nakamura","year":"2004","journal-title":"FEBS Letters"},{"key":"10.1016\/j.phrs.2013.02.002_bib0185","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/j.bbrc.2008.02.018","article-title":"Preconditioning by sesquiterpene lactone enhances h2o2-induced nrf2\/are activation","volume":"368","author":"Umemura","year":"2008","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"10.1016\/j.phrs.2013.02.002_bib0190","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1007\/s10620-011-2012-4","article-title":"Alpha-lipoic acid prevents the induction of iNOS gene expression through destabilization of its mRNA in proinflammatory cytokine-stimulated hepatocytes","volume":"57","author":"Yamada","year":"2012","journal-title":"Digestive Diseases and Sciences"},{"key":"10.1016\/j.phrs.2013.02.002_bib0195","article-title":"Kaempferol inhibits prevotella intermedia lipopolysaccharide-induced production of nitric oxide through translational regulation in murine macrophages: critical role of heme oxygenase-1-mediated reactive oxygen species reduction","author":"Choi","year":"2012","journal-title":"Journal of Periodontology"},{"key":"10.1016\/j.phrs.2013.02.002_bib0200","doi-asserted-by":"crossref","first-page":"374542","DOI":"10.1155\/2011\/374542","article-title":"Peroxidation of n-3 polyunsaturated fatty acids inhibits the induction of iNOS gene expression in proinflammatory cytokine-stimulated hepatocytes","volume":"2011","author":"Araki","year":"2011","journal-title":"Journal of Nutrition and Metabolism"},{"key":"10.1016\/j.phrs.2013.02.002_bib0205","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1677\/JOE-08-0507","article-title":"Exendin-4 inhibits interleukin-1beta-induced iNOS expression at the protein level, but not at the transcriptional and posttranscriptional levels, in rinm5f beta-cells","volume":"202","author":"Kang","year":"2009","journal-title":"Journal of Endocrinology"},{"key":"10.1016\/j.phrs.2013.02.002_bib0210","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1016\/j.freeradbiomed.2004.08.017","article-title":"Dual role of camp in iNOS expression in glial cells and macrophages is mediated by differential regulation of p38-mapk\/atf-2 activation and iNOS stability","volume":"37","author":"Won","year":"2004","journal-title":"Free Radical Biology and Medicine"},{"key":"10.1016\/j.phrs.2013.02.002_bib0215","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1002\/jps.2600771203","article-title":"Uptake into mouse brain of four compounds present in the psychoactive beverage kava","volume":"77","author":"Keledjian","year":"1988","journal-title":"Journal of Pharmaceutical Sciences"}],"container-title":["Pharmacological Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661813000376?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661813000376?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T04:25:14Z","timestamp":1714969514000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1043661813000376"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5]]},"references-count":43,"alternative-id":["S1043661813000376"],"URL":"https:\/\/doi.org\/10.1016\/j.phrs.2013.02.002","relation":{},"ISSN":["1043-6618"],"issn-type":[{"value":"1043-6618","type":"print"}],"subject":[],"published":{"date-parts":[[2013,5]]}}}