Daphnane diterpenes from Daphne genkwa activate Nurr1 and have a neuroprotective effect in an animal model of Parkinson's disease

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dc.contributor.authorBaek Soo Han-
dc.contributor.authorKyoung Shim Kim-
dc.contributor.authorYu Jin Kim-
dc.contributor.authorHoe-Yune Jung-
dc.contributor.authorYoung Mi Kang-
dc.contributor.authorGyu Suk Lee-
dc.contributor.authorM J Sohn-
dc.contributor.authorC H Kim-
dc.contributor.authorK S Kim-
dc.contributor.authorWon Gon Kim-
dc.date.accessioned2017-04-19T10:24:58Z-
dc.date.available2017-04-19T10:24:58Z-
dc.date.issued2016-
dc.identifier.issn0163-3864-
dc.identifier.uri10.1021/acs.jnatprod.6b00110ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/13349-
dc.description.abstractNurr1 is an orphan nuclear receptor that is essential for the differentiation and maintenance of dopaminergic neurons in the brain, and it is a therapeutic target for Parkinson's disease (PD). During the screening for Nurr1 activators from natural sources using cell-based assay systems, a methanol extract of the combined stems and roots of Daphne genkwa was found to activate the transcriptional function of Nurr1 at a concentration of 3 μg/mL. The active components were isolated and identified as genkwanine N (1) and yuanhuacin (2). Both compounds 1 and 2 significantly enhanced the function of Nurr1 at 0.3 μM. Nurr1-specific siRNA abolished the activity of 1 and 2, strongly suggesting that transcriptional activation by 1 and 2 occurred through the modulation of Nurr1 function. Additionally, treatment with 1 and 2 inhibited 6-hydroxydopamine (6-OHDA)-induced neuronal cell death and lipopolysaccharide (LPS)-induced neuroinflammation. Moreover, in a 6-OHDA-lesioned rat model of PD, intraperitoneal administration of 2 (0.5 mg/kg/day) for 2 weeks significantly improved behavioral deficits and reduced tyrosine hydroxylase (TH)-positive dopaminergic neuron death induced by 6-OHDA injection and had a beneficial effect on the inflammatory response in the brain. Accordingly, compounds 1 and 2, the first reported Nurr1 activators of natural origin, are potential lead compounds for the treatment of PD-
dc.publisherAmer Chem Soc-
dc.titleDaphnane diterpenes from Daphne genkwa activate Nurr1 and have a neuroprotective effect in an animal model of Parkinson's disease-
dc.title.alternativeDaphnane diterpenes from Daphne genkwa activate Nurr1 and have a neuroprotective effect in an animal model of Parkinson's disease-
dc.typeArticle-
dc.citation.titleJournal of Natural Products-
dc.citation.number6-
dc.citation.endPage1609-
dc.citation.startPage1604-
dc.citation.volume79-
dc.contributor.affiliatedAuthorBaek Soo Han-
dc.contributor.affiliatedAuthorKyoung Shim Kim-
dc.contributor.affiliatedAuthorYu Jin Kim-
dc.contributor.affiliatedAuthorHoe-Yune Jung-
dc.contributor.affiliatedAuthorYoung Mi Kang-
dc.contributor.affiliatedAuthorGyu Suk Lee-
dc.contributor.affiliatedAuthorWon Gon Kim-
dc.contributor.alternativeName한백수-
dc.contributor.alternativeName김경심-
dc.contributor.alternativeName김유진-
dc.contributor.alternativeName정회윤-
dc.contributor.alternativeName강영미-
dc.contributor.alternativeName이규석-
dc.contributor.alternativeName손미진-
dc.contributor.alternativeName김천형-
dc.contributor.alternativeName김광수-
dc.contributor.alternativeName김원곤-
dc.identifier.bibliographicCitationJournal of Natural Products, vol. 79, no. 6, pp. 1604-1609-
dc.identifier.doi10.1021/acs.jnatprod.6b00110-
dc.description.journalClassY-
Appears in Collections:
Division of Research on National Challenges > Biodefense Research Center > 1. Journal Articles
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
Division of Research on National Challenges > Infectious Disease Research Center > 1. Journal Articles
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