Cited 31 time in
- Title
- Daphnane diterpenes from Daphne genkwa activate Nurr1 and have a neuroprotective effect in an animal model of Parkinson's disease
- Author(s)
- Baek Soo Han; Kyoung Shim Kim; Yu Jin Kim; Hoe-Yune Jung; Young Mi Kang; Gyu Suk Lee; M J Sohn; C H Kim; K S Kim; Won Gon Kim
- Bibliographic Citation
- Journal of Natural Products, vol. 79, no. 6, pp. 1604-1609
- Publication Year
- 2016
- Abstract
- Nurr1 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
- ISSN
- 0163-3864
- Publisher
- Amer Chem Soc
- DOI
- http://dx.doi.org/10.1021/acs.jnatprod.6b00110
- Type
- Article
- 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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