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Title 

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

Authors 

Baek Soo HanKyoung Shim KimYu Jin KimHoe-Yune JungYoung Mi KangGyu Suk LeeM J SohnC H KimK S KimWon Gon Kim

Publisher 

American Chemical Society

Issue Date 

2016

Citation 

Journal of Natural Products, vol. 79, no. 6, pp. 1604-1609

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

Link 

http://dx.doi.org/10.1021/acs.jnatprod.6b00110

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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