Daphnane and phorbol diterpenes, anti-neuroinflammatory compounds with Nurr1 activation from the roots and stems of Daphne genkwa = 팥꽃나무 줄기 뿌리에서 분리한 Nurr1 활성화 물질

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Title
Daphnane and phorbol diterpenes, anti-neuroinflammatory compounds with Nurr1 activation from the roots and stems of Daphne genkwa = 팥꽃나무 줄기 뿌리에서 분리한 Nurr1 활성화 물질
Author(s)
Baek Soo Han; N V Minh; Ha Young Choi; Jung Su ByunWon Gon Kim
Bibliographic Citation
Biological & Pharmaceutical Bulletin, vol. 40, no. 12, pp. 2205-2211
Publication Year
2017
Abstract
The methanol extract of the roots and stems of Daphne genkwa and its constituents yuanhuacin (1) and genkwanine N were previously reported to have Nurr1 activating effects and neuroprotective effects in an animal model of Parkinson’s disease (PD). In this study, four more daphnane-type diterpenes (acutilonine F (2), wikstroemia factor M1 (3), yuanhuadine (5), and yuanhuatine (6)) and two phorbol-type diterpenes (prostratin Q (4) and 12-O-n-deca-2,4,6-trienoyl-phorbol-(13)-acetate (7)) were isolated as Nurr1 activating compounds from the D. genkwa extract. Consistent with their higher Nurr1 activating activity, compounds 1, 4, 5, and 7 exhibited higher inhibitory activity on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine microglial BV-2 cells with an IC50 (μM) of 1?2, which was 15?30 times more potent than that of minocycline (29.9μM), a well-known anti-neuroinflammatory agent. Additionally, these diterpenes reduced expression and transcription of LPS-induced pro-inflammatory cytokines in BV-2 cells. Thus, the daphnane-type and phorbol-type diterpenes had anti-neuroinflammatory activity with Nurr1 activation and could be responsible for the anti-PD effect of the roots and stems of D. genkwa.
Keyword
Anti-neuroinflammatoryDaphnane-type diterpeneDaphne genkwaNurr1Phorbol-type diterpene
ISSN
0918-6158
Publisher
Pharmaceutical Soc Japan
DOI
http://dx.doi.org/10.1248/bpb.b17-00641
Type
Article
Appears in Collections:
Division of Research on National Challenges > Biodefense Research Center > 1. Journal Articles
Division of Research on National Challenges > Infectious Disease Research Center > 1. Journal Articles
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