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  • 标题:Daphnane and Phorbol Diterpenes, Anti-neuroinflammatory Compounds with Nurr1 Activation from the Roots and Stems of Daphne genkwa
  • 本地全文:下载
  • 作者:Baek-Soo Han ; Nguyen Van Minh ; Ha-Young Choi
  • 期刊名称:Biological and Pharmaceutical Bulletin
  • 印刷版ISSN:0918-6158
  • 电子版ISSN:1347-5215
  • 出版年度:2017
  • 卷号:40
  • 期号:12
  • 页码:2205-2211
  • DOI:10.1248/bpb.b17-00641
  • 语种:English
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:

    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 (29.9 µM), 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 .

  • 关键词:Daphne genkwa;daphnane-type diterpene;Nurr1;phorbol-type diterpene;anti-neuroinflammatory
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