Newly Synthesized 'Hidabeni' Chalcone Derivatives Potently Suppress LPS-Induced NO Production via Inhibition of STAT1, but Not NF-κB, JNK, and p38, Pathways in Microglia

• Hara Hirokazu

  Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University

• Ikeda Ryoko

  Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University

• Ninomiya Masayuki

  Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University

• Kamiya Tetsuro

  Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University

• Koketsu Mamoru

  Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University

• Adachi Tetsuo

  Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University

書誌事項

タイトル別名

• Newly Synthesized ‘Hidabeni’ Chalcone Derivatives Potently Suppress LPS-Induced NO Production <i>via</i> Inhibition of STAT1, but Not NF-κB, JNK, and p38, Pathways in Microglia

抄録

Chalcones are open-chain flavonoids that are biosynthesized in various plants. Some of them possess anti-inflammatory activity. We previously found that chalcone glycosides from Brassica rapa L. ‘hidabeni’ suppress lipopolysaccharide (LPS)-induced nitric oxide (NO) production in rat microglia highly aggressively proliferating immortalized (HAPI) cells. In this study, to explore chalcone derivatives with potent NO inhibitory activity, we synthesized ten compounds based on ‘hidabeni’ chalcone and examined their effects on LPS-triggered inducible NO synthase (iNOS) expression and NO production. Compounds C4 and C10 potently inhibited NO production (IC₅₀: 4.19, 2.88 µM, respectively). C4 and C10 suppressed LPS-induced iNOS expression via the inhibition of the signal transduction and activator of transcription 1 (STAT1), but not nuclear factor-kappa B (NF-κB), c-Jun N terminal kinase (JNK), and p38, pathways. C10, but not C4, inhibited activation of the MEK/extracellular signal-regulated kinase (ERK) pathway. C4 and C10 also suppressed LPS-induced expression of interferon regulatory factor 1 (IRF-1), which is an important transcription factor involved in iNOS expression. Our findings indicate that these chalcone derivatives are candidate compounds for preventing microglia-mediated neuroinflammation.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

  Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ 37 (6), 1042-1049, 2014

  公益社団法人 日本薬学会

キーワード

• microglia
• nitric oxide (NO)
• inducible NO synthase
• lipopolysaccharide
• interferon β
• signal transduction and activator of transcription 1 (STAT1)

詳細情報

• CRID: 1390282679607992448
• NII論文ID: 130004147351
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.b14-00116
• COI: 1:STN:280:DC%2BC2cjot1GgsQ%3D%3D
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 025478979
• PubMed: 24882415
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I025478979
• Web Site: https://www.jstage.jst.go.jp/article/bpb/37/6/37_b14-00116/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2015049395
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
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