Inhibition of nitric oxide production and inducible nitric oxide synthase expression by a polymethoxyflavone from young fruits of Citrus unshiu in rat primary astrocytes

Hideshi Ihara, Hideyuki Yamamoto, Tomoaki Ida, Hiroyasu Tsutsuki, Tatsuji Sakamoto, Tomoyuki Fujita, Toshiya Okada, Shunji Kozaki

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

Abnormal activation of astrocytes (e.g., the overproduction of cytokines and nitric oxide) is relevant to neurodegenerative disease. It is important, therefore, to search for inhibitors of the abnormal activation of astrocytes that can be derived from natural substances. This study focused on the effects of extracts from young fruits of Citrus unshiu on lipopolysaccharide (LPS)-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in rat primary astrocytes. The methanol extract of young citrus inhibited NO production in a concentration-dependent manner. After reverse-phase extraction of the extract, we found that polymethoxyflavone, nobiletin, 3,5,6,7,8,3′,4′-heptamethoxyflavone, and tangeletin inhibited NO production by primary astrocytes. These polymethoxyflavones also inhibited LPS-induced iNOS protein and mRNA expression by suppressing nuclear factor-κB (NF-κB) activation and p38-mitogen-activated protein kinase (MAPK) phosphorylation. To evaluate possible applications of these neuroprotective agents in vivo, we examined the effects of young citrus fruit on delayed neurodegeneration in hippocampal CA1 neurons of the Mongolian gerbil after global ischemia. Oral administration of young citrus fruit significantly suppressed delayed neuronal death in hippocampal CA1 neurons. This suggests a possible application of young citrus fruit as a neuroprotective agent.

Original languageEnglish
Pages (from-to)1843-1848
Number of pages6
JournalBioscience, Biotechnology and Biochemistry
Volume76
Issue number10
DOIs
Publication statusPublished - 2012

Keywords

  • Astrocytes
  • Neuroprotective agent
  • Nitric oxide
  • Polymethoxyflavone
  • Young citrus

ASJC Scopus subject areas

  • Biotechnology
  • Analytical Chemistry
  • Biochemistry
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Organic Chemistry

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