Anti-inflammatory effects of rhynchophylline and isorhynchophylline in mouse N9 microglial cells and the molecular mechanism

Dan Yuan, Bin Ma, Jing yu Yang, Yuan yuan Xie, Li Wang, Li jia Zhang, Yoshihiro Kano, Chun fu Wu

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Excessive production of nitric oxide (NO) and proinflammatory cytokines from activated microglia contributes to human neurodegenerative disorders. Our previous study demonstrated the potent inhibition of lipopolysaccharide (LPS)-induced NO production in rat primary microglial cells by rhynchophylline (RIN) and isorhynchophylline (IRN), a pair of isomeric alkaloids of Uncaria rhynchophylla (Miq.) Jacks. that has been used in China for centuries as a "cognitive enhancer" as well as to treat strokes. We further investigated whether RIN and IRN effectively suppress release of proinflammatory cytokines in LPS-activated microglial cells and the underling molecular mechanism for the inhibition of microglial activation. RIN and IRN concentration-dependently attenuated LPS-induced production of proinflammatory cytokines such as TNF-α and IL-1β as well as NO in mouse N9 microglial cells, with IRN showing more potent inhibition of microglial activation. The western blotting analysis indicated that the potential molecular mechanism for RIN or IRN-mediated attenuation was implicated in suppressions of iNOS protein level, phosphorylation of ERK and p38 MAPKs, and degradation of IκBα. In addition, the differential regulation of the three signaling pathways by two isomers was shown. Our results suggest that RIN and IRN may be effective therapeutic candidates for use in the treatment of neurodegenerative diseases accompanied by microglial activation.

Original languageEnglish (US)
Pages (from-to)1549-1554
Number of pages6
JournalInternational Immunopharmacology
Volume9
Issue number13-14
DOIs
StatePublished - Dec 2009

Keywords

  • Anti-inflammation
  • iNOS
  • Microglia
  • Oxindole alkaloid
  • Signaling pathway
  • TNF-α and IL-1β

PubMed: MeSH publication types

  • Comparative Study
  • Journal Article
  • Research Support, Non-U.S. Gov't

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