Journal of Pharmacological Sciences (Jan 2011)

Anti-neuroinflammatory Activity of Kamebakaurin From Isodon japonicus via Inhibition of c-Jun NH2-Terminal Kinase and p38 Mitogen-Activated Protein Kinase Pathway in Activated Microglial Cells

  • Byung-Wook Kim,
  • Sushruta Koppula,
  • In Su Kim,
  • Hyung-Woo Lim,
  • Sun-Min Hong,
  • Sang-Don Han,
  • Bang-Yeon Hwang,
  • Dong-Kug Choi

Journal volume & issue
Vol. 116, no. 3
pp. 296 – 308

Abstract

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Abstract.: Compelling evidence supports the notion that the majority of neurodegenerative diseases are associated with microglia-mediated neuroinflammation. Therefore, quelling of microglial activation may lead to neuronal cell survival. The present study investigated the effects of Kamebakaurin (KMBK), a kaurane diterpene isolated from Isodon japonicus HARA (Labiatae), on the production of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated cytotoxicity in rat primary microglial cultures and the BV-2 cell line. KMBK significantly inhibited the LPS-induced production of nitric oxide (NO) in a concentration-dependent fashion in activated microglial cells. The mRNA and protein levels of inducible nitric oxide synthase (iNOS) and cyclooxycenase-2 (COX-2) were also decreased dose-dependently. Furthermore KMBK inhibited the JNK and p38 mitogen-activated protein kinases (MAPKs) in LPS-stimulated BV-2 microglial cells. Considering the results obtained, the present study authenticated the potential benefits of KMBK as a therapeutic target in ameliorating microglia-mediated neuroinflammatory diseases. Keywords:: microglia, neuroinflammation, nitrite, inducible nitric oxide synthase, Kamebakaurin