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

• Main Authors: Byung-Wook Kim (Author), Sushruta Koppula (Author), In Su Kim (Author), Hyung-Woo Lim (Author), Sun-Min Hong (Author), Sang-Don Han (Author), Bang-Yeon Hwang (Author), Dong-Kug Choi (Author)
• Format: Book
• Published: Elsevier, 2011-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1347-8613; 10.1254/jphs.10324FP
• Keywords: Therapeutics. Pharmacology; RM1-950
• Source: Journal of Pharmacological Sciences, Vol 116, Iss 3, Pp 296-308 (2011)

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