A pinusolide derivative, 15-methoxypinusolidic acid from Biota orientalis inhibits inducible nitric oxide synthase in microglial cells: implication for a potential anti-inflammatory effect.

Abstract

The inhibitory effect of 15-methoxypinusolidic acid (15-MPA) isolated from Biota orientalis (Cupressaceae) on lipopolysaccharide (LPS)-induced inflammation in microglial BV2 cells was investigated. 15-MPA significantly reduced the expression of inducible nitric oxide synthase (iNOS), the activity of iNOS, and the production of nitric oxide (NO) in LPS-stimulated BV2 cells. In addition, 15-MPA significantly suppressed the expressions of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and cyclooxygenase (COX)-2. However, 15-MPA did not affect LPS-induced degradation of inhibitor kappaB-alpha (IkappaB-alpha) and translocation of nuclear factor-kappaB (NF-kappaB) into the nucleus. LPS-activated p38 MAPK, extracellular signal-regulated kinase (ERK)-1/2, and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) were not affected by 15-MPA. Taken together, this study demonstrates that 15-MPA inhibits LPS-induced iNOS expression and NO production, independent on MAPK and NF-kappaB, suggesting a potential anti-inflammatory effect of the compound on microglial cells.

• Authors: Youngju Choi, Aree Moon, Young Choong Kim
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 8 Issue 4 Pg. 548-55 (Apr 2008) ISSN: 1567-5769 [Print] Netherlands
• PMID: 18328446 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 15-methoxypinusolidic acid
• Anti-Inflammatory Agents, Non-Steroidal
• Diterpenes
• I-kappa B Proteins
• Lipopolysaccharides
• NF-kappa B
• Nfkbia protein, mouse
• NF-KappaB Inhibitor alpha
• Nitric Oxide
• Nitric Oxide Synthase Type II
• Ptgs2 protein, mouse
• Cyclooxygenase 2
• Mitogen-Activated Protein Kinase 3
• p38 Mitogen-Activated Protein Kinases
• MAP Kinase Kinase 4

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Cell Line
• Cell Nucleus (metabolism)
• Cyclooxygenase 2 (metabolism)
• Diterpenes (pharmacology)
• I-kappa B Proteins (metabolism)
• Lipopolysaccharides (immunology)
• MAP Kinase Kinase 4 (metabolism)
• Mice
• Microglia (drug effects, enzymology, immunology, metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• NF-KappaB Inhibitor alpha
• NF-kappa B (metabolism)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Thuja
• p38 Mitogen-Activated Protein Kinases (drug effects, immunology, metabolism)